bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-Sectional Evaluation of the Economic Burden on Patients Seeking Surgical Treatment for Chronic Nerve Injuries
Authors: Felder John M. , Ducic Ivica
Published: June 2021

Introduction

Little emphasis has been paid toward characterizing the socioeconomic burdens experienced by patients seeking treatment for chronic nerve injuries. The aim of this study was to characterize the direct and indirect costs faced by patients with chronic nerve injuries and their attendant health care utilization.

Materials and Methods

A cross-sectional survey was distributed to all patients (N = 767) from a single nerve surgeon's practice treated for chronic nerve injuries in the ambulatory setting between 2014 and 2020. Data collected included demographics, etiology, comorbidities, duration and severity of symptoms, history of prior medical and interventional treatments, work or school time lost due to injury or treatment, money spent on treatment, and health care utilization.

Results

Of the 767 patients, 209 (27.2%) completed the survey. Average age was 48.8 (SD = 19.1) years, 68.9% female and 31.1% male. Patients with chronic nerve injury reported significant direct costs, indirect costs, and health care utilization associated with their nerve injury symptoms. Direct costs consisted of out-of-pocket spending (68.4% had spent >$1000 per year), physician specialists visits (71.3% had seen at least 4 specialists), and prior interventional procedures intended to address symptoms. Indirect costs included lost time from work or school (24.6% had missed more than 12 months). Health care utilization, represented by annual emergency room visits and hospitalizations related to nerve symptoms, was increased relative to the general population. Detailed statistics are presented in the manuscript.

Conclusions

Chronic nerve injuries may be associated with a notable socioeconomic burden to the patient, including missed work or school, frequent physician visits and procedures, hospital visits, and out-of-pocket costs. Interdisciplinary algorithms recognizing a role for surgical evaluation in patients with chronic neuropathic pain due to underlying nerve injuries would facilitate future research into whether timely surgical intervention may reduce this economic burden.
Determinants of heart rate in Svalbard reindeer reveal mechanisms of seasonal energy management
Authors: Trondrud L. Monica , Pigeon Gabriel , Albon Steve , Arnold Walter , Evans Alina L. , Irvine R. Justin , Król Elżbieta , Ropstad Erik , Stien Audun , Veiberg Vebjørn , Speakman John R. , Loe Leif Egil
Published: June 2021

Seasonal energetic challenges may constrain an animal's ability to respond to changing individual and environmental conditions. Here, we investigated variation in heart rate, a well-established proxy for metabolic rate, in Svalbard reindeer (Rangifer tarandus platyrhynchus), a species with strong seasonal changes in foraging and metabolic activity. In 19 adult females, we recorded heart rate, subcutaneous temperature and activity using biologgers. Mean heart rate more than doubled from winter to summer. Typical drivers of energy expenditure, such as reproduction and activity, explained a relatively limited amount of variation (2–6% in winter and 16–24% in summer) compared to seasonality, which explained 75% of annual variation in heart rate. The relationship between heart rate and subcutaneous temperature depended on individual state via body mass, age and reproductive status, and the results suggested that peripheral heterothermy is an important pathway of energy management in both winter and summer. While the seasonal plasticity in energetics makes Svalbard reindeer well-adapted to their highly seasonal environment, intraseasonal constraints on modulation of their heart rate may limit their ability to respond to severe environmental change. This study emphasizes the importance of encompassing individual state and seasonal context when studying energetics in free-living animals.

This article is part of the theme issue ‘Measuring physiology in free-living animals (Part II)’.
Out of the laboratory, into the field: perspectives on social, ethical and regulatory challenges in UK wildlife research
Authors: Palmer Alexandra , Greenhough Beth
Published: June 2021

Drawing on insights from qualitative social science research, this paper aims to prompt reflection on social, ethical and regulatory challenges faced by scientists undertaking invasive animal research in the field and propose ways of addressing these challenges to promote good care for animals and environments. In particular, we explore challenges relating to the management of (i) relationships with publics and stakeholders, who may be present at field sites or crucial to research success; (ii) ethical considerations not present in the laboratory, such as the impacts of research on populations and ecosystems; (iii) working under an array of regulations, which may operate in accordance with competing ethical principles or objectives; and (iv) relationships with regulators (especially vets), which may involve disagreements over ethics and expertise, especially because regulators may be more accustomed to overseeing research in the laboratory than the field. We argue that flexibility—at a personal and policy level—and respect for others' expertise emerged as two key ways of negotiating ethical challenges, fostering positive working relationships and promoting good care for individual animals and broader ecosystems. While our analysis focuses on the UK, we propose that many of these lessons are broadly applicable to international contexts.

This article is part of the theme issue ‘Measuring physiology in free-living animals (Part II)’.
A brief introduction to the analysis of time-series data from biologging studies
Authors: Harrison Xavier A.
Published: June 2021

Recent advances in tagging and biologging technology have yielded unprecedented insights into wild animal physiology. However, time-series data from such wild tracking studies present numerous analytical challenges owing to their unique nature, often exhibiting strong autocorrelation within and among samples, low samples sizes and complicated random effect structures. Gleaning robust quantitative estimates from these physiological data, and, therefore, accurate insights into the life histories of the animals they pertain to, requires careful and thoughtful application of existing statistical tools. Using a combination of both simulated and real datasets, I highlight the key pitfalls associated with analysing physiological data from wild monitoring studies, and investigate issues of optimal study design, statistical power, and model precision and accuracy. I also recommend best practice approaches for dealing with their inherent limitations. This work will provide a concise, accessible roadmap for researchers looking to maximize the yield of information from complex and hard-won biologging datasets.

This article is part of the theme issue ‘Measuring physiology in free-living animals (Part II)’.
Animal tag technology keeps coming of age: an engineering perspective
Authors: Holton Mark D. , Wilson Rory P. , Teilmann Jonas , Siebert Ursula
Published: June 2021

Animal-borne tags (biologgers) have now become extremely sophisticated, recording data from multiple sensors at high frequencies for long periods and, as such, have become a powerful tool for behavioural ecologists and physiologists studying wild animals. But the design and implementation of these tags is not trivial because engineers have to maximize performance and ability to function under onerous conditions while minimizing tag mass and volume (footprint) to maximize the wellbeing of the animal carriers. We present some of the major issues faced by tag engineers and show how tag designers must accept compromises while maintaining systems that can answer the questions being posed. We also argue that basic understanding of engineering issues in tag design by biologists will help feedback to engineers to better tag construction but also reduce the likelihood that tag-deploying biologists will misunderstand their own results. Finally, we suggest that proper consideration of conventional technology together with new approaches will lead to further step changes in our understanding of wild-animal biology using smart tags.

This article is part of the theme issue ‘Measuring physiology in free-living animals (Part II)’.
Comparative genomic insights into culturable symbiotic cyanobacteria from the water fern Azolla
Authors: Pratte Brenda S. , Thiel Teresa
Published: June 2021

Species of the floating, freshwater fern Azolla form a well-characterized symbiotic association with the non-culturable cyanobacterium Nostoc azollae, which fixes nitrogen for the plant. However, several cyanobacterial strains have over the years been isolated and cultured from Azolla from all over the world. The genomes of 10 of these strains were sequenced and compared with each other, with other symbiotic cyanobacterial strains, and with similar strains that were not isolated from a symbiotic association. The 10 strains fell into three distinct groups: six strains were nearly identical to the non-symbiotic strain,

Nostoc

(

Anabaena

) variabilis ATCC 29413; three were similar to the symbiotic strain,

Nostoc punctiforme

, and one,

Nostoc

sp. 2RC, was most similar to non-symbiotic strains of Nostoc linckia. However,

Nostoc

sp. 2RC was unusual because it has three sets of nitrogenase genes; it has complete gene clusters for two distinct Mo-nitrogenases and an alternative V-nitrogenase. Genes for Mo-nitrogenase, sugar transport, chemotaxis and pili characterized all the symbiotic strains. Several of the strains infected the liverwort Blasia, including N. variabilis ATCC 29413, which did not originate from Azolla but rather from a sewage pond. However, only

Nostoc

sp. 2RC, which produced highly motile hormogonia, was capable of high-frequency infection of Blasia. Thus, some of these strains, which grow readily in the laboratory, may be useful in establishing novel symbiotic associations with other plants.
No effect of tDCS on fatigue and depression in chronic stroke patients: an exploratory randomized sham-controlled trial combining tDCS with computerized cognitive training
Authors: Ulrichsen Kristine M. , Kolskår Knut K. , Richard Geneviève , Pedersen Mads L. , Alnæs Dag , Dørum Erlend S. , Sanders Anne-Marthe , Tornås Sveinung , Maglanoc Luigi A. , Engvig Andreas , Ihle-Hansen Hege , Nordvik Jan E. , Westlye Lars T.
Published: June 2021

Fatigue and emotional distress rank high among self-reported unmet needs in stroke survivors. Currently, few treatment options exist for post stroke fatigue, a condition frequently associated with depression. Non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have shown promise in alleviating fatigue and depression in other patient groups, but the acceptability and effects for chronic phase stroke survivors are not established. Here, we used a randomized sham-controlled design to evaluate the added effect of tDCS combined with computerized cognitive training to alleviate symptoms of fatigue and depression. 74 patients were enrolled at baseline (mean time since stroke = 26 months) and 54 patients completed the intervention. Self-report measures of fatigue and depression were collected at five consecutive timepoints, spanning a period of two months. While fatigue and depression severity were reduced during the course of the intervention, Bayesian analyses provided evidence for no added effect of tDCS. Less severe symptoms of fatigue and depression were associated with higher improvement rate in select tasks, and study withdrawal was higher in patients with more severe fatigue and younger age. Time-resolved analyses of individual symptoms by a network-approach suggested overall higher centrality of fatigue symptoms (except item 1 and 2) than depression symptoms. In conclusion, the results support the notion of fatigue as a significant stroke sequela with possible implications for treatment adherence and response, but reveal no effect of tDCS on fatigue or depression.
Quantifying representativeness in randomized clinical trials using machine learning fairness metrics
Authors: Qi Miao , Cahan Owen , Foreman Morgan A. , Gruen Daniel M. , Das Amar K. , Bennett Kristin P.
Published: June 2021

Objective

We formulate population representativeness of randomized clinical trials (RCTs) as a machine learning (ML) fairness problem, derive new representation metrics, and deploy them in visualization tools which help users identify subpopulations that are underrepresented in RCT cohorts with respect to national, community-based or health system target populations.

Materials and Methods

We represent RCT cohort enrollment as random binary classification fairness problems, and then show how ML fairness metrics based on enrollment fraction can be efficiently calculated using easily computed rates of subpopulations in RCT cohorts and target populations. We propose standardized versions of these metrics and deploy them in an interactive tool to analyze three RCTs with respect to type-2 diabetes and hypertension target populations in the National Health and Nutrition Examination Survey (NHANES).

Results

We demonstrate how the proposed metrics and associated statistics enable users to rapidly examine representativeness of all subpopulations in the RCT defined by a set of categorical traits (e.g., sex, race, ethnicity, smoker status, and blood pressure) with respect to target populations.

Discussion

The normalized metrics provide an intuitive standardized scale for evaluating representation across subgroups, which may have vastly different enrollment fractions and rates in RCT study cohorts. The metrics are beneficial complements to other approaches (e.g., enrollment fractions and GIST) used to identify generalizability and health equity of RCTs.

Conclusion

By quantifying the gaps between RCT and target populations, the proposed methods can support generalizability evaluation of existing RCT cohorts, enrollment target decisions for new RCTs, and monitoring of RCT recruitment, ultimately contributing to more equitable public health outcomes.
Macro-Level Drivers of SARS-CoV-2 Transmission: A Data-Driven Analysis of Factors Contributing to Epidemic Growth During the First Wave of outbreaks in the United States
Authors: Watts Matthew J
Published: June 2021

Background

Many questions remain unanswered about how SARS-CoV-2 transmission is influenced by aspects of the economy, environment, and health. A better understanding of how these factors interact can help us to design early health prevention and control strategies, and develop better predictive models for public health risk management of SARS-CoV-2. This study examines the associations between COVID-19 epidemic growth and macro-level determinants of transmission such as climate, socio-economic factors, demographic factors, and population health, during the first wave of outbreaks in the United States.

Methods

A spatial-temporal data-set was created by collating information from a variety of data sources including the Johns Hopkins University’s Centre for Systems Science and Engineering, the United States Census Bureau, the USDA Economic Research Service, the United States EPA, the National Climatic Data Center, the CDC and the Oxford COVID-19 Government Response Tracker (OxCGRT). A unique data-driven study design was implemented that allows us to assess the relationship between COVID-19 case and death epidemic doubling times and explanatory variables using a Generalized Additive Model (GAM).

Results

The main factors associated with case doubling times are higher population density, home overcrowding, manufacturing, and recreation industries. Poverty was also an important predictor of faster epidemic growth perhaps because of factors associated with in-work poverty-related conditions, although poverty is also a predictor of poor population health which is likely driving case and death reporting. Air pollution and diabetes were other important drivers of case reporting. Warmer temperatures are associated with slower epidemic growth, which is most likely explained by human behaviors associated with warmer locations i.e ventilating homes and workplaces. and socializing outdoors. The main factors associated with death doubling times were population density, poverty older age, diabetes, and air pollution. Temperature was also slightly significant slowing death doubling times.

Conclusions

Such findings help underpin current understanding of the disease epidemiology and also supports current policy and advice recommending ventilation of homes, work-spaces, and schools, along with social distancing and mask-wearing. The results also suggest that states which adopted more stringent containment measures early on did have some success suppressing the virus. We can presume that if this was replicated at a federal level, much better outcomes would have been observed across the United States.
An extract of hops (Humulus lupulus L.) modulates gut peptide hormone secretion and reduces energy intake in healthy weight men: a randomised, cross-over clinical trial
Authors: Walker Edward G , Lo Kim R , Pahl Malcolm C , Shin Hyun Sang , Lang Claudia , Wohlers Mark W , Poppitt Sally D , Sutton Kevin H , Ingram John R
Published: June 2021

Background

Gastrointestinal enteroendocrine cells express a range of chemosensory receptors involved in detecting the chemical composition of food during digestion. These receptors, including bitter taste receptors (T2Rs), may play an important role in regulating gut function and appetite.

Objective

To establish the ability of Amarasate®, a bitter supercritical CO2 extract of hops (Humulus lupulus L.) to modify acute energy intake, appetite and hormonal responses and establish a site of action.

Design

Nineteen healthy-weight (BMI = 23.5 ± 0.3 kg/m2) male volunteers completed a randomised three-treatment, double blind, cross-over study with a 1 week washout between treatments. Overnight-fasted participants were cannulated and provided with a standardised 2 MJ breakfast meal at 0900h. Treatments comprised a vehicle control (Placebo) or 500 mg of hops extract administered in either delayed release capsules (Duodenal) at 1100 h or quick release capsules (Gastric) at 1130 h. Ad libitum energy intake was recorded at an outcome meal (1200 h) and afternoon snack (1400 h), with blood samples taken and subjective ratings of appetite, gastrointestinal discomfort, vitality, meal palatability and mood assessed throughout the day.

Results

Compared with placebo, both gastric and duodenal treatments significantly reduced (p < 0.05) total ad libitum energy intake by 911 ± 308 kJ and 944 ± 309 kJ, respectively. Both gastric and duodenal treatments significantly increased (p < 0.05) pre-meal ghrelin and post-prandial CCK, GLP-1 and PYY responses while reducing postprandial insulin, GIP and PP secretion with no significant impact on glycemia. In addition, gastric and duodenal treatments produced small but significant (p < 0.05) changes in vitality and gastrointestinal discomfort (e.g. nausea, bloating, abdominal discomfort) with mild-moderate adverse GI symptoms reported in the gastric treatment only. However, no significant treatment effects were observed for any subjective measures of appetite or meal palatability.

Conclusion

Both gastric and duodenal delivery of Amarasate® modulate the release of hormones involved in appetite and glycaemic regulation, providing a potential “bitter brake” on energy intake in healthy-weight men.
Sleep as a random walk - A superstatistical analysis of EEG data across sleep stages
Authors: Metzner C. , Schilling A. , Traxdorf M. , Schulze H. , Krauss P.
Published: June 2021

In clinical practice, human sleep is classified into stages, each associated with different levels of muscular activity and marked by characteristic patterns in the EEG signals. It is however unclear whether this subdivision into discrete stages with sharply defined boundaries is truly reflecting the dynamics of human sleep. To address this question, we consider one-channel EEG signals as heterogeneous random walks: stochastic processes controlled by hyper-parameters that are themselves time-dependent. We first demonstrate the heterogeneity of the random process by showing that each sleep stage has a characteristic distribution and temporal correlation function of the raw EEG signals. Next, we perform a superstatistical analysis by computing ‘hyper-parameters’, such as the standard deviation, kurtosis and skewness of the raw signal distributions, within subsequent 30-second epochs. It turns out that also the hyper-parameters have characteristic, sleep-stage-dependent distributions, which can be exploited for a simple Bayesian sleep stage detection. Moreover, we find that the hyper-parameters are not piece-wise constant, as the traditional hypnograms would suggest, but show rising or falling trends within and across sleep stages, pointing to an underlying continuous rather than subdivided process that controls human sleep.
Temporal derivative computation in the dorsal raphe network revealed by an experimentally-driven augmented integrate-and-fire modeling framework
Authors: Harkin Emerson F. , Lynn Michael B. , Payeur Alexandre , Boucher Jean-François , Caya-Bissonnette Léa , Cyr Dominic , Stewart Chloe , Longtin André , Naud Richard , Béïque Jean-Claude
Published: June 2021

By means of an expansive innervation, the serotonin (5-HT) neurons of the dorsal raphe nucleus (DRN) are positioned to enact coordinated modulation of circuits distributed across the entire brain in order to adaptively regulate behavior. Yet the network computations that emerge from the excitability and connectivity features of the DRN are still poorly understood. To gain insight into these computations, we began by carrying out a detailed electrophysiological characterization of genetically-identified mouse 5-HT and somatostatin (SOM) neurons. We next developed a single-neuron modeling framework that combines the realism of Hodgkin-Huxley models with the simplicity and predictive power of generalized integrate-and-fire (GIF) models. We found that feedforward inhibition of 5-HT neurons by heterogeneous SOM neurons implemented divisive inhibition, while endocannabinoid-mediated modulation of excitatory drive to the DRN increased the gain of 5-HT output. Our most striking finding was that the output of the DRN encodes a mixture of the intensity and temporal derivative of its input, and that the temporal derivative component dominates this mixture precisely when the input is increasing rapidly. This network computation primarily emerged from prominent adaptation mechanisms found in 5-HT neurons, including a previously undescribed dynamic threshold. By applying a bottom-up neural network modeling approach, our results suggest that the DRN is particularly apt to encode input changes over short timescales, reflecting one of the salient emerging computations that dominate its output to regulate behavior.
Prediction of antibiotic resistant strains of bacteria from their beta-lactamases protein
Authors: Maryam Lubna , Dhall Anjali , Patiyal Sumeet , Usmani Salman Sadullah , Sharma Neelam , Raghava Gajendra Pal Singh
Published: June 2021

Number of beta-lactamase variants have ability to deactivate ceftazidime antibiotic, which is the most commonly used antibiotic for treating infection by Gram-negative bacteria. In this study an attempt has been made to develop a method that can predict ceftazidime resistant strains of bacteria from amino acid sequence of beta-lactamases. We obtained beta-lactamases proteins from the β-lactamase database, corresponding to 87 ceftazidime-sensitive and 112 ceftazidime-resistant bacterial strains. All models developed in this study were trained, tested, and evaluated on a dataset of 199 beta-lactamases proteins. We generate 9149 features for beta-lactamases using Pfeature and select relevant features using different algorithms in scikit-learn package. A wide range of machine learning techniques (like KNN, DT, RF, GNB, LR, SVC, XGB) has been used to develop prediction models. Our random forest-based model achieved maximum performance with AUROC of 0.80 on training dataset and 0.79 on the validation dataset. The study also revealed that ceftazidime-resistant beta-lactamases have amino acids with non-polar side chains in abundance. In contrast, ceftazidime-sensitive beta-lactamases have amino acids with polar side chains and charged entities in abundance. Finally, we developed a webserver “ABCRpred”, for the scientific community working in the era of antibiotic resistance to predict the antibiotic resistance/susceptibility of beta-lactamase protein sequences. The server is freely available at (http://webs.iiitd.edu.in/raghava/abcrpred/).

Key Points

Ceftazidime is commonly used to treat infection caused by Gram-negative bacteria.

Beta-lactamase is responsible for lysing ceftazidime, make it resistant to bacteria.

Comparison of resistant and sensitive variants of beta-lactamase.

Classification of sensitive and resistant strain of bacteria based on beta-lactamase.

Prediction models have been developed using different machine learning techniques.
Atomic reconstruction of biomolecular structures from AFM images and quantitative validation of experimental data using simulated AFM scanning
Authors: Amyot Romain , Marchesi Arin , Franz Clemens M , Casuso Ignacio , Flechsig Holger
Published: June 2021

We provide the BioAFMviewer-Toolbox, an extension of our previously developed software platform for simulated AFM scanning of biomolecular structures and dynamics. The focus was on developing a toolbox of methods which employ simulated AFM scanning combined with quantitative analysis to facilitate the interpretation of resolution-limited AFM images. The key advancement is the automatized fitting of biomolecular structures to experimental AFM images, which allows to reconstruct 3D atomistic structures from AFM surface scans. Moreover, several methods for detailed analysis and comparison of surface topographies in simulated and experimental AFM images are provided. We demonstrate the applicability of the developed tools in the interpretation of high-speed AFM observations of proteins. The toolbox is implemented into the versatile interactive interface of the BioAFMviewer, which is a free software package available at www.bioafmviewer.com.
Disrupted choline clearance and sustained acetylcholine release in vivo by a common choline transporter coding variant associated with poor attentional control in humans
Authors: Donovan Eryn , Avila Cassandra , Klausner Sarah , Parikh Vinay , Fenollar-Ferrer Cristina , Blakely Randy D. , Sarter Martin
Published: June 2021

Transport of choline via the neuronal high-affinity choline transporter (CHT; SLC5A7) is essential for cholinergic terminals to synthesize and release acetylcholine (ACh). In humans, we previously demonstrated an association between a common CHT coding substitution (rs1013940; Ile89Val) and reduced attentional control as well as attenuated frontal cortex activation. Here, we used a CRISPR/Cas9 approach to generate mice expressing the I89V substitution and assessed, in vivo, CHT-mediated choline transport, and ACh release. Relative to wild type (WT) mice, CHT-mediated clearance of choline in mice expressing one or two Val89 alleles was reduced by over 80% cortex and by over 50% in striatum. Choline clearance in CHT Val89 mice was further reduced by neuronal inactivation. Deficits in ACh release, 5 and 10 min after repeated depolarization at a low, behaviorally relevant frequency, support an attenuated reloading capacity of cholinergic neurons in mutant mice. The density of CHTs in total synaptosomal lysates and neuronal plasma-membrane-enriched fractions was not impacted by the Val89 variant, indicating a selective impact on CHT function. When challenged with a visual disruptor to reveal attentional control mechanisms, Val89 mice failed to adopt a more conservative response bias. Structural modeling revealed that Val89 may attenuate choline transport by altering conformational changes of CHT that support normal transport rates. Our findings support the view that diminished, sustained cholinergic signaling capacity underlies perturbed attentional performance in individuals expressing CHT Val89. The CHT Val89 mouse serves as a valuable model to study heritable risk for cognitive disorders arising from cholinergic dysfunction.

Significance Statement

Acetylcholine (ACh) signaling depends on the functional capacity of the neuronal choline transporter (CHT). Previous research demonstrated that humans expressing the common CHT coding variant Val89 exhibit attentional vulnerabilities and attenuated fronto-cortical activation during attention. Here, we find that mice engineered to express the Val89 variant exhibit reduced CHT-mediated choline clearance and a diminished capacity to sustain ACh release. Additionally, Val89 mice lack cognitive flexibility in response to an attentional challenge. These findings provide a mechanistic and cognitive framework for interpreting the attentional phenotype associated with the human Val89 variant and establish a model that permits a more invasive interrogation of CNS effects as well as the development of therapeutic strategies for those, including Val89 carriers, with presynaptic cholinergic perturbations.
Aerobiology in High Latitudes: Evidence of Bacteria Acting as Tracer of Warm Air Mass Advection reaching Northern Antarctic Peninsula
Authors: Cataldo Marcio , Evangelista Heitor , Pereira José Augusto Adler , Bertho Álvaro Luiz , Pellizari Vivian , Kuhn Emanuele , Sampaio Marcelo , da Cunha Kenya Dias , dos Santos Alencar Alexandre , Amaral Cesar
Published: June 2021

Despite the extent use of geochemical tracers to track warm air mass origin reaching the Antarctic continent, we present here evidences that microorganisms being transported by the atmosphere and deposited in fresh snow layers of Antarctic ice sheets do act as tracers of air mass advection from the Southern Patagonia region to Northern Antarctic Peninsula. We combined atmospheric circulation data with microorganism content in snow/firn samples collected in two sites of the Antarctic Peninsula (King George Island/Wanda glacier and Detroit Plateau) by using flow cytometer quantification. In addition, we cultivated, isolated and submitted samples to molecular sequencing to precise species classification. Viable gram-positive bacteria were found and recovered in different snow/firn layers samples, among dead and living cells, their number concentration was compared to northern wind component, stable isotopes of oxygen, δ18O, and the concentration of crustal elements (Fe, Ti and Ca). Use of satellite images combined with air mass back-trajectory analysis obtained from the NOAA/ HYSPLIT model corroborated the results.
Carbohydrate sulfation as a mechanism for fine-tuning Siglec ligands
Authors: Jung Jaesoo , Enterina Jhon R. , Bui Duong T. , Mozaneh Fahima , Lin Po-Han , Nitin  , Kuo Chu-Wei , Rodrigues Emily , Bhattacherjee Abhishek , Raeisimakiani Parisa , Daskhan Gour C. , St. Laurent Chris D. , Khoo Kay-Hooi , Mahal Lara K. , Zandberg Wesley F. , Huang Xuefei , Klassen John S. , Macauley Matthew S.
Published: June 2021

The immunomodulatory family of Siglecs recognize sialic acid-containing glycans as ‘self’, which is exploited in cancer for immune-evasion. The biochemical nature of Siglec ligands remains incompletely understood with emerging evidence suggesting the importance of carbohydrate sulfation. Here, we investigate how specific sulfate modifications affect Siglec ligands by overexpressing eight carbohydrate sulfotransferases (CHSTs) in five cell lines. Overexpression of three CHSTs (CHST1, CHST2, or CHST4) significantly enhances the binding of numerous Siglecs. Unexpectedly, two other CHSTs (Gal3ST2 and Gal3ST3) diminish Siglec binding, suggesting a new mode to modulate Siglec ligands via sulfation. Results are cell type dependent, indicating that the context in which sulfated glycans are presented is important. Moreover, pharmacological blockade of N- and O-glycan maturation reveals a cell type-specific pattern of importance for either class of glycan. Production of a highly homogenous CD33 (Siglec-3) fragment enabled a mass spectrometry-based binding assay to determine 10-fold and 3-fold enhanced affinity for Neu5Acα2-3(6-O-sulfo)Galβ1-4GlcNAc and Neu5Acα2-3Galβ1-4(6-O- sulfo)GlcNAc, respectively, over Neu5Acα2-3Galβ1-4GlcNAc. CD33 showed significant additivity in affinity (36-fold) for the disulfated ligand, Neu5Acα2-3(6-O-sulfo)Galβ1-4(6-O-sulfo)GlcNAc. Moreover, overexpression of both CHST1 and CHST2 in cells greatly enhanced the binding of several Siglecs, including CD33. Finally, we reveal that CHST1 is upregulated in numerous cancers, correlating with poorer survival rates and sodium chlorate sensitivity for the binding of Siglecs to cancer cell lines. These results provide new insights into carbohydrate sulfation as a modification that is a general mechanism for tuning Siglec ligands on cells, including in cancer.
Single-cell reconstitution reveals persistence of clonal heterogeneity in the murine hematopoietic system
Authors: Kubasova Nadiya , Alves-Pereira Clara F. , Gupta Saumya , Vinogradova Svetlana , Gimelbrant Alexander , Barreto Vasco M.
Published: June 2021

The persistence of patterns of monoallelic expression is a controversial matter. We report a genome-wide in vivo transcriptomics approach based on allelic expression imbalance to evaluate whether the transcriptional allelic patterns of single murine hematopoietic stem cells (HSC) are still present in the respective differentiated clonal B-cell populations. For 14 genes, we show conclusive evidence for a remarkable persistence in HSC-derived B clonal cells of allele-specific autosomal transcriptional states already present in HSCs. In a striking contrast to the frequency of genes with clonal allelic expression differences in clones expanded without differentiation (up to 10%), we find that clones that have undergone multiple differentiation steps in vivo are more similar to each other. These data suggest that most of the random allele-specific stable transcriptional states on autosomal chromosomes are established de novo during cell lineage differentiation. Given that allele-specific transcriptional states are more stable in cells not undergoing extensive differentiation than in the clones we assessed after full lineage differentiation in vivo, we introduce the “Punctuated Disequilibria” model: random allelic expression biases are stable if the cells are not undergoing differentiation, but may change during differentiation between developmental stages and reach a new stable equilibrium that will only be challenged if the cell engages in further differentiation. Thus, the transcriptional allelic states may not be a stable feature of the differentiating clone, but phenotypic diversity between clones of a population at any given stage of the cell lineage is still ensured.
A NANOG-pERK reciprocal regulatory circuit mediates Nanog autoregulation and ERK signaling dynamics
Authors: Kale Hanuman T , Rajpurohit Rajendra Singh , Jana Debabrata , Vijay Vishnu V , Srivastava Mansi , Mourya Preeti R , Srinivas Gunda , Chandra Shekar P
Published: June 2021

The self-renewal and differentiation potential of Embryonic stem cells (ESCs) is maintained by the regulated expression of core pluripotency factors. The expression level of core pluripotency factor Nanog is tightly regulated by a negative feedback autorepression loop. However, it remains unclear how the ESCs perceive the NANOG levels and execute autorepression. Here, we show that a dose-dependent induction of Fgfbp1 and Fgfr2 by NANOG activates an autocrine mediated ERK signaling in high-Nanog cells to trigger autorepression. pERK recruits NONO to Nanog locus to repress transcription by preventing POL2 loading. The Nanog autorepression process establishes a self-perpetuating NANOG-pERK reciprocal regulatory circuit. We further demonstrate that the reciprocal regulatory circuit induces the pERK heterogeneity and ERK signaling dynamics in pluripotent stem cells.
Detecting quantitative trait loci and exploring chromosomal pairing in autopolyploids usingpolyqtlR
Authors: Bourke Peter M. , Voorrips Roeland E. , Hackett Christine A. , van Geest Geert , Willemsen Johan H. , Arens Paul , Smulders Marinus J. M. , Visser Richard G. F. , Maliepaard Chris
Published: June 2021

Motivation

The investigation of quantitative trait loci (QTL) is an essential component in our understanding of how organisms vary phenotypically. However, many important crop species are polyploid (carrying more than two copies of each chromosome), requiring specialised tools for such analyses. Moreover, deciphering meiotic processes at higher ploidy levels is not straightforward, but is necessary to understand the reproductive dynamics of these species, or uncover potential barriers to their genetic improvement.

Results

Here we presentpolyqtlR, a novel software tool to facilitate such analyses in (auto)polyploid crops. It performs QTL interval mapping in F1populations of outcrossing polyploids of any ploidy level using identity-by-descent (IBD) probabilities. The allelic composition of discovered QTL can be explored, enabling favourable alleles to be identified and tracked in the population. Visualisation tools within the package facilitate this process, and options to include genetic co-factors and experimental factors are included. Detailed information on polyploid meiosis including prediction of multivalent pairing structures, detection of preferential chromosomal pairing and location of double reduction events can be performed.

Availability and implementation

polyqtlRis freely available from the Comprehensive R Archive Network (CRAN) athttp://cran.r-project.org/package=polyqtlR.

Contact

peter.bourke@wur.nlorchris.maliepaard@wur.nl

Supplementary information

Supplementary data are available
ARID1A loss derepresses human endogenous retrovirus-H to modulate BRD4-dependent transcription
Authors: Yu Chunhong , Lei Xiaoyun , Chen Fang , Mao Song , Lv Lu , Liu Honglu , Hu Xueying , Wang Runhan , Shen Licong , Zhang Na , Meng Yang , Shen Yunfan , Li Pishun , Huang Shi , Shao Hao , Lin Changwei , Zhang Zhuohua , Yuan Kai
Published: June 2021

The transposable elements (TEs) through evolutionary exaptation have become an integral part of human genome, offering ample regulatory sequences and shaping chromatin 3D architecture. While the functional impacts of TE-derived sequences on early embryogenesis are recognized, their role in malignancy has only started to emerge. Here we show that many TEs, especially the pluripotency-related endogenous retrovirus H (HERVH), are abnormally activated in colorectal cancer (CRC) samples. The transcriptional upregulation of HERVH is associated with mutations of several tumor suppressors including ARID1A. Knockout of ARID1A in CRC cells leads to increased accessibility at HERVH loci and enhanced transcription, which is dependent on ARID1B. Suppression of HERVH in CRC cells and patient-derived organoids impairs tumor growth. Mechanistically, HERVH transcripts colocalize with nuclear BRD4 foci, modulate their dynamics, and co-regulate many target genes. Altogether, we uncover a critical role for ARID1A in restraining HERVH, which can promote tumorigenesis by stimulating BRD4-dependent transcription when ARID1A is mutated.
Tumor Necrosis Factor induces pathogenic programmed macrophage necrosis in
tuberculosis through a mitochondrial-lysosomal-endoplasmic reticulum
circuit
Authors: Roca Francisco J. , Redmond Sarah , Ramakrishnan Lalita
Published: June 2021

Necrosis of infected macrophages constitutes a critical pathogenetic event
in tuberculosis releasing mycobacteria into the extracellular environment where
they can grow unrestricted. In zebrafish infected with
Mycobacterium marinum, a close relative of
Mycobacterium tuberculosis, excess Tumor Necrosis
Factor triggers programmed necrosis of infected macrophages through the
production of mitochondrial reactive oxygen species (ROS) and the participation
of cyclophilin D, a component of the mitochondrial permeability transition pore.
Here we show that this necrosis pathway is not mitochondrion-intrinsic but
rather results from an interorganellar circuit initiating and culminating in the
mitochondrion. Mitochondrial ROS induce production of lysosomal ceramide which
ultimately activates the cytosolic protein BAX. BAX promotes calcium flow from
the endoplasmic reticulum into the mitochondrion through ryanodine receptors.
The resultant mitochondrial calcium overload triggers cyclophilin D-mediated
necrosis. We identify ryanodine receptors and plasma membrane L-Type calcium
channels as specific druggable targets to intercept mitochondrial calcium
overload so as to inhibit macrophage necrosis.
Allelic diversification after transposable element exaptation promotedgsdfas the master sex determining gene of sablefish
Authors: Herpin Amaury , Schartl Manfred , Depincé Alexandra , Guiguen Yann , Bobe Julien , Hua-Van Aurélie , Hayman Edward S. , Octavera Anna , Yoshizaki Goro , Nichols Krista M. , Goetz Giles W. , Luckenbach J. Adam
Published: June 2021

Concepts of evolutionary biology suggest that morphological change may occur by rare punctual but rather large changes, or by more steady and gradual transformations. It can therefore be asked whether genetic changes underlying morphological, physiological, and/or behavioral innovations during evolution occur in a punctual manner, whereby a single mutational event has prominent phenotypic consequences, or if many consecutive alterations in the DNA over longer time periods lead to phenotypic divergence. In the marine teleost, sablefish (Anoplopoma fimbria), complementary genomic and genetic studies led to the identification of a sex locus on the Y Chromosome. Further characterization of this locus resulted in identification of thetransforming growth factor, beta receptor 1a(tgfbr1a) gene,gonadal somatic cell derived factor(gsdf), as the main candidate for fulfilling the master sex determining (MSD) function. The presence of different X and Y Chromosome copies of this gene indicated that the male heterogametic (XY) system of sex determination in sablefish arose by allelic diversification. ThegsdfYgene has a spatio-temporal expression profile characteristic of a male MSD gene. We provide experimental evidence demonstrating a pivotal role of a transposable element (TE) for the divergent function ofgsdfY. By insertion within thegsdfYpromoter region, this TE generated allelic diversification by bringingcis-regulatory modules that led to transcriptional rewiring and thus creation of a new MSD gene. This points out, for the first time in the scenario of MSD gene evolution by allelic diversification, a single, punctual molecular event in the appearance of a new trigger for male development.
Structural investigations into a new polymorph of F4TCNQ: towards enhanced semiconductor properties
Authors: Johnson Natalie T. , Probert Michael R. , Waddell Paul G.
Published: June 2021

During the course of research into the structure of 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ), C12F4N4, an important compound in charge-transfer and organic semiconductor research, a previously unreported polymorph of F4TCNQ was grown concomitantly with the known polymorph from a saturated solution of dichloromethane. The structure was elucidated using single-crystal X-ray diffraction and it was found that the new polymorph packs with molecules in parallel layers, in a similar manner to the layered structure of F2TCNQ. The structure was analysed using Hirshfeld surface analysis, fingerprint plots and pairwise interaction energies, and compared to existing data. The structure of a toluene solvate of F4TCNQ is also reported.
How does ambidextrous leadership promote innovation in project-based construction companies? Through mediating role of knowledge-sharing and moderating role of innovativeness
Authors: Haider Syed Arslan , Zubair Muhammad , Tehseen Shehnaz , Iqbal Shahid , Sohail Mariam
Published: June 2021

Purpose

Research on adopting leadership style like ambidextrous leadership to enhance employees' innovative work behavior (IWB) is in an initial stage. Moreover, employees need a high knowledge sharing attitude to show more IWB. The purpose of this study is to empirically test the impact of ambidextrous leadership on IWB with the mediating role of knowledge sharing and the moderating role of innovativeness as a project requirement (IAPR).

Design/methodology/approach

The simple random sampling technique was used to collect data from 542 employees of project-based construction companies operating in Pakistan. Smart partial least squares-structural equation modeling (Smart PLS SEM v.3.2.8) was used to test the hypotheses.

Findings

The result revealed that ambidextrous leadership has a significant and positive effect on knowledge sharing but negative effect on IWB at the workplace. Additionally, the mediating role of knowledge sharing has been tested and proved to be a potential mediator between ambidextrous leadership and IWB. Also, IAPR as moderator has a significant and positive effect on knowledge sharing and IWB.

Practical implications

The managers need to develop an ambidexterity-oriented strategy and communicate this strategy across the members of the whole organization. These processes can be facilitated by ambidextrous leaders with complex behavioral repertoires and specific constellations and characteristics of top management teams.

Originality/value

The relationship between ambidextrous leadership and IWB is the new contribution through the mediating of knowledge sharing between AL and IWB also moderation role IWB between knowledge sharing and IWB.
“I played a song with the help of a magic banana”: assessing short-term making events
Authors: Nixon Jessie , Halverson Erica , Stoiber Andy , Garbacz Andy
Published: June 2021

Purpose

The purpose of this study is to understand how learners describe their experiences with short-term, introductory maker experiences and to test a method for assessing learners’ experiences authentic to short-term learning.

Design/methodology/approach

The authors collected written responses from participants at a two-day event, STEM Center Learning Days. Through an analysis of 707 unique instances of learner responses to participation in drop-in maker activities, they examined how participants describe their short-term learning experiences.

Findings

The authors found that although some activities appear to onlookers to create passive experiences for learners, these seemingly passive moments have a significant impact on learners. In addition, some learners described themselves as working in tandem with tools to make something work and other learners viewed the tools as working autonomously. They found that the assessment method allowed them to gain an understanding of how learners describe their experiences offering important implications for understanding short-term learning events.

Originality/value

The findings provide researchers studying short-term learning in its natural setting a new method to understand how learners make sense of their individual experience. Further, designers of short-term learning experiences may gain insights into their unique activities and indications of where additional guidance and scaffolds will improve small learning moments.