bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-opening hairdressing salons, barber shops and gyms following COVID-19 lockdown: reducing risks from Legionella species through successful domestic steam disinfection of showerheads
Authors: Millar Beverley C. , Ferris Jonalyn , Murphy Alan , Reid Norman , Moore John E.
Published: May 2021

Given the importance of disinfecting showerheads from

Legionella

species and the lack of instructions as to how to successfully achieve this, the aim of this study was to examine the ability of domestic steam disinfection to successfully disinfect showerheads from

Legionella

species. Steam disinfection of

Legionella pneumophila

[n=3;

L. pneumophila

serogroup 2–15 (wildtype environmental water isolate);

L. pneumophila

serogroup 1 NCTC11192 (reference strain);

L. pneumophila

serogroup 1 (wildtype environmental water isolate)],

L. erythra

(wildtype environmental water isolate) and

L. bozemanii

CRM11368M (reference strain) were examined in this study. Steam disinfection employing a baby bottle steam disinfector device eradicated all

Legionella

organisms tested. Steam disinfection, when performed properly under the manufacturer’s instructions, offers a relatively inexpensive, simple, versatile and widely available technology for the elimination of

Legionella

species from contaminated showerheads. We therefore advocate the employment of such devices to regularly disinfect showerheads and shower tubing in hairdressing salons, barber shops and gyms, as a critical control in the elimination of these organisms from these sources, thereby enhancing customer/client/staff safety.
Changes in English NHS outpatient activity during the early Covid-19 period
Authors: Morris Jessica , Georghiou Theo , Appleby John
Published: May 2021

Objective

To describe changes in NHS outpatient activity connected to the Covid-19 pandemic

Design

Nationwide population-based retrospective study

Setting

England, UK, 31 December 2018 to 25 October 2020

Data source

Outpatient Hospital Episode Statistics data

Results

Between early March and late October 2020, there was a total reduction of 16.6 million outpatient attendances compared to the same period in 2019, equivalent to a 27% decline. The largest weekly drop of 48% relative to 2019 occurred the week beginning 30 March. Activity recovered more slowly than it fell, and by the end of the study period remained 16% lower than the equivalent week in 2019. Changes in patterns of attendances were broadly similar across most patient characteristic groups. There was a substantial increase in the proportion of attendances taking place remotely, peaking at more than one in three during April and May 2020. Differences were observed in trends of remote consultations between age and sex categories, ethnic groups, and proxy deprivation levels. There was also substantial variation in overall activity and use of remote consultations by clinical specialty.

Conclusions

The large increase in remote outpatient consultations during the early Covid-19 period, variations in remote care use by specialty as well as proxy deprivation and ethnic groups all suggest a need to evaluate the impact of these changes particularly in light of national policy to encourage greater use of remote consultations.

SUMMARY BOX

What is already known on this topic

Numbers of outpatient attendances in England have increased substantially over recent years.

Historically, the vast majority of attendances have been face-to-face, with remote consultations accounting for ∼4% of all attendances.

The emergence of the Covid-19 pandemic in 2020 had a large impact on outpatient services in English hospitals, and on health services more generally in England and around the world.

What this study adds

There were significant differences by clinical specialty in changes to patterns of attendances and remote consultations.

Changes in the volume of outpatient attendances as a result of responses to the pandemic were broadly similar across patient groups.

However, there were marked differences across patient groups in trends in remote consultations.
SARS-CoV-2 seroprevalence and gender-related haematological features in asymptomatic blood donors
Authors: Martín M Carmen , González M Isabel , Holgado Nuria , Jimenez Ana I , Ortega Nuria , Page Isabel , Parrado Alba , Pérez María , Blanco-Peris Lydia
Published: May 2021

Background and objectives

COVID-19 can either cause death or go unnoticed but antibodies will remain protecting us of SARS-CoV-2 reinfection for an uncertain time and to an uncertain extent. Our aim was to describe seroprevalence evolution from summer 2019 to autumn 2020 in Spain and to describe its relationship with age, blood group and haematological parameters.

Materials and methods

Sera and plasma from historical donation archives excluding convalescent were randomized and a total of 12,313 donations tested by a Chemiluminiscent analysis for anti SARS-CoV-2 N protein total immunoglobulins. Blood donors were 60.9% males, average age 46+/-13. Sex, age, blood group, blood cell counts and percentages and immunoglobulin concentrations were extracted from electronic recordings.

Results

A seroprevalence of 6.7% in blood donors was found by the end of the first wave. No differences by sex, age or blood group were found regarding antibodies. Leukocyte count (p=0.026), haematocrit (p<0.001) and haemoglobin (p<0.001) were lower in positive donations than in negative ones. Sex differences were present in neutrophils, leukocytes, haemoglobin and haematocrit as related to SARS-CoV-2 antibodies.

Conclusions

Seroprevalence due to asymptomatic cases would resemble that of global population. Sex and age would not affect COVID-19 susceptibility but its severity. Gender differences related to COVID-19 in leukocytes, haemoglobin and haematocrit would be present in asymptomatic individuals. Further studies are needed to confirm these gender differences as they can help better understand the immune response to COVID-19, its pathogenesis and prognosis.
Examining the Factor Structure of the DSM-5 Level 1 Cross-Cutting Symptom Measure
Authors: Gibbons Alison , Farmer Cristan , Shaw Jacob S , Chung Joyce Y
Published: May 2021

Objectives

The DSM-5 Level 1 Cross-Cutting Symptom Measure (DSM-XC) is a transdiagnostic mental health symptom measure that has shown promise in informing clinical diagnostic evaluations and as a screening tool for research. However, few studies have assessed the latent dimensionality of the DSM-XC. We examined the factor structure of the DSM-XC in a large convenience sample of participants with varying degrees of psychological health.

Methods

Participants (n=3533) enrolled in a protocol conducted at the National Institute of Mental Health (NCT04339790). We used a factor analytic framework to evaluate an existing two-factor solution (Lace & Merz, 2020) and two additional candidate solutions.

Results

The Lace and Merz solution had acceptable fit. Exploratory factor analysis yielded two candidate solutions: a six-factor (characterized as mood, worry, activation, somatic, thoughts, and substance use) and a bifactor (general factor of non-specific psychopathology, residual factors characterized as internalizing and thought disorder), which both had good fit and full measurement invariance across age, sex, and enrollment date.

Conclusions

Our findings confirm that the DSM-XC may be conceptualized as a multidimensional instrument and provide a scoring solution for researchers who wish to measure distinct constructs. Future research on the psychometric profile of the DSM-XC is needed, focused on the validity of these candidate solutions and their performance across research populations and settings.
Reduced Pediatric Urgent Asthma Utilization and Exacerbations During the COVID-19 Pandemic
Authors: Hurst Jillian H. , Zhao Congwen , Fitzpatrick Nicholas S. , Goldstein Benjamin A. , Lang Jason E.
Published: May 2021

Background and Objectives

The COVID-19 pandemic has had a profound impact on healthcare access and utilization, which could have important implications for children with chronic diseases, including asthma. We sought to evaluate changes in healthcare utilization and outcomes in children with asthma during the COVID-19 pandemic.

Methods

We used electronic health records data to evaluate healthcare use and asthma outcomes in 3,959 children and adolescents, 5-17 years of age, with a prior diagnosis of asthma who had a history of well child visits and encounters within the healthcare system. We assessed all-cause healthcare encounters and asthma exacerbations in the 12-months preceding the start of the COVID-19 pandemic (March 1, 2019 – February 29, 2020) and the first 12-months of the pandemic (March 1, 2020 – February 28, 2021).

Results

All-cause healthcare encounters decreased significantly during the pandemic compared to the preceding year, including well child visits (48.1% during the pandemic vs. 66.6% in the prior year; p < 0.01), emergency department visits (9.7% vs. 21.0%; p < 0.01), and inpatient admissions (1.6% vs. 2.5%; p < 0.01), though there was over a 100-fold increase in telehealth encounters. Asthma exacerbations that required treatment with systemic steroids also decreased (127 vs. 504 exacerbations; p < 0.01). Race/ethnicity was not associated with changes in healthcare utilization or asthma outcomes.

Conclusion

The COVID-19 pandemic corresponded to dramatic shifts in healthcare utilization, including increased telehealth use and improved outcomes among children with asthma. Social distancing measures may have also reduced asthma trigger exposure.
Subchondral bone length in knee osteoarthritis: A deep learning derived imaging measure and its association with radiographic and clinical outcomes
Authors: Chang Gary H. , Park Lisa K. , Le Nina A. , Jhun Ray S. , Surendran Tejus , Lai Joseph , Seo Hojoon , Promchotichai Nuwapa , Yoon Grace , Scalera Jonathan , Capellini Terence D. , Felson David T. , Kolachalama Vijaya B.
Published: May 2021

Objective

Develop a bone shape measure that reflects the extent of cartilage loss and bone flattening in knee osteoarthritis (OA) and test it against estimates of disease severity.

Methods

A fast region-based convolutional neural network was trained to crop the knee joints in sagittal dual-echo steady state MRI sequences obtained from the Osteoarthritis Initiative (OAI). Publicly available annotations of the cartilage and menisci were used as references to annotate the tibia and the femur in 61 knees. Another deep neural network (U-Net) was developed to learn these annotations. Model predictions were compared with radiologist-driven annotations on an independent test set (27 knees). The U-Net was applied to automatically extract the knee joint structures on the larger OAI dataset (9,434 knees). We defined subchondral bone length (SBL), a novel shape measure characterizing the extent of overlying cartilage and bone flattening, and examined its relationship with radiographic joint space narrowing (JSN), concurrent WOMAC pain and disability as well as subsequent partial or total knee replacement (KR). Odds ratios for each outcome were estimated using relative changes in SBL on the OAI dataset into quartiles.

Result

Mean SBL values for knees with JSN were consistently different from knees without JSN. Greater changes of SBL from baseline were associated with greater pain and disability. For knees with medial or lateral JSN, the odds ratios between lowest and highest quartiles corresponding to SBL changes for future KR were 5.68 (95% CI:[3.90,8.27]) and 7.19 (95% CI:[3.71,13.95]), respectively.

Conclusion

SBL quantified OA status based on JSN severity. It has promise as an imaging marker in predicting clinical and structural OA outcomes.
The comparison of vaccine hesitancy of COVID-19 vaccination in China and the United States
Authors: Liu Taoran , He Zonglin , Huang Jian , Yan Ni , Chen Qian , Huang Fengqiu , Zhang Yuejia , Akinwunmi Omolola M , Akinwunmi Babatunde , Zhang Casper J.P , Wu Yibo , Ming Wai-Kit
Published: May 2021

Objectives

To investigate the differences in vaccine hesitancy and preference of the currently available COVID-19 vaccines between two countries, viz. China and the United States (US).

Method

A cross-national survey was conducted in both China and the US, and discrete choice experiments as well as Likert scales were utilized to assess vaccine preference and the underlying factors contributing to the vaccination acceptance. A propensity score matching (PSM) was performed to enable a direct comparison between the two countries.

Results

A total of 9,077 (5,375 and 3,702, respectively, from China and the US) respondents have completed the survey. After propensity score matching, over 82.0% respondents from China positively accept the COVID-19 vaccination, while 72.2% respondents form the US positively accept it. Specifically, only 31.9% of Chinese respondents were recommended by a doctor to have COVID-19 vaccination, while more than half of the US respondents were recommended by a doctor (50.2%), local health board (59.4%), or friends and families (64.8%). The discrete choice experiments revealed that respondents from the US attached the greatest importance to the efficacy of COVID-19 vaccines (44.41%), followed by the cost of vaccination (29.57%), whereas those from China held a different viewpoint that the cost of vaccination covers the largest proportion in their trade-off (30.66%), and efficacy ranked as the second most important attribute (26.34%). Also, respondents from China tend to concerned much more about the adverse effect of vaccination (19.68% vs 6.12%) and have lower perceived severity of being infected with COVID-19.

Conclusion

While the overall acceptance and hesitancy of COVID-19 vaccination in both countries are high, underpinned distinctions between countries are observed. Owing to the differences in COVID-19 incidence rates, cultural backgrounds, and the availability of specific COVID-19 vaccines in two countries, the vaccine rollout strategies should be nation-dependent.
Alternative somatic and germline gene-regulatory strategies during starvation-induced developmental arrest
Authors: Webster Amy K. , Chitrakar Rojin , Baugh L. Ryan
Published: May 2021

Nutrient availability governs growth and quiescence, and many animals arrest development when starved. Somatic and germline cells have distinct functions and constraints, suggesting different regulatory mechanisms contribute to an integrated starvation response. UsingC. elegansL1 arrest as a model, we show that gene expression changes deep into starvation. Surprisingly, relative expression of germline-enriched genes increases for days. We conditionally degraded the large subunit of RNA Polymerase II and found that early but not late somatic transcription is required for survival and that germline transcription does not affect survival. Expression analysis revealed that thousands of genes are continuously transcribed in the soma, though their absolute abundance declines, while the germ line is transcriptionally quiescent with extreme transcript stability. This work reveals alternative somatic and germline gene-regulatory strategies during starvation, with the soma relying on a robust transcriptional response to support immediate survival while the germ line relies on transcriptional quiescence and mRNA stability to maintain future reproductive success.
Preserved motor memory in Parkinson’s disease
Authors: Lahlou Soraya , Gabitov Ella , Owen Lucy , Shohamy Daphna , Sharp Madeleine
Published: May 2021

Patients with Parkinson’s disease, who lose the dopaminergic projections to the striatum, are impaired in certain aspects of motor learning. Recent evidence suggests that, in addition to its role in motor performance, the striatum plays a key role in the memory of motor learning. Whether Parkinson’s patients have impaired motor memory and whether motor memory is modulated by dopamine at the time of initial learning is unknown. To address these questions, we measured memory of a learned motor sequence in Parkinson’s patients who were either On or Off their dopaminergic medications. We compared them to a group of older and younger controls. Contrary to our predictions, motor memory was not impaired in patients compared to older controls, and was not influenced by dopamine state at the time of initial learning. To probe post-learning consolidation processes, we also tested whether learning a new sequence shortly after learning the initial sequence would interfere with later memory. We found that, in contrast to younger adults, neither older adults nor patients were susceptible to this interference. These findings suggest that motor memory is preserved in Parkinson’s patients and raise the possibility that motor memory in patients is supported by compensatory non-dopamine sensitive mechanisms. Furthermore, given the similar performance characteristics observed in the patients and older adults and the absence of an effect of dopamine, these results raise the possibility that aging and Parkinson’s disease affect motor memory in similar ways.
Ultraspecific somatic SNV and indel detection in single neurons using primary template-directed amplification
Authors: Luquette Lovelace J. , Miller Michael B. , Zhou Zinan , Bohrson Craig L. , Galor Alon , Lodato Michael A. , Gawad Charles , West Jay , Walsh Christopher A. , Park Peter J.
Published: May 2021

Primary template-directed amplification (PTA) is an improved amplification technique for single-cell DNA sequencing. We generated whole-genome analysis of 76 single neurons and developed SCAN2, a computational method to accurately identify both clonal and non-clonal somatic (i.e., limited to a single neuron) single nucleotide variants (SNVs) and small insertions and deletions (indels) using PTA data. Our analysis confirms an increase in non-clonal somatic mutation in single neurons with age, but revises estimates for the rate of this accumulation to be 15 SNVs per year. We also identify artifacts in other amplification methods. Most importantly, we show that somatic indels also increase by at least 2 indels per year per neuron and that indels may have a larger impact on gene function than somatic SNVs in human neurons.
Intracortical probe arrays with silicon backbone and microelectrodes on thin polyimide wings enable long-term stable recordings in vivo
Authors: Kilias Antje , Lee Yu-Tao , Froriep Ulrich P. , Moser Dominik , Holzhammer Tobias , Egert Ulrich , Fang Weileun , Paul Oliver , Ruther Patrick
Published: May 2021

Objective

Recording and stimulating neuronal activity across different brain regions requires interfacing at multiple sites using dedicated tools while tissue reactions at the recording sites often prevent their successful long-term application. This implies the technological challenge of developing complex probe geometries while keeping the overall footprint minimal, and of selecting materials compatible with neural tissue. While the potential of soft materials in reducing tissue response is uncontested, the implantation of these materials is often limited to reliably target neuronal structures across large brain volumes.

Approach

We report on the development of a new multi-electrode array exploiting the advantages of soft and stiff materials by combining 7-μm-thin polyimide wings carrying platinum electrodes with a silicon backbone enabling a safe probe implantation. The probe fabrication applies microsystems technologies in combination with a temporal wafer fixation method for rear side processing, i.e., grinding and deep reactive ion etching, of slender probe shanks and electrode wings. The wing-type neural probes are chronically implanted into the entorhinal-hippocampal formation in the mouse forin vivorecordings of freely behaving animals.

Main results

Probes comprising the novel wing-type electrodes have been realized and characterized in view of their electrical performance and insertion capability. Chronic electrophysiologicalin vivorecordings of the entorhinal-hippocampal network in the mouse of up to 104 days demonstrated a stable yield of channels containing identifiable multi-unit and single-unit activity outperforming probes with electrodes residing on a Si backbone.

Significance

The innovative fabrication process using a process compatible, temporary wafer bonding allowed to realize new Michigan style probe arrays. The wing-type probe design enables a precise probe insertion into brain tissue and long-term stable recordings of unit activity due to the application of a stable backbone and 7-μm-thin probe wings provoking locally a minimal tissue response and protruding from the glial scare of the backbone.
The effect of habitat type on population distribution and abundance of Rothschild’s Giraffe (Giraffa camelopardalis rothschildi) in Ruma National Park and Mwea National Reserve in Kenya
Authors: Gathuku George N. , Chiawo David O. , Warui Charles M. , Gichuki Cecilia M. , Ngare Innocent O.
Published: May 2021

The Rothschild’s giraffe is currently listed as vulnerable by the International Union for Conservation of Nature (IUCN). This is attributed to the loss of habitat due to human activities. This study examined the effect of habitat type on population structure and distribution of Rothschild’s giraffe in Ruma National Park (RNP) and Mwea National Reserve (MNR) in Kenya. The study employed road transects to collect data on the number, age class and sex distribution in three habitat types, open, medium and closed. Data was collected along three road transects of equal lengths measuring 14.2 km in each site (RNP and MNR) for comparison. A driving speed of 20 km per hour was maintained along each transect for standardization of survey effort and a maximum giraffe detection rate. Photographic capture of the coat patterns of the right side of all the giraffes sighted within 500 m from the transect was done for identification of age classes. The field visits were replicated 12 times for each transect giving 36 replications for each site spread equally through wet and dry seasons from March 2017 to November 2018. The effect of habitat type on population structure and distribution was analysed using ANOVA and Tukey HSD to test for significant differences. T-test was used to compare the mean population size of giraffe across the wet and dry seasons. Coat pattern analysis for age class identification was done using WildID software. The findings indicated that MNR had more males to females compared to RNP that registered more females and calves. Habitat type had a significant effect on the distribution of giraffes. The giraffe population showed a preference for medium habitat types. The findings are key for the management of habitat quality for giraffe populations at the interface where conservation areas overlap with human land use.
Crossbill: an open access single objective light-sheet microscopy platform
Authors: Kumar Manish , Kishore Sandeep , McLean David L. , Kozorovitskiy Yevgenia
Published: May 2021

We present an open access scanned oblique plane microscopy platformCrossbill. It combines a new optical configuration, open hardware assembly, a systematic alignment protocol, and dedicated control software to provide a compact, versatile, high resolution single objective light-sheet microscopy platform. The demonstrated configuration yields the most affordable sub-micron resolution oblique plane microscopy system to date. We add galvanometer enabled tilt-invariant lateral scan for multi-plane, multi-Hz volumetric imaging capability. A precision translation stage extends stitched field of view to centimeter scale. The accompanying open software is optimized forCrossbilland can be easily extended to include alternative configurations. UsingCrossbill, we demonstrate large volume structural fluorescence imaging with sub-micron lateral resolution in zebrafish and mouse brain sections.Crossbillis also capable of multiplane functional imaging, and time-lapse imaging. We suggest multiple alternative configurations to extendCrossbillto diverse microscopy applications.
EEG biomarkers of free recall
Authors: Katerman B. S. , Li Y. , Pazdera J. K. , Keane C. , Kahana M. J.
Published: May 2021

Brain activity in the moments leading up to spontaneous verbal recall provide a window into the cognitive processes underlying memory retrieval. But these same recordings also subsume neural signals unrelated to mnemonic retrieval, such as response-related motor activity. Here we examined spectral EEG biomarkers of memory retrieval under an extreme manipulation of mnemonic demands: subjects either recalled items after a few seconds or after several days. This manipulation helped to isolate EEG components specifically related to long-term memory retrieval. In the moments immediately preceding recall we observed increased theta (4-8 Hz) power (+T), decreased alpha (8-20 Hz) power (-A), and increased gamma (40-128 Hz) power (+G), with this spectral pattern (+T-A+G) distinguishing the long-delay and immediate recall conditions. As subjects vocalized the same set of studied words in both conditions, we interpret the spectral +T-A+G as a biomarker of episodic memory retrieval.
Hierarchical, Memory-based Movement Models for Translocated Elk (Cervus canadensis)
Authors: Falcón-Cortés Andrea , Boyer Denis , Merrill Evelyn , Frair Jacqueline L. , Morales Juan Manuel
Published: May 2021

The use of spatial memory is well documented in many animal species and has been shown to be critical for the emergence of spatial learning. Adaptive behaviors based on learning can emerge thanks to an interdependence between the acquisition of information over time and movement decisions. The study of how spatio-ecological knowledge is constructed throughout the life of an individual has not been carried out in a quantitative and comprehensive way, hindered by the lack of knowledge of the information an animal already has of its environment at the time monitoring begins. Identifying how animals use memory to make beneficial decisions is fundamental to developing a general theory of animal movement and space use. Here we propose several mobility models based on memory and perform hierarchical Bayesian inference on 11-month trajectories of 21 elk after they were released in a completely new environment. Almost all the observed animals exhibited preferential returns to previously visited patches, such that memory and random exploration phases occurred. Memory decay was mild or negligible over the study period. The fact that individual elk rapidly become used to a relatively small number of patches was consistent with the hypothesis that they seek places with predictable resources and reduced mortality risks such as predation.
Modularity and connectivity of nest structure scale with colony size
Authors: Miller Julie S. , Wan Emma , O’Fallon Sean , Pinter-Wollman Noa
Published: May 2021

Large body sizes have evolved structures to facilitate resource transport. Like unitary organisms, social insect colonies must transport information and resources. Colonies with more individuals may experience transport challenges similar to large-bodied organisms. In ant colonies, transport occurs in the nest, which may consist of structures that facilitate movement. We examine three attributes of nests that might have evolved to mitigate transport challenges related to colony size: (1) subdivision - nests of species with large colonies are more subdivided to reduce crowd viscosity; (2) branching - nest tunnels increase branching in species with large colonies to reduce travel distances; and (3) short-cuts – nests of species with large colonies have cross-linking tunnels to connect distant parts of the nest and create alternative routes. We test these hypotheses by comparing nest structures of species with different colony sizes in phylogenetically controlled meta-analyses. Our findings support the hypothesis that nest subdivision and branching evolved to mitigate transport challenges related to colony size. Nests of species with large colonies contain more chambers and branching tunnels. The similarity in how ant nests and bodies of unitary organisms have evolved in response to increasing size suggests common solutions across taxa and levels of biological organization.
High-density spinal cord stimulation selectively activates lower urinary tract afferents
Authors: Jantz Maria K , Gopinath Chaitanya , Kumar Ritesh , Chin Celine , Wong Liane , Ogren John I , Fisher Lee E , McLaughlin Bryan L , Gaunt Robert A
Published: May 2021

Epidural spinal cord stimulation (SCS) has recently been reported as a potential intervention to improve limb and autonomic functions, with lumbar stimulation improving locomotion and thoracic stimulation regulating blood pressure. We asked whether sacral SCS could be used to target the lower urinary tract. Here we show that high-density epidural SCS over the sacral spinal cord and cauda equina of anesthetized cats evokes responses in nerves innervating the bladder and urethra and that these nerves can be activated selectively. Sacral epidural SCS always recruited the pelvic and pudendal nerves and selectively recruited these nerves in all but one animal. Individual branches of the pudendal nerve were always recruited as well. Electrodes that selectively recruited specific peripheral nerves were spatially clustered on the arrays, suggesting anatomically organized sensory pathways. This selective recruitment demonstrates a mechanism to directly modulate bladder and urethral function through known reflex pathways, which could be used to restore bladder and urethral function after injury or disease.
GhostiPy: an efficient signal processing and spectral analysis toolbox for large data
Authors: Chu Joshua P. , Kemere Caleb T.
Published: May 2021

Recent technological advances have enabled neural recordings consisting of hundreds to thousands of channels. As the pace of these developments continues to grow rapidly, it is imperative to have fast, flexible tools supporting the analysis of neural data gathered by such large scale modalities. Here we introduceghostipy(generalhubofspectraltechniquesinPython), a Python open source software toolbox implementing various signal processing and spectral analyses including optimal digital filters and time-frequency transforms.ghostipyprioritizes performance and efficiency by using parallelized, blocked algorithms. As a result, it is able to outperform commercial software in both time and space complexity for high channel count data and can handle out-of-core computation in a user-friendly manner. Overall, our software suite reduces frequently encountered bottlenecks in the experimental pipeline, and we believe this toolset will enhance both the portability and scalability of neural data analysis.
q-mer analysis: a generalized method for analyzing RNA-Seq data
Authors: Shoji Tatsuma , Sato Yoshiharu
Published: May 2021

RNA-Seq data are usually summarized by counting the number of transcript reads aligned to each gene. However, count-based methods do not take alignment information, where and how each read was mapped in the gene, into account. This information is essential to characterize samples accurately. In this study, we developed a method to summarize RNA-Seq data without losing alignment information. To include alignment information, we introduce “q-mer analysis,” which summarizes RNA-Seq data with 4q kinds of q-length oligomers. Using publicly available RNA-Seq datasets, we demonstrate that at least q ≧ 9 is required for capturing alignment information inHomo sapiens. Furthermore, principal component analysis showed that q-mer analysis with q = 14 linearly distinguished samples from controls, while a count-based method failed. These results indicate that alignment information is essential to characterize transcriptomics samples. In conclusion, we introduce q-mer analysis to include alignment information in RNA-Seq analysis and demonstrate the superiority of q-mer analysis over count-based methods in that q-mer analysis can distinguish case samples from controls. Combining RNA-Seq research with q-mer analysis could be useful for identifying distinguishing transcriptomic features that could provide hypotheses for disease mechanisms.
Diverse Hotspot Thermal Profiling Methods Detect Phosphorylation-Dependent Changes in Protein Stability
Authors: Stein Benjamin D. , Huang Jun X. , Wu David , Cantley Lewis C. , Moellering Raymond E.
Published: May 2021

Hotspot thermal profiling (HTP) methods utilize modified-peptide level information in order to interrogate proteoform-specific stability inside of live cells. The first demonstration of HTP involved the integration of phosphopeptide enrichment into a TMT-based, single-LC separation thermal profiling workflow1. Here we present a new ‘label-fractionate-enrich’ (LFE)-HTP method that involves high-pH reverse phase fractionation of TMT-labeled peptides prior to phosphopeptide enrichment, followed by peptide detection and quantitation using multi-notch LC-MS3. We find that LFE-HTP, while more resource intensive, improves the depth and precision of (phospho)proteoform coverage relative to the initial published HTP workflow. The fraction of detected phosphorylation sites that are significantly perturbed in this new dataset are consistent with those seen in our previous study, as well as those published by others, when compared head-to-head with the same analysis pipelines. Likewise, many ‘hotspot’ phosphorylation sites identified in our paper are consistently reproduced by LFE-HTP as well as other modified HTP methods. The LFE-HTP dataset contains many novel ‘hotspot’ phosphorylation sites that regulate the stability of diverse proteins, including phosphosites in the central glycolytic enzyme Aldolase A that are associated with monomer-to-oligomer formation, enzymatic activity and metabolic regulation in cancer cells. Our comparative analyses confirm that several variants of the HTP method can track modified proteoforms in live cells to detect and prioritize PTM-dependent changes in protein stability that may be associated with function.
Foxd3 controls heterochromatin-mediated silencing of repeat elements in mouse embryonic stem cells and represses the 2-cell transcription program
Authors: Puri Deepika , Koschorz Birgit , Engist Bettina , Onishi-Seebacher Megumi , Ryan Devon , Montavon Thomas
Published: May 2021

Repeat element transcription plays a vital role in early embryonic development. Expression of repeats such as MERVL characterises mouse embryos at the 2-cell stage, and defines a 2-cell-like cell (2CLC) population in a mouse embryonic stem cell culture. Repeat element sequences contain binding sites for numerous transcription factors. We identify the forkhead domain transcription factor FOXD3 as a regulator of repeat element transcription in mouse embryonic stem cells. FOXD3 binds to and recruits the histone methyltransferase SUV39H1 to MERVL and major satellite repeats, consequentially repressing the transcription of these repeats by the establishment of the H3K9me3 heterochromatin modification. Notably, depletion of FOXD3 leads to the de-repression of MERVL and major satellite repeats as well as a subset of genes expressed in the 2-cell state, shifting the balance between the stem cell and 2-cell like population in culture. Thus, FOXD3 acts as a negative regulator of repeat transcription, ascribing a novel function to this transcription factor.
Oligomerization-driven MLKL ubiquitylation antagonises necroptosis
Authors: Liu Zikou , Dagley Laura F. , Shield-Artin Kristy , Young Samuel N. , Bankovacki Aleksandra , Wang Xiangyi , Tang Michelle , Howitt Jason , Stafford Che A. , Nachbur Ueli , Fitzgibbon Cheree , Garnish Sarah E. , Webb Andrew I. , Komander David , Murphy James M. , Hildebrand Joanne M. , Silke John
Published: May 2021

Mixed lineage kinase domain-like (MLKL) is the executioner in the caspase-independent form of programmed cell death called necroptosis. Receptor Interacting serine/threonine Protein Kinase 3 (RIPK3) phosphorylates MLKL, triggering MLKL oligomerization, membrane translocation and membrane disruption. MLKL also undergoes ubiquitylation during necroptosis, yet neither the mechanism nor significance of this event have been demonstrated. Here we show that necroptosis-specific, multi-mono-ubiquitylation of MLKL occurs following its activation and oligomerization. Ubiquitylated MLKL accumulates in a digitonin insoluble cell fraction comprising plasma/organellar membranes and protein aggregates. This ubiquitylated form is diminished by a plasma membrane located deubiquitylating enzyme. MLKL is ubiquitylated on at least 4 separate lysine residues once oligomerized, and this correlates with proteasome- and lysosome-dependent turnover. Using a MLKL-DUB fusion strategy, we show that constitutive removal of ubiquitin from MLKL licences MLKL auto-activity independent of necroptosis signalling in mouse and human cells. Therefore, besides its role in the kinetic regulation of MLKL-induced death following an exogenous necroptotic stimulus, ubiquitylation also contributes to the restraint of basal levels of activated MLKL to avoid errant cell death.
Terrestrial force production by the limbs of a semi-aquatic salamander provides insight into the evolution of terrestrial locomotor mechanics
Authors: Kawano Sandy M. , Blob Richard W.
Published: May 2021

Amphibious fishes and salamanders are valuable functional analogs for vertebrates that spanned the water-to-land transition. However, investigations of walking mechanics have focused on terrestrial salamanders and, thus, may better reflect the capabilities of stem tetrapods that were already terrestrial. The earliest tetrapods were aquatic, so salamanders that are not primarily terrestrial may yield more appropriate data for modelling the incipient stages of terrestrial locomotion. In the present study, locomotor biomechanics were quantified from semi-aquaticPleurodeles waltl, a salamander that spends most of its adult life in water, and then compared to a primarily terrestrial salamander (Ambystoma tigrinum) and semi-aquatic fish (Periophthalmus barbarus) to evaluate whether walking mechanics show greater similarity between species with ecological versus phylogenetic similarities. Ground reaction forces (GRFs) from individual limbs or fins indicated that the pectoral appendages of each taxon had distinct patterns of force production, but hind limb forces were comparable between the salamanders. The rate of force development (‘yank’) was sometimes slower inP. waltlbut generally comparable between the three species. Finally, medial inclination of the GRF inP. waltlwas intermediate between semi-aquatic fish and terrestrial salamanders, potentially elevating bone stresses among more aquatic taxa as they move on land. These data provide a framework for modelling stem tetrapods using an earlier stage of quadrupedal locomotion that was powered primarily by the hind limbs (i.e., “rear-wheel drive”), and reveal mechanisms for appendages to generate propulsion in three locomotor strategies that are presumed to have occurred across the water-to-land transition in vertebrate evolution.

Summary statement

Semi-aquatic salamanders had limb mechanics that were intermediate in magnitude yet steadier than the appendages of terrestrial salamanders and semi-aquatic fish, providing a framework to model semi-aquatic early tetrapods.
Retention Time Standardization and Registration (RTStaR): An algorithm that matches corresponding and identifies unique species in nanoliquid chromatography-nanoelectrospray ionization-mass spectrometry lipidomic datasets
Authors: Blanchard Alexandre P. , Wang Yun , Taylor Graeme P. , Granger Matthew W. , Fai Stephen , Figeys Daniel , Paus Tomas ,   SYS Consortium, Pausova Zdenka , Xu Hongbin , Bennett Steffany A.L.
Published: May 2021

Bioinformatic tools capable of registering, rapidly and reproducibly, large numbers of nanoliquid chromatography-nanoelectrospray ionization-tandem mass spectrometry (nLC-nESI-MS/MS) lipidomic datasets are lacking. We provide here a freely available Retention Time Standardization and Registration (RTStaR) algorithm that aligns nLC-nESI-MS/MS spectra within a single dataset and compares these aligned retention times across multiple datasets. This two-step calibration matches corresponding and identifies unique lipid species in different lipidomes from different matrices and organisms. RTStaR was developed using a population-based study of 1001 human serum samples composed of 71 distinct glycerophosphocholine metabolites comprising a total of 68,572 analytes. Platform and matrix independence were validated using different MS instruments, nLC methodologies, and mammalian lipidomes. The complete algorithm is packaged in two modular ExcelTM workbook templates for easy implementation. RTStaR is freely available from the India Taylor Lipidomics Research Platformhttp://www.neurolipidomics.ca/rtstar/rtstar.html. Technical support is provided throughldomic@uottawa.ca
Evolutionary dynamics of circular RNAs in primates
Authors: Santos-Rodriguez Gabriela , Voineagu Irina , Weatheritt Robert J
Published: May 2021

Many primate genes produce non-coding circular RNAs (circRNAs). However, the extent of circRNA conservation between closely related species remains unclear. By comparing tissue-specific transcriptomes across over 70 million years of primate evolution, we identify that within 3 million years circRNA expression profiles diverged such that they are more related to species identity than organ type. However, our analysis also revealed a subset of circRNAs with conserved neural expression across tens of millions of years of evolution. These circRNAs are defined by an extended downstream intron that has shown dramatic lengthening during evolution due to the insertion of novel retrotransposons. Our work provides comparative analyses of the mechanisms promoting circRNAs to generate increased transcriptomic complexity in primates.
Left Hemisphere Dominance for Bilateral Kinematic Encoding in the Human Brain
Authors: Merrick Christina M. , Dixon Tanner C. , Breska Assaf , Lin Jack J. , Chang Edward F. , King-Stephens David , Laxer Kenneth D. , Weber Peter B. , Carmena Jose M. , Knight Robert T. , Ivry Richard B.
Published: May 2021

Neurophysiological studies in humans and non-human primates have revealed movement representations in both the contralateral and ipsilateral hemisphere. Inspired by clinical observations, we ask if this bilateral representation differs for the left and right hemispheres. Electrocorticography (ECoG) was recorded in human participants during an instructed-delay reaching task, with movements produced with either the contralateral or ipsilateral arm. Using a cross-validated kinematic encoding model, we found stronger bilateral encoding in the left hemisphere, an effect that was present during preparation and was amplified during execution. Consistent with this asymmetry, we also observed better across-arm generalization in the left hemisphere, indicating similar neural representations for right and left arm movements. Notably, these left hemisphere electrodes were centered over premotor and parietal regions. The more extensive bilateral encoding in the left hemisphere adds a new perspective to the pervasive neuropsychological finding that the left hemisphere plays a dominant role in praxis.
Transmembrane helices are an overlooked and evolutionarily conserved source of major histocompatibility complex class I and II epitopes
Authors: Bilderbeek Richèl J.C. , Baranov Maxim , van den Bogaart Geert , Bianchi Frans
Published: May 2021

Cytolytic T cell responses are predicted to be biased towards membrane proteins. The peptide-binding grooves of most haplotypes of histocompatibility complex class I (MHC-I) are relatively hydrophobic, therefore peptide fragments derived from human transmembrane helices (TMHs) are predicted to be presented more often as would be expected based on their abundance in the proteome. However, the physiological reason of why membrane proteins might be over-presented is unclear. In this study, we show that the over-presentation of TMH-derived peptides is general, as it is predicted for bacteria and viruses and for both MHCI and MHC-II. Moreover, we show that TMHs are evolutionarily more conserved, because single nucleotide polymorphisms (SNPs) are present relatively less frequently in TMH-coding chromosomal regions compared to regions coding for extracellular and cytoplasmic protein regions. Thus, our findings suggest that both cytolytic and helper T cells respond more to membrane proteins, because these are evolutionary more conserved. We speculate that TMHs therefore are less prone to escape mutations that enable pathogens to evade T cell responses.
Vibrio choleraebiofilm dispersal regulator causes cell release from matrix through type IV pilus retraction
Authors: Singh Praveen K. , Rode Daniel K.H. , Buffard Pauline , Nosho Kazuki , Bayer Miriam , Jeckel Hannah , Jelli Eric , Neuhaus Konstantin , Jiménez-Siebert Eva , Peschek Nikolai , Glatter Timo , Papenfort Kai , Drescher Knut
Published: May 2021

The extracellular matrix is a defining feature of bacterial biofilms and provides structural stability to the community by binding cells to the surface and to each other. Transitions between bacterial biofilm initiation, growth, and dispersion require different regulatory programs, all of which result in modifications to the extracellular matrix composition, abundance, or functionality. However, the mechanisms by which individual cells in biofilms disengage from the matrix to enable their departure during biofilm dispersal are unclear. Here, we investigated active biofilm dispersal ofVibrio choleraeduring nutrient starvation, resulting in the discovery of the conservedVibriobiofilm dispersal regulator VbdR. We show that VbdR triggers biofilm dispersal by controlling cellular release from the biofilm matrix, which is achieved by inducing the retraction of the mannose-sensitive hemagglutinin (MSHA) type IV pili and the expression of a matrix protease IvaP. We further show that MSHA pili have numerous binding partners in the matrix and that the joint effect of MSHA pilus retraction and IvaP activity is necessary and sufficient for causing biofilm dispersal. These results highlight the crucial role of type IV pilus dynamics during biofilm dispersal and provide a new target for controllingV. choleraebiofilm abundance through the induction and manipulation of biofilm dispersal.
Multi-tissue methylation clocks for age estimation in the common bottlenose dolphin
Authors: Robeck Todd R. , Fei Zhe , Haghani Amin , Zoller Joseph A. , Li Caesar Z. , Steinman Karen J. , DiRocco Stacy , Staggs Lydia , Schmitt Todd , Osborn Steve , Montano Gisele , Rodriguez Magdalena , Horvath Steve
Published: May 2021

Accurate identification of individual ages within wild bottlenose dolphins (Tursiops truncatus) is critical for determining population health and the development of population management strategies. As such, we analyzed DNA methylation patterns by applying a custom methylation array (HorvathMammalMethyl40) to both blood (n = 140) and skin samples (n = 87) from known age or approximate age (0 to 57 years) bottlenose dolphins. We present three bottlenose dolphin specific age estimation clocks using combined blood and skin (48 CpGs, R = 0.93, median absolute error = 2.13 years), blood only (64 CpGs, R = 0.97, error= 1.46 years) and skin only (39 CpGs, R = 0.95, error= 2.53). Our sex estimator based on 71 CpGs predicts the sex of any odontocete species with 99.5% accuracy. We characterize individual cytosines that correlate with sex and age in dolphins.

The presented epigenetic clocks are expected to be useful for conservation efforts and for studying anthropogenic events.