bluuebunny/crossref_metadata_2025_split huggingface dataset:
New adaptive peaks for crops – an example from improvement of drought-resilience of sorghum in Ethiopia
Authors: Birhan Techale , Dong Hongxu , Abajebel Nezif , Wakjira Misganu , Lemke Cornelia , Vadez Vincent , Paterson Andrew H. , Bantte Kassahun 
Published: October 2021

SummaryAs the center of diversity for sorghum [Sorghum bicolor (L.) Moench], elite cultivars selected in Ethiopia are of central importance to sub-Saharan food security. Despite being presumably well adapted to their center of diversity, elite Ethiopian sorghums nonetheless experience constraints to productivity, for example associated with shifting rainfall patterns associated with climate change.A sorghum backcross nested association mapping (BC-NAM) population developed by crossing thirteen diverse lines pre-identified to have various drought resilience mechanisms, with an Ethiopian elite cultivar, Teshale, was tested under three rain-fed environments in Ethiopia.27, 15, and 15 QTLs with predominantly small additive effects were identified for days to flowering, days to maturity, and plant height, respectively. Many associations detected in this study corresponded closely to known or candidate genes or previously mapped QTLs, supporting their validity. Field tests show drought resilience to be improved by incorporation of adaptations from the diverse donor lines.The expectation that genotypes such as Teshale from near the center of diversity tend to have a history of strong balancing selection, with novel variations more likely to persist in small marginal populations, was strongly supported in that for these three traits, nearly equal numbers of alleles from the donor lines conferred increases and decreases in phenotype relative to the Teshale allele. Such rich variation provides a foundation for selection to traverse a ‘valley’ of reduced yield and arrive at a new ‘adaptive peak’, exemplifying the nature of efforts that may be necessary to adapt many crops to new climate extremes.Societal Impact StatementIn Ethiopia, agriculture is the largest economic sector and contributes 48% of the nation’s GDP, and sorghum provides more than one third of the cereal diet and is widely grown for food, feed, brewing, and construction purposes. With a worldwide water crisis looming, developing drought tolerant sorghum is vital in rain-fed environments, particularly in sub-Saharan Africa. Addressing such issues often requires a far-reaching approach to identify and incorporate new traits into a gene pool, followed by a period of selection to re-establish an overall adaptive phenotype. This study revealed that with the enormous altitudinal variation of a country such as Ethiopia, somewhat different lines may be needed for different locales.
Mechanical compressive forces increase PI3K output signaling in breast and pancreatic cancer cells
Authors: Di-Luoffo M. , Schmitter C. , Barrere E.C. , Therville N. , Chaouki M. , D’Angelo R. , Arcucci S. , Thibault B. , Delarue M. , Guillermet-Guibert J. 
Published: October 2021

AbstractContextMechanical stresses, including compression, arise during cancer progression. In solid cancer, especially breast and pancreatic cancers, the rapid tumor growth and the environment remodeling explain their high intensity of compressive forces. However, the sensitivity of compressed cells to targeted therapies remains poorly known.ResultsIn breast and pancreatic cancer cells, pharmacological PI3K inactivation decreased cell number and induced apoptosis. These effects were accentuated when we applied 2D compression forces in mechanically responsive cells. Compression selectively induced overexpression of PI3K isoforms and PI3K/AKT pathway activation. Further, transcriptional effects of PI3K inhibition and compression converged to control the expression of an autophagy regulator, GABARAP, which level was inversely associated with PI3K inhibitor sensitivity under compression. Compression alone blocked autophagy flux in all tested cells, while inactivation of basal PI3K activity restored autophagy flux only in mechanically non-responsive compressed cells.ConclusionThis study provides direct evidence for the role of PI3K/AKT pathway in compression-induced mechanotransduction. PI3K inhibition promotes apoptosis or autophagy, explaining PI3K importance to control cancer cell survival under compression.
The relative speed of the glucorticoid stress response varies independently of scope and is predicted by environmental variability and longevity across birds
Authors: Taff Conor C. , Wingfield John C. , Vitousek Maren N. 
Published: October 2021

ABSTRACTThe acute glucocorticoid response is a key mediator of the coordinated vertebrate response to unpredictable challenges. Rapid glucocorticoid increases initiate changes that allow animals to cope with stressors. The scope of the glucocorticoid response — defined here as the absolute increase in glucocorticoids — is associated with individual differences in performance and varies across species with environment and life history. In addition to varying in scope, responses can differ enormously in speed; however, relatively little is known about whether speed and absolute glucocorticoid levels covary, how selection shapes speed, or what aspects of speed are important. We used corticosterone samples collected at 5 time points from 1,750 individuals of 60 species of birds to ask i) how the speed and scope of the glucocorticoid response covary and ii) whether variation in absolute or relative speed is predicted by environmental context or life history. As predicted by a recent model, faster absolute glucocorticoid responses were strongly associated with a larger scope. Despite this covariation, the relative speed of the glucocorticoid response (standardized within species) varied independently of absolute scope, suggesting that selection could operate on both features independently. Species with faster relative glucocorticoid responses lived in locations with more variable temperature and had shorter lifespans. Our results suggest that rapid changes associated with the speed of the glucocorticoid response, such as those occurring through non-genomic receptors, might be an important determinant of coping ability and we emphasize the need for studies designed to measure speed independently of absolute glucocorticoid levels.
Good moms: dependent-young and their mothers cope better than others with longer dry season in plains zebras
Authors: Thel Lucie , Bonenfant Christophe , Chamaillé-Jammes Simon 
Published: October 2021

AbstractIn large herbivores, the timing of births often coincides with the seasonal peak of food resources availability, likely to improve juvenile survival and reduce reproduction costs. Some species however, breed year-round, even in seasonal environments. Demographic processes, such as to what extent being born during the lean season reduces survival of juveniles and reproductive females, remain understudied in large mammals inhabiting tropical ecosystems. We investigated survival rates in plains zebras (Equus quagga) in Hwange National Park (Zimbabwe), a highly seasonal savanna ecosystem. We used capture-recapture models to analyse long-term demographic data (2008-2019). We investigated the effect of seasonality as a categorical (wet versus dry season) and continuous (duration of the dry season) variable on survival. We found little variability in early juvenile survival (φ = 0.458 ± 0.044 SE, < 6 m.o.), whereas late juvenile and yearling survival was higher and decreased with increasing length of the dry season (from 0.850 ± 0.095 SE to 0.480 ± 0.120 SE). Female survival was high (> 0.703 ± 0.057 SE and up to 0.995 ± 0.006 SE) but decreased with increasing exposure to the dry season in non-reproductive females. The probability of females becoming reproductive in the following year was not affected by the length of the dry season (0.423 and 0.420 for reproductive and non-reproductive females respectively). Our results highlight the importance of individual quality in reproductive performance, as reproductive females seem to buffer the effect of environmental variability on their own survival and that of their foal.
Cross-border investigations on the prevalence and transmission dynamics of Cryptosporidium species in dairy cattle farms in western mainland Europe
Authors: Pinto Pedro , Ribeiro Cláudia A. , Hoque Sumaiya , Hammouma Ourida , Leruste Hélène , Detriche Sébastien , Canniere Evi , Daandels Yvonne , Dellevoet Martine , Roemen Janine , Bourgeois Anne Barbier , Kváč Martin , Follet Jérôme , Tsaousis Anastasios D. 
Published: October 2021

AbstractCryptosporidium is comprised an apicomplexan parasitic protist, which infects a wide range of hosts, causing cryptosporidiosis. In cattle farms, the incidence of cryptosporidiosis results in high mortality in calves leading to considerable economic loss in the livestock industry. Infected animals may also act as a major reservoir of Cryptosporidium spp., in particular C. parvum, the most common cause of cryptosporidiosis in calves. This poses a significant risk to other farms via breeding centres, to trading of livestock and to human health. This study, funded by the Interreg-2-seas programme, is a part of a global project aimed at strategies to tackle cryptosporidiosis. To reach this target, it was essential to determine whether prevalence was dependent on the studied countries or if the issue was borderless. Indeed, C. parvum occurrence was assessed across dairy farms in certain regions of Belgium, France and the Netherlands. At the same time, the animal-to-animal transmission of the circulating C. parvum subtypes was studied. To accomplish this, 1084 faecal samples, corresponding to 57 dairy-farms from all three countries, were analysed. Well-established protocols amplifying the 18S rDNA and gp60 genes fragments, followed by DNA sequencing, were used for the detection and subtyping C. parvum; the DNA sequences obtained were further characterised using a combination of bioinformatics and phylogenetics methods. Our results show 25.7%, 24.9% and 20.8% prevalence of Cryptosporidium spp. in Belgium, France and the Netherlands respectively. Overall, 93% of the farms were Cryptosporidium positive. The gp60 subtyping demonstrated a significant number of the C. parvum positives belonged to the IIa allelic family, which has been also detected in humans. Consequently, this study highlights how widespread is C. parvum in dairy farms and endorses cattle as a major carrier of zoonotic C. parvum subtypes, which subsequently pose a significant threat to human health.
Chronic alcohol drinking persistently suppresses thalamostriatal excitation of cholinergic neurons to impair cognitive flexibility
Authors: Ma Tengfei , Huang Zhenbo , Xie Xueyi , Cheng Yifeng , Zhuang Xiaowen , Childs Matthew , Gangal Himanshu , Wang Xuehua , Smith Laura , Smith Rachel , Zhou Yubin , Wang Jun 
Published: October 2021

AbstractExposure to addictive substances impairs flexible decision-making. Cognitive flexibility is mediated by striatal cholinergic interneurons (CINs). However, how chronic alcohol drinking alters cognitive flexibility through CINs remains unclear. Here, we report that chronic alcohol consumption and withdrawal impaired reversal of instrumental learning. Chronic alcohol consumption and withdrawal also caused a long-lasting (21 d) reduction of excitatory thalamic inputs onto CINs and reduced pause response of CINs in the dorsomedial striatum (DMS). CINs are known to inhibit glutamatergic transmission in dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) but facilitate this transmission in D2-MSNs, which may contribute to flexible behavior. We discovered that chronic alcohol drinking impaired CIN-mediated inhibition in D1-MSNs and facilitation in D2-MSNs. Importantly, in vivo optogenetic induction of long-term potentiation of thalamostriatal transmission in DMS CINs rescued alcohol-induced reversal learning deficits. These results demonstrate that chronic alcohol drinking reduces thalamic excitation of DMS CINs, compromising their regulation of glutamatergic transmission in MSNs, which may contribute to alcohol-induced impairment of cognitive flexibility. These findings provide a neural mechanism underlying inflexible drinking in alcohol use disorder.
Mitochondrial Haplogroup Association with Fasting Glucose Response in African Americans Treated with a Thiazide Diuretic
Authors: Minniefield Bre A. , Armstrong Nicole D. , Srinivasasainagendra Vinodh , Tiwari Hemant K. , Ballinger Scott W. , Chong Zechen , Aslibekyan Stella , Arnett Donna K. , Irvin Marguerite R. 
Published: October 2021

AbstractHypertensive African Americans have ~50% response rate to thiazide diuretic treatment. This contributes to a high prevalence of uncontrolled high blood pressure. Here, we examine the role the mitochondrial genome has on thiazide diuretic treatment response in hypertensive African Americans enrolled in a clinical trial. Participants from the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT, n= 4279) were genotyped using the Illumina Infinium Multi-Ethnic Beadchip. Haplotype groups were called using HaploGrep. We used linear regression analysis to examine the association between mitochondrial haplogroups (L, M, and N) and change in blood pressure and change in fasting glucose over 6 months and two years, respectively. The analysis revealed a null association between mitochondrial haplogroups M and N vs. L for each of the outcomes. In subgroup analysis, the L subclades L1, L2, and L3/L4 (vs. L0) were each inversely associated with fasting glucose response (p < 0.05). This discovery analysis suggests the mitochondrial genome has a small effect on fasting glucose but not blood pressure response to thiazide diuretic treatment in African Americans.
Rapid and Effective Inactivation of SARS-CoV-2 by a Cationic Conjugated Oligomer with Visible Light: Studies of Antiviral Activity in Solutions and on Supports
Authors: Kaya Kemal , Khalil Mohammed I. , Fetrow Benjamin , Fritz Hugh , Jagadesan Pradeepkumar , Bondu Virginie , Ista Linnea , Chi Eva Y. , Schanze Kirk S. , Whitten David G. , Kell Alison M. 
Published: October 2021

ABSTRACTThis paper presents results of a study of a new cationic oligomer that contains end groups and a chromophore affording inactivation of SARS-Cov-2 by visible light irradiation in solution or as a solid coating on wipes paper and glass fiber filtration substrates. A key finding of this study is that the cationic oligomer with a central thiophene ring and imidazolium charged groups give outstanding performance in both killing of E. coli bacterial cells and inactivation of the virus at very short times. Our introduction of cationic N-Methyl Imidazolium groups enhances the light-activation process for both E. coli and SARS-Cov-2 but dampens the dark killing of the bacteria and eliminates the dark inactivation of the virus. For the studies with this oligomer in solution at concentration of 1 μg/mL and E. coli we obtain 3 log killing of the bacteria with 10 min irradiation with LuzChem cool white lights (mimicking indoor illumination). With the oligomer in solution at a concentration of 10 μg/mL, we observe 4 logs inactivation (99.99 %) in 5 minutes of irradiation and total inactivation after 10 min. The oligomer is quite active against E. coli on oligomer-coated wipes papers and glass fiber filter supports. The SARS-Cov-2 is also inactivated by the oligomer coated glass fiber filter papers. This study indicates that these oligomer-coated materials may be very useful as wipes and filtration materials.
Precision localization of cellular proteins with fluorescent Fab-based probes
Authors: Liccardo F. , Lo Monte M. , Corrado B. , Veneruso M. , Celentano S. , Coscia M.R. , Coppola G. , Pucci P. , Palumbo G. , Luini A. , Lampe M. , Marzullo V.M. 
Published: October 2021

ABSTRACTCurrently, a major technical limitation of microscopy based image analysis is the linkage error – which describes the distance between e.g. the target epitope of cellular protein to the fluorescence emitter, which position is finally detected in a microscope. With continuously improving resolution of today’s (super-resolution) microscopes, the linkage errors can severely hamper the correct interpretation of images and is usually introduced in experiments by the use of standard intracellular staining reagents such as fluorescently labelled antibodies. The linkage error of standard labelled antibodies is caused by the size of the antibody and the random distribution of fluorescent emitters on the antibody surface. Together, these two factors account for a fluorescence displacement of ~40nm when staining proteins by indirect immunofluorescence; and ~20nm when staining with fluorescently coupled primary antibodies. In this study, we describe a class of staining reagents that effectively reduce the linkage error by more than five-fold when compared to conventional staining techniques. These reagents, called Fluo-N-Fabs, consist of an antigen binding fragment of a full-length antibody (Fab / fragment antigen binding) that is selectively conjugated at the N-terminal amino group with fluorescent organic molecules, thereby reducing the distance between the fluorescent emitter and the protein target of the analysis. Fluo-N-Fabs also exhibit the capability to penetrate tissues and highly crowded cell compartments, thus allowing for the efficient detection of cellular epitopes of interest in a wide range of fixed samples. We believe this class of reagents realize an unmet need in cell biological super resolution imaging studies where the precise localization of the target of interest is crucial for the understanding of complex biological phenomena.
Comparative linkage mapping uncovers massive chromosomal inversions that suppress recombination between locally adapted fish populations
Authors: Akopyan Maria , Tigano Anna , Jacobs Arne , Wilder Aryn P. , Baumann Hannes , Therkildsen Nina O. 
Published: October 2021

AbstractThe role of recombination in genome evolution has long been studied in theory, but until recently empirical investigations had been limited to a small number of model species. Here we compare the recombination landscape and genome collinearity between two populations of the Atlantic silverside (Menidia menidia), a small fish distributed across the steep latitudinal climate gradient of the North American Atlantic coast. Using ddRADseq, we constructed separate linkage maps for locally adapted populations from New York and Georgia and their inter-population lab cross. First, we used one of the linkage maps to improve the current silverside genome assembly by anchoring three large unplaced scaffolds to two chromosomes. Second, we estimated sex-specific recombination rates, finding 2.75-fold higher recombination rates in females than males—one of the most extreme examples of heterochiasmy in a fish. While recombination occurs relatively evenly across female chromosomes, it is restricted to only the terminal ends of male chromosomes. Furthermore, comparisons of female linkage maps revealed suppressed recombination along several massive chromosomal inversions spanning nearly 16% of the genome and segregating between locally adapted populations. Finally, we discerned significantly higher recombination rates across chromosomes in the northern population. In addition to providing valuable resources for ongoing evolutionary and comparative genomic studies, our findings represent a striking example of structural variation that impacts recombination between adaptively divergent populations, providing empirical support for theorized genomic mechanisms facilitating adaptation despite gene flow.
Identification of a specific biomarker ofAcinetobacter baumanniiGlobal Clone 1 by machine learning and PCR related to metabolic fitness of ESKAPE pathogens
Authors: Álvarez Verónica Elizabeth , Quiroga María Paula , Centrón Daniela 
Published: October 2021

ABSTRACTSince the emergence of high-risk clones worldwide, constant investigations have been undertaken to comprehend the molecular basis that led to their prevalent dissemination in nosocomial settings over time. So far, the complex and multifactorial genetic traits of this type of epidemic clones have only allowed the identification of biomarkers with low specificity. A machine learning algorithm was able to recognize unequivocally a biomarker for the early and accurate detection ofAcinetobacter baumanniiGlobal Clone 1 (GC1), one of the most disseminated high-risk clones. Support Vector Machine identified the U1 sequence with 367 nucleotides length that matched a fragment of themoaCBgene, which encodes the molybdenum cofactor biosynthesis C and B proteins. U1 differentiates specifically betweenA. baumanniiGC1 and non-GC1 strains, becoming a suitable biomarker capable of being translated into clinical settings as a molecular typing method for early diagnosis based on PCR as shown here. Since the metabolic pathways of Mo enzymes have been recognized as putative therapeutic targets for ESKAPE pathogens, our findings highlighted that machine learning can be also useful in intricate knowledge gaps of high-risk clones and implies noteworthy support to the literature to identify challenging nosocomial biomarkers for other multidrug-resistant high-risk clones.IMPORTANCEA. baumanniiGC1 is an important high-risk clone that rapidly develops extreme drug resistance in the nosocomial niche. Furthermore, several strains were identified worldwide in environmental samples exacerbating the risk of human interactions. Early diagnosis is mandatory to limit its dissemination and to outline appropriate antibiotic stewardship schedules. A region of 367 bp length (U1) within themoaCBgene not subjected to Lateral Genetic Transfer or to antibiotic pressures was successfully found by Support Vector Machine algorithm that predictsA. baumanniiGC1 strains. PCR assays have confirmed that U1 specifically identifiesA. baumanniiGC1 strains. At the same time, research on the group of Mo enzymes proposed this metabolic pathway related to superbuǵs metabolism as a potential future drug target site for ESKAPE pathogens due to its central role in bacterial fitness during infection. These findings confirmed the importance of machine learning applied to the burden of the rise of antibiotic resistance.
Triazolopyrimidines target aerobic respiration in Mycobacterium tuberculosis
Authors: Shelton Catherine , McNeil Matthew , Flint Lindsay , Russell Dara , Berube Bryan , Korkegian Aaron , Ovechkina Yulia , Parish Tanya 
Published: October 2021

AbstractWe previously identified a series of triazolopyrimidines with anti-tubercular activity. We determined that Mycobacterium tuberculosis strains with mutations in a component of the cytochrome bc1 system (QcrB) were resistant to the series. A cytochrome bd oxidase deletion strain was also more sensitive to this series. We isolated resistant mutants, all of which had mutations in Rv1339. Compounds were active against intracellular bacteria but did not inhibit mitochondrial respiration in human HepG2 cells. These data are consistent with triazolopyrimidines acting via inhibition of M. tuberculosis QcrB.