bluuebunny/crossref_metadata_2025 huggingface dataset:
The distinctive sleep pattern of the human calcarine cortex: a stereo-electroencephalographic study
Authors: Gorgoni Maurizio , Sarasso Simone , Moroni Fabio , Sartori Ivana , Ferrara Michele , Nobili Lino , De Gennaro Luigi
Published: February 2021

Study Objectives

The aim of this study was to describe the spontaneous electroencephalographic (EEG) features of sleep in the human calcarine cortex, comparing them with the well-established pattern of the parietal cortex.

Methods

We analyzed presurgical intracerebral EEG activity in calcarine and parietal cortices during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in seven patients with drug-resistant focal epilepsy. The time course of the EEG spectral power and NREM vs REM differences was assessed. Sleep spindles were automatically detected. To assess homeostatic dynamics, we considered the first vs second half of the night ratio in the delta frequency range (0.5–4 Hz) and the rise rate of delta activity during the first sleep cycle.

Results

While the parietal area showed the classically described NREM and REM sleep hallmarks, the calcarine cortex exhibited a distinctive pattern characterized by: (1) the absence of sleep spindles; (2) a large similarity between EEG power spectra of NREM and REM; and (3) reduced signs of homeostatic dynamics, with a decreased delta ratio between the first and the second half of the night, a reduced rise rate of delta activity during the first NREM sleep cycle, and lack of correlation between these measures.

Conclusions

Besides describing for the first time the peculiar sleep EEG pattern in the human calcarine cortex, our findings provide evidence that different cortical areas may exhibit specific sleep EEG pattern, supporting the view of sleep as a local process and promoting the idea that the functional role of sleep EEG features should be considered at a regional level.
Nocardia bovistercoris sp. nov., an actinobacterium isolated from cow dung
Authors: Zhang Xue , Zhang Lida , Yu XiaoYan , Zhang Jing , Jiao Yanjie , Ju Hanxun , Wang Xiangjing , Zhao Junwei , Xiang Wensheng
Published: February 2021

A novel actinobacterium, designated strain NEAU-351T, was isolated from cow dung collected from Shangzhi, Heilongjiang Province, northeast PR China and characterized using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NEAU-351T belonged to the genus

Nocardia

, with the highest similarity (98.96 %) to

Nocardia takedensis

DSM 44801T and less than 98.0 % identity with other type strains of the genus

Nocardia

. The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. The major menaquinone was observed to contain MK-8(H4, ω-cycl) (78.2 %). The fatty acid profile mainly consisted of C16 : 0, C18 : 1
 ω9c and 10-methyl C18 : 0. Mycolic acids were present. The genomic DNA G+C content of strain NEAU-351T was 68.1 mol%. In addition, the average nucleotide identity values between strain NEAU-351T and its reference strains,

Nocardia takedensis

DSM 44801T and

Nocardia arizonensis

NBRC 108935T, were found to be 81.4 and 82.9 %, respectively, and the level of digital DNA–DNA hybridization between them were 24.8 % (22.5–27.3 %) and 26.3 % (24–28.8 %), respectively. Here we report on the taxonomic characterization and classification of the isolate and propose that strain NEAU-351T represents a new species of the genus

Nocardia

, for which the name Nocardia bovistercoris is proposed. The type strain is NEAU-351T (=CCTCC AA 2019090T=DSM 110681T).
Development and Validation of a Simplified Risk Score for the Prediction of Critical COVID-19 Illness in Newly Diagnosed Patients
Authors: Werfel Stanislas , Jakob Carolin E. M. , Borgmann Stefan , Schneider Jochen , Spinner Christoph , Schons Maximilian , Hower Martin , Wille Kai , Haselberger Martina , Heuzeroth Hanno , Rüthrich Maria M. , Dolff Sebastian , Kessel Johanna , Heemann Uwe , Vehreschild Jörg Janne , Rieg Siegbert , Schmaderer Christoph
Published: February 2021

Scores for identifying patients at high risk of progression of the coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), are discussed as key instruments for clinical decision-making and patient management during the current pandemic.

Here we used the patient data from the multicenter Lean European Open Survey on SARS-CoV-2 - Infected Patients (LEOSS) and applied a technique of variable selection in order to develop a simplified score to identify patients at increased risk of critical illness or death.

A total of 1,946 patients, who were tested positive for SARS-CoV-2 were included in the initial analysis. They were split into a derivation and a validation cohort (n=1,297 and 649, respectively). A stability selection among a total of 105 baseline predictors for the combined endpoint of progression to critical phase or COVID-19-related death allowed us to develop a simplified score consisting of five predictors: CRP, Age, clinical disease phase (uncomplicated vs. complicated), serum urea and D-dimer (abbreviated as CAPS-D score). This score showed an AUC of 0.81 (CI95%: 0.77-0.85) in the validation cohort for predicting the combined endpoint within 7 days of diagnosis and 0.81 (CI95%: 0.77-0.85) during the full follow-up. Finally, we used an additional prospective cohort of 682 patients, who were diagnosed largely after the “first wave” of the pandemic to validate predictive accuracy of the score, observing similar results (AUC for an event within 7 days: 0.83, CI95%, 0.78-0.87; for full follow-up: 0.82, CI95%, 0.78-0.86).

We thus successfully establish and validate an easily applicable score to calculate the risk of disease progression of COVID-19 to critical illness or death.
Rapid Impact Analysis of B 1.1.7 Variant on the Spread of SARS-CoV-2 in North Carolina
Authors: DeWitt Michael
Published: February 2021

Background

Several cases of the B1.1.7 variant of the SARS-CoV-2 virus were identified in North Carolina first on January 23, 2021 in Mecklenburg County and later in Guilford County on January 28, 2021.[1,2] This variant has been associated with higher levels of transmissibility.[3–6] This study examines the potential impact of increased transmissibility as the B1.1.7 variant becomes more predominant given current vaccine distribution plans and existing non-pharmaceutical interventions (NPIs).

Method

We explored the anticipated impact on the effective reproduction number for North Carolina and Guilford County given the date of import of B1.1.7. The approximate growth rate in proportion of B1.1.7 observed in the United Kingdom was fit and used to establish the estimate share of B1.1.7 circulating in North Carolina. Using the nowcasted reproduction numbers, a stochastic discrete compartmental model was fit with the current vaccination rates and B1.1.7 transmissibility to estimate the impact on the effective reproduction number.

Results

We found that the effective reproduction number for North Carolina and Guilford County may exceed one, indicating a return to accelerating spread of infection in April as the proportion of B1.1.7 increases. The effective reproduction number will likely decrease into March, then increase as the proportion of B1.1.7 increases in circulation in the population.

Conclusions

Existing non-pharmaceutical interventions will need to remain in effect through the spring. Given the current vaccination rate and these interventions, it is likely that there will be an increase in SARS-CoV-2 infections. The impact of the variant will likely be heterogeneous across North Carolina given the reproduction number and volume of susceptible persons in each county at the time of introduction of the variant. Age-based vaccinations will likely reduce the overall impact on hospitalizations. This analysis underlines the need for population level genetic surveillance to confirm the proportion of variants circulating.
Robust immune responses after one dose of BNT162b2 mRNA vaccine dose in SARS-CoV-2 experienced individuals
Authors: Samanovic Marie I. , Cornelius Amber R. , Gray-Gaillard Sophie L. , Allen Joseph Richard , Karmacharya Trishala , Wilson Jimmy P. , Hyman Sara Wesley , Tuen Michael , Koralov Sergei B. , Mulligan Mark J. , Herati Ramin Sedaghat
Published: February 2021

The use of COVID-19 vaccines will play the major role in helping to end the pandemic that has killed millions worldwide. COVID-19 vaccines have resulted in robust humoral responses and protective efficacy in human trials, but efficacy trials excluded individuals with a prior diagnosis of COVID-19. As a result, little is known about how immune responses induced by mRNA vaccines differ in individuals who recovered from COVID-19. Here, we evaluated longitudinal immune responses to two-dose BNT162b2 mRNA vaccination in 15 adults who recovered from COVID-19, compared to 21 adults who did not have prior COVID-19 diagnosis. Consistent with prior studies of mRNA vaccines, we observed robust cytotoxic CD8+ T cell responses in both cohorts following the second dose. Furthermore, SARS-CoV-2-naive individuals had progressive increases in humoral and antigen-specific antibody-secreting cell (ASC) responses following each dose of vaccine, whereas SARS-CoV-2-experienced individuals demonstrated strong humoral and antigen-specific ASC responses to the first dose but muted responses to the second dose of the vaccine at the time points studied. Together, these data highlight the relevance of immunological history for understanding vaccine immune responses and may have significant implications for personalizing mRNA vaccination regimens used to prevent COVID-19, including booster shots.

One Sentence Summary

Prior history of COVID-19 affects adaptive immune responses to mRNA vaccination.
Current quantitative polymerase chain reaction to detect severe acute respiratory syndrome coronavirus 2 may give positive results for other described coronavirus
Authors: Martínez-Murcia Antonio , García-Sirera Adrián , Navarro Aaron , Ros-Tárraga Patricia , Pérez Laura
Published: February 2021

Some weeks after the first CoVID-19 outbreak, the WHO published some qPCR protocol assays developed by different institutions worldwide. These qPCR designs are being used to detect the presence of SARS-CoV-2 in the population, which allow us to monitore the prevalence of the virus during the pandemic. Moreover, the use of these designs is wide spreading and nowadays they are used to detect SARS-CoV-2 in environmental samples to act as epidemiological surveillance tool. However, at the time of designing the published RT-qPCR assays, a lack of SARS-CoV-2 genomes available may explain a low exclusivity in some cases. In this study, we are reporting experimental data which demonstrate that some of the current qPCR used to detect SARS-CoV-2 may give positive results for other described coronavirus different from SARS-CoV-2.
Dysautonomia in hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders is associated with exercise intolerance and cardiac atrophy
Authors: Maya Tania Ruiz , Fettig Veronica , Mehta Lakshmi , Gelb Bruce D. , Kontorovich Amy R.
Published: February 2021

Dysautonomia is a recognized manifestation in patients with joint hypermobility (JH) disorders. Symptoms can be highly debilitating and commonly include physical deconditioning and poor aerobic fitness. In this study, the prevalence of dysautonomia, range of associated symptoms, patient-reported physical activity levels and echocardiographic features were assessed retrospectively in a cohort of 144 patients (94% female) with hypermobile Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorder (HSD). Echocardiographic parameters of LV size and function were compared between patients with and without dysautonomia, as well as to reported values from healthy controls. Dysautonomia was identified in 71% of female and 56% of male subjects and was associated with a high burden of symptomatology, most commonly exercise intolerance (78%). Exercise capacity was limited by dysautonomia, often postural symptoms, in half of all patients. We observed a reduction in physical activity following the onset or significant flare of hEDS/HSD, most strikingly noting the proportion of dysautonomic patients with sedentary lifestyle, which increased from 39% to >80%. JH-related dysautonomia was associated with smaller cardiac chamber sizes, consistent with previous reports in positional orthostatic tachycardia syndrome. Dysautonomia is highly prevalent in patients with hEDS/HSD, exercise intolerance is a key feature and leads to drastic decline in physical activity. Unfavorable cardiac geometry may underlie dysautonomia symptoms and may be due to cardiac atrophy in the setting of aerobic deconditioning.
Effect of using a physical assistance device for movements involving trunk bending
Authors: Jelti Z. , Lebel K. , Bastide S. , Le Borgne P. , Slangen P. , Vignais N.
Published: February 2021

Exoskeletons are a solution to physically relieve workers while allowing them to control the execution of their tasks and assist them(Baltrusch et al.2018).

The study investigated in the search for elements able to quantify the action of a physical assistance device (PAD) on the human body for movements responsible for pathologies recognized as occupational diseases.

The evaluation of a PAD allows to determine in which framework the exoskeleton can be useful for the realization of the movement. It is specified that a relevant way to insert exoskeletons in a company by always implementing a study or analysis beforehand to ensure its good integration.

The objective of the study is to perform several tasks with and without the Posture Harness (HAPO) in order to analyze the kinematics of the movements and the electrical activity of erector muscles of the spine involved in carrying a load at work to understand its effects on the human body.
The envelope cytoplasmic tail regulates HIV-1 assembly and spread
Authors: Snetkov Xenia , Haider Tafhima , Mesner Dejan , Groves Nicholas , Engelenburg Schuyler van , Jolly Clare
Published: February 2021

The HIV-1 envelope (Env) is an essential determinant of viral infectivity, tropism and spread between T cells. Lentiviral Env contain an unusually long 150 amino acid cytoplasmic tail (EnvCT) but the function of the EnvCT and conserved domains within it remain largely uncharacterised. Here we identified a highly conserved tryptophan motif at position 757 (W757) in the LLP-2 alpha helix of the EnvCT as a key determinant for HIV-1 replication and spread between T cells. Strikingly we find that mutating W757 had wide-ranging consequences including altering Env mobility in the plasma membrane, preventing Env and Gag recruitment to sites of cell-cell contact for virological synapse (VS) formation and cell-cell spread, and impeding viral fusion. Notably, W757 was also required for efficient virus budding, revealing a previously unappreciated role for the EnvCT in regulating HIV-1 assembly and egress. We conclude that W757 is a key residue that stabilises the structural integrity and function of Env, consistent with the recent model that this region of the EnvCT acts as a critical supporting baseplate for Env.
POPULATION GENOMIC ANALYSIS OFCRYPTOCOCCUSBRAZILIAN ISOLATES REVEALS AN AFRICAN TYPE SUBCLADE DISTRIBUTION
Authors: Maufrais Corinne , de Oliveira Luciana , Bastos Rafael W. , Moyrand Frédérique , Reis Flavia C. G. , Valero Clara , Gimenez Bianca , Josefowicz Luisa J. , Goldman Gustavo H. , Rodrigues Marcio L. , Janbon Guilhem
Published: February 2021

The genomes of a large number ofCryptococcus neoformansisolates have been sequenced and analyzed in recent years. These genomes have been used to understand the global population structure of this opportunistic pathogen. However, only a small number of South American isolates have been considered in these studies, and the population structure ofC. neoformansin this part of the world remains elusive. Here, we analyzed the genomic sequences of 53 BrazilianCryptococcus isolates and deciphered theC. neoformanspopulation structure in this country. Our data reveal an African-like structure that suggested repeated intercontinental transports from Africa to South America. We also identified a mutator phenotype in one VNBII Brazilian isolate, exemplifying how fast-evolving isolates can shape theCryptococcuspopulation structure. Finally, phenotypic analyses revealed wide diversity but not lineage specificity in the expression of classical virulence traits within the set of isolates.
5-Azacytidine: Effects on the Expression of alpha-Cardiac Actin in Pericytes from Human Adipose Tissue
Authors: Ferreira-Silva Valéria , Baqui Munira M. A. , Molfetta Greice A. , Fontes Aparecida M. , Zanette Dalila I. , Ferreira Fernanda U. , Orellana Maristela D. , Silva Wilson A. , Covas Dimas T.
Published: February 2021

DNA methylation patterns are closely related to the chromatin structure, and its remodeling is considered an important mechanism in the control of gene transcription during cell differentiation. In rodent, several studies have related the possibility that multipotent mesenchymal stromal cells (MSCs) undergo cardiomyogenesis. However, it has not been completely elucidated if human adult stem cell exhibits true differentiation potential for a cardiac lineage. In this study, the action of the DNA methylation inhibitor 5-azacytidine (5-aza) was examined in human adipose tissue pericytes (hATPCs: 3G5+) regarding their possible capacity to induce myocytesin vitro. Real-Time PCR revealed that cells treated with 5-aza presented time-dependent decrease in the mRNA expression of α-cardiac actin (α-CA). At 24 h, this diminution was statistically significant; however, there was not a correlation with the highest level of DNA demethylation at the same period using Methylation-Sensitive High Resolution Melting-PCR (MS-HRM-PCR). An evident increase in the α-CA protein expression was observed by Western blotting in hATPCs treated with 5-aza at 24 h. The mRNA expression of α-SMA (α-smooth actin) also showed a time-dependent decrease after the treatment, however, it was not significant. The ultrastructural analysis showed similar structures such as like-cell junctions, caveolae, and actin myofilaments, which aligned in parallel. These phenotypic alterations were found only after the treatment; however, the hTAPCs after 5-aza treatment were not able to form thick myofilaments and consequently sarcomeres. These results indicated that a terminal cardiac differentiation of hTAPCs was not achieved and that the cardiomyogenesis failure could be related to the non-muscle origin of the adipose tissue.
Unexpected distribution of the 4-formylaminooxyvinylglycine (FVG) biosynthetic pathway inPseudomonasand beyond
Authors: Davis Edward W. , Okrent Rachel A. , Manning Viola A. , Trippe Kristin M.
Published: February 2021

The biological herbicide and antibiotic 4-formylaminooxyvinylglycine (FVG) was originally isolated from several rhizosphere-associated strains ofPseudomonas fluorescens. Biosynthesis of FVG is dependent on thegvgbiosynthetic gene cluster inP. fluorescens. In this investigation, we used comparative genomics to identify strains with the genetic potential to produce FVG due to presence of agvggene cluster. These strains primarily belong to two groups ofPseudomonas, P. fluorescensandP. syringae, however, a few strains with thegvgcluster were found outside ofPseudomonas. Mass spectrometry confirmed that all tested strains of theP. fluorescensspecies group produced FVG. However,P. syringaestrains did not produce FVG under standard conditions. Several lines of evidence regarding the transmission of thegvgcluster including a robust phylogenetic analysis suggest that it was introduced multiple times through horizontal gene transfer within thePseudomonaslineage as well as in select lineages ofThiomonas, BurkholderiaandPantoea. Together, these data broaden our understanding of the evolution and diversity of FVG biosynthesis. In the course of this investigation, additional gene clusters containing only a subset of the genes required to produce FVG were identified in a broad range of bacteria, including many non-pseudomonads.
Architecture of cell-cell junctions in situ reveals a mechanism for bacterial biofilm inhibition
Authors: Melia Charlotte E. , Bolla Jani R. , Katharios-Lanwermeyer Stefan , Mihaylov Daniel B. , Hoffmann Patrick C. , Huo Jiandong , Wozny Michael R. , Elfari Louis M. , Böhning Jan , Owens Raymond J. , Robinson Carol V. , O’Toole George A. , Bharat Tanmay A.M.
Published: February 2021

Many bacteria, including the major human pathogenPseudomonas aeruginosa, are naturally found in multicellular, antibiotic-tolerant biofilm communities, where cells are embedded in an extracellular matrix of polymeric molecules. Cell-cell interactions withinP. aeruginosabiofilms are mediated by CdrA, a large, membrane-associated adhesin present in the extracellular matrix of biofilms, regulated by the cytoplasmic concentration of cyclic diguanylate. Here, using electron cryotomography of focused-ion beam milled specimens, we report the architecture of CdrA molecules in the extracellular matrix ofP. aeruginosabiofilms at intact cell-cell junctions. Combining ourin situobservations at cell-cell junctions with biochemistry, native mass spectrometry and cellular imaging, we demonstrate that CdrA forms an extended structure that projects from the outer membrane to tether cells together via polysaccharide binding partners. We go on to show the functional importance of CdrA using custom single-domain antibody (nanobody) binders. Nanobodies targeting the tip of functional cell-surface CdrA molecules could be used to inhibit bacterial biofilm formation or disrupt pre-existing biofilms in conjunction with bactericidal antibiotics. These results reveal a functional mechanism for cell-cell interactions within bacterial biofilms and highlight the promise of using inhibitors targeting biofilm cell-cell junctions to prevent or treat problematic, chronic bacterial infections.
Enhanced habit formation in Tourette syndrome: dopamine release and striatal disinhibition modulate shortcut connections in a hierarchical model of cortico-basal ganglia loops
Authors: Scholl Carolin , Baladron Javier , Vitay Julien , Hamker Fred H.
Published: February 2021

In the Gilles de la Tourette syndrome, tics are often considered as habitual responses towards unwanted premonitory urges. Support for the relationship between tics and habits comes from devaluation protocols, which reveal that unmedicated Tourette patients show an increased tendency towards responses to devalued outcomes. We use a neuro-computational model of hierarchically organized cortico-basal ganglia-thalamo-cortical loops to shed more light on enhanced habit formation of Tourette patients. In our model, habitual behavior emerges from cortico-thalamic shortcut connections, where enhanced habit formation can be linked to faster plasticity in the shortcut or to a stronger feedback from the shortcut to the basal ganglia. Irregular activity in such shortcut connections may have different pathophysiological origins. Based on our model, we explore decreased local striatal inhibition, which may correspond to a loss of inhibitory interneurons, and increased dopaminergic modulation of striatal medium spiny neurons as causes for irregular shortcut plasticity or activation. Both lead to higher rates of response towards devalued outcomes in our model, similar to what is observed in Tourette patients. Our results support the view of tics in Tourette syndrome as maladaptive habits. We suggest to reveal more shortcuts between cortico-basal ganglia-thalamo-cortical loops in the human brain and study their potential role in the development of the Tourette syndrome.
Using induced pluripotent stem cells to investigate human neuronal phenotypes in 1q21.1 deletion and duplication syndrome
Authors: Chapman Gareth , Alsaqati Mouhamed , Lunn Sharna , Singh Tanya , Linden Stefanie C , Linden David E. J. , van den Bree Marianne B.M. , Ziller Mike , Owen Michael J , Hall Jeremy , Harwood Adrian J. , Syed Yasir Ahmed
Published: February 2021

Copy Number Variation (CNV) at the 1q21.1 locus is associated with a range of neurodevelopmental and psychiatric disorders in humans, including abnormalities in head size and motor deficits. Yet, the functional consequences of these CNVs (both deletion and duplication) on neuronal development remain unknown. To determine the impact of CNV at the 1q21.1 locus on neuronal development, we generated induced pluripotent stem cells from individuals harbouring 1q21.1 deletion or duplication and differentiated them into functional cortical neurons. We show that neurons with 1q21.1 deletion or duplication display reciprocal phenotype with respect to proliferation, differentiation potential, neuronal maturation, synaptic density, and functional activity. Deletion of the 1q21.1 locus was also associated with an increased expression of lower cortical layer markers. This difference was conserved in the mouse model of 1q21.1 deletion, which displayed altered corticogenesis. Importantly, we show that neurons with 1q21.1 deletion and duplication are associated with differential expression of calcium channels and demonstrate that physiological deficits in neurons with 1q21.1 deletion or duplication can be pharmacologically modulated by targeting Ca2+channel activity. These findings provide biological insight into the neuropathological mechanism underlying 1q21.1 associated brain disorder and indicate a potential target for therapeutic interventions.
The CIP2A-TOPBP1 complex safeguards chromosomal stability during mitosis
Authors: De Marco Zompit Mara , Mooser Clémence , Adam Salomé , Rossi Silvia Emma , Jeanrenaud Alain , Leimbacher Pia-Amata , Fink Daniel , Durocher Daniel , Stucki Manuel
Published: February 2021

The accurate repair of DNA double-strand breaks (DSBs), highly toxic DNA lesions, is crucial for genome integrity and is tightly regulated during the cell cycle. In mitosis, cells inactivate DSB repair in favor of a tethering mechanism that stabilizes broken chromosomes until they are repaired in the subsequent cell cycle phases. How this is achieved mechanistically is not yet understood, but the adaptor protein TOPBP1 is critically implicated in this process. Here, we identify CIP2A as a TOPBP1-interacting protein that regulates TOPBP1 localization specifically in mitosis. Cells lacking CIP2A display increased micronuclei formation, DSB repair defects and chromosomal instability. CIP2A is actively exported from the cell nucleus in interphase but, upon nuclear envelope breakdown at the onset of mitosis, gains access to chromatin where it forms a complex with MDC1 and TOPBP1 to promote TOPBP1 recruitment to sites of mitotic DSBs. Collectively, our data uncover CIP2A-TOPBP1 as a mitosis-specific genome maintenance complex.
Zoom in on Ca2+pattern and ion flux dynamics to decode spatial and temporal regulation of cotton fiber growth
Authors: Yang Jia-Shuo , Bose Jayakumar , Shabala Sergey , Ruan Yong-Ling
Published: February 2021

Cotton fibers are single-celled trichomes initiated from ovule epidermis prior to anthesis. Thereafter, the fibers undergo rapid elongation for 20 d before switching to intensive cell wall cellulose synthesis. The final length attained determines fiber yield and quality. As such, cotton fiber represents an excellent single cell model to study regulation of cell growth and differentiation, with significant agronomical implications. One major unresolved question is whether fiber elongation follows a diffusive or a tip growth pattern. We addressed this issue by using cell biology and electrophysiological approaches. Confocal imaging of Ca2+binding dye, fluo-3 acetoxymethyl (Fluo-3), andin situmicroelectrode ion flux measurement revealed that cytosolic Ca2+was evenly distributed along the elongating fiber cells with Ca2+and H+fluxes oscillating from apical to basal regions of the elongating fibers. These findings demonstrate that, contrary to growing pollen tubes or root hairs, cotton fiber growth follows a diffusive, but not the tip growth, pattern. Further analyses showed that the elongating fibers exhibited substantial net H+efflux, indicating a strong activity of the plasma membrane H+-ATPase required for energy dependent solute uptake. Interestingly, the growing cotton fibers were responding to H2O2treatment, know to promote fiber elongation, by a massive increase in the net Ca2+and H+efflux in both tip and basal zones, while non-growing cells lacked this ability. These observations suggest that desensitization of the cell and a loss of its ability to respond to H2O2may be causally related to the termination of the cotton fiber elongation.

One sentence summary

Confocal imaging of Ca2+patterning andin situmicroelectrode ion flux measurements demonstrate that, contrary to growing pollen tubes or root hairs, cotton fiber growth follows a diffusive, but not the tip growth, pattern.
Acoustic context modulates natural sound discrimination in auditory cortex through frequency specific adaptation
Authors: López-Jury Luciana , García-Rosales Francisco , González-Palomares Eugenia , Kössl Manfred , Hechavarria Julio C.
Published: February 2021

Vocal communication is essential to coordinate social interactions in mammals and it requires a fine discrimination of communication sounds. Auditory neurons can exhibit selectivity for specific calls, but how it is affected by preceding sounds is still debated. We tackled this using ethologically relevant vocalizations in a highly vocal mammalian species: Seba’s short-tailed bat. We show that cortical neurons present several degrees of selectivity for echolocation and distress calls. Embedding vocalizations within natural acoustic streams leads to stimulus-specific suppression of neuronal responses that changes sound selectivity in disparate manners: increases in neurons with poor discriminability in silence and decreases in neurons selective in silent settings. A computational model indicates that the observed effects arise from two forms of adaptation: presynaptic frequency specific adaptation acting in cortical inputs and stimulus unspecific postsynaptic adaptation. These results shed light into how acoustic context modulates natural sound discriminability in the mammalian cortex.
All-Atom MD Simulations of the HBV Capsid Complexed with AT130 Reveal Secondary and Tertiary Structural Changes and Mechanisms of Allostery
Authors: Pérez Segura Carolina , Goh Boon Chong , Hadden-Perilla Jodi A.
Published: February 2021

The hepatitis B virus (HBV) capsid is an attractive drug target, relevant to combating viral hepatitis as a major public health concern. Among small molecules known to interfere with capsid assembly, the phenylpropenamides, including AT130, represent an important anti-viral paradigm based on disrupting the timing of genome encapsulation. Crystallographic studies of AT130-bound complexes have been essential in explaining the effects of the small molecule on HBV capsid structure; however, computational examination reveals that key changes attributed to AT130 were erroneous, likely a consequence of interpreting poor resolution arising from a highly flexible protein. Here, all-atom molecular dynamics simulations of an intact AT130-bound HBV capsid reveal that, rather than damaging spike helicity, AT130 enhances the capsid’s ability to recover it. A new conformational state is identified, which can lead to dramatic opening of the intradimer interface and disruption of communication within the spike tip. A novel salt bridge is also discovered, which can mediate contact between the spike tip and fulcrum even in closed conformations, revealing a mechanism of direct communication across these domains. Combined with dynamical network analysis, results describe a connection between the intra- and interdimer interfaces and enable mapping of allostery traversing the entire capsid protein dimer.
Integrated analysis of the methylome and transcriptome of twin almonds (Prunus dulcis[Mill.] D.A.Webb) reveals genomic features associated with non-infectious bud failure
Authors: D’Amico-Willman Katherine M. , Niederhuth Chad E. , Willman Matthew R. , Gradziel Thomas M. , Ouma Wilburforce Z. , Meulia Tea , Fresnedo-Ramírez Jonathan
Published: February 2021

I.

Almond (Prunus dulcis[Mill.] D.A.Webb) exhibits an age-related disorder called non-infectious bud-failure (BF) affecting vegetative bud development and nut yield. The underlying cause of BF remains unknown but is hypothesized to be associated with heritable epigenetic mechanisms. To address this disorder and its epigenetic components, we utilized a monozygotic twin study model profiling genome-wide DNA methylation and gene expression in two sets of twin almonds discordant for BF-exhibition. Analysis of DNA methylation patterns show that BF-exhibition and methylation, namely hypomethylation, are not independent phenomena. Transcriptomic data generated from the twin pairs also shows genome-wide differential gene expression associated with BF-exhibition. After identifying differentially methylated regions (DMRs) in each twin pair, a comparison revealed 170 shared DMRs between the two twin pairs. These DMRs and the associated genetic components may play a role in BF-exhibition. A subset of 52 shared DMRs are in close proximity to genes involved in meristem maintenance, cell cycle regulation, and response to heat stress. Annotation of specific genes included involvement in processes like cell wall development, calcium ion signaling, and DNA methylation. Results of this work support the hypothesis that BF-exhibition is associated with hypomethylation in almond, and identified DMRs and differentially expressed genes can serve as potential biomarkers to assess BF-potential in almond germplasm. Our results contribute to an understanding of the contribution of epigenetic disorders in agricultural performance and biological fitness of perennials.

II.

Significance

This study examines epigenetic components underlying noninfectious bud failure, an aging-related disorder affecting almond. Results from this work contribute to our understanding of the implications of DNA methylation on agricultural production, namely perennial fruit and nut production, due to effects on growth, development, and reproduction. Describing the methylome of discordant, monozygotic twin almonds enables the study of genomic features underlying noninfectious bud failure in this economically important crop.
Environmental effects on genetic variance are likely to constrain adaptation in novel environments
Authors: Walter Greg M. , Monro Keyne , Terranova Delia , la Spina Enrico , Majorana Maria , Pepe Giuseppe , Clark James , Cozzolino Salvatore , Cristaudo Antonia , Hiscock Simon J. , Bridle Jon R.
Published: February 2021

Adaptive plasticity allows populations to cope with environmental variation but is expected to fail as conditions become unfamiliar. In novel conditions, populations may instead rely on rapid adaptation to increase fitness and avoid extinction. Adaptation should be fastest when both plasticity and selection occur in directions of the multivariate phenotype that contain abundant genetic variation. However, tests of this prediction from field experiments are rare. Here, we quantify how additive genetic variance in a multivariate phenotype changes across an elevational gradient, and test whether plasticity and selection align with genetic variation. We do so using two closely related, but ecologically distinct, sister species of Sicilian daisy (Senecio,Asteraceae) adapted to high and low elevations on Mount Etna. Using a paternal half-sibling breeding design, we generated and then reciprocally planted c.19,000 seeds of both species, across an elevational gradient spanning each species’ native elevation, and then quantified mortality and five leaf traits of emergent seedlings. We found that genetic variance in leaf traits changed more across elevations than between species. The high-elevation species at novel lower elevations showed changes in the distribution of genetic variance among the leaf traits, which reduced the amount of genetic variance in the directions of selection and the native phenotype. By contrast, the low-elevation species mainly showed changes in the amount of genetic variance at the novel high elevation, and genetic variance was concentrated in the direction of the native phenotype. For both species, leaf trait plasticity across elevations was in a direction of the multivariate phenotype that contained a moderate amount of genetic variance. Together, these data suggest that where plasticity is adaptive, selection on genetic variance for an initially plastic response could promote adaptation. However, large environmental effects on genetic variance are likely to reduce adaptive potential in novel environments.
The anterior Hox geneceh-13andelt-1/GATAactivate the posterior Hox genesnob-1andphp-3to specify posterior lineages in theC. elegansembryo
Authors: Murray John Isaac , Preston Elicia , Crawford Jeremy P. , Rumley Jonathan D. , Amom Prativa , Anderson Breana D. , Sivaramakrishnan Priya , Patel Shaili D. , Bennett Barrington Alexander , Lavon Teddy D. , Peng Felicia , Zacharias Amanda L.
Published: February 2021

Hox transcription factors play a conserved role in specifying positional identity during animal development, with posterior Hox genes typically repressing the expression of more anterior Hox genes. Here, we dissect the regulation of the posterior Hox genesnob-1andphp-3in the nematodeC. elegans. We show thatnob-1andphp-3are co-expressed in gastrulation-stage embryos in cells that previously expressed the anterior Hox geneceh-13. This expression is controlled by several partially redundant transcriptional enhancers. These enhancers requireceh-13for expression, providing a striking example of an anterior Hox gene positively regulating a posterior Hox gene. Several other regulators also act positively throughnob-1/php-3enhancers, includingelt-1/GATA,ceh-20/ceh-40/Pbx,unc-62/Meis,pop-1/TCF,ceh-36/Otxandunc-30/Pitx. We identified defects in both cell position and cell division patterns inceh-13andnob-1;php-3mutants, suggesting that these factors regulate lineage identity in addition to positional identity. Together, our results highlight the complexity and flexibility of Hox gene regulation and function and the ability of developmental transcription factors to regulate different targets in different stages of development.

Author Summary

Hox genes are critical for head-to-tail patterning during embryonic development in all animals. Here we examine the factors that are necessary to turn on two posterior Hox genes, nob-1andphp-3, in the nematode worm, C. elegans. We identified six new transcription factors and three enhancer regions of DNA that can activate expression ofnob-1/php-3. Unexpectedly, these activating transcription factors includedceh-13, an anterior Hox gene, andelt-1, a regulator of skin development that is briefly expressed in many cells that do not adopt skin fates, including the cells that expressnob-1. Furthermore, the cellular defects we observed inceh-13andnob- 1;php-3mutant embryos indicate that the early embryonic functions of these Hox genes help determine the identity of cells as well as their position within the embryo. Our findings identify new roles for Hox genes inC. elegansand emphasize the ability of transcription factors to contribute to the diversification of cell types and the adoption of specific cell types at different phases of embryonic development.
High-temperature deformation followed in situ by X-ray microtomography: a methodology to track features under large strain
Authors: Lhuissier Pierre , Bormann Therese , Pelloux Guillaume , Bataillon Xavier , Pelloux Franck , Josserond Charles , Gravier Pauline , Blandin Jean-Jacques , Boller Elodie , Salvo Luc
Published: February 2021

Metallic materials processing such as rolling, extrusion or forging often involves high-temperature deformation. Usually under such conditions the samples are characterized post mortem, under pseudo in situ conditions with interrupted tests, or in situ with a limited strain rate. A full in situ 3D characterization, directly during high-temperature deformation with a prescribed strain-rate scheme, requires a dedicated sample environment and a dedicated image-analysis workflow. A specific sample environment has been developed to enable highly controlled (temperature and strain rate) high-temperature deformation mechanical testing to be conducted while performing in situ tomography on a synchrotron beamline. A dedicated digital volume correlation algorithm is used to estimate the strain field and track pores while the material endures large deformations. The algorithm is particularly suitable for materials with few internal features when the deformation steps between two images are large. An example of an application is provided: a high-temperature compression test on a porous aluminium alloy with individual pore tracking with a specific strain-rate scheme representative of rolling conditions.
Tax Credits as an accounting technology of government: “showing my boys they have to work, because that is what happens”
Authors: Closs-Davies Sara C. , Merkl-Davies Doris M. , Bartels Koen P.R.
Published: February 2021

Purpose

The study explores the role of accounting technologies of government (ATGs) associated with UK Tax Credits and their impact on claimants' motivations, behaviour and identities. The aim of this study is to deepen empirical and conceptual understandings of how ATGs of tax authorities transform claimants into “entrepreneurs of the self”.

Design/methodology/approach

The authors approach Tax Credits (TC) as a case study to examine how ATGs articulate and operationalise neoliberal ideology through a complex network of inscription devices, expertise and locales. They adopt an ethnographic approach based on interviews, archival data and field notes to gain a deep understanding of citizens' lived experiences of ATGs when claiming Tax Credits.

Findings

The authors find that ATGs play a key role in transforming TC claimants into self-disciplined “citizen-subjects” whose decisions are informed by market logic. When claiming TC, citizens interact with ATGs and are transformed into “entrepreneurs of the self” who internalise neoliberal ideology and associated beliefs and assumptions of poverty, work and the welfare state. In this process of subjectification, ATGs (re)construct their identities from welfare recipients to “responsible” and “accountable” hardworking individuals and families. However, ATGs perversely disempower claimants who lack the required human capital for becoming responsible for their own welfare, and thus ultimately maintain socio-economic inequality.

Research limitations/implications

Participants were drawn from a relatively narrow geographic area.

Practical implications

The authors reveal how accounting as a technology of government (dis)empowers individuals vis-à-vis the state and spurs inequality dependent on personal circumstances and calculative skills.

Originality/value

The authors contribute to the accounting literature by showing how neoliberal ideology is articulated, operationalised and reinforced by dynamic and repetitive interactions with ATGs of the UK TC scheme. The study helps deepen the understanding of the processes through which socially and economically disadvantaged individuals are transformed into self-governing economic agents responsible for their own welfare.
Psychological impact of the COVID-19 pandemic on local and international students in Malaysian universities
Authors: Yassin Amr Abdullatif , Razak Norizan Abdul , Saeed Murad Abdu , Al-Maliki Mohammed Ali Abbod , Al-Habies Feras Ali
Published: February 2021

Purpose

This paper aims to investigate the psychological impact of the COVID-19 pandemic on university students in Malaysian universities as well as its effect on their learning.

Design/methodology/approach

The study employed a quantitative design, as the data were collected through a survey. The participants were 219 students, divided as follows: 102 local students and 117 international students in Malaysian universities.

Findings

The findings showed no significant difference in terms of the psychological impact of COVID-19 among students according to the variables, nationality (local and international), gender and level of study. The descriptive analysis showed that the outbreak of COVID-19 made the students anxious, worried and restless. Besides, the outbreak of COVID-19 made the students unable to focus on their study, feel anxious about studying, have less confidence on their leaning and commit more mistakes than normal days. The psychological stress made online learning during the isolation period less effective and less helpful for students, which made them more worried about their academic achievement and future study plans.

Originality/value

COVID-19 is a current issue, and the psychological effect of COVID-19 on local and international students and their learning has not been covered in previous literature.
Exploring how to deliver videoconference-mediated psychological therapy to adults with an intellectual disability during the coronavirus pandemic
Authors: Rawlings Gregg Harry , Gaskell Christopher , Rolling Keeley , Beail Nigel
Published: February 2021

Purpose

The novel coronavirus and associated restrictions have resulted in mental health services across the UK having to adapt how they deliver psychological assessments and interventions. The purpose of this paper is to explore the accessibility and prospective acceptability of providing telephone and videoconference-mediated psychological interventions in individuals with intellectual disabilities.

Design/methodology/approach

As part of a service evaluation, a mixed-methods questionnaire was developed and completed by clients who had been referred for psychological therapy at an adult intellectual disabilities’ community health service in the north of England. All clients were assessed using the Red/Amber/Green (RAG) system by a consultant clinical psychologist for risk and potential suitability for indirect service delivery given their ability and needs.

Findings

Overall, 22 clients were invited to take part, of which, only seven (32%) were accepting of telephone or videoconference-mediated psychological therapy. Most of the clients were unable to engage in video-conference therapy and therefore, only suitable for phone therapy. This paper presents the remaining findings and discusses the clinical implications and unique considerations for intellectual disability services drawing on the existing literature.

Originality/value

This is the first paper that the authors are aware of, examining videoconference-mediated psychological therapy in this population. It is hoped the data will be used to help inform practice or policy when using such therapeutic approaches in adults with an intellectual disability.