bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual variation and plasticity in the infant-directed communication of orang-utan mothers
Authors: Fröhlich Marlen , van Schaik Carel P. , van Noordwijk Maria A. , Knief Ulrich
Published: May 2022

Between-individual variation in behavioural expression, such as social responsiveness, has been shown to have important eco-evolutionary consequences. However, most comparative research on non-human primate communication has focused on species- or population-level variation, while among- and within-individual variation has been largely ignored or considered as noise. Here, we apply a behavioural reaction norm framework to repeated observations of mother–offspring interactions in wild and zoo-housed orang-utans (Pongo abelii, P. pygmaeus) to tease apart variation on the individual level from population-level and species-level differences. Our results showed that mothers not only differed in the composition of their infant-directed gestural repertoires, but also in communicative tactics, such as gestural redoings (i.e. persistence) and responsiveness to infants' requests. These differences remained after controlling for essential moderators, including species, setting, parity and infant age. Importantly, mothers differed in how they adjusted their behaviour across social contexts, making a strong case for investigating within-individual variation. Our findings highlight that partitioning behavioural variation into its within-individual, between-individual and environmental sources allows us to estimate the extent of plastic responses to the immediate environment in great ape communication.
Dispersal ability and its consequences for population genetic differentiation and diversification
Authors: Suárez Daniel , Arribas Paula , Jiménez-García Eduardo , Emerson Brent C.
Published: May 2022

Dispersal ability is known to influence geographical structuring of genetic variation within species, with a direct relationship between low vagility and population genetic structure, which can potentially give rise to allopatric speciation. However, our general understanding of the relationship between dispersal ability, population differentiation and lineage diversification is limited. To address this issue, we sampled mitochondrial DNA variation within lineages of beetles and spiders across the Canary Islands to explore the relationships between dispersal ability, differentiation within lineages and diversification. We found positive relationships between population genetic structure and diversification for both beetles and spiders. Comparisons between dispersive and non-dispersive lineages revealed significant differences for both lineage differentiation and diversification. For both taxa, non-dispersive lineages had stronger population genetic structure. Genus-level endemic species richness and proxies for diversification rate within genera were higher in non-dispersive taxa for both beetles and spiders. Comparisons of average and maximum node divergences within genera suggest that species turnover may be higher in non-dispersive genera. Our results reveal a model where dispersal limitation may shape the diversity of lineages across evolutionary timescales by positively influencing intraspecific and species diversity, moderated by higher extinction rates compared to more dispersive lineages.
Streptomyces barringtoniae sp. nov., isolated from rhizosphere of plant with antioxidative potential
Authors: Wai Khaing Zar , Luechapudiporn Rataya , Tedsree Nisachon , Phongsopitanun Wongsakorn , Malisorn Kingchan , Tanasupawat Somboon
Published: May 2022

A novel actinomycete strain, JA03T, belonging to the genus

Streptomyces

, was isolated from the rhizosphere of Barringtonia racemosa (L.) Spreng. It was characterized taxonomically using a polyphasic approach. It grew at 25–37 °C, at pH 5–10 and with 6 % (w/v) NaCl. It contained ll-diaminopimelic acid in the cell-wall peptidoglycan. Ribose and glucose were detected in its whole-cell hydrolysate. The predominant cellular fatty acids were iso-C16 : 0, anteiso-C15 : 0, C16 : 0, iso-C14 : 0 and iso-C15 : 0. Detected polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannosides, unidentified phospholipids and unidentified amino lipids. Based on the results of 16S rRNA gene sequence analyses, strain JA03T showed highest similarity to

Streptomyces filipinensis

NBRC 12860T (98.76 %),

Streptomyces fodineus

TW1S1T (98.69 %) and Streptomyces shenzhennensis 172115T (98.68 %). Strain JA03T has a genome size of 9 092 851 bp with DNA G+C content of 71.28 mol%. The average nucleotide identity (ANI)-blast and ANI-MUMmer values of strain JA03T and related type strains were 79.6–89.2 and 86.7–92.5 %, respectively, and the digital DNA–DNA hybridization values were 27.3–46.4 %. Ethyl acetate extract of JA03T exhibited total phenolic content (33.4±0.6 µg mg−1 gallic acid equivalent), ferric reducing power value (70.8±1.8 µg mg−1 ascorbic acid equivalent) and 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity (IC50=67.0±21.1 µg ml−1). Intracellular reactive oxygen species and NO production in RAW264.7 macrophage cells induced by H2O2 and lipopolysaccharide were inhibited with IC50 of 67.40 and 16.95 µg ml−1, respectively. Based on the taxonomic results, it has been concluded that strain JA03T represents a novel species of the genus

Streptomyces

for which the name Streptomyces barringtoniae sp. nov., is proposed. The type strain is JA03T (=LMG 32415T=TISTR 2999T).
Phenylobacterium glaciei sp. nov., isolated from Vestrebroggerbreen, a valley glacier in Svalbard, Arctic
Authors: Thomas Femi Anna , Sinha Rupesh Kumar , Hatha A. A. Mohamed , Krishnan K. P.
Published: May 2022

A Gram-stain-negative, rod-shaped bacterial strain designated as 20VBR1T was isolated from a valley glacier (Vestrebroggerbreen) snout ice sample from Ny-Ålesund, Svalbard, Arctic. The colonies were smooth, circular and light creamish on half-strength R2A agar and grew at 10–35 °C (optimum, 20 °C), at pH 6.5–8.0 (optimum, 7.0) and with 0–2.5 % (w/v) NaCl (optimum, 0.5 %). 16S rRNA gene sequence analysis revealed that strain 20VBR1T belonged to the genus

Phenylobacterium

and was most closely affiliated to

Phenylobacterium aquaticum

W2-3-4T (97.65 % similarity),

Phenylobacterium haematophilum

LMG 11050T (97.57 %) and

Phenylobacterium koreense

Slu-01T (96.91 %). 20VBR1T has a genome size of 4.24 Mb, comprising 4185 predicted genes with a DNA G+C content of 67.86 mol%. DNA–DNA hybridization experiments indicated that the DNA–DNA relatedness between strain 20VBR1T and

P. aquaticum

KACC 18306T was 41.95±4.36 %, well below the threshold (<70 %) to delineate bacterial species. Genome relatedness indexes revealed that the average nucleotide identity and digital DNA–DNA hybridization values between 20VBR1T and its closest phylogenomic relative,

P. aquaticum

KACC 18306T, were 78.97 and 22.10 %, respectively. The predominant isoprenoid quinone was ubiquinone (Q-10) and the major polar lipids were phosphatidylglycerol, one unknown phospholipid, one unknown glycolipid and four unidentified polar lipids. The major fatty acids (>10 %) of strain 20VBR1T were summed feature 8 (comprising C18 : 1
ω7c and/or C18 : 1
ω6c), summed feature 3 (comprising C16 : 1
ω6c and/or C16 : 1
ω7c) and C16 : 0. Based on the physiological, biochemical, chemotaxonomic, phylogenetic and phylogenomic analyses, isolate 20VBR1T is considered to represent a novel species of the genus

Phenylobacterium

, for which the name Phenylobacterium glaciei sp. nov. is proposed. The type strain is 20VBR1T (=JCM 33227 T=DSM 111428 T=MCC 4220 T).
ClearSpeechTogether: a rater blinded, single, controlled feasibility study of speech intervention for people with progressive ataxia
Authors: Lowit Anja , Cox Jessica , Loucas Melissa , Grassly Jennifer , Egan Aisling , van Brenk Frits , Hadjivassiliou Marios
Published: May 2022

Background

Progressive ataxias frequently lead to speech disorders and consequently impact on communication participation and psychosocial wellbeing. Whilst recent studies demonstrate the potential for improvements in these areas, these treatments generally require intensive input which can reduce acceptability of the approach.

A new model of care – ClearSpeechTogether – is proposed which maximises treatment intensity whilst minimising demands on clinician. This study aimed to establish feasibility and accessibility of this approach and at the same time determine the potential benefits and adverse effects on people with progressive ataxias.

Method

The study targeted people with progressive ataxia and mild-moderate speech and gross motor impairment. ClearSpeechTogether consisted of four individual sessions over two weeks followed by 20 patient-led group sessions over four weeks. All sessions were provided online. Quantitative and qualitative data were collected for evaluation.

Results

Nine participants completed treatment. Feasibility and acceptability were high and no adverse effects were reported. Statistical tests found significantly reduced vocal strain, improved intelligibility for reading, and increased participation and confidence. Participant interviews highlighted the value of group support, from psychosocial perspectives and in supporting speech strategy internalisation and generalisation.

Discussion

ClearSpeechTogether presented an effective intervention in a small group of people with progressive ataxia. It matched or exceeded the outcomes previously reported for intensive, individual therapy while minimising clinician time demands. Furthermore, its unique peer led group intervention design appeared effective in addressing intractable psychosocial issues. ClearSpeechTogether is potentially cost-effective, providing intensive delivery with few clinician sessions, thus maximising the input available from health care providers.
Rasch Validation of the Revised Body Awareness Rating Questionnaire (BARQ-R) in Adults with Musculoskeletal Pain, Adults with Spinal Cord Injury, and Community-Dwelling Adults in the US
Authors: Carpentier Sydney , Deng Wei , Blackwood Jena , Van de Winckel Ann
Published: May 2022

Background

To establish Rasch validation of the Revised Body Awareness Rating Questionnaire (BARQ-R) in adults with musculoskeletal pain, community-dwelling adults without pain, and adults with spinal cord injury (SCI) who have neuropathic pain.

Materials and Method

The BARQ-R has 12 items with scores ranging from 0 (completely disagree) to 3 (completely agree). Through Rasch analysis, we evaluated unidimensionality through item and person fit, targeting of the population, person separation reliability (PSR), local item dependence (LID), and principal components analysis of residuals (PCAR).

Results

The BARQ-R in adults with musculoskeletal pain (n=152; average age = 52.26±16.13 years) showed good targeting (person mean location: -0.36±0.88 logits), minimal floor effect (0.01%), and no ceiling effect (0.00%) and had good reliability (PSR=0.75). The BARQ-R in community-dwelling adults (n=471; average age = 49.63±17.57 years) had a person mean location of -0.62±1.09 logits, minimal floor (2.63%), and minimal ceiling effect (0.43%) after rescoring 2 items and deleting 3 items and had good reliability (PSR=0.74). The BARQ-R in adults with SCI-related neuropathic pain (n=44; average age = 55.45±13.47 years) showed good targeting after rescoring 7 items (person mean location: -0.33±0.71 logits), no floor effect (0.00%) or ceiling effect (0.00%) but had poor reliability (PSR=0.65).

Conclusions

The BARQ-R shows sufficient fit to be used in clinical settings for group decision-making for both adults with musculoskeletal pain and community-dwelling adults. However, in adults with SCI-related neuropathic pain, preliminary Rasch analysis of the BARQ-R showed low reliability and therefore the BARQ-R is not recommended for clinical use in that population. Validation in larger groups of adults with SCI as well as more diverse samples are needed.
Exploring biomarkers of processing speed and executive function: the role of the anterior thalamic radiations
Authors: Ferris Jennifer , Greeley Brian , Yeganeh Negin Motamed , Rinat Shie , Ramirez Joel , Black Sandra , Boyd Lara
Published: May 2022

Introduction

Processing speed and executive functioning are often impaired after stroke and in typical aging. However, there are no reliable neurological markers of these cognitive impairments. The trail making test (TMT) is a common index of processing speed and executive function. Here, we tested candidate MRI markers of TMT performance in a cohort of older adults and individuals with chronic stroke.

Methods

In 61 older adults and 32 individuals with chronic stroke, we indexed white matter structure with region-specific lesion load (WMH and stroke lesions) and diffusion tensor imaging (DTI) from four regions related to TMT performance: the anterior thalamic radiations (ATR), superior longitudinal fasciculus (SLF), forceps minor, and cholinergic pathways. Regression modelling was used to identify the marker(s) that best predicted TMT performance.

Results

DTI metrics of the ATR predicted processing speed in both the older adult (TMT A: β=-3.431, p<0.001) and chronic stroke (TMT A: β=11.282, p<0.001) groups. In the stroke group executive function was best predicted by a combination of ATR and forceps minor DTI metrics in the chronic stroke group (TMT B: adjustedR2=0.438, p<0.001); no significant predictors of executive function (TMT B) emerged in the older adult group. No imaging metrics related to set shifting (TMT B-A). For all TMT outcome measures with significant imaging predictors, regional DTI metrics predicted TMT performance above and beyond whole-brain stroke and WMH volumes and removing whole-brain lesion volumes improved model fits.

Conclusions

In this comprehensive assessment of candidate imaging markers, we demonstrate an association between ATR microstructure and processing speed and executive function performance. Regional DTI metrics provided better predictors of cognitive performance than whole-brain lesion volumes or regional lesion load, emphasizing the importance of lesion location in understanding cognition. We propose ATR DTI metrics as novel candidate imaging biomarker of post-stroke cognitive impairment.
Different conformations of EGF-induced receptor dimers involved in signaling and internalization
Authors: Haubrich Jordi , Zwier Jurriaan M. , Charrier-Savournin Fabienne , Prézeau Laurent , Pin Jean-Philippe
Published: May 2022

The structural basis of the activation of EGF receptors (EGFR) is still a matter of debate despite the importance of this target in cancer treatment. Whether agonists induce dimer formation or act on pre-formed dimers remain discussed. Here we provide direct evidence that EGFR activation results from EGF-induced dimer formation. This is well illustrated by i) a large increase in time resolved (TR)-FRET between snap-tagged EGFR subunits induced by agonists, ii) a similar effect of Erlotinib-related TK inhibitors despite the inactive state of the binding domain of the subunits, and iii) a similar TR-FRET efficacy in EGFR dimers stabilized by EGF or erlotinib with binding domains in active and inactive states, respectively. Surprisingly, TK inhibitors do not inhibit EGF-induced EGFR internalization despite their ability to fully block EGFR signaling. Only Erlotinib-related TK inhibitors promoting asymmetric dimers could slow down this process, while the lapatinib-related ones have almost no effect. These results reveal that the conformation of the intracellular TK dimer, rather than the known EGFR signaling is critical for EGFR internalization. These results also illustrate clear differences in the mode of action of TK inhibitors on the EGFR.
Compellingly high SARS-CoV-2 susceptibility of Golden Syrian hamsters suggests multiple zoonotic infections of pet hamsters during the COVID-19 pandemic
Authors: Blaurock Claudia , Breithaupt Angele , Weber Saskia , Wylezich Claudia , Keller Markus , Mohl Björn-Patrick , Görlich Dirk , Groschup Martin H. , Sadeghi Balal , Höper Dirk , Mettenleiter Thomas C. , Balkema-Buschmann Anne
Published: May 2022

Golden Syrian hamsters (Mesocricetus auratus) are used as a research model for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Millions of Golden Syrian hamsters are also kept as pets in close contact to humans. To determine the minimum infective dose (MID) for assessing the zoonotic transmission risk, and to define the optimal infection dose for experimental studies, we orotracheally inoculated hamsters with SARS-CoV-2 doses from 1*105 to 1*10−4 tissue culture infectious dose 50 (TCID50). Body weight and virus shedding were monitored daily. 1*10−3 TCID50 was defined as the MID, and this was still sufficient to induce virus shedding at levels up to 102.75 TCID50/ml, equaling the estimated MID for humans. Virological and histological data revealed 1*102 TCID50 as the optimal dose for experimental infections. This compellingly high susceptibility resulting in productive infections in Golden Syrian hamsters needs to be considered also as a source of SARS-CoV-2 infections in humans.
Spinal cord damage in Friedreich’s ataxia: Results from the ENIGMA-Ataxia
Authors: Rezende Thiago JR , Adanyeguh Isaac M , Arrigoni Filippo , Bender Benjamin , Cendes Fernando , Corben Louise A , Deistung Andreas , Delatycki Martin , Dogan Imis , Egan Gary F , Göricke Sophia L , Georgiou-Karistianis Nellie , Henry Pierre-Gilles , Hutter Diane , Jahanshad Neda , Joers James M , Lenglet Christophe , Lindig Tobias , Martinez Alberto RM , Martinuzzi Andrea , Paparella Gabriella , Peruzzo Denis , Reetz Kathrin , Romanzetti Sandro , Schöls Ludger , Schulz Jörg B , Synofzik Matthis , Thomopoulos Sophia I , Thompson Paul M , Timmann Dagmar , Harding Ian H , França Marcondes C.
Published: May 2022

Objective

Spinal cord damage is a hallmark of Friedreich ataxia (FRDA), but its progression and clinical correlates remain unclear. Here we performed a characterization of cervical spinal cord structural abnormalities in a large multisite FRDA cohort.

Methods

We performed a cross-sectional analysis of cervical spinal cord (C1 to C4) cross-sectional area (CSA) and eccentricity using MRI data from eight sites within the ENIGMA-Ataxia initiative, including 256 individuals with FRDA and 223 age- and sex-matched controls. Correlations and subgroup analyses within the FRDA cohort were undertaken based on disease duration, ataxia severity, and onset age.

Results

Individuals with FRDA, relative to controls, had significantly reduced CSA at all examined levels, with large effect sizes (d>2.1) and significant correlations with disease severity (r<-0.4). Similarly, we found significantly increased eccentricity (d>1.2), but without significant clinical correlations. Subgroup analyses showed that CSA and eccentricity are abnormal at all disease stages. However, while CSA appears to decrease progressively, eccentricity remains stable over time.

Interpretation

Previous research has shown that increased eccentricity reflects dorsal column (DC) damage, while decreased CSA reflects either DC or corticospinal tract (CST) damage or both. Hence, our data support the hypothesis that damage to DC and CST follow distinct courses in FRDA: developmental abnormalities likely define the DC, whereas CST alterations may be both developmental and degenerative. These results provide new insights about FRDA pathogenesis and indicate that CSA of the cervical spinal cord should be investigated further as a potential biomarker of disease progression.
Weakly supervised and transfer learning for adenocarcinoma classification in transurethral resection of the prostate whole slide images
Authors: Tsuneki Masayuki , Abe Makoto , Kanavati Fahdi
Published: May 2022

The transurethral resection of the prostate (TUR-P) is generally considered an option for benign prostatic diseases especially nodular hyperplasia patients who have moderate to severe urinary problems that have not responded to medication. Importantly, incidental prostate cancer are diagnosed at the time of TUR-P for benign prostatic disease. Since diagnosing a large number of cases containing TUR-P specimens which are characterized by a very large volume of tissue fragments by pathologists using a conventional microscope is time-consuming and limited in terms of human resources. Thus, it is necessary to develop new techniques which can rapidly and accurately screen large numbers of TUR-P specimens. Computational pathology applications which can assist pathologists in detecting prostate adenocarcinoma from TUR-P whole slide images (WSIs) would be of great benefit for routine histopathological workflow. In this study, we trained deep learning models to classify TUR-P WSIs into prostate adenocarcinoma and benign (non-neoplastic) lesions using transfer and weakly supervised learning. We evaluated the models on TUR-P, needle biopsy, and The Cancer Genome Atlas (TCGA) public dataset test sets, achieving an ROC-AUC up to 0.984 in TUR-P test sets for adenocarcinoma. The results demonstrate the high promising potential of deployment in a practical TUR-P histopathological diagnostic workflow system.
Geospatial distribution of Hepatitis B prevention services in Wakiso District, Central Uganda
Authors: Ssekamatte Tonny , Isunju John Bosco , Nalugya Aisha , Wafula Solomon Tsebeni , Nuwematsiko Rebecca , Doreen Nakalembe , Kansiime Winnifred K. , Naume Muyanga , Nakiggala Joana , Bukenya Justine N. , Mugambe Richard K.
Published: May 2022

Introduction

Despite global and national efforts in place for the prevention and control of Hepatitis B, there remains a gap in access to hepatitis B prevention services such as testing and vaccination. Nonetheless, there is limited evidence of the geospatial distribution of Hepatitis B services. This study established the geospatial distribution of HBV vaccination services in Wakiso District, Uganda.

Materials and methods

A cross-sectional quantitative descriptive study was conducted among 55 healthcare facilities including 6 hospitals, and 49 primary care facilities in Wakiso district. Data were collected using the KoboCollect application. Quantitative data were analysed using STATA 14.0. A chi-square test was performed to establish the relationship between healthcare facility characteristics and the availability of hepatitis B services. ArcGIS (version 10.1) was used for analysis of geospatial data.

Results

The hepatitis B vaccine was available in only 27.3 % (15) of the facilities, and 60% (33) had testing services. Receipt of the hepatitis B vaccine doses in the last 12 months was associated with the level of healthcare facility (p=≤0.001) and location (p=0.030). Availability of the Hepatitis B vaccines at the time of the survey was associated with the level of healthcare facility (p=0.002) and location (p=0.010). Availability of hepatitis B testing services was associated with level of healthcare facility (p=0.031), ownership (p≤0.001) and location (p=0.010). Healthcare facilities offering vaccination and testing services were mostly in urban healthcare facilities, and close to Kampala, Uganda’s capital.

Conclusion

Hepatitis B services were sub-optimal across all healthcare facility levels, locations, and ownership. The majority of the hepatitis B prevention services were provided in urban settings, close to major towns, municipalities, and the city. This calls a extension of hepatitis B prevention services to rural, public and PNFP healthcare facilities.
Association of Sedentary and Physical Activity Behaviors with Body Composition: a Genome-Wide Association and Mendelian Randomization Study
Authors: Ramadan Ferris , Bea Jennifer W. , Garcia David O. , Ellingson Katherine , Canales Robert A. , Raichlen David A. , Klimentidis Yann C.
Published: May 2022

Objectives

Studies suggest that body composition can be independently improved through physical activity (PA). We performed a Mendelian randomization (MR) study to test the incremental benefits of sedentary behavior and various physical activity (PA) exposures on body composition outcomes as assessed by anthropometric indices, lean body mass (LBM) (kg), body fat (%), and visceral adipose tissue (VAT) (kg).

Methods

Genetic instruments were identified for both self-reported and accelerometer-measured sedentary behavior and PA. Outcomes included anthropometric and dual-energy X-ray absorptiometry measures of adiposity, extracted from the UK Biobank and the largest available consortia. Multivariable MR (MVMR) included educational attainment as a covariate to address potential confounding. Sensitivity analyses were evaluated for weak instrument bias and pleiotropic effects.

Results

We did not identify consistent associations between genetically-predicted self-reported and accelerometer-measured sedentary behavior and body composition outcomes. All analyses for self-reported moderate PA were null for body composition outcomes. Genetically-predicted PA at higher intensities was protective against VAT in MR and MVMR analyses of both accelerometer-measured vigorous PA (MVMR β = -0.15, 95% Confidence Interval (CI): -0.24, -0.07, p<0.001) and self-reported participation in strenuous sports or other exercises (MVMR β = -0.27, 95%CI: -0.52, -0.01, p=0.034) was robust across several sensitivity analyses.

Conclusions

We did not identify evidence of a causal relationship between genetically-predicted PA and body composition, with the exception of a putatively protective effect of higher-intensity PA on VAT. Protective effects of PA against VAT may support prior evidence of biological pathways through which PA decreases risk of downstream cardiometabolic diseases.
Heterozygous and homozygous variants in STX1A cause a neurodevelopmental disorder with or without epilepsy
Authors: Luppe Johannes , Sticht Heinrich , Lecoquierre François , Goldenberg Alice , Gorman Kathleen , Molloy Ben , Agolini Emanuele , Novelli Antonio , Briuglia Silvana , Kuismin Outi , Marcelis Carlo , Vitobello Antonio , Denommé-Pichon Anne-Sophie , Julia Sophie , Lemke Johannes R. , Jamra Rami Abou , Platzer Konrad
Published: May 2022

The neuronal SNARE complex drive synaptic vesicle exocytosis. Therefore, one of its core proteins syntaxin 1A (STX1A) has long been suspected to play a role in neurodevelopmental disorders. We assembled eight individuals harboring rare variants in STX1A who present with a spectrum of intellectual, autism and epilepsy. Causative variants comprise a homozygous splice variant, three de novo missense variants and two inframe deletions of a single amino acid. We observed a phenotype mainly driven by epilepsy in the individuals with missense variants in contrast to intellectual disability and autistic behavior in individuals with single amino acid deletions and the splicing variant. In silico modeling of missense variants and single amino acid deletions show different impaired protein-protein interactions. We hypothesize the two phenotypic courses of affected individuals to be dependent on two different pathogenic mechanisms: (1) a weakened inhibitory STX1A-STXBP1 interaction due to missense variants results in an STX1A-related developmental epileptic encephalopathy and (2) a hampered SNARE complex formation due to inframe deletions causes an STX1A-related intellectual disability and autism phenotype.
Genetic diversity and spatiotemporal distribution of SARS-CoV-2 alpha variant in India
Authors: Parasar Jahnavi , Pandey Rudra Kumar , Patel Yashvant , Singh Prajjval Pratap , Srivastava Anshika , Mishra Rahul , Kumar Bhupendra , Rai Niraj , Mishra Vijay Nath , Shrivastava Pankaj , Suravajhala Prashanth , Chaubey Gyaneshwer
Published: May 2022

After the spill to humans, in the timeline of SARS-CoV-2, several positively selected variants have emerged. A phylogeographic study on these variants can reveal their spatial and temporal distribution. In December 2020, the alpha variant of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which has been designated as a variant of concern (VOC) by WHO, was discovered in the southeastern United Kingdom (UK). Slowly, it expanded across India, with a considerable number of cases, particularly in North India. The study focuses on determining the prevalence and expansion of the alpha variants in various parts of India. The genetic diversity estimation helped us understand various evolutionary forces that have shaped the spatial distribution of this variant during the peak. Overall, our study paves the way to understand the evolution and expansion of a virus variant.
Physiotherapists Use Different Motivational Strategies Tailored to an Individual’s Condition: A Qualitative Study
Authors: Oyake Kazuaki , Sue Keita , Sumiya Motofumi , Tanaka Satoshi
Published: May 2022

Question

How do physiotherapists use different motivational strategies for individuals in stroke rehabilitation?

Design

A qualitative study using in-depth semi-structured online interviews.

Participants

A criterion sample of 15 physiotherapists who have worked in rehabilitation for over 10 years and have an interest in an individual’s motivation.

Intervention

Not applicable.

Outcome measures

Physiotherapists’ perspectives and experiences regarding motivational strategies used depending on the individual’s condition.

Results

A total of nine themes emerged from the data upon thematic analysis and inductive coding. The participants used different strategies to encourage individuals’ active participation in physiotherapy depending on their (1) mental health problems, (2) physical difficulties, (3) level of cognitive function, (4) personality, (5) activities and participation, (6) age, (7) human environment, and (8) type of rehabilitation service where the individual undergoes treatment. For example, in cases where an individual lost self-confidence, participants offered practice tasks that the individual could achieve with little effort to make them experience success. Conversely, for individuals with overconfidence, participants would provide them with a relatively difficult practice task to help them realize the necessity of practice through the experience of failure. The interviews also revealed (9) motivational strategies used regardless of the individual’s condition. For instance, patient-centred communication was used to build a rapport with individuals, irrespective of their condition.

Conclusion

This qualitative study is the first to demonstrate motivational strategies that physiotherapists use based on the individual’s condition. Our findings provide a deeper understanding of the selection of motivational strategies in stroke rehabilitation.
‘Ripple effects’ of urban environmental characteristics on cognitive performances in Eurasian red squirrels
Authors: Chow Pizza Ka Yee , Uchida Kenta , Koizumi Itsuro
Published: May 2022

Urban areas are expanding exponentially, leading more wildlife species to reside and settle in this environment. Urban environmental characteristics, such as human disturbance or green coverage, have been shown to affect some cognitive abilities such as innovative problem-solving performance of wildlife species. However, an untested hypothesis is that due to the shared underlying cognitive mechanisms, these affected performances may induce a ‘ripple’ effect, and continue to affect other related cognitive processes (the ripple effect hypothesis).

We tested this hypothesis by targeting two cognitive abilities, generalisation and memory, that overlap the cognitive mechanisms (learning and memory) of the original problem solving task in urban Eurasian red squirrels. These squirrels reside in 11 urban areas where they had previously repeatedly solved the original task (the innovators), and that their solving performance in the original task was affected by the selected urban environmental characteristics. We presented two established food-extraction tasks to the innovators to measure their performance in applying the learned successful solutions when solving a similar but novel problem (i.e., generalisation process) and recalling the learned solution of the original problem when solving the same task after an extended period of time (i.e., memory).

Our results provide more detailed information to refine the hypothesis; the initial effects of urban environmental characteristics on the performance of the original task affect performance at individual level but not at population level. These affected performance includes individuals’ generalisation solving latency across successes as well as their first solving latency in the memory task.

Urban environmental characteristics affect solving performance at both population and individual levels. Some environmental characteristics such as direct and indirect human disturbance affect the success of solving the generalisation task and the memory task at site level whereas other environmental characteristics such as green coverage affect the individuals’ solving latency in both tasks.

Overall, our results support the ripple effect hypothesis, indicating that urban environmental characteristics have a more global impact on shaping cognitive performance than previously has shown, and thus provide a better understanding of the mechanism that supports wildlife in adapting to urban environments.
Hybridization In The Late Pleistocene: Merging Morphological and Genetic Evidence
Authors: Harvati K. , Ackermann R.R.
Published: May 2022

This is an exciting time for our understanding of the origin of our species. Previous scientific consensus saw human evolution as defined by adaptive differences (behavioural and/or biological) and the emergence ofHomo sapiensas the ultimate replacement of non-modern groups by a modern, adaptively more competitive one. However, recent research has shown that the process underlying our origins was considerably more complex. While archaeological and fossil evidence suggests that behavioural complexity may not be confined to the modern human lineage, recent paleogenomic work shows that gene flow between distinct lineages (e.g. Neanderthals, Denisovans, earlyH. sapiens) occurred repeatedly in the Late Pleistocene, likely contributing elements to our genetic make-up that might have been crucial to our success as a diverse, adaptable species. Following these advances, the prevailing human origins model has shifted from one of near-complete replacement to a more nuanced view of partial replacement with considerable reticulation. Here we provide a brief introduction to the current genetic evidence for hybridization among hominins, its prevalence in, and effects on, comparative mammal groups, and especially how it manifests in the skull. We then explore the degree to which cranial variation seen in the fossil record of Late Pleistocene hominins from Western Eurasia corresponds with our current genetic and comparative data. We are especially interested in understanding the degree to which skeletal data can reflect admixture. Our findings indicate some correspondence between these different lines of evidence, flag individual fossils as possibly admixed, and suggest that different cranial regions may preserve hybridisation signals differentially. We urge further studies of the phenotype in order to expand our ability to detect the ways in which migration, interaction and genetic exchange have shaped the human past, beyond what is currently visible with the lens of ancient DNA.
The nanoCUT&RUN technique visualizes telomeric chromatin in Drosophila
Authors: Chen Tao , Wei Xiaolu , Courret Cécile , Cui Min , Cheng Lin , Wu Jing , Ahmad Kami , Larracuente Amanda M. , Rong Yikang S.
Published: May 2022

Advances in genomic technology led to a more focused pattern for the distribution of chromosomal proteins and a better understanding of their functions. The recent development of the CUT&RUN technique marks one of the important such advances. Here we develop a modified CUT&RUN technique that we termed nanoCUT&RUN, in which a high affinity nanobody to GFP is used to bring micrococcal nuclease to the binding sites of GFP-tagged chromatin proteins. Subsequent activation of the nuclease cleaves the chromatin, and sequencing of released DNA identifies binding sites. We show that nanoCUT&RUN efficiently produces high quality data for the TRL transcription factor in Drosophila embryos, and distinguishes binding sites specific between two TRL isoforms. We further show that nanoCUT&RUN dissects the distributions of the HipHop and HOAP telomere capping proteins, and uncovers unexpected binding of telomeric proteins at centromeres. nanoCUT&RUN can be readily applied to any system in which a chromatin protein of interest, or its isoforms, carries the GFP tag.
Myeloid-Derived Suppressor Cells are relevant factors to predict the severity of multiple sclerosis
Authors: Ortega María Cristina , Lebrón-Galán Rafael , Machín-Díaz Isabel , Naughton Michelle , Pérez-Molina Inmaculada , García-Arocha Jennifer , García-Domínguez Jose Manuel , Goicoechea-Briceño Haydee , Vila-del Sol Virginia , Quintanero-Casero Víctor , García-Montero Rosa , Galán Victoria , Camacho-Toledano Celia , Martínez-Ginés María Luisa , Fitzgerald Denise C. , Clemente Diego
Published: May 2022

Multiple Sclerosis (MS) is a highly heterogeneous demyelinating disease of the central nervous system (CNS) that needs for reliable biomarkers to foresee disease severity. Previous retrospective investigations in the MS model, experimental autoimmune encephalomyelitis (EAE), highlighted the important relationship between monocytic-myeloid-derived suppressor cells (M-MDSCs) and the experimented severity of the clinical course. In this work, we show for the first time cells resembling M-MDSCs associated to MS lesions, whose abundance was related to milder MS clinical courses. Moreover, Ly-6Chi cells (which are indistinguishable from circulating M-MDSCs in mice) are useful biomarkers to predict a milder severity of the EAE disease course and a lesser tissue damage extent. Finally, the abundance of M-MDSCs in blood from untreated MS patients at their first relapse was inversely correlated with EDSS at baseline and relapse recovery one-year later. In summary, our data point to M-MDSC load as a promising biomarker of patient’s clinical course severity.

Teaser

The abundance of myeloid-derived suppressor cells is related to a milder clinical course in multiple sclerosis patients.
Vision-dependent and -independent molecular maturation of mouse retinal ganglion cells
Authors: Whitney Irene E. , Butrus Salwan , Dyer Michael A. , Rieke Fred , Sanes Joshua R. , Shekhar Karthik
Published: May 2022

The development and connectivity of retinal ganglion cells (RGCs), the retina’s sole output neurons, are patterned by activity-independent transcriptional programs and activity-dependent remodeling. To inventory the molecular correlates of these influences, we applied high-throughput single-cell RNA sequencing (scRNA-seq) to mouse RGCs at six embryonic and postnatal ages. We identified temporally regulated modules of genes that correlate with, and likely regulate, multiple phases of RGC development, ranging from differentiation and axon guidance to synaptic recognition and refinement. Some of these genes are expressed broadly while others, including key transcription factors and recognition molecules, are selectively expressed by one or a few of the 45 transcriptomically distinct types defined previously in adult mice. Next, we used these results as a foundation to analyze the transcriptomes of RGCs in mice lacking visual experience due to dark rearing from birth or to mutations that ablate either bipolar or photoreceptor cells. 98.5% of visually deprived (VD) RGCs could be unequivocally assigned to a single RGC type based on their transcriptional profiles, demonstrating that visual activity is dispensable for acquisition and maintenance of RGC type identity. However, visual deprivation significantly reduced the transcriptomic distinctions among RGC types, implying that activity is required for complete RGC maturation or maintenance. Consistent with this notion, transcriptomic alternations in VD RGCs significantly overlapped with gene modules found in developing RGCs. Our results provide a resource for mechanistic analyses of RGC differentiation and maturation, and for investigating the role of activity in these processes.
Endogenous production of hyaluronan, PRG4, and cytokines is sensitive to cyclic loading in synoviocytes
Authors: Pendyala Meghana , Woods Paige S , Brubaker Douglas K , Blaber Elizabeth A , Schmidt Tannin A , Chan Deva D
Published: May 2022

Synovial fluid is composed of hyaluronan and proteoglycan-4 (PRG4 or lubricin), which work synergistically to maintain joint lubrication. In diseases like osteoarthritis, hyaluronan and PRG4 concentrations can be altered, resulting in lowered synovial fluid viscosity, and pro-inflammatory cytokine concentrations within the synovial fluid increase. Synovial fibroblasts within the synovium are responsible for contributing to synovial fluid and can be targeted to improve endogenous production of hyaluronan and PRG4 and to alter the cytokine profile. We cyclically loaded SW982 synoviocytes to 0%, 5%, 10%, or 20% strain for three hours at 1 Hz. To assess the impact of substrate stiffness, we compared the 0% strain group to cells grown on tissue culture plastic. We measured the expression of hyaluronan turnover genes, hyaluronan localization within the cell layer, hyaluronan concentration, PRG4 concentration, and the cytokine profile within the media. Our results show that the addition of cyclic loading increased HAS3 expression, but not in a magnitude-dependent response. Hyaluronidase expression was impacted by strain magnitude, which is exemplified by the decrease in hyaluronan concentration due to cyclic loading. We also show that PRG4 concentration is increased at 5% strain, while higher strain magnitude decreases overall PRG4 concentration. Finally, 10% and 20% strain show a distinct, more pro-inflammatory cytokine profile when compared to the unloaded group. Multivariate analysis showed distinct separation between certain strain groups in being able to predict strain group, hyaluronan concentration, and PRG4 concentration from gene expression or cytokine concentration data, highlighting the complexity of the system. Overall, this study shows that cyclic loading can be used tool to modulate the endogenous production of hyaluronan, PRG4, and cytokines from synovial fibroblasts.
Microbiota-induced active translocation of peptidoglycan across the intestinal barrier dictates its within-host dissemination
Authors: Wheeler Richard , Bastos Paulo A. D. , Disson Olivier , Rifflet Aline , Spielbauer Julia , Lecuit Marc , Boneca Ivo Gomperts
Published: May 2022

Peptidoglycan, the major structural polymer forming the cell wall of bacteria, is an important mediator of physiological and behavioral effects in mammalian hosts. These effects are frequently linked to its translocation from the intestinal lumen to host tissues. However, the modality and regulation of this translocation across the gut barrier has not been precisely addressed. In this study, we characterized the absorption of peptidoglycan across the intestine and its systemic dissemination. We report that peptidoglycan has a distinct tropism for host organs when absorbed via the gut, most notably by favoring access to the brain. We demonstrate that intestinal translocation of peptidoglycan occurs through a microbiota-induced active process. This process is regulated by the parasympathetic pathway via the muscarinic acetylcholine receptors. Together, this study reveals fundamental parameters concerning the uptake of a major microbiota molecular signal from the steady-state gut.
Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data
Authors: Li Shuang , Schmid Katharina T. , de Vries Dylan , Korshevniuk Maryna , Oelen Roy , van Blokland Irene ,   BIOS Consortium,   sc-eQTLgen Consortium, Groot Hilde E. , Swertz Morris , van der Harst Pim , Westra Harm-Jan , van der Wijst Monique , Heinig Matthias , Franke Lude
Published: May 2022

Background

Expression quantitative trait loci (eQTL) studies have shown how genetic variants affect downstream gene expression. To identify the upstream regulatory processes, single-cell data can be used. Single-cell data also offers the unique opportunity to reconstruct personalized co-expression networks—by exploiting the large number of cells per individual, we can identify SNPs that alter co-expression patterns (co-expression QTLs, co-eQTLs) using a limited number of individuals.

Results

To tackle the large multiple testing burden associated with a genome-wide analysis (i.e. the need to assess all combinations of SNPs and gene pairs), we conducted a co-eQTL meta-analysis across four scRNA-seq peripheral blood mononuclear cell datasets from three studies (reflecting 173 unique participants and 1 million cells) using a novel filtering strategy followed by a permutation-based approach. Before analysis, we evaluated the co-expression patterns to be used for co-eQTL identification using different external resources. The subsequent analysis identified a robust set of cell-type-specific co-eQTLs for 72 independent SNPs that affect 946 gene pairs, which we then replicated in a large bulk cohort. These co-eQTLs provide novel insights into how disease-associated variants alter regulatory networks. For instance, one co-eQTL SNP, rs1131017, that is associated with several autoimmune diseases affects the co-expression of RPS26 with other ribosomal genes. Interestingly, specifically in T cells, the SNP additionally affects co-expression of RPS26 and a group of genes associated with T cell-activation and autoimmune disease. Among these genes, we identified enrichment for targets of five T-cell-activation-related transcriptional factors whose binding sites harbor rs1131017. This reveals a previously overlooked process and pinpoints potential regulators that could explain the association of rs1131017 with autoimmune diseases.

Conclusion

Our co-eQTL results highlight the importance of studying gene regulation at the context-specific level to understand the biological implications of genetic variation. With the expected growth of sc-eQTL datasets, our strategy—combined with our technical guidelines—will soon identify many more co-eQTLs, further helping to elucidate unknown disease mechanisms.
A Quantum Dot Biomimetic for SARS-CoV-2 to Interrogate Dysregulation of the Neurovascular Unit Relevant to Brain Inflammation
Authors: Chiang Wesley , Stout Angela , Yanchik-Slade Francine , Li Herman , Nilsson Bradley , Gelbard Harris , Krauss Todd
Published: May 2022

Despite limited evidence for competent infection and viral replication of SARS-CoV-2 in the central nervous system (CNS), neurologic dysfunction is a common post-acute medical condition reported in “recovered” COVID-19 patients. To identify a potential noninfectious route for SARS-CoV-2-mediated neurological damage, we constructed colloidal nanocrystal quantum dots linked to micelles decorated with spike protein (COVID-QDs) as a biomimetic to interrogate how blood-brain barrier (BBB) dysregulation may subsequently induce neuroinflammation in the absence of infection. In transwell co-culture of endothelial bEnd.3 monolayers and primary neuroglia, we exposed only the bEnd.3 monolayers to COVID-QDs and examined by fluorescence microscopy whether such treatment led to (i) increased inflammation and leakage across the bEnd.3 monolayers, (ii) permeability of the COVID-QDs across the monolayers, and (iii) induction of neuroinflammation in neuroglial cultures. The results of our study provide evidence of neuroinflammatory hallmarks in cultured neurons and astrocytes without direct exposure to SARS-CoV-2-like nanoparticles. Additionally, we found that pre-treatment of our co-cultures with a small-molecule, broad-spectrum inhibitor of mixed lineage and leucine rich repeat kinases led to reversal of the observed dysregulation in endothelial monolayers and resulted in neuroglial protection. The results reported here may serve to guide future studies into the potential mechanisms by which SARS-CoV-2 mediates neurologic dysfunction.