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Whole-genome duplication (WGD) occurs in all kingdoms and impacts speciation, domestication, and cancer outcome. However, doubled DNA management can be challenging for nascent polyploids. The study of within-species polyploidy (autopolyploidy) permits focus on this DNA management aspect, decoupling it from the confounding effects of hybridization (in allopolyploid hybrids). How is autopolyploidy tolerated, and how do young polyploids stabilize? Here, we introduce a powerful model to address this: the genus Cochlearia, which has experienced many polyploidization events. We assess meiosis and other polyploid-relevant phenotypes, generate a chromosome-scale genome, and sequence 113 individuals from 33 ploidy-contrasting populations. We detect an obvious autopolyploidy-associated selection signal at kinetochore components and ion transporters. Modeling the selected alleles, we detail evidence of the kinetochore complex mediating adaptation to polyploidy. We compare candidates in independent autopolyploids across three genera separated by 40 million years, highlighting a common function at the process and gene levels, indicating evolutionary flexibility in response to polyploidy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To characterize the periosteal and endosteal arterial perfusion of the proximal phalanx using micro-computed tomography angiography (micro-CTA)., Methods: Cadaveric upper extremities were injected with a barium sulfate/gelatin suspension. Phalanges were imaged using micro-CTA and analyzed with a focus on osseous arterial anatomy. Periosteal and endosteal perfusion was characterized by number of vessels, length, anatomic course, and caliber., Results: The base of the proximal phalanx had a significantly greater number (8.0 ± 3.5) of periosteal vessels than those of the shaft (4.1 ± 1.6) and head (1.3 ± 1.1). One-third (34.4%) of the specimens demonstrated a complete absence of periosteal vessels in the head. A nutrient endosteal vessel was noted in 100% of the specimens. Entering at the junction of the middle and distal third of the bone (25.8 ± 3.9 mm from base), the nutrient vessel entered the proximal phalanx of the index finger along its ulnar aspect (8 of 8 specimens), the middle finger along its radial aspect (6 of 8), the ring finger along its ulnar aspect (5 of 8), and the little finger along its radial aspect (7 of 8). The nutrient vessel branched into proximal and distal extensions toward the shaft and head, respectively, with an average endosteal length of 10.7 ± 5.2 mm and average diameter of 0.36 ± 0.11 mm., Conclusions: Periosteal contributions to the perfusion of the proximal phalanx appear to diminish distally. The endosteal arterial anatomy remains consistent, with a single nutrient vessel entering the intramedullary canal with reliable laterality on each digit. This is often the only vessel supplying the head of the proximal phalanx, making this area particularly susceptible to vascular compromise., Clinical Relevance: An understanding of the patterns of perfusion of the proximal phalanx provides some insight into clinically observed pathology, as well as guidance for operative management., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Purpose: Patients with Kienbock disease can present with coronal fracture and collapse of the proximal lunate (Unified B2/Bain grade 1, 2B). Traditionally, this was considered unsalvageable. However, medial femoral trochlea (MFT) osteochondral reconstruction, used to recreate the proximal lunate surface, can be paired with reduction and repair of the coronal plane fracture, thus restoring midcarpal congruity. The purpose of this study was to report radiographic and clinical outcomes following lunate coronal fracture fixation at the time of MFT osteochondral reconstruction., Methods: This was a retrospective study performed at a single institution. We identified patients with Kienbock disease who underwent MFT osteochondral reconstruction from 2014 to 2023. Patients were included if they had a coronal fracture of the lunate distal articular surface fixed at the time of surgery. Radiographic and clinical parameters were evaluated, including carpal height ratio, union rate, presence of heterotopic ossification, need for revision surgery, and patient-reported outcome measures., Results: Thirty-three patients were included, with a mean age of 27.5 years (range: 15-41); 19 (58%) were women. Mean radiographic follow-up time was 5.8 months, and mean clinical follow-up time was 22.6 months. Union was achieved in 30/33 patients (91%). Carpal height ratio improved from 1.32 to 1.4. Two patients (6%) required reoperation, one for removal of heterotopic ossification and another for conversion to proximal row carpectomy. Patients demonstrated meaningful improvement in brief Michigan Hand Questionnaire and Patient-Reported Outcomes Measurement Information Upper Extremity scores. Range of motion before and after surgery was similar., Conclusions: Lunate coronal fracture fixation with MFT osteochondral reconstruction represents an additional management option in select patients with Kienbock disease. This technique restores the midcarpal joint during lunate reconstruction and may allow patients to avoid salvage procedures. Early radiographic and clinical outcomes are promising., Type of Study/level of Evidence: Therapeutic IV., Competing Interests: Conflicts of Interest No benefits in any form have been received or will be received related directly to this article., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Purpose: The medial femoral trochlea flap has been described as a method of scaphoid proximal pole nonunion reconstruction when the proximal pole is deemed nonsalvageable. The lateral femoral trochlea (LFT) is an alternative donor site providing a comparable vascularized convex osteochondral flap. We describe the technique and outcomes of our first 17 cases of LFT flap reconstruction of the proximal scaphoid pole with a minimum follow-up of 14 months., Methods: Seventeen of the first 24 patients who underwent LFT scaphoid reconstruction at 3 institutions were able to be contacted for clinical follow-up and chart reviews. We recorded patient age and sex, duration of nonunion, number of previous surgical procedures, details of surgical technique, achievement of osseous union, complications, additional postoperative procedures, preoperative and postoperative pain, and range of motion. Preoperative and postoperative scapholunate and radiolunate angles were analyzed on x-rays and achievement of osseous union on computerized tomography scans., Results: The average age of patients included was 35 years (range, 16-55 years). Follow-up data were recorded at an average of 33 months (range, 14-62 months). Ten patients had previous procedures (average, 1; range, 0-2). Median duration from trauma to LFT was 3.4 years (range, 8 months-12 years) among patients who had a recognized date of injury. Osseous healing was achieved in 16 of 17 patients and confirmed by computerized tomograpy scan. Twelve patients reported complete pain relief, while 5 reported partial pain relief. Final postoperative range of motion was 59°extension (range, 30°-85°) and 50° flexion (range, 10°-80°), which was comparable to preoperative values. Preoperative (59°) and postoperative (55°) scapholunate angles were similar to normal wrists., Conclusion: Vascularized LFT flaps provide an alternative donor site for vascularized osteochondral reconstruction of proximal pole scaphoid nonunion. Rate of union, range of motion, and pain relief are similar to reported results with medial femoral trochlea flap reconstruction., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Meiotic crossovers (COs) generate genetic diversity and are crucial for viable gamete production. Plant COs are typically limited to 1-3 per chromosome pair, constraining the development of improved varieties, which in wheat is exacerbated by an extreme distal localisation bias. Advances in wheat genomics and related technologies provide new opportunities to investigate, and possibly modify, recombination in this important crop species. Here, we investigate the disruption of FIGL1 in tetraploid and hexaploid wheat as a potential strategy for modifying CO frequency/position. We analysed figl1 mutants and virus-induced gene silencing lines cytogenetically. Genetic mapping was performed in the hexaploid. FIGL1 prevents abnormal meiotic chromosome associations/fragmentation in both ploidies. It suppresses class II COs in the tetraploid such that CO/chiasma frequency increased 2.1-fold in a figl1 msh5 quadruple mutant compared with a msh5 double mutant. It does not appear to affect class I COs based on HEI10 foci counts in a hexaploid figl1 triple mutant. Genetic mapping in the triple mutant suggested no significant overall increase in total recombination across examined intervals but revealed large increases in specific individual intervals. Notably, the tetraploid figl1 double mutant was sterile but the hexaploid triple mutant was moderately fertile, indicating potential utility for wheat breeding., (© 2024 The Authors. New Phytologist © 2024 New Phytologist Foundation.)

Vascularized bone flaps from the descending genicular artery system are versatile and effective for the use of recalcitrant nonunions from the tubular bones of the hand to the long bones of the upper extremity. Familiarity with the vascular pedicle, various techniques of harvest and inset, and skin paddle harvest and application are essential for the reconstructive surgeon., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We present the results of our 15th horizon scan of novel issues that could influence biological conservation in the future. From an initial list of 96 issues, our international panel of scientists and practitioners identified 15 that we consider important for societies worldwide to track and potentially respond to. Issues are novel within conservation or represent a substantial positive or negative step-change with global or regional extents. For example, new sources of hydrogen fuel and changes in deep-sea currents may have profound impacts on marine and terrestrial ecosystems. Technological advances that may be positive include benchtop DNA printers and the industrialisation of approaches that can create high-protein food from air, potentially reducing the pressure on land for food production., Competing Interests: Declaration of interests The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Meiotic crossovers can be formed through the interfering pathway, in which one crossover prevents another from forming nearby, or by an independent non-interfering pathway. In Arabidopsis, local sequence polymorphism between homologs can stimulate interfering crossovers in a MSH2-dependent manner. To understand how MSH2 regulates crossovers formed by the two pathways, we combined Arabidopsis mutants that elevate non-interfering crossovers with msh2 mutants. We demonstrate that MSH2 blocks non-interfering crossovers at polymorphic loci, which is the opposite effect to interfering crossovers. We also observe MSH2-independent crossover inhibition at highly polymorphic sites. We measure recombination along the chromosome arms in lines differing in patterns of heterozygosity and observe a MSH2-dependent crossover increase at the boundaries between heterozygous and homozygous regions. Here, we show that MSH2 is a master regulator of meiotic DSB repair in Arabidopsis, with antagonistic effects on interfering and non-interfering crossovers, which shapes the crossover landscape in relation to interhomolog polymorphism., (© 2023. Springer Nature Limited.)

Background: Free fibula flap (FFF) and medial femoral condyle (MFC) flap are commonly used for upper extremity osseous reconstruction, yet donor-site morbidity has never been systematically compared., Methods: Patients who underwent an FFF or MFC for upper extremity extra-carpal osseous reconstruction at 3 academic hand centers were retrospectively identified. Only patients who underwent reconstruction for a defect in which either flap type is routinely used or has been described in the literature were deemed eligible. Patients who agreed to participate were asked to complete the Lower Extremity Functional Scale (LEFS) and Lower Limb Core Scale (LLCS). The reported population norm median score of LEFS is 77 points. The LLCS population norm mean score is 90.52 points., Results: Twenty-one patients (10 MFC, 11 FFF) were enrolled. The median LEFS score for patients after MFC was 76 (interquartile range [IQR], 49-80) points and 75 (IQR, 56-79) points after FFF. The median LLCS score for patients after MFC was 96.4 (IQR, 87.9-100) points and 100 (IQR, 91-100) points after FFF. Median LEFS scores were slightly below the population norm, whereas median LLCS scores were above the norm for both FFF and MFC. All patients stated they would have the surgery again and that any dysfunction or pain in the leg was justified by the benefit in the arm., Conclusions: When considering whether to use an MFC or FFF for upper extremity reconstruction, both flap types appear to result in modest and comparable donor-site morbidity.

Background: Which treatments patients continue to use more than 1 year after primary thumb carpometacarpal arthritis surgery, and how such use relates to patient-reported outcomes, is largely unknown., Methods: The authors identified patients who had isolated primary trapeziectomy alone or with ligament reconstruction ± tendon interposition and were 1 to 4 years postoperative. Participants completed a surgical site-focused electronic questionnaire about what treatments they still used. Patient-reported outcome measures were the Quick Disability of the Arm, Shoulder, and Hand questionnaire and visual analog/numerical rating scales for current pain, pain with activities, and typical worst pain., Results: A total of 112 patients met inclusion and exclusion criteria and participated. At a median of 3 years after surgery, over 40% reported current use of at least one treatment for their thumb carpometacarpal surgical site, with 22% using more than one treatment. Of those who still used treatments, 48% used over-the-counter medications, 34% used home or office-based hand therapy, 29% used splinting, 25% used prescription medications, and 4% used corticosteroid injections. A total of 108 participants completed all patient-reported outcome measures. With bivariate analyses, the authors found that use of any treatment after recovering from surgery was associated with statistically and clinically significantly worse scores for all measures., Conclusions: Clinically relevant proportions of patients continue to use various treatments a median of 3 years after primary thumb carpometacarpal arthritis surgery. Continued use of any treatment is associated with significantly worse patient-reported outcomes for function and pain., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Landscape fires are a natural component of the Earth System. However, they are of growing global concern due to climate change exacerbating their multiple impacts on biodiversity, ecosystems, carbon storage, human health, economies, and wider society. Temperate regions are predicted to be at greatest risk of increasing fire activity due to climate change, where fires can seriously impact important ecosystems for biodiversity and carbon storage, such as peatlands and forests. There is insufficient literature on the background prevalence, distribution, and drivers of fires in these regions, especially within Europe, to assess and mitigate their risks. Using a global database of fire patches based on the MODIS FireCCI51 product, we address this knowledge gap by quantifying the current prevalence and size of fires in Polesia, a 150,000 km 2 area comprising a mosaic of peatland, forest, and agricultural habitats in northern Ukraine and southern Belarus. Between 2001 and 2019, fires burned 31,062 km 2 of land, and were most frequent in spring and autumn. Although most fires started in agricultural land, fires disproportionately affected natural and semi-natural land cover types, particularly in protected areas. Over one fifth of protected land burned. Coniferous forests were the most common land cover type in protected areas, but fires mostly occurred in meadows, open peatlands (especially fen and transition mires), and native deciduous forests. These land cover types were highly susceptible to fires under low soil moisture conditions, but the risk of fire was low under average or higher soil moisture conditions. Restoring and maintaining natural hydrological regimes could be an effective nature-based solution to increase the resilience of fire-vulnerable ecosystems and support global biodiversity and carbon storage commitments under the United Nations Framework Conventions on Climate Change and Convention on Biological Diversity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Failure to adapt migration timing to changes in environmental conditions along migration routes and at breeding locations can result in mismatches across trophic levels, as occurs between the brood parasitic common cuckoo Cuculus canorus and its hosts. Using satellite tracking data from 87 male cuckoos across 11 years, we evaluate why the cuckoo has not advanced its arrival to the UK. Across years, breeding ground arrival was primarily determined by timing of departure from stopover in West Africa before northward crossing of the Sahara. Together with high population synchrony and low apparent endogenous control of this event, this suggests that a seasonal ecological constraint operating here limits overall variation in breeding grounds arrival, although this event was itself influenced by carry-over from timing of arrival into tropical Africa. Between-year variation within individuals was, in contrast, mostly determined by northward migration through Europe, probably due to weather conditions. We find evidence of increased mortality risk for (a) early birds following migration periods positively impacting breeding grounds arrival, and (b) late birds, possibly suffering energy limitation, after departure from the breeding grounds. These results help identify areas where demands of responding to global change can potentially be alleviated by improving stopover quality.

During meiosis, the chromosome axes and synaptonemal complex mediate chromosome pairing and homologous recombination to maintain genomic stability and accurate chromosome segregation. In plants, ASYNAPSIS 1 (ASY1) is a key component of the chromosome axis that promotes inter-homolog recombination, synapsis and crossover formation. Here, the function of ASY1 has been cytologically characterized in a series of hypomorphic wheat mutants. In tetraploid wheat, asy1 hypomorphic mutants experience a reduction in chiasmata (crossovers) in a dosage-specific manner, resulting in failure to maintain crossover (CO) assurance. In mutants with only one functional copy of ASY1, distal chiasmata are maintained at the expense of proximal and interstitial chiasmata, indicating that ASY1 is required to promote chiasma formation away from the chromosome ends. Meiotic prophase I progression is delayed in asy1 hypomorphic mutants and is arrested in asy1 null mutants. In both tetraploid and hexaploid wheat, single asy1 mutants exhibit a high degree of ectopic recombination between multiple chromosomes at metaphase I. To explore the nature of the ectopic recombination, Triticum turgidum asy1b-2 was crossed with wheat-wild relative Aegilops variabilis . Homoeologous chiasmata increased 3.75-fold in Ttasy1b-2/Ae. variabilis compared to wild type/ Ae. variabilis , indicating that ASY1 suppresses chiasma formation between divergent, but related chromosomes. These data suggest that ASY1 promotes recombination along the chromosome arms of homologous chromosomes whilst suppressing recombination between non-homologous chromosomes. Therefore, asy1 mutants could be utilized to increase recombination between wheat wild relatives and elite varieties for expediting introgression of important agronomic traits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Di Dio, Serra, Sourdille and Higgins.)

Large-scale declines in terrestrial insects have been reported over much of Europe and across the world, however, population change assessments of other key invertebrate groups, such as soil invertebrates, have been largely neglected through a lack of available monitoring data. This study collates historic data from previously published studies to assess whether it is possible to infer previously undocumented long-term changes in soil invertebrate abundance. Earthworm and tipulid data were collated from over 100 studies across the UK, spanning almost 100 years. Analyses suggested long-term declines in earthworm abundance of between 1.6 to 2.1% per annum, equivalent to a 33% to 41% decline over 25 years. These appeared greatest in broadleaved woodlands and farmland habitats, and were greater in pasture than arable farmland. Significant differences in earthworm abundance between habitats varied between models but appeared to be highest in urban greenspaces and agricultural pasture. More limited data were available on tipulid abundance, which showed no significant change over time or variation between enclosed farmland and unenclosed habitats. Declines in earthworm populations could be contributing to overall declines in ecosystem function and biodiversity as they are vital for a range of ecosystem services and are keystone prey for many vertebrate species. If robust, our results identify a previously undetected biodiversity decline that would be a significant conservation and economic issue in the UK, and if replicated elsewhere, internationally. We highlight the need for long-term and large-scale soil invertebrate monitoring, which potentially could be carried out by citizen/community scientists., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Barnes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Reproductive success hinges on precisely coordinated meiosis, yet our understanding of how structural rearrangements of chromatin and phase transitions during meiosis are transcriptionally regulated is limited. In crop plants, detailed analysis of the meiotic transcriptome could identify regulatory genes and epigenetic regulators that can be targeted to increase recombination rates and broaden genetic variation, as well as provide a resource for comparison among eukaryotes of different taxa to answer outstanding questions about meiosis. We conducted a meiotic stage-specific analysis of messenger RNA (mRNA), small non-coding RNA (sncRNA), and long intervening/intergenic non-coding RNA (lincRNA) in wheat (Triticum aestivum L.) and revealed novel mechanisms of meiotic transcriptional regulation and meiosis-specific transcripts. Amidst general repression of mRNA expression, significant enrichment of ncRNAs was identified during prophase I relative to vegetative cells. The core meiotic transcriptome was comprised of 9309 meiosis-specific transcripts, 48 134 previously unannotated meiotic transcripts, and many known and novel ncRNAs differentially expressed at specific stages. The abundant meiotic sncRNAs controlled the reprogramming of central metabolic pathways by targeting genes involved in photosynthesis, glycolysis, hormone biosynthesis, and cellular homeostasis, and lincRNAs enhanced the expression of nearby genes. Alternative splicing was not evident in this polyploid species, but isoforms were switched at phase transitions. The novel, stage-specific regulatory controls uncovered here challenge the conventional understanding of this crucial biological process and provide a new resource of requisite knowledge for those aiming to directly modulate meiosis to improve crop plants. The wheat meiosis transcriptome dataset can be queried for genes of interest using an eFP browser located at https://bar.utoronto.ca/efp_wheat/cgi-bin/efpWeb.cgi?dataSource=Wheat_Meiosis., (© 2023 National Research Council Canada and The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd. Reproduced with the permission of the Minister of Innovation, Science, and Economic Development.)

Purpose: The purpose of this study was to evaluate the use of an AI conversational agent during the postoperative recovery of patients undergoing elective hip arthroscopy., Methods: Patients undergoing hip arthroscopy were enrolled in a prospective cohort for their first 6 weeks following surgery. Patients used standard SMS text messaging to interact with an artificial intelligence (AI) chatbot ("Felix") used to initiate automated conversations regarding elements of postoperative recovery. Patient satisfaction was measured at 6 weeks after surgery using a Likert scale survey. Accuracy was determined by measuring the appropriateness of chatbot responses, topic recognition, and examples of confusion. Safety was measured by evaluating the chatbot's responses to any questions with potential medical urgency., Results: Twenty-six patients were enrolled with a mean age of 36 years, and 58% ( n  = 15) were male. Overall, 80% of patients ( n  = 20) rated the helpfulness of Felix as good or excellent. In the postoperative period, 12/25 (48%) patients reported being worried about a complication but were reassured by Felix and, thus, did not seek medical attention. Of a total of 128 independent patient questions, Felix handled 101/128 questions appropriately (79%), either by addressing them independently, or facilitating contact with the care team. Felix was able to adequately answer the patient question independently 31% of the time ( n  = 40/128). Of 10 patient questions that were thought to potentially represent patient complications, in 3 cases Felix did not adequately address or recognize the health concern-none of these situations resulted in patient harm., Conclusion: The results of this study demonstrate that the use of a chatbot or conversational agent can enhance the postoperative experience for hip arthroscopy patients, as demonstrated by high levels of patient satisfaction., Levels of Evidence: Level IV, therapeutic case series., (© 2023 The Authors.)

Background: The medial femoral trochlea (MFT) osteochondral flap is employed for reconstruction of unsalvageable scaphoid proximal pole nonunions. The convex surface of the cartilage-bearing proximal trochlea is used to replace the similarly contoured proximal scaphoid and articulate with the concave scaphoid fossa of the radius. A magnetic resonance imaging (MRI) comparison of the shape of the MFT as it relates to the native proximal scaphoid has not been previously performed. Our study aimed to quantifiably compare the shape of the MFT, proximal scaphoid, and scaphoid fossa., Methods: Using imaging processing software, we measured radius of curvature of the articular segments in MRI scans of 10 healthy subjects' wrists and knees., Results: Compared with the scaphoid fossa, average ratio of the radius of circumference of the proximal scaphoid was 0.79 and 0.78 in the coronal and sagittal planes, respectively. Compared with the scaphoid fossa, average ratio of the radius of circumference of the MFT was 0.98 and 1.31 in the coronal and sagittal planes, respectively. The radius of curvature of the MFT was larger than the proximal scaphoid, in the coronal and sagittal planes. In the coronal plane, the MFT radius of curvature is nearly identical to the scaphoid fossa, a closer match than the scaphoid itself. In the sagittal plane, the radius of curvature of the MFT was larger than the radius of curvature of the scaphoid fossa., Conclusions: Our data suggest that the radius of curvature, in the sagittal and coronal planes, of the MFT and proximal scaphoid is disparate.

Increasing crop yields through plant breeding is time consuming and laborious, with the generation of novel combinations of alleles being limited by chromosomal linkage blocks and linkage-drag. Meiotic recombination is essential to create novel genetic variation via the reshuffling of parental alleles. The exchange of genetic information between homologous chromosomes occurs at crossover (CO) sites but CO frequency is often low and unevenly distributed. This bias creates the problem of linkage-drag in recombination 'cold' regions, where undesirable variation remains linked to useful traits. In plants, programmed meiosis-specific DNA double-strand breaks, catalysed by the SPO11 complex, initiate the recombination pathway, although only ~5% result in the formation of COs. To study the role of SPO11-1 in wheat meiosis, and as a prelude to manipulation, we used CRISPR/Cas9 to generate edits in all three SPO11-1 homoeologues of hexaploid wheat. Characterization of progeny lines shows plants deficient in all six SPO11-1 copies fail to undergo chromosome synapsis, lack COs and are sterile. In contrast, lines carrying a single copy of any one of the three wild-type homoeologues are phenotypically indistinguishable from unedited plants both in terms of vegetative growth and fertility. However, cytogenetic analysis of the edited plants suggests that homoeologues differ in their ability to generate COs and in the dynamics of synapsis. In addition, we show that the transformation of wheat mutants carrying six edited copies of SPO11-1 with the TaSPO11-1B gene, restores synapsis, CO formation, and fertility and hence opens a route to modifying recombination in this agronomically important crop., (© 2022 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Studies investigating the effects of language intervention on the re-organization of language networks in chronic aphasia have resulted in mixed findings, likely related to-among other factors-the language function targeted during treatment. The present study investigated the effects of the type of treatment provided on neural reorganization. Seventy individuals with chronic stroke-induced aphasia, recruited from three research laboratories and meeting criteria for agrammatism, anomia or dysgraphia were assigned to either treatment (N = 51) or control (N = 19) groups. Participants in the treatment group received 12-weeks of language intervention targeting sentence comprehension/production, naming, or spelling. At baseline and post-testing, all participants performed an fMRI story comprehension task, with blocks of auditorily-presented stories alternated with blocks of reversed speech. Participants in the treatment, but not control, group significantly improved in the treated language domain. FMRI region-of-interest (ROI) analyses, conducted within regions that were either active (or homologous to active) regions in a group of 22 healthy participants on the story comprehension task, revealed a significant increase in activation from pre-to post-treatment in right-hemisphere homologues of these regions for participants in the sentence and spelling, but not naming, treatment groups, not predicted by left-hemisphere lesion size. For the sentence (but not the spelling) treatment group, activation changes within right-hemisphere homologues of language regions were positively associated with changes in measures of verb and sentence comprehension. These findings support previous research pointing to recruitment of right hemisphere tissue as a viable route for language recovery and suggest that sentence-level treatment may promote greater neuroplasticity on naturalistic, language comprehension tasks, compared to word-level treatment., Competing Interests: Declaration of competing interest Drs Thompson and Kiran serve as Associate Editors for Cortex. The other authors have no conflicts of interest to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We present the results of our 14th horizon scan of issues we expect to influence biological conservation in the future. From an initial set of 102 topics, our global panel of 30 scientists and practitioners identified 15 issues we consider most urgent for societies worldwide to address. Issues are novel within biological conservation or represent a substantial positive or negative step change at global or regional scales. Issues such as submerged artificial light fisheries and accelerating upper ocean currents could have profound negative impacts on marine or coastal ecosystems. We also identified potentially positive technological advances, including energy production and storage, improved fertilisation methods, and expansion of biodegradable materials. If effectively managed, these technologies could realise future benefits for biological diversity., Competing Interests: Declaration of interests No interests are declared., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

The algorithm and rationale described is a reflection of our own surgical experience for this challenging disorder and can be compared with other publications. Our algorithm has evolved from treatment of a large volume of patients with Kienböck disease in a referral practice. However, it is limited to the management that we have found logical, effective, and within our scope of experience. The treatment guidelines for our specialty as a whole will evolve as our understanding of the etiology and our ability to quantify efficacy improves., Competing Interests: Disclosure The authors have nothing to disclose, such as no conflicts of interest, commercial associations, or intent of financial gain regarding this research., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Pollen development is dependent on the tapetum, a sporophytic anther cell layer surrounding the microspores that functions in pollen wall formation but is also essential for meiosis-associated development. There is clear evidence of crosstalk and co-regulation between the tapetum and microspores, but how this is achieved is currently not characterized. ABORTED MICROSPORES (AMS), a tapetum transcription factor, is important for pollen wall formation, but also has an undefined role in early pollen development. We conducted a detailed investigation of chromosome behaviour, cytokinesis, radial microtubule array (RMA) organization, and callose formation in the ams mutant. Early meiosis initiates normally in ams, shows delayed progression after the pachytene stage, and then fails during late meiosis, with disorganized RMA, defective cytokinesis, abnormal callose formation, and microspore degeneration, alongside abnormal tapetum development. Here, we show that selected meiosis-associated genes are directly repressed by AMS, and that AMS is essential for late meiosis progression. Our findings indicate that AMS has a dual function in tapetum-meiocyte crosstalk by playing an important regulatory role during late meiosis, in addition to its previously characterized role in pollen wall formation. AMS is critical for RMA organization, callose deposition, and therefore cytokinesis, and is involved in the crosstalk between the gametophyte and sporophytic tissues, which enables synchronous development of tapetum and microspores., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Objectives: Excess dietary salt and chronic kidney disease (CKD) are acknowledged stroke risk factors. The development of small vessel disease, similarly affecting the cerebral and renal microvasculatures, may be an important mechanistic link underlying this interaction. Therefore, we aimed to evaluate if the dietary salt intake and markers of CKD (estimated glomerular filtration rate, albuminuria) relate to transcranial Doppler (TCD) markers of cerebral small vessel disease (CSVD) in hypertensive patients., Materials and Methods: Fifty-six hypertensive patients (57% with diabetes) underwent TCD monitoring in the middle (MCA) and posterior (PCA) cerebral arteries for evaluating neurovascular coupling (NVC), dynamic cerebral autoregulation (dCA), and vasoreactivity to carbon dioxide (VRCO 2 ). We investigated the relation between renal parameters and TCD studies using Pearson's correlation coefficient and linear regression analyses., Results: There were no associations between dCA, VRCO 2 , NVC, and renal function tests. However, there was a negative association between the daily salt intake and the natural frequency during visual stimulation (r 2 =0.101, ß=-0.340, p=0.035), indicative of increased rigidity of the cerebral resistance vessels that react to cognitive activation., Conclusions: In this cross-sectional study, we found an association between excess dietary salt consumption and CSVD in hypertensive patients. Future research is needed to evaluate whether the natural frequency could be an early, non-invasive, surrogate marker for microvascular dysfunction in hypertension., Competing Interests: Declarations of Competing Interest None., (Copyright © 2022. Published by Elsevier Inc.)

Wheat is a major cereal crop that possesses a large allopolyploid genome formed through hybridisation of tetraploid and diploid progenitors. During meiosis, crossovers (COs) are constrained in number to 1-3 per chromosome pair that are predominantly located towards the chromosome ends. This reduces the probability of advantageous traits recombining onto the same chromosome, thus limiting breeding. Therefore, understanding the underlying factors controlling meiotic recombination may provide strategies to unlock the genetic potential in wheat. In this mini-review, we will discuss the factors associated with restricted CO formation in wheat, such as timing of meiotic events, chromatin organisation, pre-meiotic DNA replication and dosage of CO genes, as a means to modulate recombination., (© 2022 The Author(s).)

FANCM suppresses crossovers in plants by unwinding recombination intermediates. In wheat, crossovers are skewed toward the chromosome ends, thus limiting generation of novel allelic combinations. Here, we observe that FANCM maintains the obligate crossover in tetraploid and hexaploid wheat, thus ensuring that every chromosome pair exhibits at least one crossover, by localizing class I crossover protein HEI10 at pachytene. FANCM also suppresses class II crossovers that increased 2.6-fold in fancm msh5 quadruple mutants. These data are consistent with a role for FANCM in second-end capture of class I designated crossover sites, whilst FANCM is also required to promote formation of non-crossovers. In hexaploid wheat, genetic mapping reveals that crossovers increase by 31% in fancm compared to wild type, indicating that fancm could be an effective tool to accelerate breeding. Crossover rate differences in fancm correlate with wild type crossover distributions, suggesting that chromatin may influence the recombination landscape in similar ways in both wild type and fancm., (© 2022. The Author(s).)

Introduction: The induced membrane technique (IMT) is a two-stage surgical procedure used to treat fracture nonunion and bone defects. Although there is an increasing number of animal studies investigating the IMT, few have examined the outcomes of bone healing after a second stage grafting procedure. This study aimed at comparing two bone grafting procedures, as part of the IMT, in order to establish a rat model providing consistent healing outcomes., Methods: In male Fischer 344 rats, we created a 5 mm defect in the right femur, stabilized the bone with a plate and screws, and inserted a polymethylmethacrylate spacer into the defect. Four weeks later, the spacer was removed. Bone graft was harvested from a donor rat and placed into the defect, followed by membrane and wound closure. Experiments were conducted in two groups. In group 1 (n = 11), the bone graft contained a variable amount of cortical and cancellous bone, the time from donor euthanasia to grafting was up to 240 min, and one donor rat provided graft for 5-6 recipients. In group 2 (n = 12), we reduced the contribution of cortical bone to the graft, included bone marrow, and kept donor euthanasia to grafting time under 150 min. One donor was used per 3-4 recipients. The volume of graft per recipient and all other elements of the protocol were the same across groups. Bone healing at 12 weeks post grafting was compared radiographically by two orthopaedic surgeons in a blinded fashion, based on union status and a modified Lane & Sandhu score., Results: Healing rates improved from 36.4% in Group 1 to 91.6% in Group 2. There was a significant relationship between the methods and resulting union status (p = 0.004). The odds of achieving full union were significantly higher in group 2 compared to group 1 (odds ratio=19.25, 95% confidence interval [1.77-209.55]; p = 0.009). The average radiographic score was also significantly higher in group 2 (p = 0.005)., Conclusion: The revised bone grafting method significantly improved the healing outcomes and contributed to establishing a consistent rat model of the IMT. This model can benefit preclinical investigations by allowing for reliable and clinically-relevant comparisons., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Poststroke recovery depends on multiple factors and varies greatly across individuals. Using machine learning models, this study investigated the independent and complementary prognostic role of different patient-related factors in predicting response to language rehabilitation after a stroke., Methods: Fifty-five individuals with chronic poststroke aphasia underwent a battery of standardized assessments and structural and functional magnetic resonance imaging scans, and received 12 weeks of language treatment. Support vector machine and random forest models were constructed to predict responsiveness to treatment using pretreatment behavioral, demographic, and structural and functional neuroimaging data., Results: The best prediction performance was achieved by a support vector machine model trained on aphasia severity, demographics, measures of anatomic integrity and resting-state functional connectivity (F1=0.94). This model resulted in a significantly superior prediction performance compared with support vector machine models trained on all feature sets (F1=0.82, P <0.001) or a single feature set (F1 range=0.68-0.84, P <0.001). Across random forest models, training on resting-state functional magnetic resonance imaging connectivity data yielded the best F1 score (F1=0.87)., Conclusions: While behavioral, multimodal neuroimaging data and demographic information carry complementary information in predicting response to rehabilitation in chronic poststroke aphasia, functional connectivity of the brain at rest after stroke is a particularly important predictor of responsiveness to treatment, both alone and combined with other patient-related factors.

Vasopressor-induced limb ischemia is an unfortunate complication that can occur in patients treated for septic shock. Current literature lacks surgical treatment recommendations for this condition, besides amputation. We describe various reconstructive surgeries and functional outcomes in patients treated surgically for vasopressor-induced limb ischemia., Methods: We retrospectively reviewed patients who were treated for septic shock and developed vasopressor-induced limb ischemia at our tertiary referral academic medical center. We reviewed presentation, treatment, surgical outcomes, and long-term functional outcomes., Results: We present three previously healthy patients who developed gangrene of multiple limbs following the use of vasopressors to treat septic shock. Each patient underwent amputations or limb salvage procedures., Conclusions: Limb ischemia is a devastating complication that can occur after prolonged vasopressor use. The decision to proceed with limb salvage versus amputation of ischemic extremities should be tailored to the individual patient. The main objective should be for the patient to obtain optimal function and quality of life, regardless of the type of surgery., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Despite their importance for biodiversity and ecosystem services, wetlands are among the most threatened ecosystems globally. The conservation of many migratory waterbirds depends on the conservation of a network of key sites along their flyways. However, the suitability of these sites is changing under climate change, and it is important that management of individual sites in the network adapts to these changes. Using bioclimatic models that also account for changes in inundation, we found that projected climate change will reduce habitat suitability for waterbirds at 57.5% of existing Critical Sites within Africa-Eurasia, varying from 20.1% in Eastern Europe to 87.0% in Africa. African and Middle East sites are particularly threatened, comprising 71 of the 100 most vulnerable sites. By highlighting priority sites for conservation and classifying Critical Sites into Climate Change Adaptation Strategy (CCAS) classes, our results can be used to support the climate change adaptation of both individual sites and the entire site network., (© 2021 John Wiley & Sons Ltd.)

There is in an ongoing expansion of powerlines as a result of an increasing global demand for energy. Powerlines have the potential to negatively impact wild bird populations through collisions and/or electrocution, and reducing bird powerline collision and electrocution risk is a priority for companies running high-voltage powerlines (known as Transmission System Operators (TSOs)). Most TSOs are legally required to assess any potentially significant impacts via Enivronmental Impact Assessments, and so potentially collect a significant amount of data on the presence of species, species behaviour, and observed mortality rates. The value of such data, if available, for reducing and preventing bird casualties could be enhanced by increasing availability across TSOs and other decision-makers. We review the extent to which the sharing of data is happening across Europe, and how the quality, scope and availability of bird data collected by European TSOs could be improved, through use of a questionnaire and workshop with TSOs, conservationists and academics. Sixteen European TSOs responded to the questionnaire and 30 stakeholders attended the workshop. There was wide recognition of the value of different types of data on birds at powerlines, and a positive attitude to working together to share and enhance data across stakeholders to achieve the shared goal of reducing bird mortalities. Key barriers to the sharing of data included a lack of a centralised database, the lack of standardised methods to collect bird data and concerns over the confidentiality of data and reports. In order to overcome these barriers and develop a collaborative approach to data sharing, and ultimately inform best practice to reduce significant negative impacts on bird populations, we suggest a stepwise approach that (1) develops guidance around the field methods and data to be collected for mitigation effectiveness and (2) shares meta-data/bibliography of studies of powerline impacts/mitigation effectiveness for birds. In time, a more structured approach to the sharing of data and information could be developed, to make data findable, accessible, interoperable and reusable., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Surgical options for advanced Kienböck's disease include proximal row carpectomy or lunate reconstruction with a medial femoral trochlea osteochondral flap. This study compares morphology of the proximal capitate and the medial femoral trochlear surfaces to the proximal lunate using three-dimensional geometric morphometric analysis. Virtual articular surfaces were extracted from MRI studies of ten healthy volunteers. Distances between corresponding points on the proximal lunate and proximal capitate or medial femoral trochlear surfaces were measured. In seven subjects, mean inter-surface distance for the medial femoral trochlea-proximal lunate pair was significantly lower than the proximal capitate-proximal lunate pairing. In three subjects, mean proximal capitate-proximal lunate distance was significantly lower. We conclude that the medial femoral trochlear flap was anatomically closer to the shape of the proximal lunate in the majority of the examined subjects. However, we found that in three out of ten cases, the proximal capitate was a better match.

Background: End-to-end microvascular anastomoses sacrifice downstream inline perfusion of the recipient vessels. End-to-side anastomoses, in theory, maintain distal inline flow of the recipient vessel. The proposed benefit of the end-to-side technique depends on patency of the distal vessels and subsequent flow parameters, but maintenance of distal perfusion has not been conclusively demonstrated., Methods: Fifteen patients who underwent a successful extremity free flap procedure via end-to-side anastomoses to a noncritical vessel between 2003 and 2017 were enrolled. Recipient artery patency distal to the anastomosis was assessed using pulse volume recordings and duplex ultrasound imaging. Resistance indices, flow velocities, vessel diameters, volumetric flow, and turbulent flow dimensionless number (Reynolds number) were measured. Comparisons were made to the ipsilateral collateral vessel as well as to the vessels on the nonoperative contralateral limb using paired t tests., Results: Downstream flow was identified in 14 of 15 patients (93 percent patency). There was no statistical difference in resistive indices comparing the anastomotic vessel (0.859 ± 0.300) and the collateral vessel (0.853 ± 0.179) of the ipsilateral extremity. Ultrasound flows were similar; the anastomotic vessel demonstrated downstream volumetric flows of 139 ± 92.0 cm3/min versus 137 ± 41.6 cm3/min within the same vessel of the nonoperative contralateral limb. The anastomotic vessel had Reynolds numbers well below the turbulent threshold (448 ± 202 and 493 ± 127 for the anastomotic and nonoperative contralateral limb, respectively)., Conclusion: End-to-side anastomosis to noncritical vessels resulted in a 93 percent long-term recipient vessel patency rate, with no statistically significant changes in volumetric flows, resistive indices, or fluid dynamics in the vessels that remained patent., Competing Interests: Disclosure:The authors have no conflicts of interest, commercial associations, or intent of financial gain regarding this research., (Copyright © 2021 by the American Society of Plastic Surgeons.)

The mechanistic link between hypertension, diabetes and cerebral small vessel disease (CSVD) is still poorly understood. We hypothesized that hypertension and diabetes could impair cerebrovascular regulation prior to irreversibly established cerebrovascular disease. In this study, 52 hypertensive patients [54% males; age 64 ± 11 years; 58% with comorbid diabetes mellitus (DM)] without symptomatic cerebrovascular disease underwent transcranial Doppler (TCD) monitoring in the middle (MCA) and posterior (PCA) cerebral arteries, to assess vasoreactivity to carbon dioxide (VRCO 2 ) and neurovascular coupling (NVC). 1.5T magnetic resonance imaging was also performed and white matter hyperintensity volume was automatically segmented from FLAIR sequences. TCD data from 17 healthy controls were obtained for comparison (47% males; age 60 ± 16 years). Hypertensive patients showed significant impairment of NVC in the PCA, with reduced increment in cerebral blood flow velocity during visual stimulation (22.4 ± 9.2 vs. 31.6 ± 5.7, p < 0.001), as well as disturbed NVC time-varying properties, with slower response (lower rate time: 0.00 ± 0.02 vs. 0.03 ± 6.81, p = 0.001), and reduced system oscillation (reduced natural frequency: 0.18 ± 0.08 vs. 0.22 ± 0.06, p < 0.001), when compared to controls. VRCO 2 remained relatively preserved in MCA and PCA. These results were worse in hypertensive diabetic patients, with lower natural frequency ( p = 0.043) than non-diabetic patients. White matter disease burden did not predict worse NVC. These findings suggest that hypertensive diabetic patients may have a precocious impairment of NVC, already occurring without symptomatic CSVD. Future research is warranted to evaluate whether NVC assessment could be useful as an early, non-invasive, surrogate marker for CSVD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Monteiro, Castro, Pereira, Ferreira, Sorond, Milstead, Higgins, Polónia and Azevedo.)

Background: Patients with symptomatic recalcitrant thumb carpometacarpal arthritis often undergo surgery. Although most surgical patients do well, the authors anticipated that a substantial portion of their thumb carpometacarpal surgery patients would have unsatisfactory experiences and express unmet expectations, dissatisfaction, and regret, regardless of surgical procedure performed. The authors hypothesized those experiences would correlate with patient-reported outcomes scores., Methods: The authors identified patients who had undergone trapeziectomy alone or with ligament reconstruction 1 to 4 years previously for primary thumb carpometacarpal arthritis. One hundred twelve patients completed Quick Disabilities of the Arm, Shoulder and Hand and visual analogue scale pain, expectations, satisfaction, and regret questionnaires., Results: More than 40 percent of patients expected to "return to normal" after surgery for pain, strength, and/or function. Including all patients, 7, 19, and 11 percent had unmet expectations for improvement in pain, strength, and function, respectively. Twelve percent expressed dissatisfaction with their outcome. Although just 4 percent regretted undergoing surgery, 13 percent would likely not recommend the procedure to someone they care about. There were no statistically significant differences for any patient-reported outcomes between trapeziectomy-alone (n = 20) and trapeziectomy with ligament reconstruction (n = 92). Visual analogue scale and Quick Disabilities of the Arm, Shoulder and Hand questionnaire scores were both moderately correlated with expectations being met for pain, strength, and function and for satisfaction with surgical outcome., Conclusions: Patients' thumb carpometacarpal surgical experiences vary considerably. Many express dissatisfaction or a lack of expectations met with the two most common procedures. A thorough understanding and review of expectations preoperatively may be uniquely pertinent for these patients. Further research should determine predictors and potentially modifiable factors for unsatisfactory outcomes., (Copyright © 2021 by the American Society of Plastic Surgeons.)

The decision regarding the use of vascularized bone grafting (VBG) or nonvascularized bone grafting for the treatment of scaphoid nonunion (SNU) needs guidelines based on patient- and fracture-specific risk factors. Historically, the presence of avascular necrosis was viewed as the primary indication for VBG; however, avascular necrosis is not the only indicator to determine whether VBG can improve our treatment of difficult SNU cases. The methods of detecting scaphoid avascular necrosis lack consensus and accuracy, limiting their use as decision-making tools. Additionally, many other preoperative risk factors for SNU surgery failure have been reported and require careful and standardized study, including the location of nonunion in the scaphoid proximal pole, the duration of nonunion, previous failed nonunion surgery, smoking, and fracture nonunion displacement or collapse. An appropriate study size and design are needed to determine the factors that guide the use of VBG or nonvascularized bone grafting to optimize the outcomes of SNU surgery., (Copyright © 2021 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

The hexaploid bread wheat genome comprises over 16 gigabases of sequence across 21 chromosomes. Meiotic crossovers are highly polarized along the chromosomes, with elevation in the gene-dense distal regions and suppression in the Gypsy retrotransposon-dense centromere-proximal regions. We profiled the genomic landscapes of the meiotic recombinase DMC1 and the chromosome axis protein ASY1 in wheat and investigated their relationships with crossovers, chromatin state, and genetic diversity. DMC1 and ASY1 chromatin immunoprecipitation followed by sequencing (ChIP-seq) revealed strong co-enrichment in the distal, crossover-active regions of the wheat chromosomes. Distal ChIP-seq enrichment is consistent with spatiotemporally biased cytological immunolocalization of DMC1 and ASY1 close to the telomeres during meiotic prophase I. DMC1 and ASY1 ChIP-seq peaks show significant overlap with genes and transposable elements in the Mariner and Mutator superfamilies. However, DMC1 and ASY1 ChIP-seq peaks were detected along the length of each chromosome, including in low-crossover regions. At the fine scale, crossover elevation at DMC1 and ASY1 peaks and genes correlates with enrichment of the Polycomb histone modification H3K27me3. This indicates a role for facultative heterochromatin, coincident with high DMC1 and ASY1, in promoting crossovers in wheat and is reflected in distalized H3K27me3 enrichment observed via ChIP-seq and immunocytology. Genes with elevated crossover rates and high DMC1 and ASY1 ChIP-seq signals are overrepresented for defense-response and immunity annotations, have higher sequence polymorphism, and exhibit signatures of selection. Our findings are consistent with meiotic recombination promoting genetic diversity, shaping host-pathogen co-evolution, and accelerating adaptation by increasing the efficiency of selection., (© 2021 Tock et al.; Published by Cold Spring Harbor Laboratory Press.)

Meditation experience has previously been shown to improve performance on behavioral assessments of attention, but the neural bases of this improvement are unknown. Two prominent, strongly competing networks exist in the human cortex: a dorsal attention network, that is activated during focused attention, and a default mode network, that is suppressed during attentionally demanding tasks. Prior studies suggest that strong anti-correlations between these networks indicate good brain health. In addition, a third network, a ventral attention network, serves as a "circuit-breaker" that transiently disrupts and redirects focused attention to permit salient stimuli to capture attention. Here, we used functional magnetic resonance imaging to contrast cortical network activation between experienced focused attention Vipassana meditators and matched controls. Participants performed two attention tasks during scanning: a sustained attention task and an attention-capture task. Meditators demonstrated increased magnitude of differential activation in the dorsal attention vs. default mode network in a sustained attention task, relative to controls. In contrast, there were no evident attention network differences between meditators and controls in an attentional reorienting paradigm. A resting state functional connectivity analysis revealed a greater magnitude of anticorrelation between dorsal attention and default mode networks in the meditators as compared to both our local control group and a n = 168 Human Connectome Project dataset. These results demonstrate, with both task- and rest-based fMRI data, increased stability in sustained attention processes without an associated attentional capture cost in meditators. Task and resting-state results, which revealed stronger anticorrelations between dorsal attention and default mode networks in experienced mediators than in controls, are consistent with a brain health benefit of long-term meditation practice.

In this study, we perform a region of interest diffusion tensor imaging and advanced diffusion complexity analysis of normal appearing white matter to determine the impact of vascular health on these diffusivity metrics in midlife adults. 77 participants (26 black, 35 female) at year 30 visit in the Coronary Artery Risk Development in Young Adults longitudinal study were scanned with an advanced diffusion-weighted imaging and fluid-attenuated inversion recovery protocol. Fractional anisotropy and non-linear diffusion complexity measures were estimated. Cumulative measures across 30 years (9 study visits) of systolic blood pressure, body mass index, glucose, smoking and cholesterol were calculated as the area under the curve from baseline up to year 30 examination. Partial correlation analyses assessed the association between cumulative vascular health measures and normal appearing white matter diffusion metrics in these participants. Midlife normal appearing white matter diffusion properties were significantly associated ( P  <   0.05) with cumulative exposure to vascular risk factors from young adulthood over the 30-year time period. Higher cumulative systolic blood pressure exposure was associated with increased complexity and decreased fractional anisotropy. Higher cumulative body mass index exposure was associated with decreased fractional anisotropy. Additionally, in the normal appearing white matter of black participants ( P  <   0.05), who exhibited a higher cumulative vascular risk exposure, fractional anisotropy was lower and complexity was higher in comparison to normal appearing white matter in white participants. Higher burden of vascular risk factor exposure from young adulthood to midlife is associated with changes in the diffusion properties of normal appearing white matter in midlife. These changes which may reflect axonal disruption, increased inflammation and/or increased glial proliferation, were primarily observed in both anterior and posterior normal appearing white matter regions of the corpus callosum. These results suggest that microstructural changes in normal appearing white matter are sensitive to vascular health during young adulthood and are possibly therapeutic targets in interventions focused on preserving white matter health across life., (Published by Oxford University Press on behalf of the Guarantors of Brain 2021. This work is written by US Government employees and is in the public domain in the US.)

Language outcomes after speech and language therapy in post-stroke aphasia are challenging to predict. This study examines behavioral language measures and resting state fMRI (rsfMRI) as predictors of treatment outcome. Fifty-seven patients with chronic aphasia were recruited and treated for one of three aphasia impairments: anomia, agrammatism, or dysgraphia. Treatment effect was measured by performance on a treatment-specific language measure, assessed before and after three months of language therapy. Each patient also underwent an additional 27 language assessments and a rsfMRI scan at baseline. Patient scans were decomposed into 20 components by group independent component analysis, and the fractional amplitude of low-frequency fluctuations (fALFF) was calculated for each component time series. Post-treatment performance was modelled with elastic net regression, using pre-treatment performance and either behavioral language measures or fALFF imaging predictors. Analysis showed strong performance for behavioral measures in anomia (R 2  = 0.948, n = 28) and for fALFF predictors in agrammatism (R 2  = 0.876, n = 11) and dysgraphia (R 2  = 0.822, n = 18). Models of language outcomes after treatment trained using rsfMRI features may outperform models trained using behavioral language measures in some patient populations. This suggests that rsfMRI may have prognostic value for aphasia therapy outcomes.

The synaptonemal complex is a tripartite proteinaceous ultrastructure that forms between homologous chromosomes during prophase I of meiosis in the majority of eukaryotes. It is characterized by the coordinated installation of transverse filament proteins between two lateral elements and is required for wild-type levels of crossing over and meiotic progression. We have generated null mutants of the duplicated Arabidopsis transverse filament genes zyp1a and zyp1b using a combination of T-DNA insertional mutants and targeted CRISPR/Cas mutagenesis. Cytological and genetic analysis of the zyp1 null mutants reveals loss of the obligate chiasma, an increase in recombination map length by 1.3- to 1.7-fold and a virtual absence of cross-over (CO) interference, determined by a significant increase in the number of double COs. At diplotene, the numbers of HEI10 foci, a marker for Class I interference-sensitive COs, are twofold greater in the zyp1 mutant compared to wild type. The increase in recombination in zyp1 does not appear to be due to the Class II interference-insensitive COs as chiasmata were reduced by ∼52% in msh5/zyp1 compared to msh5 These data suggest that ZYP1 limits the formation of closely spaced Class I COs in Arabidopsis Our data indicate that installation of ZYP1 occurs at ASY1-labeled axial bridges and that loss of the protein disrupts progressive coalignment of the chromosome axes., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Meiotic recombination generates genetic variation and provides physical links between homologous chromosomes (crossovers) essential for accurate segregation. In cereals the distribution of crossovers, cytologically evident as chiasmata, is biased toward the distal regions of chromosomes. This creates a bottleneck for plant breeders in the development of varieties with improved agronomic traits, as genes situated in the interstitial and centromere proximal regions of chromosomes rarely recombine. Recent advances in wheat genomics and genome engineering combined with well-developed wheat cytogenetics offer new opportunities to manipulate recombination and unlock genetic variation. As a basis for these investigations we have carried out a detailed analysis of meiotic progression in hexaploid wheat ( Triticum aestivum ) using immunolocalization of chromosome axis, synaptonemal complex and recombination proteins. 5-Bromo-2'-deoxyuridine (BrdU) labeling was used to determine the chronology of key events in relation to DNA replication. Axis morphogenesis, synapsis and recombination initiation were found to be spatio-temporally coordinated, beginning in the gene-dense distal chromosomal regions and later occurring in the interstitial/proximal regions. Moreover, meiotic progression in the distal regions was coordinated with the conserved chromatin cycles that are a feature of meiosis. This mirroring of the chiasma bias was also evident in the distribution of the gene-associated histone marks, H3K4me3 and H3K27me3; the repeat-associated mark, H3K27me1; and H3K9me3. We believe that this study provides a cytogenetic framework for functional studies and ongoing initiatives to manipulate recombination in the wheat genome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Osman, Algopishi, Higgins, Henderson, Edwards, Franklin and Sanchez-Moran.)

Climate warming has caused the seasonal timing of many components of ecological food chains to advance. In the context of trophic interactions, the match-mismatch hypothesis postulates that differential shifts can lead to phenological asynchrony with negative impacts for consumers. However, at present there has been no consistent analysis of the links between temperature change, phenological asynchrony and individual-to-population-level impacts across taxa, trophic levels and biomes at a global scale. Here, we propose five criteria that all need to be met to demonstrate that temperature-mediated trophic asynchrony poses a growing risk to consumers. We conduct a literature review of 109 papers studying 129 taxa, and find that all five criteria are assessed for only two taxa, with the majority of taxa only having one or two criteria assessed. Crucially, nearly every study was conducted in Europe or North America, and most studies were on terrestrial secondary consumers. We thus lack a robust evidence base from which to draw general conclusions about the risk that climate-mediated trophic asynchrony may pose to populations worldwide.

The mammalian BREAST CANCER 2 ( BRCA2 ) gene is a tumor suppressor that plays a crucial role in DNA repair and homologous recombination (HR). Here, we report the identification and characterization of OsBRCA2 , the rice orthologue of human BRCA2 . Osbrca2 mutant plants exhibit normal vegetative growth but experience complete male and female sterility as a consequence of severe meiotic defects. Pairing, synapsis and recombination are impaired in osbrca2 male meiocytes, leading to chromosome entanglements and fragmentation. In the absence of OsBRCA2, localization to the meiotic chromosome axes of the strand-invasion proteins OsRAD51 and OsDMC1 is severely reduced and in vitro OsBRCA2 directly interacts with OsRAD51 and OsDMC1. These results indicate that OsBRCA2 is essential for facilitating the loading of OsRAD51 and OsDMC1 onto resected ends of programmed double-strand breaks (DSB) during meiosis to promote single-end invasions of homologous chromosomes and accurate recombination. In addition, treatment of osbrca2-1 seedlings with mitomycin C (MMC) led to hypersensitivity. As MMC is a genotoxic agent that creates DNA lesions in the somatic cells that can only be repaired by HR, these results suggest that OsBRCA2 has a conserved role in DSB repair and HR in rice., (Copyright © 2020 Fu, Wang, Shen, Zhang, Higgins and Liang.)

During meiosis, DNA double-strand breaks undergo interhomolog repair to yield crossovers between homologous chromosomes. To investigate how interhomolog sequence polymorphism affects crossovers, we sequenced multiple recombinant populations of the model plant Arabidopsis thaliana. Crossovers were elevated in the diverse pericentromeric regions, showing a local preference for polymorphic regions. We provide evidence that crossover association with elevated diversity is mediated via the Class I crossover formation pathway, although very high levels of diversity suppress crossovers. Interhomolog polymorphism causes mismatches in recombining molecules, which can be detected by MutS homolog (MSH) mismatch repair protein heterodimers. Therefore, we mapped crossovers in a msh2 mutant, defective in mismatch recognition, using multiple hybrid backgrounds. Although total crossover numbers were unchanged in msh2 mutants, recombination was remodelled from the diverse pericentromeres towards the less-polymorphic sub-telomeric regions. Juxtaposition of megabase heterozygous and homozygous regions causes crossover remodelling towards the heterozygous regions in wild type Arabidopsis, but not in msh2 mutants. Immunostaining showed that MSH2 protein accumulates on meiotic chromosomes during prophase I, consistent with MSH2 regulating meiotic recombination. Our results reveal a pro-crossover role for MSH2 in regions of higher sequence diversity in A. thaliana., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

Objective: Report pilot findings of neurobehavioral gains and network changes observed in persons with disordered consciousness (DoC) who received repetitive transcranial magnetic stimulation (rTMS) or amantadine (AMA), and then rTMS+AMA., Participants: Four persons with DoC 1 to 15 years after traumatic brain injury (TBI)., Design: Alternate treatment-order, within-subject, baseline-controlled trial., Main Measures: For group and individual neurobehavioral analyses, predetermined thresholds, based on mixed linear-effects models and conditional minimally detectable change, were used to define meaningful neurobehavioral change for the Disorders of Consciousness Scale-25 (DOCS) total and Auditory-Language measures. Resting-state functional connectivity (rsFC) of the default mode and 6 other networks was examined., Results: Meaningful gains in DOCS total measures were observed for 75% of treatment segments and auditory-language gains were observed after rTMS, which doubled when rTMS preceded rTMS+AMA. Neurobehavioral changes were reflected in rsFC for language, salience, and sensorimotor networks. Between networks interactions were modulated, globally, after all treatments., Conclusions: For persons with DoC 1 to 15 years after TBI, meaningful neurobehavioral gains were observed after provision of rTMS, AMA, and rTMS+AMA. Sequencing and combining of treatments to modulate broad-scale neural activity, via differing mechanisms, merits investigation in a future study powered to determine efficacy of this approach to enabling neurobehavioral recovery.

Optimizing transcranial magnetic stimulation (TMS) treatments in traumatic brain injury (TBI) and co-occurring conditions may benefit from neuroimaging-based customization., Participants: Our total sample (N = 97) included 58 individuals with TBI (49 mild, 8 moderate, and 1 severe in a state of disordered consciousness), of which 24 had co-occurring conditions (depression in 14 and alcohol use disorder in 10). Of those without TBI, 6 individuals had alcohol use disorder and 33 were healthy controls. Of our total sample, 54 were veterans and 43 were civilians., Design: Proof-of-concept study incorporating data from 5 analyses/studies that used multimodal approaches to integrate neuroimaging with TMS., Main Measures: Multimodal neuroimaging methods including structural magnetic resonance imaging (MRI), MRI-guided TMS navigation, functional MRI, diffusion MRI, and TMS-induced electric fields. Outcomes included symptom scales, neuropsychological tests, and physiological measures., Results: It is feasible to use multimodal neuroimaging data to customize TMS targets and understand brain-based changes in targeted networks among people with TBI., Conclusions: TBI is an anatomically heterogeneous disorder. Preliminary evidence from the 5 studies suggests that using multimodal neuroimaging approaches to customize TMS treatment is feasible. To test whether this will lead to increased clinical efficacy, studies that integrate neuroimaging and TMS targeting data with outcomes are needed.

Background: Our goal was to investigate patients' upper extremity tissue perfusion changes using an indocyanine green laser angiography imaging system for various pathologic states and interventions. Methods: This prospective observational study used Spy Elite/LUNA laser angiography to evaluate perfusion in patients with upper extremity vascular compromise. All patients had Spy Elite/LUNA imaging as well as clinical and handheld Doppler examinations preintervention, intraoperatively, if applicable, and at 1 week, 2 weeks, and 2 months postintervention. For each laser angiography scan, we used an unaffected control area with uninjured skin to quantitatively compare with the dysvascular tissues. Results: Twelve patients, 7 men and 5 women, had a total of 16 upper extremities evaluated. The mean age was 53 years, and half of the patients entering the study were smokers. Etiologies of vascular compromise were trauma, primary and secondary vasospastic disease, scleroderma, and intravascular drug injection. Interventions included surgical repair/reconstruction, botulinum toxin injections, and/or systemic medications. Improvement in perfusion following intervention was statistically significant, demonstrated by an increase in Spy Elite/LUNA quantitative score postintervention compared with preintervention scans. Adjusting for other variables, such as smoking and handheld Doppler signal status, demonstrated an independent statistically significant increase in Spy Elite/LUNA scores at all postintervention time points compared with preintervention scores. Laser angiography was able to confirm adequate vascular status, with ultimate tissue survival, in some cases when Doppler signals were not initially present. Conclusions: Laser angiography provided objective data to document improved upper extremity tissue perfusion following various interventions.

For people with disordered consciousness (DoC) after traumatic brain injury (TBI), relationships between treatment-induced changes in neural connectivity and neurobehavioral recovery have not been explored. To begin building a body of evidence regarding the unique contributions of treatments to changes in neural network connectivity relative to neurobehavioral recovery, we conducted a pilot study to identify relationships meriting additional examination in future research. To address this objective, we examined previously unpublished neural connectivity data derived from a randomized clinical trial (RCT). We leveraged these data because treatment efficacy, in the RCT, was based on a comparison of a placebo control with a specific intervention, the familiar auditory sensory training (FAST) intervention, consisting of autobiographical auditory-linguistic stimuli. We selected a subgroup of RCT participants with high-quality imaging data (FAST n = 4 and placebo n = 4) to examine treatment-related changes in brain network connectivity and how and if these changes relate to neurobehavioral recovery. To discover promising relationships among the FAST intervention, changes in neural connectivity, and neurobehavioral recovery, we examined 26 brain regions and 19 white matter tracts associated with default mode, salience, attention, and language networks, as well as three neurobehavioral measures. Of the relationships discovered, the systematic filtering process yielded evidence supporting further investigation of the relationship among the FAST intervention, connectivity of the left inferior longitudinal fasciculus, and auditory-language skills. Evidence also suggests that future mechanistic research should focus on examining the possibility that the FAST supports connectivity changes by facilitating redistribution of brain resources. For a patient population with limited treatment options, the reported findings suggest that a simple, yet targeted, passive sensory stimulation treatment may have altered functional and structural connectivity. If replicated in future research, then these findings provide the foundation for characterizing the unique contributions of the FAST intervention and could inform development of new treatment strategies. For persons with severely damaged brain networks, this report represents a first step toward advancing understanding of the unique contributions of treatments to changing brain network connectivity and how these changes relate to neurobehavioral recovery for persons with DoC after TBI. Clinical Trial Registry: NCT00557076, The Efficacy of Familiar Voice Stimulation During Coma Recovery (http://www.clinicaltrials.gov)., (Copyright © 2020 Bender Pape, Livengood, Kletzel, Blabas, Guernon, Bhaumik, Bhaumik, Mallinson, Weaver, Higgins, Wang, Herrold, Rosenow and Parrish.)

Vascularized osteochondral flaps are a new technique described for the reconstruction of challenging articular defects of the carpus. The medial femoral trochlea osteochondral flap is supplied by the descending geniculate artery. This osteochondral flap has shown promise in the treatment of recalcitrant scaphoid proximal pole nonunions and advanced avascular necrosis of the lunate. The anatomy, surgical technique, and results are discussed, with clinical cases provided., (Copyright © 2020 Elsevier Inc. All rights reserved.)