Search

Electrospinning of nonwoven nanofibrous mats has received significant attention in recent years due to the high versatility and porosity of electrospun mats. However, electrospun mats generally suffer from low mechanical strength. This work reports a method to improve the mechanical strength of nanofiber mats by coaxial electrospinning combined with thermal treatment, without incurring significant dimensional shrinkage. Coaxial polyacrylonitrile (PAN)/polyvinylidene fluoride‐hexafluoropropylene (PVDF‐HFP) mats showed no shrinkage when tested at temperatures up to 240°C for 20 min, compared to a shrinkage of 94% for the homogenous PVDF‐HFP mats when treated at 190°C for 20 min. When treated at 178°C for up to 30 min, the coaxial fibres consistently showed changes in thickness of less than 10% and no significant change in area. The coaxial PAN/PVDF‐HFP mats showed negligible changes in average porosity after treatment at 178°C for 20 min. The mechanical strength of the coaxial samples heat treated at 178°C for 5 min was 7.72 MPa, a 22% increase from that before heating, and a 54% increase compared to the as‐spun homogenous PVDF‐HFP. Thus, the proposed technique of combining heat treatment with coaxial morphologies demonstrates significant potential for improving mechanical strength without dimensional shrinkage. [ABSTRACT FROM AUTHOR]

Dietary countermeasures to mitigate detrimental spaceflight‐induced effects on bone health would alleviate the requirements and the consequences imposed by other types of countermeasures for this risk. We hypothesised that antioxidant supplementation during 60 days of 6° head‐down tilt bed rest (HDBR), an analogue of spaceflight, would have a protective effect on bone mineral density (BMD), content (BMC) and bone structure parameters. An exploratory, randomised, controlled, single‐blind intervention trial was conducted in a parallel design with 20 healthy male volunteers (age 34 ± 8 y, weight 74 ± 6 kg). The study included 14 days of baseline data collection (BDC) before bed rest, followed by 60 days of HDBR and a 14‐day recovery period. Ten subjects in the antioxidant group received a supplement (741 mg/d polyphenols, 2.1 g/d omega‐3 fatty acids, 168 mg/d vitamin E and 80 μg/d selenium) daily. Ten subjects in the control group received no supplement. The diet was consistent with dietary reference intakes, individually tailored based on the subject's bodyweight and strictly controlled. We measured whole‐body, lumbar spine and femur BMD and BMC, as well as BMD of the cortical and trabecular compartments of the distal radius and tibia, and cortical and trabecular thickness during BDC, HDBR and recovery. Data were analysed using linear mixed models. The supplementation of an antioxidant cocktail did not mitigate the deteriorating effects of HDBR on BMD, BMC and bone structure parameters. Our findings do not support a recommendation for antioxidant supplementation for astronauts. [ABSTRACT FROM AUTHOR]

Mechanical distortion of working skeletal muscle induces sympathoexcitation via thin fibre afferents, a reflex response known as the skeletal muscle mechanoreflex. However, to date, the receptor ion channels responsible for mechanotransduction in skeletal muscle remain largely undetermined. Transient receptor potential vanilloid 4 (TRPV4) is known to sense mechanical stimuli such as shear stress or osmotic pressure in various organs. It is hypothesized that TRPV4 in thin‐fibre primary afferents innervating skeletal muscle is involved in mechanotransduction. Fluorescence immunostaining revealed that 20.1 ± 10.1% of TRPV4 positive neurons were small dorsal root ganglion (DRG) neurons that were DiI‐labelled, and among them 9.5 ± 6.1% of TRPV4 co‐localized with the C‐fibre marker peripherin. In vitro whole‐cell patch clamp recordings from cultured rat DRG neurons demonstrated that mechanically activated current amplitude was significantly attenuated after the application of the TRPV4 antagonist HC067047 compared to control (P = 0.004). Such reductions were also observed in single‐fibre recordings from a muscle–nerve ex vivo preparation where HC067047 significantly decreased afferent discharge to mechanical stimulation (P = 0.007). Likewise, in an in vivo decerebrate rat preparation, the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to passive stretch of hindlimb muscle were significantly reduced by intra‐arterial injection of HC067047 (ΔRSNA: P = 0.019, ΔMAP: P = 0.002). The findings suggest that TRPV4 plays an important role in mechanotransduction contributing to the cardiovascular responses evoked by the skeletal muscle mechanoreflex during exercise. Key points: Although a mechanical stimulus to skeletal muscle reflexively activates the sympathetic nervous system, the receptors responsible for mechanotransduction in skeletal muscle thin fibre afferents have not been fully identified.Evidence suggests that TRPV4 is a mechanosensitive channel that plays an important role in mechanotransduction within various organs.Immunocytochemical staining demonstrates that TRPV4 is expressed in group IV skeletal muscle afferents. In addition, we show that the TRPV4 antagonist HC067047 decreases the responsiveness of thin fibre afferents to mechanical stimulation at the muscle tissue level as well as at the level of dorsal root ganglion neurons. Moreover, we demonstrate that intra‐arterial HC067047 injection attenuates the sympathetic and pressor responses to passive muscle stretch in decerebrate rats.These data suggest that antagonism of TRPV4 attenuates mechanotransduction in skeletal muscle afferents.The present study demonstrates a probable physiological role for TRPV4 in the regulation of mechanical sensation in somatosensory thin fibre muscle afferents. [ABSTRACT FROM AUTHOR]

Serrated polyps (SPs) are precursors to one‐third of colorectal cancers (CRCs), with histological subtypes: hyperplastic polyps (HPs), sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs). The incidence of early‐onset CRC before the age of 50 is increasing, with limited understanding of SPs in younger cohorts. Using a large colonoscopy‐based cohort, we characterized epidemiologic profiles of SP subtypes, compared to conventional adenomas, with secondary analysis on early‐onset polyps. Ninety‐four thousand four hundred and twenty‐seven patients underwent screening colonoscopies between 2010 and 2018. Demographic, endoscopic and histopathologic characteristics of each polyp subtype were described. High‐risk polyps included SSLs ≥10 mm/with dysplasia and conventional adenomas ≥10 mm/with tubulovillous/villous histology/high‐grade dysplasia. We examined polyp prevalence with age and compared early‐ (age < 50) and late‐onset polyps (age ≥ 50). Eighteen thousand one hundred and twenty‐five patients had SPs (4357 SSLs, 15 415 HPs, 120 TSAs) and 26 699 had conventional adenomas. High‐risk SSLs were enriched in the ascending colon (44.1% vs 2.6‐35.8% for other locations; P <.003). Early‐ and late‐onset SPs had similar subsite distribution. Early‐onset conventional adenomas were more enriched in the distal colon/rectum (51.8% vs 43.4%, P <.001). Multiple conventional adenomas were more represented in late‐onset groups (40.8% vs 33.8%, P <.001), with no difference in SSLs. The prevalence of conventional adenomas/high‐risk conventional adenomas increased continuously with age, whereas the prevalence of SSLs/high‐risk SSLs was stable from age 40 years onwards. A higher proportion of women were diagnosed with early‐onset than late‐onset SSLs (62.9% vs 57.6%, P =.03). Conventional adenomas, SSLs, early‐ and late‐onset polyps have distinct epidemiology. The findings have implications for improved colonoscopy screening and surveillance and understanding the etiologic heterogeneity of CRC. [ABSTRACT FROM AUTHOR]

With Cyber warfare, detection of hardware Trojans, malicious digital circuit components that can leak data and degrade performance, is an urgent issue. Quasi‐Delay Insensitive asynchronous digital circuits, such as NULL Convention Logic (NCL) and Sleep Convention Logic, also known as Multi‐Threshold NULL Convention Logic (MTNCL), have inherent security properties and resilience to large fluctuations in temperatures, which make them very alluring to extreme environment applications, such as space exploration, automotive, power industry etc. This paper shows how dual‐rail encoding used in NCL and MTNCL can be exploited to design Trojans, which would not be detected using existing methods. Generic threat models for Trojans are given. Formal verification methods that are capable of accurate detection of Trojans at the Register‐Transfer‐Level are also provided. The detection methods were tested by embedding Trojans in NCL and MTNCL Rivest‐Shamir‐Adleman (RSA) decryption circuits. The methods were applied to 25 NCL and 25 MTNCL RSA benchmarks of various data path width and provided 100% rate of detection. [ABSTRACT FROM AUTHOR]

Diamond–Blackfan anemia is a rare genetic disease characterized by erythroblastopenia and a large spectrum of developmental anomalies. The vast majority of the cases genetically described are linked to heterozygous pathogenic variants in more than 20 ribosomal protein genes. Here we report an atypical clinical case of DBA associated with a missense variant in RPL8, which encodes RPL8/uL2, a protein of the 60S large ribosomal subunit. RPL8 has been previously implicated as a candidate disease gene in one patient with DBA bearing another type of missense variant; however, evidence for pathogenicity was limited to computational tools. Using functional studies in lymphoblastoid cells as well as yeast models, we show that the RPL8 variants detected in these two patients encode functionally deficient proteins that affect ribosome production and are therefore likely pathogenic. We propose to include RPL8 in the list of DBA‐associated genes. [ABSTRACT FROM AUTHOR]

Systemic insulin administration evokes sympathoexcitatory actions, but the mechanisms underlying these observations are unknown. We reported that insulin sensitizes the response of thin‐fibre primary afferents, as well as the dorsal root ganglion (DRG) that subserves them, to mechanical stimuli. However, little is known about the effects of insulin on primary neuronal responses to chemical stimuli. TRPV1, whose agonist is capsaicin (CAP), is widely expressed on chemically sensitive metaboreceptors and/or nociceptors. The aim of this investigation was to determine the effects of insulin on CAP‐activated currents in small DRG neurons and CAP‐induced action potentials in thin‐fibre muscle afferents of normal healthy rodents. Additionally, we investigated whether insulin potentiates sympathetic nerve activity (SNA) responses to CAP. In whole‐cell patch‐clamp recordings from cultured mice DRG neurons in vitro, the fold change in CAP‐activated current from pre‐ to post‐application of insulin (n = 13) was significantly (P < 0.05) higher than with a vehicle control (n = 14). Similar results were observed in single‐fibre recording experiments ex vivo as insulin potentiated CAP‐induced action potentials compared to vehicle controls (n = 9 per group, P < 0.05). Furthermore, insulin receptor blockade with GSK1838705 significantly suppressed the insulin‐induced augmentation in CAP‐activated currents (n = 13) as well as the response magnitude of CAP‐induced action potentials (n = 9). Likewise, the renal SNA response to CAP after intramuscular injection of insulin (n = 8) was significantly (P < 0.05) greater compared to vehicle (n = 9). The findings suggest that insulin potentiates TRPV1 responsiveness to CAP at the DRG and muscle tissue levels, possibly contributing to the augmentation in sympathoexcitation during activities such as physical exercise. Key points: Evidence suggests insulin centrally activates the sympathetic nervous system, and a chemical stimulus to tissues activates the sympathetic nervous system via thin fibre muscle afferents.Insulin is reported to modulate putative chemical‐sensitive channels in the dorsal root ganglion neurons of these afferents.In the present study, it is demonstrated that insulin potentiates the responsiveness of thin fibre afferents to capsaicin at muscle tissue levels as well as at the level of dorsal root ganglion neurons. In addition, it is demonstrated that insulin augments the sympathetic nerve activity response to capsaicin in vivo.These data suggest that sympathoexcitation is peripherally mediated via insulin‐induced chemical sensitization.The present study proposes a possible physiological role of insulin in the regulation of chemical sensitivity in somatosensory thin fibre muscle afferents. [ABSTRACT FROM AUTHOR]

Muskellunge Esox masquinongy fisheries have increased in abundance and popularity in numerous southern and mid‐Atlantic rivers. However, the paucity of information for these fisheries has limited biologists' ability to effectively manage these resources. We utilized data from simultaneously conducted fishery‐dependent tag return and fishery‐independent capture–recapture studies to estimate catch‐and‐release exploitation and abundance of Muskellunge in the James River, Virginia. During winter electrofishing surveys in 2016–2019, we tagged 747 individual Muskellunge with dart tags and PIT tags. Thirty‐seven percent of tags were returned by anglers, and 33% of tagged Muskellunge were recaptured at least once during subsequent electrofishing surveys. Eighty‐eight percent of angled fish were caught by individuals targeting Muskellunge, and only 1.1% of returned tags were from fish that were harvested. Catch‐and‐release exploitation (u) estimates obtained using a Brownie dead recovery model differed between the upriver (mean u ± SE = 0.57 ± 0.09) and downriver (1.00 ± 0.10) reaches of our study area. Similarly, densities of adult (≥762‐mm) Muskellunge differed between the two areas (upriver: 0.80 fish/ha; downriver: 0.50 fish/ha) but were comparable to densities observed in lakes and at least one other river. The greatest site‐specific density (4.69 fish/ha) was observed at a 1.6‐km reach below the lowest dam, which concentrated fish and restricted upstream movement. Given the high values of u in the James River and the growing popularity of Muskellunge angling in southern waters, investigations into the effects of this level of angling on Muskellunge populations (e.g., trophy potential, abundance) will provide managers with the information needed to develop comprehensive Muskellunge management strategies. [ABSTRACT FROM AUTHOR]

Granulocytes mediate broad immunoprotection through phagocytosis, extracellular traps, release of cytotoxic granules, antibody effector functions and recruitment of other immune cells against pathogens. However, descriptions of granulocytes in HIV infection and mucosal tissues are limited. Our goal was to characterize granulocyte subsets in systemic, mucosal and lymphoid tissues during lentiviral infection using the rhesus macaque (RM) model. Mononuclear cells from jejunum, colon, cervix, vagina, lymph nodes, spleen, liver and whole blood from experimentally naïve and chronically SHIVsf162p3‐infected RM were analysed by microscopy and polychromatic flow cytometry. Granulocytes were identified using phenotypes designed specifically for RM: eosinophils—CD45+ CD66+ CD49d+; neutrophils—CD45+ CD66+ CD14+; and basophils—CD45+ CD123+ FcRε+. Nuclear visualization with DAPI staining and surface marker images by ImageStream (cytometry/microscopy) further confirmed granulocytic phenotypes. Flow cytometric data showed that all RM granulocytes expressed CD32 (FcRγII) but did not express CD16 (FcRγIII). Additionally, constitutive expression of CD64 (FcRγI) on neutrophils and FcRε on basophils indicates the differential expression of Fc receptors on granulocyte subsets. Granulocytic subsets in naïve whole blood ranged from 25·4% to 81·5% neutrophils, 0·59% to 13·3% eosinophils and 0·059% to 1·8% basophils. Interestingly, elevated frequencies of circulating neutrophils, colorectal neutrophils and colorectal eosinophils were all observed in chronic lentiviral disease. Conversely, circulating basophils, jejunal eosinophils, vaginal neutrophils and vaginal eosinophils of SHIVsf162p3‐infected RM declined in frequency. Overall, our data suggest modulation of granulocytes in chronic lentiviral infection, most notably in the gastrointestinal mucosae where a significant inflammation and disruption occurs in lentivirus‐induced disease. Furthermore, granulocytes may migrate to inflamed tissues during infection and could serve as targets of immunotherapeutic intervention. Granulocyte subsets were characterized in systemic, mucosal and lymphoid tissues during lentiviral infection using the rhesus macaque model. We identified elevated neutrophils and eosinophils in the infected gastrointestinal mucosa, where significant inflammation and disruption occurs in lentivirus‐induced disease. [ABSTRACT FROM AUTHOR]

Numerous studies have demonstrated that sympathetic nervous system overactivation during exercise in hypertensive rodents and humans is due, in part, to an exaggerated reflex response known as the exercise pressor reflex. Our prior studies have implicated a key role of mineralocorticoid receptor activation in mediating an augmented exercise pressor reflex in spontaneously hypertensive rats, which is mitigated by blockade with eplerenone. However, the effect of eplerenone on exercise pressor reflex has not been assessed in human hypertension. Accordingly, the authors performed a randomized crossover study to compare the effects of eplerenone to another antihypertensive drug from a different class amlodipine on sympathetic nerve activity (SNA) in 14 patients with uncomplicated hypertension. The authors found that amlodipine unexpectedly augmented the increase in SNA during the second minute of isometric handgrip, which persisted into the post‐exercise circulatory arrest period (∆ SNA, from rest of 15 ± 2 vs. 9 ± 2 vs. 10 ± 2 bursts/min, amlodipine vs. baseline vs. eplerenone, respectively, p <.01), suggesting an exaggerated muscle metaboreflex function. Eplerenone did not alter sympathetic responses to exercise or post‐exercise circulatory arrest in the same hypertensive individuals. In conclusions, our studies provide the first direct evidence for a potentially unfavorable potentiation of muscle metaboreflex by amlodipine during isometric handgrip exercise in hypertensive patients whereas eplerenone has no significant effect. Our study may have clinical implications in terms of selection of antihypertensive agents that have the least detrimental effects on sympathetic neural responses to isometric exercise. [ABSTRACT FROM AUTHOR]

Following long‐duration spaceflight, some astronauts exhibit ophthalmic structural changes referred to as Spaceflight Associated Neuro‐ocular Syndrome (SANS). Optic disc edema is a common sign of SANS. The origin and effects of SANS are not understood as signs of SANS have not manifested in previous spaceflight analog studies. In the current spaceflight analog study, 11 subjects underwent 30 days of strict head down‐tilt bed rest in elevated ambient carbon dioxide (HDBR+CO2). Using functional magnetic resonance imaging (fMRI), we acquired resting‐state fMRI data at 6 time points: before (2), during (2), and after (2) the HDBR+CO2 intervention. Five participants developed optic disc edema during the intervention (SANS subgroup) and 6 did not (NoSANS group). This occurrence allowed us to explore whether development of signs of SANS during the spaceflight analog impacted resting‐state functional connectivity during HDBR+CO2. In light of previous work identifying genetic and biochemical predictors of SANS, we further assessed whether the SANS and NoSANS subgroups exhibited differential patterns of resting‐state functional connectivity prior to the HDBR+CO2 intervention. We found that the SANS and NoSANS subgroups exhibited distinct patterns of resting‐state functional connectivity changes during HDBR+CO2 within visual and vestibular‐related brain networks. The SANS and NoSANS subgroups also exhibited different resting‐state functional connectivity prior to HDBR+CO2 within a visual cortical network and within a large‐scale network of brain areas involved in multisensory integration. We further present associations between functional connectivity within the identified networks and previously identified genetic and biochemical predictors of SANS. Subgroup differences in resting‐state functional connectivity changes may reflect differential patterns of visual and vestibular reweighting as optic disc edema develops during the spaceflight analog. This finding suggests that SANS impacts not only neuro‐ocular structures, but also functional brain organization. Future prospective investigations incorporating sensory assessments are required to determine the functional significance of the observed connectivity differences. [ABSTRACT FROM AUTHOR]

Evidence links the liver to development of colorectal cancer (CRC). However, it remains unknown how liver function may influence CRC risk in the general population. We conducted a prospective cohort study in the UK Biobank of 375 693 participants who provided blood samples in 2006 to 2010. Circulating levels of liver function markers (alanine transaminase [ALT], aspartate transaminase [AST], total bilirubin [TBIL], gamma glutamyltransferase [GGT], alkaline phosphatase [ALP], total protein [TP] and albumin [ALB]) were measured. Incident cancer cases were identified through linkage to the national cancer registry up to 2019. Repeated biomarker measurements were available from a subset of 11 320 participants who were re‐assessed in 2012 to 2013. After a median follow‐up of 10.0 years, we documented 2662 cases of CRC. Circulating levels of ALT, AST, TBIL, GGT, TP and ALB at baseline were inversely associated with CRC risk (P <.01), with multivariable hazard ratio (95% confidence interval) comparing decile 10 vs 1 of 0.62 (0.51‐0.75), 0.63 (0.53‐0.75), 0.85 (0.72‐1.02), 0.74 (0.61‐0.89), 0.70 (0.59‐0.84) and 0.66 (0.55‐0.79), respectively. Strengthened associations were found after recalibration for repeated measurements. The associations appeared stronger for proximal colon cancer than distal colon cancer and rectal cancer, but consistent for early‐, mid‐ and late‐onset CRC. In a large cohort of general population, the UK Biobank, higher circulating levels of ALT, AST, TBIL, GGT, TP and ALB, largely within the normal range, were associated with a lower risk of CRC. The findings support a link between liver function and CRC, and may spur future research on the gut‐microbiota‐liver axis. What's new? Recent studies have reported a possible relationship between circulating liver metabolites and colorectal cancer (CRC) risk, but nothing has been proven conclusively. Here, the authors examined the relationship between various circulating liver function markers and CRC risk, using data from the UK Biobank. Over 10 years of follow up, they documented 2,662 cases of CRC. They tested levels of 7 different circulating liver function markers. For 6 of the markers, higher circulating levels corresponded to a lower risk of CRC. The work may prompt future investigations into the gut‐microbiota‐liver axis. [ABSTRACT FROM AUTHOR]

A common mesofilter approach to conservation of biological diversity and ecosystem function used in agricultural and urban landscapes is maintenance of wetlands and an undisturbed terrestrial buffer surrounding wetlands. Although it is generally accepted that forest buffers protect wetland‐associated biological diversity and ecosystem function, the effectiveness and optimal spatial extent of buffers is still an area of debate. During 2007 and 2008 we surveyed amphibians and environmental conditions associated with 54 depression wetlands on the Delmarva Peninsula of Maryland, USA, to examine the role of forest buffers and wetland characteristics in structuring amphibian communities. Forest cover within a 50‐m buffer surrounding wetlands was correlated (r = −0.81) with wetland pH but no other wetland characteristics. Wetland pH, canopy cover, hydroperiod, and adjacent forest cover were important predictors of wetland use by individual amphibian species, with many species more likely to occur at wetlands that dried late in the hydrological year and with open canopies. At least one common species preferred circumneutral pH and several restricted‐distribution species preferred lower pH (<5). Contrary to expectations, relationships between species occurrence and adjacent forest cover were negative. Our results suggest that current regulations that provide buffers of 30 m or less do not provide adequate protection of wetland water chemistry but that forest encroachment into wetlands may be a threat to the integrity of amphibian communities and should be the target of monitoring, future research, and management efforts. © 2021 The Wildlife Society. Depression wetlands of the Atlantic Coastal Plain maybe threatened by tree encroachment and invasion, and managers will need to monitor and potentially manage tree encroachment into depression wetlands that currently support non‐forest vegetative communities. Moreover, terrestrial forested buffers of ≥50 m are needed to protect the water quality and breeding amphibian assemblages associated with depression wetlands of the Atlantic Coastal Plain. [ABSTRACT FROM AUTHOR]

Bifunctional catalysis in zeolites possessing both Brønsted and Lewis acid sites offers unique opportunities to tailor shape selectivity and enhance catalyst performance. Here, we examine the impact of framework and extra‐framework gallium species on enriched aromatics production in zeolite ZSM‐5. We compare three distinct methods of preparing Ga‐ZSM‐5 and reveal direct (single step) synthesis leads to optimal catalysts compared to post‐synthesis methods. Using a combination of state‐of‐the‐art characterization, catalyst testing, and density functional theory calculations, we show that Ga Lewis acid sites strongly favor aromatization. Our findings also suggest Ga(framework)–Ga(extra‐framework) pairings, which can only be achieved in materials prepared by direct synthesis, are the most energetically favorable sites for reaction pathways leading to aromatics. Calculated acid site exchange energies between extra‐framework Ga at framework sites comprised of either Al or Ga reveal a site‐specific preference for stabilizing Lewis acids, which is qualitatively consistent with experimental measurements. These findings indicate the possibility of tailoring Lewis acid siting by the placement of Ga heteroatoms at distinct tetrahedral sites in the zeolite framework, which can have a marked impact on catalyst performance relative to conventional H‐ZSM‐5. [ABSTRACT FROM AUTHOR]

Missense variants in TUBB3 have historically been associated with either congenital fibrosis of the extraocular muscles type 3 (CFEOM3) or malformations of cortical development (MCD). Until a recent report identified two amino acid substitutions in four patients that had clinical features of both disorders, pathogenic variants of TUBB3 were thought distinct to either respective disorder. Three recurrent de novo Gly71Arg TUBB3 substitutions and a single patient with a de novo Gly98Ser substitution blurred the MCD and CFEOM3 phenotypic distinctions. Here we report a second patient with a missense c.292G>A (p.Gly98Ser) substitution, but without CFEOM3, the first reported evidence that even the same TUBB3 substitution can produce a spectrum of TUBB3 syndrome phenotypes. Our patient presented with amblyopia, exotropia, optic disc pallor, and developmental delay. Neuroimaging identified hypoplasia of the corpus callosum, interdigitation of the frontal lobe gyri, and dysplasia or hypoplasia of the optic nerves, basal ganglia, brainstem, and cerebellum. This report identifies the TUBB3 Gly98Ser substitution to be recurrent but inconsistently including CFEOM3, and identifies the absence of joint contractures and the presence of optic disc abnormalities that may be genotype‐specific to the TUBB3 Gly98Ser substitution. [ABSTRACT FROM AUTHOR]

Hexaploid oat (Avena sativa L.) is a commercially important cereal crop due in part to (1‐3,1‐4)‐β‐D‐glucan (β‐glucan), a hemicellulose important to human health. Cellulose synthase‐like (Csl) genes have been shown to contribute to β‐glucan production, with CslF6 likely being of major importance. Here, we report a genome‐wide association study (GWAS) to identify quantitative trait loci (QTLs) controlling β‐glucan production in oat. Three panels of elite accessions (Spring, Winter, and World Diversity) of oat were grown in multiple North American locations and genotyped using the Oat 6K Custom Infinium iSelect BeadChip. Independent GWAS were performed on each set of accessions and locations, with a meta‐analysis identifying 58 significantly associated markers. Synteny with the barley (Hordeum vulgare L.) genome identified four major regions of interest revealing the CslF and CslH gene families along with UGPase and AGPase as candidate genes. Subgenome‐specific expression of the A, C, and D AsCslF6 homoeologs revealed that AsCslF6_C is the least expressed in all tissue types and time points, with low‐β‐glucan varieties recording the highest proportion of AsCslF6_C expression. Linkage mapping of the homoeologs placed AsCslF6_D on consensus linkage group Mrg02 overlapping with QTL 2.2 and AsCslF6_A on Mrg12 flanked by markers associated with QTL 12.2. Many QTLs identified in this study were homoeologous, representing different gene copies duplicated in ancestral genomes, suggesting that multiple homoeologous copies of β‐glucan biosynthesis genes are contributing to the overall phenotype. [ABSTRACT FROM AUTHOR]

Key points: Insulin is known to activate the sympathetic nervous system centrally. A mechanical stimulus to tissues activates the sympathetic nervous system via thin fibre afferents. Evidence suggests that insulin modulates putative mechanosensitive channels in the dorsal root ganglion neurons of these afferents. In the present study, we report the novel finding that insulin augments the mechanical responsiveness of thin fibre afferents not only at dorsal root ganglion, but also at muscle tissue levels. Our data suggest that sympathoexcitation is mediated via the insulin‐induced mechanical sensitization peripherally. The present study proposes a novel physiological role of insulin in the regulation of mechanical sensitivity in somatosensory thin fibre afferents. Insulin activates the sympathetic nervous system, although the mechanism underlying insulin‐induced sympathoexcitation remains to be determined. A mechanical stimulus to tissues such as skin and/or skeletal muscle, no matter whether the stimulation is noxious or not, activates the sympathetic nervous system via thin fibre afferents. Evidence suggests that insulin modulates putative mechanosensitive channels in the dorsal root ganglion (DRG) neurons of these afferents. Accordingly, we investigated whether insulin augments whole‐cell current responses to mechanical stimuli in small DRG neurons of normal healthy mice. We performed whole‐cell patch clamp recordings using cultured DRG neurons and observed mechanically‐activated (MA) currents induced by mechanical stimuli applied to the cell surface. Local application of vehicle solution did not change MA currents or mechanical threshold in cultured DRG neurons. Insulin (500 mU mL−1) significantly augmented the amplitude of MA currents (P < 0.05) and decreased the mechanical threshold (P < 0.05). Importantly, pretreatment with the insulin receptor antagonist, GSK1838705, significantly suppressed the insulin‐induced potentiation of the mechanical response. We further examined the impact of insulin on thin fibre muscle afferent activity in response to mechanical stimuli in normal healthy rats in vitro. Using a muscle–nerve preparation, we recorded single group IV fibre activity to a ramp‐shaped mechanical stimulation. Insulin significantly decreased mechanical threshold (P < 0.05), although it did not significantly increase the response magnitude to the mechanical stimulus. In conclusion, these data suggest that insulin augments the mechanical responsiveness of small DRG neurons and potentially sensitizes group IV afferents to mechanical stimuli at the muscle tissue level, possibly contributing to insulin‐induced sympathoexcitation. Key points: Insulin is known to activate the sympathetic nervous system centrally. A mechanical stimulus to tissues activates the sympathetic nervous system via thin fibre afferents. Evidence suggests that insulin modulates putative mechanosensitive channels in the dorsal root ganglion neurons of these afferents. In the present study, we report the novel finding that insulin augments the mechanical responsiveness of thin fibre afferents not only at dorsal root ganglion, but also at muscle tissue levels. Our data suggest that sympathoexcitation is mediated via the insulin‐induced mechanical sensitization peripherally. The present study proposes a novel physiological role of insulin in the regulation of mechanical sensitivity in somatosensory thin fibre afferents. [ABSTRACT FROM AUTHOR]

ARID2 loss‐of‐function is associated with a rare genetic disorder characterized in 14 reported patients to date. ARID2 encodes a member of the SWItch/sucrose non‐fermentable chromatin remodeling complex. Other genes encoding subunits of this complex, such as ARID1A, ARID1B, and SMARCA2, are mutated in association with Coffin‐Siris syndrome (CSS) and Nicolaides Baraitser syndrome (NCBRS) phenotypes. Previously reported ARID2 mutations manifested clinically with a CSS‐like phenotype including intellectual disability, coarsened facial features, fifth toenail hypoplasia, and other recognizable dysmorphisms. However, heterogeneity exists between previously reported patients with some patients showing more overlapping features with NCBRS. Herein, we present a patient with a novel disease‐causing ARID2 loss‐of‐function mutation. His clinical features included intellectual disability, coarse and dysmorphic facial features, toenail hypoplasia, ADHD, short stature, and delayed development consistent with prior reports. Our patient also presented with previously unreported clinical findings including ophthalmologic involvement, persistent fetal fingertip and toetip pads, and diffuse hyperpigmentary and hypopigmentary changes sparing his face, palms, and soles. The anomalous skin findings are particularly of interest given prior literature outlining the role of ARID2 in melanocyte homeostasis and melanoma. This clinical report and review of the literature is further affirming of the characteristic symptoms and expands the phenotype of this newly described and rare syndrome. [ABSTRACT FROM AUTHOR]

Objectives: This study was to investigate the association between central obesity and tooth loss in non‐obese population. Material and Methods: This national cross‐sectional study included 19436 participants, aged 19–74 years with body mass index(BMI) 18.5–29.9 kg/m2, from the National Health and Nutrition Examination Survey(NHANES) 1999–2012. Tooth loss was measured by the number of teeth missing. Central obesity was defined by a categorized 3‐level waist circumference according to the WHO recommendation. A zero‐inflated negative binomial model was used to investigate the association between tooth loss and central obesity. All models were adjusted for demographic, socioeconomic status, lifestyles, medical conditions and inflammatory biomarkers. Results: For an overweight person with central obesity, the prevalence of tooth loss increased by 31% (Prevalence ratio [PR]: 1.31, 95% CI: 1.20–1.44) compared with a person with similar BMI but no central obesity, and increased by 40% (PR: 1.40, 95% CI: 1.26–1.56) if compared with a normal‐weight person without central obesity. There was a clear stepwise association between tooth loss and central obesity. Conclusion: The results reveal that central obesity is significantly associated with tooth loss in the non‐obese population, which suggests that non‐obese individuals with central obesity may represent an important target population for oral health preventive strategies. [ABSTRACT FROM AUTHOR]

Metastatic human papillomavirus-positive oropharyngeal carcinoma mimicking primary cutaneous sweat-gland carcinoma In addition, there are a growing number of HPV-related head and neck cancers that can mimic sweat gland or skin adnexal tumors including the newly defined entity HPV-related multiphenotypical sinonasal carcinoma which can mimic adenoid cystic carcinoma.6 In addition, it is important to know that there have also been reports of adenoid cystic carcinoma7 and mucoepidermoid carcinoma8 associated with HPV infection, though rare. HPV-related multiphenotypic sinonasal carcinoma: an expanded series of 49 cases of the tumor formerly known as HPV-related carcinoma with adenoid cystic carcinoma-like features. [Extracted from the article]

Follicular lymphoma (FL) patients treated with firstline R‐CHOP who experience progression of disease (POD) within 2 years have a shorter survival than those who do not have POD within 2 years. Whether this observation holds for patients treated initially with biologic immunotherapy alone is unknown. We performed a retrospective analysis of 174 patients pooled from three frontline rituximab (R)‐based nonchemotherapy doublet trials: R‐galiximab (Anti‐CD80, CALGB 50402), R‐epratuzumab (Anti‐CD22, CALGB 50701), and R‐lenalidomide (CALGB 50803) to determine outcomes of early progressors and risk factors for early POD, defined as progression within 24 months from study entry. Twenty‐eight percent (48/174) of patients had early POD. After adjusting for the Follicular Lymphoma International Prognostic Index (FLIPI), patients with early POD from study entry had a worse OS compared with patients who did not progress within 2 years (HR = 4.33 (95% CI 1.50‐12.5), P = 0.007). For early POD, the 2‐year survival was 80% vs 99% for nonearly POD, and the 5‐year survival was 74% vs 90%, respectively. These findings suggest that the adverse survival of patients with early POD may be independent of initial treatment modality. In this combined analysis of three CALGB clinical trials, patients with early progression of follicular lymphoma following frontline immunotherapy doublets are at increased risk of death. PFS24 is a prognostic marker for overall survival in patients treated with rituximab‐containing immunotherapy. [ABSTRACT FROM AUTHOR]

Summary: This study assessed whether hypoxia during high‐load resistance exercise could enhance the acute physiological responses related to muscular development. Twelve trained men performed exercise in three conditions: normoxia (fraction of inspired oxygen [FIO2] = 21%), moderate‐level hypoxia (FIO2 = 16%) and high‐level hypoxia (FIO2 = 13%). Exercise comprised high‐load squats and deadlifts (5 × 5 using 80% of 1‐repetition maximum with 180‐s rest). Muscle oxygenation and activation were monitored during exercise. Metabolic stress was estimated via capillary blood sampling. Perceived fatigue and soreness were also quantified following exercise. While the hypoxic conditions appeared to affect muscle oxygenation, significant differences between conditions were only noted for maximal deoxyhaemoglobin in the deadlift (P = 0·009). Blood lactate concentration increased from 1·1 to 1·2 mmol l−1 at baseline to 9·5–9·8 mmol l−1 after squats and 10·4–10·5 mmol l−1 after deadlifts (P≤0·001), although there were no between‐condition differences. Perceived fatigue and muscle soreness were significantly elevated immediately and at 24 h following exercise, respectively, by similar magnitudes in all conditions (P≤0·001). Muscle activation did not differ between conditions. While metabolic stress is thought to moderate muscle activation and subsequent muscular development during hypoxic resistance training, it is not augmented during traditional high‐load exercise. This may be explained by the low number of repetitions performed and the long interset rest periods employed during this training. These findings suggest that high‐load resistance training might not benefit from additional hypoxia as has been shown for low‐ and moderate‐load training. [ABSTRACT FROM AUTHOR]

Abstract: As technological interest and environmental emissions of the rare earth elements increase, it is becoming more important to assess their potential environmental impact. Samarium (Sm) is a lanthanide of intermediate molar mass that is used in numerous high‐technology applications including wind turbines, solar panels, and electric vehicles. The present study relates the speciation of Sm determined in the presence of natural organic matter (NOM) to its bioavailability to the unicellular green alga Chlamydomonas reinhardtii. The free ion concentration was determined using a cation exchange resin (ion exchange technique) in dynamic mode and compared with thermodynamic modeling. Short‐term biouptake experiments were performed in the presence of 4 types of NOM: Suwannee River fulvic acids, Pahokee Peat fulvic acids, Suwannee River humic acids, and a Luther Marsh dissolved organic matter isolate (90–95% humic acids). It was clearly shown that even a small amount of NOM (0.5 mg C L−1) resulted in a significant decrease (10 times) in the Sm internalization fluxes. Furthermore, complexation with humic acids (and the corresponding reduction in Sm bioavailability) was stronger than that with fulvic acids. The results showed that the experimentally measured (free) Sm was a better predictor of Sm internalization than either the total concentrations or the free ion concentrations obtained using thermodynamic modeling. Environ Toxicol Chem 2018;37:1623–1631. © 2018 SETAC [ABSTRACT FROM AUTHOR]

Altered bone quality, caused by underlying metabolic changes of type 2 diabetes (T2D), has been hypothesized to cause altered bone strength and turnover leading to increased fracture risk in T2D patients. Current understanding about changes in bone turnover markers in T2D patients is mainly based on studies focused on Caucasian men and women. However, Hispanic populations have the highest prevalence of both T2D and osteoporosis in the US. We investigated associations of glycemic control (in terms of glycated hemoglobin [HbA1c]) and bone turnover rate in 69 older (≥50 years) Mexican American Cameron County Hispanic Cohort (CCHC) participants with T2D. Multivariable analyses were conducted to assess the associations between HbA1c (%), serum osteocalcin (OC), and serum sclerostin. In agreement with published reports from other racial/ethnic populations, our study found that lower bone turnover (indicated by lower serum OC) occurred in Mexican American men with T2D who had poorer glycemic control. For the women in our study, we found no significant association between glycemic control and OC. In contrast, HbA1c was positively associated with sclerostin for women, with near significance (p = 0.07), while no association was found in men. We recommend screening Mexican American individuals with T2D, specifically those with poor glycemic control, for bone loss and fracture risk. [ABSTRACT FROM AUTHOR]

Abstract: Bilayer donor–acceptor molecular junctions are successfully fabricated with active layer thickness <15 nm to study the mechanism of photo‐induced charge transport. The bilayer devices exhibit lifetimes greater than 1 h with laser irradiation, and a strong dependence of the sign and magnitude of the photovoltage and photocurrent on structure and order of the molecular layers. A distinct feature of the bilayer structure is covalent bonding between the donor and acceptor molecular layers, which permits simultaneous absorption and charge separation across a covalent heterojunction. In addition to providing probes of internal energy levels and charge transport in molecular junctions, photo‐induced currents and voltages may potentially be useful in light‐weight, durable, and flexible photodetectors. [ABSTRACT FROM AUTHOR]

Given limited global food supplies and the fact that the global population is expected to double by 2050, there is an urgent need for the development of high-calorie foods, including culinary oils. The seeds of oil crops contain high-energy density oil composed of triacylglycerides (TAGs) at up to 80% by dry mass. However, maize (Zea mays L.) seeds are relatively poor in calorie and nutritional values. Therefore, in this report, we address this constraint via metabolic engineering to improve maize seed lipids including TAG and seed TAG nutritional values by overexpression of three major genes, including: (i) the Arabidopsis thaliana (L.) Heynh. diacylglycerol acyltransferase 1 (AtDGAT1), a gene that catalyzes the TAG biosynthesis final step prior to packaging of TAGs into oil bodies; (ii) the transcription factor WRINKLED 1 (WRI1), which promotes the regulation of the expression of genes involved in fatty acid biosynthesis; and (i) the A. thaliana oleosin (AtOleosin) gene, a gene coding for a protein that protects TAGs from degradation. The overexpression of the above three genes, and probably certain unintentional in vitro culture genetic variabilities, resulted in 117% increase of seed TAGs and 25% increase in total oil contents when compared with the wild-type control corn seeds. In addition, the above genetic modifications led to major shifts in the fatty acid profiles in favor of human health. [ABSTRACT FROM AUTHOR]

Study Objectives The primary objective was to determine the impact of hematologic malignancies and/or conditioning regimens on the risk of developing Clostridium difficile infection (CDI) in patients undergoing hematopoietic stem cell transplantation (HSCT). Secondary objectives were to determine if traditional CDI risk factors applied to patients undergoing HSCT and to determine the presence of CDI markers of severity of illness among this patient population. Design Single-center retrospective case-control study. Setting Quaternary care academic medical center. Patients A total of 105 patients who underwent HSCT between December 2009 and December 2014; of these patients, 35 developed an initial episode of CDI (HSCT/CDI group [cases]), and 70 did not (controls). Controls were matched in a 2:1 ratio to cases based on age (± 10 yrs) and date of HSCT (± 6 mo). Measurements and Main Results Baseline characteristics of the two groups were well balanced regarding age, sex, race, ethnicity, and type of HSCT. No significant differences in conditioning regimen, hematologic malignancy, total body irradiation received for HSCT, use of antibiotics within 60 days of HSCT, or use of prophylactic antibiotics after HSCT were noted between the two groups. Patients in the control group were 10.57 (95% confidence interval 1.24-492.75) more likely to have received corticosteroids prior to HSCT than patients in the HSCT/CDI group (p=0.01). Use of proton pump inhibitors at the time of HSCT was greater among the control group than among patients in the HSCT/CDI group (97% vs 86%, p=0.048). No significant difference in mortality was noted between the groups at 3, 6, and 12 months after HSCT. Metronidazole was frequently prescribed for patients in the HSCT/CDI group (34 patients [97%]). Severe CDI was not common among patients within the HSCT/CDI group (13 patients [37%]); vancomycin was infrequently prescribed for these patients ([31%] 4/13 patients). Conclusion Hematologic malignancies and a conditioning regimen administered for HSCT were not significant risk factors for the development of CDI after HSCT. Use of corticosteroids prior to HSCT and use of proton pump inhibitors at the time of HSCT were associated with a significantly decreased risk of CDI. [ABSTRACT FROM AUTHOR]

ABSTRACT Zoonotic diseases in wildlife present substantial challenges and risks to host populations, susceptible domestic livestock populations, and affected stakeholders. Brucellosis, a disease caused by the bacterium Brucella abortus, is endemic among elk ( Cervus canadensis) attending winter feedgrounds and adjacent areas of western Wyoming, USA. To minimize transmission of brucellosis from elk to elk and elk to livestock, managers initiated a B. abortus strain 19 ballistic vaccination program in 1985. We used brucellosis prevalence (1971-2015) and reproductive outcome (2006-2015) data collected from female elk attending feedgrounds to assess efficacy of the strain 19 program while controlling for potentially confounding factors such as site and age. From our generalized linear models, we found that seroprevalence of brucellosis was 1) not lower following inception of vaccination; 2) not inversely associated with proportion of juveniles vaccinated over time; 3) not inversely associated with additional yearlings and adults vaccinated over time; and 4) associated more with feeding end-date than proportion of juveniles vaccinated. Using vaginal implant transmitters in adult females that were seropositive for brucellosis, we found little effect of vaccination coverage at reducing reproductive failures (i.e., abortion or stillbirth). Because we found limited support for efficacy of the strain 19 program, we support research to develop an oral vaccine and suggest that continuing other spatio-temporal management actions will be most effective to minimize transmission of brucellosis and reduce dependency of elk on supplemental winter feeding. © 2017 The Wildlife Society. [ABSTRACT FROM AUTHOR]

An applied approach for in situ characterization of oxide ore samples exposed to a thiosulfate-based leaching solution with shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) is discussed. Differences in passive layer growth during thiosulfate leaching were observed in the SHINERS spectra between the untreated and pressure oxidation (POX)-treated oxide ore samples received from Barrick Gold Corporation. The SHINERS spectra revealed that the passive layer at the untreated oxide ore-electrolyte interface contains metal sulfides and significant quantities of polysulfide chains [ABSTRACT FROM AUTHOR]

Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma ( DLBCL) and B cell lymphoma unclassifiable ( BCLU), particularly in the setting of double hit lymphoma ( DHL). However, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma ( SHL), 22 patients with MYC-amplified lymphoma ( MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification ( MYC normal) and 45 patients with DHL, all treated with either R- CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or intensive induction therapy. For SHL and MYC amp patients, the 2-year progression-free survival rate ( PFS) was 49% and 48% and 2-year overall survival rate ( OS) was 59% and 71%, respectively. SHL patients receiving intensive induction experienced higher 2-year PFS (59% vs. 23%, P = 0·006) but similar 2-year OS as compared with SHL patients receiving R- CHOP. SHL DLBCL patients treated with R- CHOP, but not intensive induction, experienced significantly lower 2-year PFS and OS ( P < 0·001 for both) when compared with MYC normal patients. SHL patients appear to have a poor prognosis, which may be improved with receipt of intensive induction. [ABSTRACT FROM AUTHOR]

The representer method is adopted for solving a weak constraints 4D-Var problem for the assimilation of ocean observations including along-track sea-surface height (SSH), using a free-surface ocean model.Direct 4D-Var assimilation of SSH observations along the satellite tracks requires that the adjoint model be integrated with Dirac impulses on the right-hand side (rhs) of the adjoint equations for the surface elevation equation. The solution of this adjoint model will inevitably include surface gravity waves, and it constitutes the forcing for the tangent linear model (TLM) according to the representer method. This yields an analysis that is contaminated by gravity waves. A method for avoiding the generation of the surface gravity waves in the analysis is proposed in this study; it consists of removing the adjoint of the free surface from the rhs of the free-surface mode in the TLM. The information from the SSH observations will still propagate to all other variables via the adjoint of the balance relationship between the barotropic and baroclinic modes, resulting in the correction to the surface elevation. Two assimilation experiments are carried out in the Gulf of Mexico: one with adjoint forcing included on the rhs of the TLM free-surface equation, and the other without. Both analyses are evaluated against the assimilated SSH observations, SSH maps from AVISO and independent surface drifters, showing that the analysis that did not include adjoint forcing in the free surface is more accurate. This study shows that when a weak constraints 4D-Var approach is considered for the assimilation of along-track SSH observations using a free-surface model, with the aim of correcting the mesoscale circulation, an independent model error should not be assigned to the free surface. [ABSTRACT FROM AUTHOR]

Ophthalmic changes have occurred in a subset of astronauts on International Space Station missions. Visual deterioration is considered the greatest human health risk of spaceflight. Affected astronauts exhibit higher concentrations of 1-carbon metabolites (e.g., homocysteine) before flight. We hypothesized that genetic variations in 1-carbon metabolism genes contribute to susceptibility to ophthalmic changes in astronauts. We investigated 5 polymorphisms in the methionine synthase reductase (MTRR), methylenetetrahydrofolate reductase (MTHFR), serine hydroxymethyltransferase (SHMT), and cystathionine β-synthase (CBS) genes and their association with ophthalmic changes after flight in 49 astronauts. The number of G alleles of MTRR 66 and C alleles of SHMT1 1420 both contributed to the odds of visual disturbances. Preflight dehydroepiandrosterone was positively associated with cotton wool spots, and serum testosterone response during flight was associated with refractive change. Block regression showed that B-vitamin status and genetics were significant predictors of many of the ophthalmic outcomes that we observed. In one example, genetics trended toward improving (P = 0.10) and B-vitamin status significantly improved (P < 0.001) the predictive model for refractive change after flight. We document an association between MTRR 66 and SHMT1 1420 polymorphisms and spaceflight-induced vision changes. This line of research could lead to therapeutic options for both space travelers and terrestrial patients.--Zwart, S. R., Gregory, J. F., Zeisel, S. H., Gibson, C. R., Mader, T. H., Kinchen, J. M., Ueland, P. M., Ploutz-Snyder, R., Heer, M. A., Smith, S. M. Genotype, B-vitamin status, and androgens affect spaceflight-induced ophthalmic changes. [ABSTRACT FROM AUTHOR]

Monkeypox virus (MPXV) infection of the prairie dog is valuable to studying systemic orthopoxvirus disease. To further characterize differences in MPXV clade pathogenesis, groups of prairie dogs were intranasally infected (8 × 10(3) p.f.u.) with Congo Basin (CB) or West African (WA) MPXV, and 28 tissues were harvested on days 2, 4, 6, 9, 12, 17, and 24 postinfection. Samples were evaluated for the presence of virus and gross and microscopic lesions. Virus was recovered from nasal mucosa, oropharyngeal lymph nodes, and spleen earlier in CB challenged animals (day 4) than WA challenged animals (day 6). For both groups, primary viremia (indicated by viral DNA) was seen on days 6-9 through day 17. CB MPXV spread more rapidly, accumulated to greater levels, and caused greater morbidity in animals compared to WA MPXV. Histopathology and immunohistochemistry (IHC) findings, however, were similar. Two animals that succumbed to disease demonstrated abundant viral antigen in all organs tested, except for brain. Dual-IHC staining of select liver and spleen sections showed that apoptotic cells (identified by TUNEL) tended to colocalize with poxvirus antigen. Interestingly splenocytes were labelled positive for apoptosis more often than hepatocytes in both MPXV groups. These findings allow for further characterization of differences between MPXV clade pathogenesis, including identifying sites that are important during early viral replication and cellular response to viral infection. [ABSTRACT FROM AUTHOR]

Over the past decade, researchers have begun to use metals of the lanthanide family for numerous applications, including liquid crystal display (LCD) screens, optical fibers, and laser technology. Unfortunately, little is presently known about their bioavailability or the mechanisms by which they might cause toxicity. The present study focuses on cerium (Ce), one of the most widely used lanthanides, and on validating the biotic ligand model as a means to predict Ce bioaccumulation. Short-term exposures to Ce were performed using the unicellular alga Chlamydomonas reinhardtii, to better relate Ce bioavailability to its chemical speciation in solution. Maximum uptake fluxes ( Jmax) and affinity constants for the binding of Ce to the biological uptake sites ( KS) were established at pH 5.0 and pH 7.0. An apparent affinity constant of 1.8 × 107 M-1 was observed at pH 5.0, with a larger value obtained at pH 7.0 (6 × 107 M-1), albeit under conditions where equilibrium could not be confirmed. By evaluating Ce speciation using centrifugal ultrafiltration and single-particle inductively coupled plasma spectrometry, it could be concluded that very little (∼30%) Ce was truly dissolved at pH 7.0, with the majority of the metal being present in colloidal species. Speciation was also monitored by fluorescence to evaluate Ce complexation by natural organic matter (NOM). The presence of NOM decreased Ce bioaccumulation in line with free Ce concentrations. Finally, competition with calcium for the metal uptake sites was shown to result in a decrease in Ce uptake by C. reinhardtii. Environ Toxicol Chem 2015;34:1711-1719. © 2015 SETAC [ABSTRACT FROM AUTHOR]

The purpose of this study was to directly assess sex differences in bone loss, bone biochemistry, and renal stone risk in bed rest. Bed rest simulates some spaceflight effects on human physiology and can be used to address the potential existence of sex-specific effects on bone metabolism and renal stone risk in space. We combined data from the control subjects in five head-down-tilt bed rest studies (combined n = 50 men, 24 women) of differing durations (14-90 days). All subjects were healthy volunteers. Mean age was 35 ± 9 years for women and 33 ± 8 years for men. The main outcome measures were bone density and biochemistry, and renal stone risk chemistry. Before bed rest began, men had higher bone mineral density and content ( P < 0.001), and excreted more biomarkers of bone resorption and calcium per day than did women ( P < 0.05). These differences remained during bed rest. A number of urine chemistry analytes increased (e.g., calcium) or decreased (e.g., sodium, citrate, and urine volume) significantly for men and women during bed rest. These changes may predispose men to higher stone risk. Men and women do not have substantially different responses to the skeletal unloading of bed rest. [ABSTRACT FROM AUTHOR]

Astronauts are exposed to increased body iron stores and radiation, both of which can cause oxidative damage leading to negative health effects. The purpose of this study was to investigate combined effects of high dietary iron (650 mg/kg diet) and radiation exposure (0.375 Gy cesium-137 every other day for 16 d) on markers of oxidative stress, immune system function, and colon mucosal environment in male Sprague-Dawley rats (n=8/group). Control rats consumed adequate iron (45 mg/kg diet) and were not irradiated. Combined treatments increased liver glutathione peroxidase, serum catalase, and colon myeloperoxidase while decreasing total fecal short-chain fatty acid concentrations. The high-iron diet alone increased leukocyte count. Radiation decreased the T-cell CD4: CD8 ratio. Plasma iron was negatively correlated with cytokine production in activated monocytes. Genes involved in colon microbial signaling, immune response, and injury repair were altered by radiation. Genes involved with injury repair and pathogen recognition changed with dietary iron. These data demonstrate that dietary iron and radiation, alone and combined, contribute to oxidative stress that is related to immune system alterations in circulation and the colon. The model presented may help us better understand the changes to these systems that have been identified among astronauts. [ABSTRACT FROM AUTHOR]

Previous phylogenetic work investigating the origins of the grain amaranths is plagued by two methodological faults. Primarily, no study to date has adequately sampled all of the grain species as well as the two putative weedy progenitors across their entire native species' ranges. Second, no study to date adequately investigates the genetic diversity component of both putative weedy species (Amaranthus hybridus L. and Amaranthus quitensis Kunth). Two hundred fifty-eight individuals from 56 taxa representing the three grain amaranth species and two putative weedy progenitors were sampled from their native species' ranges and subjected to microsatellite testing. Data were analyzed using principal component analysis, clustering algorithms, and genetic distance neighbor-joining tree dendrograms. Standard genetic diversity measures indicate strong inbreeding coefficients in all studied taxa. Principal component analysis, clustering algorithms, private alleles, and tree dendrograms all resolve a distinct A. quitensis group. The grain amaranths and A. hybridus were found to group together. Results from 11 simple sequence repeat loci indicate the following: (i) A. hybridus is the progenitor of all three grain amaranths in at least two separate domestication events, (ii) A. quitensis is its own species and not a variant of A. hybridus, and (iii) Amaranthus caudatus L. and Amaranthus hypochondriacus L. appear to be closely related. [ABSTRACT FROM AUTHOR]

RATIONALE Radical-directed dissociation techniques provide structural information which is complementary to that from conventional collision-induced dissociation (CID). The analysis of phosphopeptide anions is warranted due to their relatively acidic character. As femtosecond laser-induced ionization/dissociation tandem mass spectrometry (fsLID-MS/MS) is uniquely initiated by field ionization, an investigation is warranted to determine whether fsLID may provide novel analytical utility for phosphopeptide anions. METHODS Twenty-three synthetic deprotonated phosphopeptide anions were introduced into a three-dimensional quadrupole ion trap mass spectrometer via electrospray ionization. The ion trap was interfaced with a near-IR (802 nm) ultrashort-pulsed (35 fs FWHM) ultrahigh-powered (peak power ~1014 W/cm2) laser system. Performance comparisons are made with other techniques applied to phosphopeptide anion analysis, including CID, electron detachment dissociation (EDD), negative electron transfer dissociation (NETD), activated electron photodetachment dissociation (activated-EPD), and ultraviolet photodissociation (UVPD). RESULTS FsLID-MS/MS of multiply deprotonated phosphopeptide anions provides sequence information via phosphorylation-intact a/ x ions in addition to other sequence ions, satellite ions, and side-chain losses. Novel fragmentation processes include selective c-ion formation N-terminal to Ser/Thr and a phosphorylation-specific correlation between xn-98 ion abundances and phosphorylation at the nth residue. Sequencing-quality data required about 30 s of signal averaging. fsLID-MS/MS of singly deprotonated phosphopeptides did not yield product anions with stable trajectories, despite significant depletion of the precursor. CONCLUSIONS Multiply deprotonated phosphopeptide anions were sequenced via negative-mode fsLID-MS/MS, with phosphosite localization facilitated by a/x ion series in addition to diagnostic xn-98 ions. fsLID-MS/MS is qualitatively competitive with other techniques. Further efficiency enhancements (e.g., implementation on a linear trap or/and higher pulse frequencies) may permit sequence analyses on chromatographic timescales. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? Does increasing NO production within the nucleus tractus solitarii (NTS) affect mechanoreflex function in normotensive and hypertensive rats?, What is the main finding and its importance? Dialysis of 1 μ m l-arginine, an NO precursor, within the NTS significantly attenuated the pressor response to muscle stretch in normotensive and hypertensive rats. In contrast, 10 μ m l-arginine had no effect in normotensive animals, while increasing and decreasing the pressor and tachycardic responses to stretch, respectively, in hypertensive rats. This suggests that increasing NO within the NTS using lower doses of l-arginine can partly normalize mechanoreflex overactivity in hypertensive rats, whereas the effects of larger doses are equivocal., The blood pressure response to exercise is exaggerated in hypertension. Recent evidence suggests that an overactive skeletal muscle mechanoreflex contributes significantly to this augmented circulatory responsiveness. Sensory information from the mechanoreflex is processed within the nucleus tractus solitarii (NTS) of the medulla oblongata. Normally, endogenously produced nitric oxide within the NTS attenuates the increase in mean arterial pressure (MAP) induced by mechanoreflex stimulation. Thus, it has been suggested that decreases in NO production in the NTS underlie the generation of mechanoreflex dysfunction in hypertension. Supporting this postulate, it has been shown that blocking NO production within the NTS of normotensive rats reproduces the exaggerated pressor response elicited by mechanoreflex activation in hypertensive animals. What is not known is whether increasing NO production within the NTS of hypertensive rats mitigates mechanoreflex overactivity. In this study, the mechanoreflex was selectively activated by passively stretching hindlimb muscle before and after the dialysis of 1 and 10 μ m l-arginine (an NO precursor) within the NTS of decerebrate normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Stretch induced larger elevations in MAP in SHRs compared with WKY rats. In both groups, dialysis of 1 μ m l-arginine significantly attenuated the pressor response to stretch. However, at the 10 μ m dose, l-arginine had no effect on the MAP response to stretch in WKY rats, while it enhanced the response in SHRs. The data demonstrate that increasing NO availability within the NTS using lower doses of l-arginine partly normalizes mechanoreflex dysfunction in hypertension, whereas higher doses do not. The findings could prove valuable in the development of treatment options for mechanoreflex overactivity in this disease. [ABSTRACT FROM AUTHOR]

Amaranth (Amaranthus caudatus L.) is an important seed crop in the Andes. It has excellent nutritional value and ample capacity for growth under drought, heat, and soil nutrient deficiency. The objective of this study was to characterize and quantify genetic diversity among a series of 178 mostly Peruvian amaranth individuals genotyped from among 48 accessions using 96 biallelic single nucleotide polymorphism (SNP) markers in KASPar assays on a 96.96 Fluidigm EP1 platform. The 178 seed genotypes included the predominant white-opaque (waxy), white-vitreous (nonwaxy), black, and brown types, all from within the Centro de Investigacion de Cultivos Andinos-Universidad Nacional de San Antonio Abad del Cusco collection. The samples separated into two groups based on the seed color parameter (black, brown, and white-vitreous versus white-opaque) with STRUCTURE analysis but did not form distinct genotypic groups based on geographic origin. When analyzed as seed-color subgroups--black vs. brown vs. white-vitreous vs. white-opaque--83.46% of the genetic variation was explained by genetic differences within subgroup. The highest average observed heterozygosity (Ho) within color-based subgroups was 0.2612 in the vitreous-seeded subgroup, and within-group expected heterozygosity (He) was highest in the brown-seeded subgroup (0.398). Cluster analysis and principal component analysis partitioned the amaranth accessions into two clusters with four distinct subclusters. Analyses also revealed evidence for selection of nonwaxy, vitreous-seeded amaranth in the Andes. [ABSTRACT FROM AUTHOR]

Evidence suggests that the muscle mechanoreflex, a circulatory reflex that raises blood pressure and heart rate (HR) upon activation of mechanically sensitive afferent fibres in skeletal muscle, is overactive in hypertension. However, the mechanisms underlying this abnormal reflex function have yet to be identified. Sensory input from the mechanoreflex is processed within the nucleus tractus solitarii (NTS) in the medulla oblongata. Within the NTS, the enzymatic activity of nitric oxide synthase produces nitric oxide (NO). This centrally derived NO has been shown to modulate muscle reflex activity and serves as a viable candidate for mediating the mechanoreflex dysfunction that develops in hypertension. We hypothesized that mechanoreflex dysfunction in hypertension is mediated by abnormal alterations in NO production in the NTS. Mechanically sensitive afferent fibres were stimulated by passively stretching hindlimb muscle before and after blocking the endogenous production of NO within the NTS via microdialysis of the NO synthase inhibitor l-NAME (1 and 5 m m) in normotensive Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs). Changes in HR and mean arterial pressure in response to stretch were significantly larger in SHRs compared with Wistar-Kyoto rats prior to l-NAME dialysis. Attenuating NO production via l-NAME in normotensive rats recapitulated the exaggerated cardiovascular response to stretch observed in SHRs. Dialysing l-NAME in SHRs further accentuated the increases in HR and mean arterial pressure elicited by stretch. These findings support the contention that reductions in NO production within the NTS contribute to the generation of abnormal cardiovascular control by the skeletal muscle mechanoreflex in hypertension. [ABSTRACT FROM AUTHOR]

. Purpose: Optic disc haemorrhages are associated with active glaucomatous neurodegeneration and ongoing visual field loss. We sought to determine whether automated alternation flicker enhances the detection of disc haemorrhages in serial images from patients with glaucoma when compared to side-by-side photographic evaluation and single-image display. Methods: Serial sets of optic nerve photographs of 394 eyes from 234 patients followed for glaucoma at the authors' institutions were included in this study. Eyes with disc haemorrhages were graded for difficulty level and randomized along with nondisc haemorrhage control images into one of three presentation groups (automated alternation flicker, side-by-side or single image). Seven graders viewed all images and assessed for the presence or absence of disc haemorrhages. Results: The sensitivity of automated alternation flicker for disc haemorrhage detection (0.878) was higher than side-by-side (0.705; p = 0.002) and single photographs (0.757; p = 0.01). There was no specificity difference between pairs of presentation groups (all p ≥ 0.7). Conclusion: Automated alternation flicker was a more sensitive method for disc haemorrhage detection than the current clinical standards and may have an important role in the management of glaucoma. [ABSTRACT FROM AUTHOR]

The Mekong River system provides a crucial source of natural resources for riparian nations. However, the increasingly rapid pace of hydro-development in the Mekong Basin is threatening the integrity of the river system, posing a real concern for Lower Basin states, which are particularly dependent on the basin. This scenario has led to warnings of armed conflict, or even 'water war', between riparian states. Certainly, the expanding scale of hydro-development can be expected to continue increasing interstate tensions in the Mekong region; but are these tensions really likely to escalate to armed conflict? This paper explores this question by drawing on the water and conflict theory of Aaron Wolf. Ultimately, this paper concludes that interstate tensions over Mekong hydro-development are unlikely to generate armed conflict. This is in part due to the strategic impracticality of such a conflict as well as the presence of a river basin management institution. Most compellingly, though, armed conflict is unlikely because the economic imperative shared by Mekong states is better served by cooperation - or at least non-interference - than conflict, over regional hydro-development. In closing, the paper urges that the study of water and conflict in the Mekong Basin be refocused at the intrastate level. [ABSTRACT FROM AUTHOR]