bluuebunny/crossref_metadata_2025 huggingface dataset:
DeepNull models non-linear covariate effects to improve phenotypic prediction and association power
Authors: McCaw Zachary R. , Colthurst Thomas , Yun Taedong , Furlotte Nicholas A. , Carroll Andrew , Alipanahi Babak , McLean Cory Y. , Hormozdiari Farhad
Published: January 2022

Genome-wide association studies (GWASs) examine the association between genotype and phenotype while adjusting for a set of covariates. Although the covariates may have non-linear or interactive effects, due to the challenge of specifying the model, GWAS often neglect such terms. Here we introduce DeepNull, a method that identifies and adjusts for non-linear and interactive covariate effects using a deep neural network. In analyses of simulated and real data, we demonstrate that DeepNull maintains tight control of the type I error while increasing statistical power by up to 20% in the presence of non-linear and interactive effects. Moreover, in the absence of such effects, DeepNull incurs no loss of power. When applied to 10 phenotypes from the UK Biobank (n = 370K), DeepNull discovered more hits (+6%) and loci (+7%), on average, than conventional association analyses, many of which are biologically plausible or have previously been reported. Finally, DeepNull improves upon linear modeling for phenotypic prediction (+23% on average).
Cancer cell-expressed BTNL2 facilitates tumour immune escape via engagement with IL-17A-producing γδ T cells
Authors: Du Yanyun , Peng Qianwen , Cheng Du , Pan Ting , Sun Wanwei , Wang Heping , Ma Xiaojian , He Ruirui , Zhang Huazhi , Cui Zhihui , Feng Xiong , Liu Zhiqiang , Zhao Tianxin , Hu Wenjun , Shen Lei , Jiang Wenyang , Gao Na , Martin Bradley N. , Zhang Cun-Jin , Zhang Zhanguo , Wang Chenhui
Published: January 2022

Therapeutic blockade of the immune checkpoint proteins programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA4) has transformed cancer treatment. However, the overall response rate to these treatments is low, suggesting that immune checkpoint activation is not the only mechanism leading to dysfunctional anti-tumour immunity. Here we show that butyrophilin-like protein 2 (BTNL2) is a potent suppressor of the anti-tumour immune response. Antibody-mediated blockade of BTNL2 attenuates tumour progression in multiple in vivo murine tumour models, resulting in prolonged survival of tumour-bearing mice. Mechanistically, BTNL2 interacts with local γδ T cell populations to promote IL-17A production in the tumour microenvironment. Inhibition of BTNL2 reduces the number of tumour-infiltrating IL-17A-producing γδ T cells and myeloid-derived suppressor cells, while facilitating cytotoxic CD8+ T cell accumulation. Furthermore, we find high BTNL2 expression in several human tumour samples from highly prevalent cancer types, which negatively correlates with overall patient survival. Thus, our results suggest that BTNL2 is a negative regulator of anti-tumour immunity and a potential target for cancer immunotherapy.
Mapping inhibitory sites on the RNA polymerase of the 1918 pandemic influenza virus using nanobodies
Authors: Keown Jeremy R. , Zhu Zihan , Carrique Loïc , Fan Haitian , Walker Alexander P. , Serna Martin Itziar , Pardon Els , Steyaert Jan , Fodor Ervin , Grimes Jonathan M.
Published: January 2022

Influenza A viruses cause seasonal epidemics and global pandemics, representing a considerable burden to healthcare systems. Central to the replication cycle of influenza viruses is the viral RNA-dependent RNA polymerase which transcribes and replicates the viral RNA genome. The polymerase undergoes conformational rearrangements and interacts with viral and host proteins to perform these functions. Here we determine the structure of the 1918 influenza virus polymerase in transcriptase and replicase conformations using cryo-electron microscopy (cryo-EM). We then structurally and functionally characterise the binding of single-domain nanobodies to the polymerase of the 1918 pandemic influenza virus. Combining these functional and structural data we identify five sites on the polymerase which are sensitive to inhibition by nanobodies. We propose that the binding of nanobodies at these sites either prevents the polymerase from assuming particular functional conformations or interactions with viral or host factors. The polymerase is highly conserved across the influenza A subtypes, suggesting these sites as effective targets for potential influenza antiviral development.
Food nanoparticles from rice vinegar: isolation, characterization, and antioxidant activities
Authors: Yu Zhaoshuo , Tan Ying , Luo Sihao , Zhou Jingru , Xu Tianhao , Zou Jianqiao , Ke Lijing , Yu Ji , Zhang Suyun , Zhou Jianwu , Rao Pingfan , Li Jiaxing
Published: January 2022

Abundant nanostructures have been constantly found in various foods, like vinegar, tea, coffee, and milk. However, these structures largely remain unexplored and even been eliminated for stability reasons in food industry. Here we report the isolation, characterization, and antioxidant activities of food nanoparticles (NPs) carrying polyphenols from Chinese rice vinegar. Using a gel-chromatography-based isolation protocol, the vinegar was separated into three major fractions. They were identified as spherical NPs (P1), lollipop-like NPs (P2) and spherical microparticles (P3) with average hydrodynamic diameter of 210, 245,1643 nm, separately. The former two fractions accounted for the major parts of dry matter in the vinegar. The P1-NPs fraction was composed of proteins, carbohydrates, and a high number of polyphenols (15 wt%), demonstrated potent antioxidant activity as determined by ABTS and ORAC assays. Moreover, they effectively quenched peroxyl free radicals in peritoneal macrophages and promoted cellular growth. The P2 fraction contained majority of organic acids, esters and mineral elements of the vinegar. It demonstrated the NPs are bioactive units of the rice vinegar, inspiring the development of novel functional nanomaterials with nutraceutical and pharmaceutical applications.
A computational method for predicting nucleocapsid protein in retroviruses
Authors: Guo Manyun , Ma Yucheng , Liu Wanyuan , Yuan Zuyi
Published: January 2022

Nucleocapsid protein (NC) in the group-specific antigen (gag) of retrovirus is essential in the interactions of most retroviral gag proteins with RNAs. Computational method to predict NCs would benefit subsequent structure analysis and functional study on them. However, no computational method to predict the exact locations of NCs in retroviruses has been proposed yet. The wide range of length variation of NCs also increases the difficulties. In this paper, a computational method to identify NCs in retroviruses is proposed. All available retrovirus sequences with NC annotations were collected from NCBI. Models based on random forest (RF) and weighted support vector machine (WSVM) were built to predict initiation and termination sites of NCs. Factor analysis scales of generalized amino acid information along with position weight matrix were utilized to generate the feature space. Homology based gene prediction methods were also compared and integrated to bring out better predicting performance. Candidate initiation and termination sites predicted were then combined and screened according to their intervals, decision values and alignment scores. All available gag sequences without NC annotations were scanned with the model to detect putative NCs. Geometric means of sensitivity and specificity generated from prediction of initiation and termination sites under fivefold cross-validation are 0.9900 and 0.9548 respectively. 90.91% of all the collected retrovirus sequences with NC annotations could be predicted totally correct by the model combining WSVM, RF and simple alignment. The composite model performs better than the simplex ones. 235 putative NCs in unannotated gags were detected by the model. Our prediction method performs well on NC recognition and could also be expanded to solve other gene prediction problems, especially those whose training samples have large length variations.
Evaluation of the characterization of acoustic emission of brittle rocks from the experiment to numerical simulation
Authors: Bu Fengchang , Xue Lei , Zhai Mengyang , Huang Xiaolin , Dong Jinyu , Liang Ning , Xu Chao
Published: January 2022

Acoustic emission (AE) characterization is an effective technique to indirectly capture the failure process of quasi brittle rock. In previous studies, both experiments and numerical simulations were adopted to investigate the AE characteristics of rocks. However, as the most popular numerical model, the moment tensor model (MTM) cannot be constrained by the experimental result because there is a gap between MTM and experiments in principle, signal processing and energy analysis. In this paper, we developed a particle-velocity-based model (PVBM) that enabled direct monitoring and analysis of the particle velocity in the numerical model and had good robustness. The PVBM imitated the actual experiment and could fill in gaps between the experiment and MTM. AE experiments of marine shale under uniaxial compression were carried out, and the results were simulated by MTM. In general, the variation trend of the experimental result could be presented by MTM. Nevertheless, the magnitudes of AE parameters by MTM presented notable differences of more than several orders of magnitude compared with those by the experiment. We sequentially used PVBM as a proxy to analyse these discrepancies and systematically evaluate the AE characterization of rocks from the experiment to numerical simulation, considering the influence of wave reflection, energy geometrical diffusion, viscous attenuation, particle size and progressive deterioration of rock material. The combination of MTM and PVBM could reasonably and accurately acquire AE characteristics of the actual AE experiment of rocks by making full use of their respective advantages.
Changes in soybean cultivars released over the past 50 years in southern Brazil
Authors: Umburanas Renan Caldas , Kawakami Jackson , Ainsworth Elizabeth Anna , Favarin José Laércio , Anderle Leonardo Zabot , Dourado-Neto Durval , Reichardt Klaus
Published: January 2022

On-farm soybean yield has increased considerably in the last 50 years in southern Brazil, but there is still little information about how selection and breeding for yield increase has changed the agronomic attributes of cultivars. The objectives of this study were to evaluate the changes in soybean yield, seed oil and protein concentration, and changes in plant attributes that might be associated with yield improvement of 26 soybean cultivars released over the past 50 years in southern Brazil, sown simultaneously in a common field environment for two growing seasons. The average rate of yield gain was 45.9 kg ha−1 yr−1 (2.1% ha−1 yr−1), mainly due increased seed number per area and harvest index. Over year of cultivar release, cultivars became less susceptible to lodging, as well as plant mortality reduced. Meanwhile, the seed oil concentration increased, and seed protein concentration decreased, which could have negative consequences for soybeans use and requires further attention for breeding of future cultivars. Breeders have successfully contributed to the annual rate of soybean yield increase in southern Brazil. By our results, as well as the official on-farm production data, there is no evidence of soybean yield reaching a plateau in the near future in southern Brazil.
Impact of age at onset on symptom profiles, treatment characteristics and health-related quality of life in Parkinson’s disease
Authors: Raket Lars Lau , Oudin Åström Daniel , Norlin Jenny M. , Kellerborg Klas , Martinez-Martin Pablo , Odin Per
Published: January 2022

Parkinson’s disease (PD) is typically considered an age-related disease, but the age at disease onset can vary by decades between patients. Aging and aging-associated diseases can affect the movement system independently of PD, and advanced age has previously been proposed to be associated with a more severe PD phenotype with accelerated progression. In this work, we investigated how interactions between PD progression and aging affect a wide range of outcomes related to PD motor and nonmotor symptoms as well as Health Related Quality of Life (HRQoL) and treatment characteristics. This population-based cohort study is based on 1436 PD patients from southern Sweden followed longitudinally for up to approximately 7.5 years from enrollment (3470 visits covering 2285 patient years, average follow-up time 1.7 years). Higher age at onset was generally associated with faster progression of motor symptoms, with a notable exception of dyskinesia and other levodopa-associated motor fluctuations that had less severe trajectories for patients with higher age at onset. Mixed results were observed for emergence of non-motor symptoms, while higher age at onset was generally associated with worse HRQoL trajectories. Accounting for these identified age-associated differences in disease progression could positively impact patient management and drug development efforts.
Potential distribution of fall armyworm in Africa and beyond, considering climate change and irrigation patterns
Authors: Paudel Timilsena Bipana , Niassy Saliou , Kimathi Emily , Abdel-Rahman Elfatih M. , Seidl-Adams Irmgard , Wamalwa Mark , Tonnang Henri E. Z. , Ekesi Sunday , Hughes David P. , Rajotte Edwin G. , Subramanian Sevgan
Published: January 2022

The fall armyworm, Spodoptera frugiperda (FAW), first invaded Africa in 2016 and has since become established in many areas across the continent where it poses a serious threat to food and nutrition security. We re-parameterized the existing CLIMEX model to assess the FAW global invasion threat, emphasizing the risk of transient and permanent population establishment in Africa under current and projected future climates, considering irrigation patterns. FAW can establish itself in almost all countries in eastern and central Africa and a large part of western Africa under the current climate. Climatic barriers, such as heat and dry stresses, may limit the spread of FAW to North and South Africa. Future projections suggest that FAW invasive range will retract from both northern and southern regions towards the equator. However, a large area in eastern and central Africa is projected to have an optimal climate for FAW persistence. These areas will serve as FAW ‘hotspots’ from where it may migrate to the north and south during favorable seasons and then pose an economic threat. Our projections can be used to identify countries at risk for permanent and transient FAW-population establishment and inform timely integrated pest management interventions under present and future climate in Africa.
Learning self-driven collective dynamics with graph networks
Authors: Wang Rui , Fang Feiteng , Cui Jiamei , Zheng Wen
Published: January 2022

Despite decades of theoretical research, the nature of the self-driven collective motion remains indigestible and controversial, while the phase transition process of its dynamic is a major research issue. Recent methods propose to infer the phase transition process from various artificially extracted features using machine learning. In this thesis, we propose a new order parameter by using machine learning to quantify the synchronization degree of the self-driven collective system from the perspective of the number of clusters. Furthermore, we construct a powerful model based on the graph network to determine the long-term evolution of the self-driven collective system from the initial position of the particles, without any manual features. Results show that this method has strong predictive power, and is suitable for various noises. Our method can provide reference for the research of other physical systems with local interactions.
Genome-wide identification and expression profiling analysis of Wnt family genes affecting adipocyte differentiation in cattle
Authors: Pan Cuili , Wang Shuzhe , Yang Chaoyun , Hu Chunli , Sheng Hui , Xue Xiaoshu , Hu Honghong , Lei Zhaoxiong , Yang Mengli , Ma Yun
Published: January 2022

The Wnt family features conserved glycoproteins that play roles in tissue regeneration, animal development and cell proliferation and differentiation. For its functional diversity and importance, this family has been studied in several species, but not in the Bovinae. Herein we identified 19 Wnt genes in cattle, and seven other species of Bovinae, and described their corresponding protein properties. Phylogenetic analysis clustered the 149 Wnt proteins in Bovinae, and 38 Wnt proteins from the human and mouse into 12 major clades. Wnt genes from the same subfamilies shared similar protein motif compositions and exon–intron patterns. Chromosomal distribution and collinearity analysis revealed that they were conservative in cattle and five species of Bovinae. RNA-seq data analysis indicated that Wnt genes exhibited tissue-specific expression in cattle. qPCR analysis revealed a unique expression pattern of each gene during bovine adipocytes differentiation. Finally, the comprehensive analysis indicated thatWnt2Bmay regulate adipose differentiation by activatingFZD5, which is worthy of further study. Our study presents the first genome-wide study of the Wnt gene family in Bovinae, and lays the foundation for further functional characterization of this family in bovine adipocytes differentiation.
Effect of linagliptin plus insulin in comparison to insulin alone on metabolic control and prognosis in hospitalized patients with SARS-CoV-2 infection
Authors: Guardado-Mendoza Rodolfo , Garcia-Magaña Miguel Angel , Martínez-Navarro Liz Jovanna , Macías-Cervantes Hilda Elizabeth , Aguilar-Guerrero Rodolfo , Suárez-Pérez Erick L. , Aguilar-García Alberto
Published: January 2022

To evaluate the effect of the combination of linagliptin and insulin on metabolic control and prognosis in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hyperglycemia. A parallel double-blind randomized clinical trial including hospitalized patients with SARS-CoV-2 infection and hyperglycemia, randomized to receive 5 mg linagliptin + insulin (LI group) or insulin alone (I group) was performed. The main outcomes were the need for assisted mechanical ventilation and glucose levels during hospitalization. Subjects were screened for eligibility at hospital admission if they were not with assisted mechanical ventilation and presented hyperglycemia, and a total of 73 patients with SARS-CoV-2 infection and hyperglycemia were randomized to the LI group (n = 35) or I group (n = 38). The average hospital stay was 12 ± 1 vs 10 ± 1 days for the I and LI groups, respectively (p = 0.343). There were no baseline clinical differences between the study groups, but the percentage of males was higher in the LI group (26 vs 18, p = 0.030). The improvements in fasting and postprandial glucose levels were better in the LI group that the I group (122 ± 7 vs 149 ± 10, p = 0.033; and 137 ± 7 vs 173 ± 12, p = 0.017, respectively), and insulin requirements tended to be lower in the LI group than the I group. Three patients in the LI group and 12 in the I group required assisted mechanical ventilation (HR 0.258, CI 95% 0.092–0.719, p = 0.009); 2 patients in the LI group and 6 in the I group died after a follow-up of 30 days (p = 0.139). No major side effects were observed. The combination of linagliptin and insulin in hospitalized patients with SARS-CoV-2 infection and hyperglycemia reduced the relative risk of assisted mechanical ventilation by 74% and improved better pre and postprandial glucose levels with lower insulin requirements, and no higher risk of hypoglycemia.

This study is registered at clinicaltrials.gov, number NCT04542213 on 09/03/2020.
A new transgene mouse model using an extravesicular EGFP tag enables affinity isolation of cell-specific extracellular vesicles
Authors: Nørgård Mikkel Ø. , Steffensen Lasse B. , Hansen Didde R. , Füchtbauer Ernst-Martin , Engelund Morten B. , Dimke Henrik , Andersen Ditte C. , Svenningsen Per
Published: January 2022

The in vivo function of cell-derived extracellular vesicles (EVs) is challenging to establish since cell-specific EVs are difficult to isolate and differentiate. We, therefore, created an EV reporter using truncated CD9 to display enhanced green fluorescent protein (EGFP) on the EV surface. CD9truc-EGFP expression in cells did not affect EV size and concentration but enabled co-precipitation of EV markers TSG101 and ALIX from the cell-conditioned medium by anti-GFP immunoprecipitation. We then created a transgenic mouse where CD9truc-EGFP was inserted in the inverse orientation and double-floxed, ensuring irreversible Cre recombinase-dependent EV reporter expression. We crossed the EV reporter mice with mice expressing Cre ubiquitously (CMV-Cre), in cardiomyocytes (αMHC-MerCreMer) and renal tubular epithelial cells (Pax8-Cre), respectively. The CD9truc-EGFP positive mice showed Cre-dependent EGFP expression, and plasma CD9truc-EGFP EVs were immunoprecipitated only from CD9truc-EGFP positiveCD9truc-EGFPxCMV-CreandCD9truc-EGFPxαMHC-Cremice, but not inCD9truc-EGFPxPax8-Cre and CD9truc-EGFP negative mice. In urine samples, CD9truc-EGFP EVs were detected by immunoprecipitation only in CD9truc-EGFP positiveCD9truc-EGFPxCMV-CreandCD9truc-EGFPxPax8-Cremice, but notCD9truc-EGFPxαMHC-Creand CD9truc-EGFP negative mice. In conclusion, our EV reporter mouse model enables Cre-dependent EV labeling, providing a new approach to studying cell-specific EVs in vivo and gaining a unique insight into their physiological and pathophysiological function.
Neutrophil-lymphoycyte-ratio, platelet-lymphocyte-ratio and procalcitonin for early assessment of prognosis in patients undergoing VA-ECMO
Authors: Roth Sebastian , M’Pembele René , Stroda Alexandra , Jansen Catrin , Lurati Buse Giovanna , Boeken Udo , Akhyari Payam , Lichtenberg Artur , Hollmann Markus W. , Huhn Ragnar , Aubin Hug
Published: January 2022

The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasing, but mortality remains high. Early assessment of prognosis is challenging and valid markers are lacking. This study aimed to investigate Neutrophil–Lymphocyte Ratio (NLR), Platelet-Lymphocyte-Ratio (PLR) and Procalcitonin (PCT) for early assessment of prognosis in patients undergoing VA-ECMO. This retrospective single-center cohort study included 344 consecutive patients ≥ 18 years who underwent VA-ECMO due to cardiogenic shock. Main exposures were NLR, PLR and PCT measured within 24 h after VA-ECMO initiation. The primary endpoint was all-cause in-hospital mortality. In total, 92 patients were included into final analysis (71.7% male, age 57 ± 14 years). In-hospital mortality rate was 48.9%. Receiver operating characteristics (ROC) curve revealed an area under the curve (AUC) of 0.65 [95% confidence interval (CI) 0.53–0.76] for NLR. The AUCs of PLR and PCT were 0.47 [95%CI 0.35–0.59] and 0.54 [95%CI 0.42–0.66], respectively. Binary logistic regression showed an adjusted odds ratio of 3.32 [95%CI 1.13–9.76] for NLR, 1.0 [95%CI 0.998–1.002] for PLR and 1.02 [95%CI 0.99–1.05] for PCT. NLR is independently associated with in-hospital mortality in patients undergoing VA-ECMO. However, discriminative ability is weak. PLR and PCT seem not to be suitable for this purpose.
Anatomical and hormonal factors determining the development of haploid and zygotic embryos of oat (Avena sativa L.)
Authors: Dziurka Kinga , Dziurka Michał , Muszyńska Ewa , Czyczyło-Mysza Ilona , Warchoł Marzena , Juzoń Katarzyna , Laskoś Kamila , Skrzypek Edyta
Published: January 2022

A critical step in the production of doubled haploids is a conversion of the haploid embryos into plants. Our study aimed to recognize the reasons for the low germination rate of Avena sativa haploid embryos obtained by distant crossing with maize. Oat cultivars of ‘Krezus’ and ‘Akt’ were investigated regarding embryo anatomy, the endogenous phytohormone profiles, and antioxidant capacity. The zygotic embryos of oat were used as a reference. It was found that twenty-one days old haploid embryos were smaller and had a less advanced structure than zygotic ones. Morphology and anatomy modifications of haploid embryos were accompanied by extremely low levels of endogenous auxins. Higher levels of cytokinins, as well as tenfold higher cytokinin to auxin ratio in haploid than in zygotic embryos, may suggest an earlier stage of development of these former. Individual gibberellins reached higher values in ‘Akt’ haploid embryos than in the respective zygotic ones, while the differences in both types of ‘Krezus’ embryos were not noticed. Additionally to the hormonal regulation of haploid embryogenesis, the poor germination of oat haploid embryos can be a result of the overproduction of reactive oxygen species, and therefore higher levels of low molecular weight antioxidants and stress hormones.
Genetic diversity and selection in Puerto Rican horses
Authors: Wolfsberger Walter W. , Ayala Nikole M. , Castro-Marquez Stephanie O. , Irizarry-Negron Valerie M. , Potapchuk Antoliy , Shchubelka Khrystyna , Potish Ludvig , Majeske Audrey J. , Oliver Luis Figueroa , Lameiro Alondra Diaz , Martínez-Cruzado Juan Carlos , Lindgren Gabriella , Oleksyk Taras K.
Published: January 2022

Since the first Spanish settlers brought horses to America centuries ago, several local varieties and breeds have been established in the New World. These were generally a consequence of the admixture of the different breeds arriving from Europe. In some instances, local horses have been selectively bred for specific traits, such as appearance, endurance, strength, and gait. We looked at the genetics of two breeds, the Puerto Rican Non-Purebred (PRNPB) (also known as the “Criollo”) horses and the Puerto Rican Paso Fino (PRPF), from the Caribbean Island of Puerto Rico. While it is reasonable to assume that there was a historic connection between the two, the genetic link between them has never been established. In our study, we started by looking at the genetic ancestry and diversity of current Puerto Rican horse populations using a 668 bp fragment of the mitochondrial DNA D-loop (HVR1) in 200 horses from 27 locations on the island. We then genotyped all 200 horses in our sample for the “gait-keeper” DMRT3 mutant allele previously associated with the paso gait especially cherished in this island breed. We also genotyped a subset of 24 samples with the Illumina Neogen Equine Community genome-wide array (65,000 SNPs). This data was further combined with the publicly available PRPF genomes from other studies. Our analysis show an undeniable genetic connection between the two varieties in Puerto Rico, consistent with the hypothesis that PRNPB horses represent the descendants of the original genetic pool, a mix of horses imported from the Iberian Peninsula and elsewhere in Europe. Some of the original founders of PRNRB population must have carried the “gait-keeper” DMRT3 allele upon arrival to the island. From this admixture, the desired traits were selected by the local people over the span of centuries. We propose that the frequency of the mutant “gait-keeper” allele originally increased in the local horses due to the selection for the smooth ride and other characters, long before the PRPF breed was established. To support this hypothesis, we demonstrate that PRNPB horses, and not the purebred PRPF, carry a signature of selection in the genomic region containing the DMRT3 locus to this day. The lack of the detectable signature of selection associated with the DMRT3 in the PRPF would be expected if this native breed was originally derived from the genetic pool of PRNPB horses established earlier and most of the founders already had the mutant allele. Consequently, selection specific to PRPF later focused on allels in other genes (including CHRM5, CYP2E1, MYH7, SRSF1, PAM, PRN and others) that have not been previously associated with the prized paso gait phenotype in Puerto Rico or anywhere else.
Vision, cognition, and walking stability in young adults
Authors: Koren Yogev , Mairon Rotem , Sofer Ilay , Parmet Yisrael , Ben-Shahar Ohad , Bar-Haim Simona
Published: January 2022

Downward gazing is often observed when walking requires guidance. This gaze behavior is thought to promote walking stability through anticipatory stepping control. This study is part of an ongoing effort to investigate whether downward gazing also serves to enhance postural control, which can promote walking stability through a feedback/reactive mechanism. Since gaze behavior alone gives no indication as to what information is gathered and the functions it serves, we aimed to investigate the cognitive demands associated with downward gazing, as they are likely to differ between anticipatory and feedback use of visual input. To do so, we used a novel methodology to compromise walking stability in a manner that could not be resolved through modulation of stepping. Then, using interference methodology and neuroimaging, we tested for (1) interference related to dual tasking, and (2) changes in prefrontal activity. The novel methodology resulted in an increase in the time spent looking at the walking surface. Further, while some dual-task interference was observed, indicating that this gaze behavior is cognitively demanding, several gaze parameters pertaining to downward gazing and prefrontal activity correlated. These correlations revealed that a greater tendency to gaze onto the walking surface was associated with lower PFC activity, as is expected when sensory information is used through highly automatic, and useful, neural circuitry. These results, while not conclusive, do suggest that gazing onto the walking surface can be used for purposes other than anticipatory stepping control, bearing important motor-control and clinical implications.
Palaeoenvironmental proxies indicate long-term development of agro-pastoralist landscapes in Inner Asian mountains
Authors: Spate Michael , Yatoo Mumtaz A. , Penny Dan , Shah Mohammad Ajmal , Betts Alison
Published: January 2022

A growing body of archaeological research on agro-pastoralist populations of the Inner Asian mountains indicates that these groups adapted various systems of mobile herding and cultivation to ecotopes across the region from as early as 5000 BP. It has been argued that these adaptations allowed the development of flexible social-ecological systems well suited to the long-term management of these mountain landscapes. At present, less attention has been paid to examining the long-term ecological legacy of these adaptations within the sedimentary or palaeoenvironmental record. Here we present sediment, palynomorph and charcoal data that we interpret as indicating agro-pastoralist environmental perturbations, taken from three cores at middle and high altitudes in the Kashmir Valley at the southern end of the Inner Asian mountains. Our data indicate spatially and temporally discontinuous patterns of agro-pastoralist land use beginning close to 4000 BP. Periods of intensification of upland herding are often coincident with phases of regional social or environmental change, in particular we find the strongest signals for agro-pastoralism in the environmental record contemporary with regionally arid conditions. These patterns support previous arguments that specialised agro-pastoralist ecologies across the region are well placed to respond to past and future climate deteriorations. Our data indicating long-term co-evolution of humans and landscape in the study area also have implications for the ongoing management of environments generally perceived as “pristine” or “wilderness”.
Updated fraction of cancer attributable to lifestyle and environmental factors in Denmark in 2018
Authors: Tybjerg Anne Julie , Friis Søren , Brown Katrina , Nilbert Mef Christina , Morch Lina , Køster Brian
Published: January 2022

Environmental exposures and avoidable risk factors account for a large proportion of cancer burden. Exposures and lifestyle vary over time and between populations, which calls for updated and population-specific quantification of how various avoidable risk factors influence cancer risk to plan and design rational and targeted prevention initiatives. The study considered 12 risk-factor groups categorized as class I carcinogens by IARC/WCRF. Exposure data was derived from national studies and surveys and were linked to cancer incidence in 2018 based on the nationwide Danish Cancer Registry. In 2018, 23,078 men and 21,196 women were diagnosed with cancer excluding non-melanoma skin cancer, in Denmark. Of these, 14,235 (32.2%) were estimated to be attributable to avoidable class I carcinogens. Tobacco smoking accounted for 14.6% of total cancers, followed by UV-radiation that accounted for 5.8%. Based on exposure data from 2008, one-third of the cancers in Denmark in 2018 are estimated to be caused by class I carcinogens with tobacco use being the main contributor followed by UV-radiation. Our results should be integrated with public health policies to effectively increase awareness and promote strategies to decrease risk factor exposures at population level.
Effects of water saving and nitrogen reduction on the yield, quality, water and nitrogen use efficiency of Isatis indigotica in Hexi Oasis
Authors: He Xiucheng , Qiu Huizhen , Xie Kuizhong , Wang Yucai , Hu Juan , Li Fuqiang , An Jing
Published: January 2022

Isatis indigotica planting is the backbone of the medicinal industry in Hexi Oasis, Gansu. In order to solve the problems insufficient water resources and excessive application of nitrogen fertilizer in this area, this paper explored the irrigation and nitrogen levels that can meet the multiple goals of Isatis indigotica. The two-factor split-plot field experiment (2018‒2019) was conducted in Minle County, Gansu Province, China, which contains 9 treatments. There were three levels of irrigation water: W1(low), W2(medium), and W3(high). The soil moisture contents were 60–70%, 70–80%, and 80–90% of the field water-holding capacity, respectively. The nitrogen application rate was classified into three levels, N1(low), N2(medium) and N3(high), which were 150, 200 and 250 kg N/ha, respectively. The standard local irrigation water amount and nitrogen application rate corresponded to W3N3. The results showed that the yield of Isatis indigotica increased first and then decreased with the increase of irrigation amount and nitrogen application rate, the yield of W2N2 is 12.2–17.1% higher than that of W1N1, the yield of W3N3 was 12.1–17.5% lower than that of W2N2. Saving water and reducing nitrogen can improve the quality of Isatis indigotica, compared with W3N3, the indigo, indirubin, (R,S)-epigoitrin and polysaccharides of W2N2 increased by 4.5–5.9%, 2.7–3.1%, 5.2–6.0%, and 1.8–2.1%, respectively. With the increase of nitrogen application rate, the water use efficiency (WUE) first increased and then decreased, as the irrigation volume increases, WUE decreases. Compared with W3N3, the WUE of W2N2 increased by 24.3–27.2%. With the increase of water input, the nitrogen fertilizer use efficiency (NUE) first increased and then decreased, as the nitrogen application rate increases, NUE decreases. Compared with W3N3, the NUE of W2W2 increased by 31.8–34.5%. Therefore, W2N2 can improve quality and increase water and nitrogen utilization efficiency on the basis of ensuring yield.
Effects of transcranial alternating current stimulation over right-DLPFC on vigilance tasks depend on the arousal level
Authors: Martínez-Pérez Víctor , Tortajada Miriam , Palmero Lucía B. , Campoy Guillermo , Fuentes Luis J.
Published: January 2022

Current theoretical accounts on the oscillatory nature of sustained attention predict that entrainment via transcranial alternating current stimulation (tACS) at alpha and theta frequencies on specific areas of the prefrontal cortex could prevent the drops in vigilance across time-on-task. Nonetheless, most previous studies have neglected both the fact that vigilance comprises two dissociable components (i.e., arousal and executive vigilance) and the potential role of differences in arousal levels. We examined the effects of theta- and alpha-tACS over the right dorsolateral prefrontal cortex in both components of vigilance and in participants who differed in arousal level according to their chronotype and time of testing. Intermediate-types performed the vigilance tasks when their arousal level was optimal, whereas evening-types performed the vigilance tasks when their arousal levels were non-optimal. Both theta- and alpha-tACS improved arousal vigilance in the psychomotor vigilance task (PVT), whereas alpha-tACS, but not theta-tACS, improved executive vigilance in the sustained attention to response task (SART), and counteracted the typical vigilance decrement usually observed in this task. Importantly, these stimulation effects were only found when arousal was low (i.e., with evening-types performing the tasks at their non-optimal time of day). The results support the multicomponent view of vigilance, the relevance of heeding individual differences in arousal, and the role of alpha oscillations as a long-range cortical scale synchronization mechanism that compensates the decrements in performance as a function of time-on-task by exerting and maintaining cognitive control attributed to activation of the right dorsolateral prefrontal cortex.
Risk of airway fire with the use of KTP laser and high flow humidified oxygen delivery in a laryngeal surgery model
Authors: Huang Lucy , Badenoch Adam , Vermeulen Marthinus , Ullah Shahid , Woods Charmaine , Athanasiadis Theodore , Ooi Eng Hooi
Published: January 2022

Airway surgery presents a unique environment for operating room fire to occur. This study aims to explore the factors of combustion when using KTP laser with high flow oxygen in an ex-vivo model. The variables tested were varying tissue type, tissue condition, oxygen concentration, laser setting, and smoke evacuation in a stainless-steel model. Outcome measures were time of lasing to the first spark and/or flame. A multivariate Cox proportional hazard model was used to determine the risk of spark and flame across the different risk factors. For every 10% increase in oxygen concentration above 60% the risk of flame increased by a factor of 2.3. Continuous laser setting at 2.6 W increased the risk by a factor of 72.8. The risk of lasing adipose tissue is 7.3 times higher than that of muscle. Charred tissue increases the risk of flame by a factor of 92.8. Flame occurred without a preceding spark 93.6% of the time. Using KTP laser in the pulsed mode with low wattages, minimising lasing time, reducing the oxygen concentration and avoiding lasing adipose or charred tissue produce a relatively low estimated risk of spark or flame.
Chromosome-level genome assembly of Bactrocera dorsalis reveals its adaptation and invasion mechanisms
Authors: Jiang Fan , Liang Liang , Wang Jing , Zhu Shuifang
Published: January 2022

Bactrocera dorsalisis an invasive polyphagous pest causing considerable ecological and economic damage worldwide. We report a high-quality chromosome-level genome assembly and combine various transcriptome data to explore the molecular mechanisms of its rapid adaptation to new environments. The expansions of the DDE transposase superfamily and key gene families related to environmental adaptation and enrichment of the expanded and unique gene families in metabolism and defence response pathways explain its environmental adaptability. The relatively high but not significantly different expression of heat-shock proteins, regardless of the environmental conditions, suggests an intrinsic mechanism underlying its adaptation to high temperatures. The mitogen-activated protein kinase pathway plays a key role in adaptation to new environments. The prevalence of duplicated genes in its genome explains the diversity in theB. dorsaliscomplex. These findings provide insights into the genetic basis of the invasiveness and diversity ofB. dorsalis, explaining its rapid adaptation and expansion.
Connectivity of Fennoscandian Shield terrestrial deep biosphere microbiomes with surface communities
Authors: Westmeijer George , Mehrshad Maliheh , Turner Stephanie , Alakangas Linda , Sachpazidou Varvara , Bunse Carina , Pinhassi Jarone , Ketzer Marcelo , Åström Mats , Bertilsson Stefan , Dopson Mark
Published: January 2022

The deep biosphere is an energy constrained ecosystem yet fosters diverse microbial communities that are key in biogeochemical cycling. Whether microbial communities in deep biosphere groundwaters are shaped by infiltration of allochthonous surface microorganisms or the evolution of autochthonous species remains unresolved. In this study, 16S rRNA gene amplicon analyses showed that few groups of surface microbes infiltrated deep biosphere groundwaters at the Äspö Hard Rock Laboratory, Sweden, but that such populations constituted up to 49% of the microbial abundance. The dominant persisting phyla included Patescibacteria, Proteobacteria, and Epsilonbacteraeota. Despite the hydrological connection of the Baltic Sea with the studied groundwaters, infiltrating microbes predominantly originated from deep soil groundwater. Most deep biosphere groundwater populations lacked surface representatives, suggesting that they have evolved from ancient autochthonous populations. We propose that deep biosphere groundwater communities in the Fennoscandian Shield consist of selected infiltrated and indigenous populations adapted to the prevailing conditions.
Chromosome-level genome assembly of Zizania latifolia provides insights into its seed shattering and phytocassane biosynthesis
Authors: Yan Ning , Yang Ting , Yu Xiu-Ting , Shang Lian-Guang , Guo De-Ping , Zhang Yu , Meng Lin , Qi Qian-Qian , Li Ya-Li , Du Yong-Mei , Liu Xin-Min , Yuan Xiao-Long , Qin Peng , Qiu Jie , Qian Qian , Zhang Zhong-Feng
Published: January 2022

Chinese wild rice (Zizania latifolia; family: Gramineae) is a valuable medicinal homologous grain in East and Southeast Asia. Here, using Nanopore sequencing and Hi-C scaffolding, we generated a 547.38 Mb chromosome-level genome assembly comprising 332 contigs and 164 scaffolds (contig N50 = 4.48 Mb; scaffold N50 = 32.79 Mb). The genome harbors 38,852 genes, with 52.89% of the genome comprising repetitive sequences. Phylogenetic analyses revealed close relation ofZ. latifoliatoLeersia perrieriandOryzaspecies, with a divergence time of 19.7–31.0 million years. Collinearity and transcriptome analyses revealed candidate genes related to seed shattering, providing basic information on abscission layer formation and degradation inZ. latifolia. Moreover, two genomic blocks in theZ. latifoliagenome showed good synteny with the rice phytocassane biosynthetic gene cluster. The updated genome will support future studies on the genetic improvement of Chinese wild rice and comparative analyses betweenZ. latifoliaand other plants.
The interplay between membrane topology and mechanical forces in regulating T cell receptor activity
Authors: Al-Aghbar Mohammad Ameen , Jainarayanan Ashwin K. , Dustin Michael L. , Roffler Steve R.
Published: January 2022

T cells are critically important for host defense against infections. T cell activation is specific because signal initiation requires T cell receptor (TCR) recognition of foreign antigen peptides presented by major histocompatibility complexes (pMHC) on antigen presenting cells (APCs). Recent advances reveal that the TCR acts as a mechanoreceptor, but it remains unclear how pMHC/TCR engagement generates mechanical forces that are converted to intracellular signals. Here we propose a TCR Bending Mechanosignal (TBM) model, in which local bending of the T cell membrane on the nanometer scale allows sustained contact of relatively small pMHC/TCR complexes interspersed among large surface receptors and adhesion molecules on the opposing surfaces of T cells and APCs. Localized T cell membrane bending is suggested to increase accessibility of TCR signaling domains to phosphorylation, facilitate selective recognition of agonists that form catch bonds, and reduce noise signals associated with slip bonds.
Unidirectional amplification with acoustic non-Hermitian space−time varying metamaterial
Authors: Wen Xinhua , Zhu Xinghong , Fan Alvin , Tam Wing Yim , Zhu Jie , Wu Hong Wei , Lemoult Fabrice , Fink Mathias , Li Jensen
Published: January 2022

Space−time modulated metamaterials support extraordinary rich applications, such as parametric amplification, frequency conversion, and non-reciprocal transmission. The non-Hermitian space−time varying systems combining non-Hermiticity and space−time varying capability, have been proposed to realize wave control like unidirectional amplification, while its experimental realization still remains a challenge. Here, based on metamaterials with software-defined impulse responses, we experimentally demonstrate non-Hermitian space−time varying metamaterials in which the material gain and loss can be dynamically controlled and balanced in the time domain instead of spatial domain, allowing us to suppress scattering at the incident frequency and to increase the efficiency of frequency conversion at the same time. An additional modulation phase delay between different meta-atoms results in unidirectional amplification in frequency conversion. The realization of non-Hermitian space−time varying metamaterials will offer further opportunities in studying non-Hermitian topological physics in dynamic and nonreciprocal systems.
Observation of the crossover between metallic and insulating regimes of the spin Hall effect
Authors: Moriya Hiroyuki , Musha Akira , Haku Satoshi , Ando Kazuya
Published: January 2022

The physics of the anomalous and spin Hall effects is one of the most intriguing aspects of condensed matter physics. An important finding from a large collection of experimental and theoretical results is the universal scaling of the anomalous or spin Hall conductivity with the electric conductivity. This scaling has been successfully described by the intrinsic Berry curvature and extrinsic scattering mechanisms for metallic systems, revealing the topological nature of these effects. In contrast, the underlying physics in the opposite limit, the disordered insulating regime, is still unclear. In particular, it remains a major challenge, both experimentally and theoretically, to explore the spin Hall effect in the insulating regime. Here, we report the observation of the crossover between the metallic and insulating regimes of the spin Hall effect. The result demonstrates a direct correspondence between the spin and anomalous Hall effects, which will advance the fundamental understanding of spin transport.
How inertial lift affects the dynamics of a microswimmer in Poiseuille flow
Authors: Choudhary Akash , Paul Subhechchha , Rühle Felix , Stark Holger
Published: January 2022

The transport of motile microorganisms is strongly influenced by fluid flows that are ubiquitous in biological environments. Here we demonstrate the impact of fluid inertia. We analyze the dynamics of a microswimmer in pressure-driven Poiseuille flow, where fluid inertia is small but non-negligible. Using perturbation theory and the reciprocal theorem, we show that in addition to the classical inertial lift of passive particles, the active nature generates a ‘swimming lift’, which we evaluate for neutral and pusher/puller-type swimmers. Accounting for fluid inertia engenders a rich spectrum of complex dynamics including bistable states, where tumbling coexists with stable centerline swimming or swinging. The dynamics is sensitive to the swimmer’s hydrodynamic signature and goes well beyond the findings at vanishing fluid inertia. Our work will have non-trivial implications on the transport and dispersion of active suspensions in microchannels.