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18 p.-9 fig., Premise: Light and gravity are fundamental cues for plant development. Our understanding of the effects of light stimuli on plants in space, without gravity, is key to providing conditions for plants to acclimate to the environment. Here we tested the hypothesis that the alterations caused by the absence of gravity in root meristematic cells can be counteracted by light., Methods: Seedlings of wild‐type Arabidopsis thaliana and two mutants of the essential nucleolar protein nucleolin (nuc1, nuc2) were grown in simulated microgravity,either under a white light photoperiod or under continuous darkness. Key variables of cell proliferation (cell cycle regulation), cell growth (ribosome biogenesis),and auxin transport were measured in the root meristem using in situ cellular markers and transcriptomic methods and compared with those of a 1 g control., Results: The incorporation of a photoperiod regime was sufficient to attenuate or suppress the effects caused by gravitational stress at the cellular level in the root meristem. In all cases, values for variables recorded from samples receiving light stimuli in simulated microgravity were closer to values from the controls than values from samples grown in darkness. Differential sensitivities were obtained for the two nucleolin mutants., Conclusions: Light signals may totally or partially replace gravity signals, significantly improving plant growth and development in microgravity. Despite that, molecular alterations are still compatible with the expected acclimation mechanisms, which need to be better understood. The differential sensitivity of nuc1 and nuc2 mutants to gravitational stress points to new strategies to produce more resilient plants to travel with humans in new extraterrestrial endeavors., This work was funded by the Agencia Estatal de Investigación of the Spanish Ministry of Science an Innovation, Grants#ESP2015‐64323‐R and #RTI2018‐099309‐B‐I00 (co‐funded by EU‐ERDF) to F.J.M., and Bonus Recherche from the UPVD to J.S.V. The use of the facilities of microgravity simulation was provided by the ESA‐CORA‐Ground Based Facilities Program, contract Ref. #4000105761 to F.J.M. and R.H. A.M. was recipient of a contract of the Program for Young Researchers Training of the Agencia Estatal de Investigación of the Spanish Ministry of Science an Innovation Ref. #BES‐2013‐063933.

Patients undergoing cardiac surgery are at significant risk of developing postoperative acute kidney injury (AKI). Neutrophil-lymphocyte ratio (NLR) is a widely available inflammatory biomarker which may be of prognostic value in this setting.We conducted a systematic review and meta-analysis of studies reporting associations between perioperative NLR with postoperative AKI. We searched Medline, Embase and the Cochrane Library, without language restriction, from inception to May 2022 for relevant studies. We meta-analysed the reported odds ratios (ORs) with 95% confidence intervals (CIs) for both elevated preoperative and postoperative NLR with risk of postoperative AKI and need for renal replacement therapy (RRT). We conducted a meta-regression to explore inter-study statistical heterogeneity.Twelve studies involving 10,724 participants undergoing cardiac surgery were included, with eight studies being deemed at high risk of bias using PROBAST modelling. We found statistically significant associations between elevated preoperative NLR and postoperative AKI (OR 1.45, 95% CI 1.18-1.77), as well as postoperative need for RRT (OR 2.37, 95% CI 1.50-3.72). Postoperative NLR measurements were not of prognostic significance.Elevated preoperative NLR is a reliable inflammatory biomarker for predicting AKI following cardiac surgery.

Our cord blood banking facility planned and executed a transferral of its entire operation to a new site in the South of Brazil. Transporting LN2 freezers is a complex process in which extensive planning is essential to minimize the risks of damaging products or storage units.To fulfill this objective, we constructed a detailed relocation plan consisting of four phases and risk mitigation measures, collaborated with the representatives of all departments, regulating agencies, and professionals from the transport company, and assembled a validation plan for cryogenic freezers and the viability of cord blood units.The new facility was prepared in accordance with the project plan, local legislation, quality system program requirements, and accreditation agency guidance. A 12-h operation of moving the cryogenic freezers was conducted successfully, with no loss or damage of client samples or equipment.Through the development and execution of a transferral plan, the engagement of appropriate partners, and compliance with security measures from health and government agencies, a successful transferral of a cord blood banking facility operation in its entirety can be successfully accomplished.

Fanconi anaemia (FA) is a rare genetic disorder marked by progressive bone marrow failure, chromosomal fragility, and increased cancer susceptibility. Laboratory diagnosis includes chromosomal instability test and mutation investigation. A total of 15%-25% of all patients may have somatic mosaicism, characterized by two distinct haematopoietic cell populations, one resistant and one sensitive to agents that induce chromosomal breakage, which complicates the diagnosis by a high incidence of reverted cells leading to inconclusive or false-negative results. The study aimed to evaluate the use of bone marrow stromal mesenchymal cells (BM-MSCs) as an alternative, non-haematopoietic tissue for diagnosis.Bone marrow mesenchymal stromal cells from 12 patients with positive diepoxybutane (DEB) tests were cultivated and analysed by cytogenetics and mutation investigation.The DEB test was performed at 0.1 and 0.01 μg/ml concentrations, with an index ranging from 0.24 to 1.00. At higher concentration, the metaphases number was lower, probably due to toxicity. Regarding the molecular investigation, all the mutations previously found in peripheral blood were identified on BM-MSC.This study demonstrated the possibility of using BM-MSCs as an alternative tissue for cytogenetic and molecular investigation. Future tests using an intermediate DEB concentration may lead to an optimal protocol that could be non-toxic to cells but provides conclusive results.

Beta‐microseminoproteins (MSMBs) are small disulfide‐rich proteins that are conserved among vertebrates. These proteins exhibit diverse biological activities and were mainly reported to play a role in male fertility, immunity, and embryogenesis. In this work, we focused on the chicken MSMB3 protein that was previously depicted as an egg antibacterial protein. We report that MSMB3 protein is exclusively expressed in the reproductive tissues of laying hens (in contrast to chicken MSMB1 and MSMB2 paralogs), to be incorporated in the egg white during the process of egg formation. We also showed that chicken MSMB3 possesses highly conserved orthologs in bird species, including Neognathae and Palaeognathae. Chicken MSMB3 was purified from egg white using heparin affinity chromatography and was analyzed by top‐down and bottom‐up proteomics. Several proteoforms could be characterized, and a homodimer was further evidenced by NMR spectroscopy. The X‐ray structure of chicken MSMB3 was solved for the first time, revealing that this protein adopts a novel dimeric arrangement. The highly cationic MSMB3 protein exhibits a distinct electrostatic distribution compared with chicken MSMB1 and MSMB2 structural models, and with published mammalian MSMB structures. The specific incorporation of MSMB3 paralog in the egg, and its phylogenetic conservation in birds together with its peculiar homodimer arrangement and physicochemical properties, suggests that the MSMB3 protein has evolved to play a critical role during the embryonic development of avian species. These new data are likely to stimulate research to elucidate the structure/function relationships of MSMB paralogs and orthologs in the animal kingdom., Beta‐microseminoproteins (MSMBs) are small proteins conserved among vertebrates. The chicken genome contains three MSMB paralogs, which exhibit distinct tissue expression profiles, with chicken beta‐MSMB 3 (MSMB3) protein being egg‐specific. Collectively, results from protein sequence analysis, mass spectrometry analysis, and 3D structure data highlight that chicken MSMB3 possesses specific features that may be related to its presumed role in avian reproduction. ​

The presence of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) has been recognized as a major risk factor for graft failure (GF) after haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide (haplo-PTCy). However, the role of DSAs in salvage haplo-PTCy for rescuing patients with nonmalignant disorders (NMDs) has not yet been reported. The present study retrospectively analyzed 22 patients with NMDs who underwent salvage haplo-PTCy from January 2008 to December 2017. The median age at the time of the rescue haplo-PTCy was 9 years (range, 1-26 years). Median time from the first transplant to second haplo-PTCy was 56 days (range, 37-591 days). Among all patients, six (27.3%) had DSAs, with a median DSA strength (mean fluorescence intensity [MFI]) of 5201 (range, 1412-11,543) in the first DSA testing. In addition, the median DSA MFI was 2672 (range, 832-10,498) before the bone marrow infusion. Overall, GF occurred in 5 (25%) of the 20 assessable patients. Three of four (75%) patients with DSAs experienced GF versus 2 of 16 (12.5%) DSA-negative patients (P = 0.032). The median DSA MFI for patients with GF was 6437 (range, 1412-10,498) versus 1845 (range, 832-2672) for those who engrafted or had early death (P = 0.030). One-year event-free survival was significantly lower in DSA-positive patients than in those without DSAs (16.7% vs. 62.5%, P = 0.002). DSA-negative patients had an acceptable 1-year survival of 62.5%. In conclusion, this study suggests that DSAs may be associated with deleterious outcomes after salvage haplo-PTCy in patients with NMDs.

Objectives The aim of this study was to analyze the outcomes of children with Diamond-Blackfan anemia (DBA) treated in Brazil with hematopoietic cell transplantation (HCT). Methods We performed a retrospective analysis of 44 pediatrics patients transplanted between 1990 and 2018. The median age of patients was 5 years, and 57% were male. Twenty-five received their first HCT from an HLA-matched sibling donor (MSD), 12 from a HLA matched unrelated bone marrow donor (MUD 10/10, n = 12) and 7 other HLA mismatched donors (MMD). Results After a median follow-up of 4 years, estimate 5-year overall survival (OS) for the entire cohort was 70%, 80% for MSD group, 73% for MUD, and 29% for MMD. Thirty-eight out of the 44 evaluable patients engrafted successfully. Primary and secondary graft failure was observed in five and three patients, respectively. Rates of grade II-IV and III-IV acute graft-versus-host disease (aGVHD) were 25% and 18%, respectively. Nine patients developed chronic GVHD (cGVHD). Conclusion Overall survival rates observed after HLA matched donors transplant for DBA were comparable to those reported from higher-income countries and international registries.

Rodents generate negative consequences for smallholder farmers in Africa that directly impact household and livestock damage, food security and public health. Ecologically Based Rodent Management (EBRM) seeks sustainable solutions for the mitigation of rodent damage through assessments of rodent population dynamics, agro-ecosystems and socio-cultural contexts. We adopt a comparative approach across three rural Afro-Malagasy smallholder farming regions in South Africa, Tanzania and Madagascar to assess the household impacts of rodent pests and current perceptions and preferences associated with several rodent control measures. We conducted focus groups questionnaires and interviews in different study site locations. Rodents assert multiple impacts on Afro-Malagasy farmers demonstrating recurrent and emerging agricultural and household costs, and public health impacts. We identify a significant knowledge gap in educating communities about the application of different EBRM approaches in favour of acute poisons that are perceived to be more effective. Cultural issues and taboos also have a significant impact on the social acceptance of rodent hunting as well as biological control using indigenous predators. We advocate for an enhanced investigation of the socio-cultural beliefs associated with different rodent practices to understand the factors underlying social acceptance. A collaborative approach that integrates the perspectives of target communities to inform the design of EBRM initiatives according to the specific agro-ecosystem and socio-cultural context is necessary to ensure programmatic success.

Funder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100000265, BACKGROUND: Social attention affords learning opportunities across development and may contribute to individual differences in developmental trajectories, such as between male and female individuals, and in neurodevelopmental conditions, such as autism. METHODS: Using eye-tracking, we measured social attention in a large cohort of autistic (n = 123) and nonautistic females (n = 107), and autistic (n = 330) and nonautistic males (n = 204), aged 6-30 years. Using mixed Growth Curve Analysis, we modelled sex and diagnostic effects on the temporal dynamics of proportional looking time to three types of social stimuli (lean-static, naturalistic-static, and naturalistic-dynamic) and examined the link between individual differences and dimensional social and nonsocial autistic traits in autistic females and males. RESULTS: In the lean-static stimulus, average face-looking was higher in females than in males of both autistic and nonautistic groups. Differences in the dynamic pattern of face-looking were seen in autistic vs. nonautistic females, but not males, with face-looking peaking later in the trial in autistic females. In the naturalistic-dynamic stimulus, average face-looking was higher in females than in males of both groups; changes in the dynamic pattern of face looking were seen in autistic vs. nonautistic males, but not in females, with a steeper peak in nonautistic males. Lower average face-looking was associated with higher observer-measured autistic characteristics in autistic females, but not in males. CONCLUSIONS: Overall, we found stronger social attention in females to a similar degree in both autistic and nonautistic groups. Nonetheless, the dynamic profiles of social attention differed in different ways in autistic females and males compared to their nonautistic peers, and autistic traits predicted trends of average face-looking in autistic females. These findings support the role of social attention in the emergence of sex-related differences in autistic characteristics, suggesting an avenue to phenotypic stratification.