bluuebunny/crossref_metadata_2025 huggingface dataset:
Prison population reductions and COVID-19: A latent profile analysis synthesizing recent evidence from the Texas state prison system
Authors: Vest Noel , Johnson Oshea , Nowotny Kathryn , Brinkley-Rubinstein Lauren
Published: September 2020

Importance

People in prison are particularly vulnerable to infectious disease due to close living conditions and the lack of protective equipment. Public health professionals and prison administrators seek information to guide best practices regarding prison population to capacity rates for the COVID-19 outbreak.

Objective

Using latent profile analysis, we sought to characterize Texas prisons on levels of COVID-19 cases and deaths among incarcerated residents, and COVID-19 cases among prison staff.

Design

This observational study was a secondary data analysis of publicly available data from the Texas Department of Criminal Justice (TBDJ). Data were downloaded and analyzed on July 24, 2020. This project was completed in collaboration with the COVID Prison Project.

Setting

One-hundred and three prisons in the state of Texas.

Participants

The unit of analysis is the individual prison units that comprise the TDCJ.

Exposures

None

Main Outcomes and Measures

Latent profiles on levels of incarcerated resident COVID-19 cases, staff COVID-19 cases, and incarcerated resident COVID-19 deaths.

Results

We identified relevant profiles from the data: a low outbreak profile, a high outbreak profile, and a high death profile. Additionally, current prison population and level of employee staffing predicted membership in the high outbreak and high death profiles when compared to the low outbreak profile.

Conclusions and Relevance

Housing persons at 85% of prison capacity may minimize the risk of infection and death related to COVID-19. Implementing this 85% standard as an absolute minimum should be prioritized at prisons across the US.

KEY POINTS

Question

Is there a population to capacity ratio for prisons to successfully reduce the number of COVID-19 infections and deaths among its incarcerated populations?

Findings

The prisons that were most effective in reducing prison outbreaks and deaths operated at 85% of their current capacity.

Meaning

Prisons should operate at 85% of capacity or less to successfully minimize the harmful effects of COVID-19 on incarcerated populations.
“Organ-in-a-column” coupled on-line with liquid chromatography-mass spectrometry
Authors: Kogler Stian , Aizenshtadt Aleksandra , Harrison Sean , Skottvoll Frøydis Sved , Berg Henriette Engen , Abadpour Shadab , Scholz Hanne , Sullivan Gareth , Thiede Bernd , Lundanes Elsa , Bogen Inger Lise , Krauss Stefan , Røberg-Larsen Hanne , Wilson Steven Ray
Published: September 2020

Organoids, i.e. laboratory-grown organ models developed from stem cells, are emerging tools for studying organ physiology, disease modeling and drug development. On-line analysis of organoids with mass spectrometry would provide analytical versatility and automation. To achieve these features with robust hardware, we have loaded liquid chromatography column housings with induced pluripotent stem cell (iPSC) derived liver organoids and coupled the “organ-in-a-column” units on-line with liquid chromatography-mass spectrometry (LC-MS). Liver organoids were co-loaded with glass beads to achieve an even distribution of organoids throughout the column while preventing clogging. The liver organoids were interrogated “on column” with heroin, followed by on-line monitoring of the drug’s phase 1 metabolism. Enzymatic metabolism of heroin produced in the “organ-in-a-column” units was detected and monitored using a triple quadrupole MS instrument, serving as a proof-of-concept for on-line coupling of liver organoids and mass spectrometry. Taken together, the technology allows direct integration of liver organoids with LC-MS, allowing selective and automated tracking of drug metabolism over time.
Action-value processing underlies the role of the dorsal anterior cingulate cortex in performance monitoring during self-regulation of affect
Authors: Bush Keith A. , James G. Andrew , Privratsky Anthony A. , Fialkowski Kevin P. , Kilts Clinton D.
Published: September 2020

In this study, we merged methods from engineering control theory, machine learning, and human neuroimaging to critically test the putative role of the dorsal anterior cingulate cortex (dACC) in goal-directed performance monitoring during an emotion regulation task. Healthy adult participants (n=94) underwent cued-recall and re-experiencing of their responses to affective image stimuli with concurrent functional magnetic resonance imaging and psychophysiological response recording. During cued-recall/re-experiencing trials, participants engaged in explicit self-regulation of their momentary affective state to match a pre-defined affective goal state. Within these trials, neural decoding methods measured affect processing from fMRI BOLD signals across the orthogonal affective dimensions of valence and arousal. Participants’ affective brain states were independently validated via facial electromyography (valence) and electrodermal activity (arousal) responses. The decoded affective states were then used to contrast four computational models of performance monitoring (i.e., error, predicted response outcome, action-value, and conflict) by their relative abilities to explain emotion regulation task-related dACC activation. We found that the dACC most plausibly encodes action-value for both valence and arousal processing. We also confirmed that dACC activation directly encodes affective arousal and also likely encodes recruitment of attention and regulation resources. Beyond its contribution to improving our understanding of the roles that the dACC plays in emotion regulation, this study introduced a novel analytical framework through which affect processing and regulation may be functionally dissociated, thereby permitting mechanistic analysis of real-world emotion regulation strategies, e.g., distraction and reappraisal, which are widely employed in cognitive behavioral therapy to address clinical deficits in emotion regulation.
Pseudomonas aeruginosainduced acute emphysema through bacterial secretion in mice
Authors: Zhu Yajie , Pan Shuming
Published: September 2020

Pulmonary emphysema is the major pathological feature of chronic obstructive pulmonary disease (COPD). Although the pathogenesis of emphysema is still not completely understood, but until now a bacterial cause has not really been considered. Recently, we found that the secretion from Pseudomonas aeruginosa could cause severe lung emphysema in mice rapidly. Since the bacterium is ubiquitous and secrets proteases, we hypothesized that direct P. aeruginosa airway infection would have a similar effect. To address this issue, we applied a unilateral lung injury model. First, we observed the dynamic pathophysiology change of acute emphysema. P. aeruginosa secretion was extracted and instilled intratracheally into the left lungs of C57BL/6 and C3H/HeJ mice, while the right lungs were saved as self-control. Alveolar diameter and lung compliance were measured. Later, we tested the effect of P. aeruginosa inoculation in normal C57BL/6 mice, immunosuppressed C57BL/6 mice, and C3H/HeJ (TLR4 deficient) mice. P. aeruginosa secretion extract caused acute panacinar emphysema and decreased dynamic lung compliance. Different types of emphysema are transformable. However, the P. aeruginosa infection could only elicit emphysema in immunosuppressed C57BL/6 mice and C3H/HeJ mice, indicating that normal immunity is essential to protect the hosts from emphysema. Emphysema induced by P. aeruginosa in mice recapitulates all the main features of human emphysema and COPD. Our finding filled a major gap in COPD pathogenesis. We believeP. aeruginosais the underlying cause of COPD.
GEM-based metabolic profiling for Human Bone Osteosarcoma under different glucose and glutamine availability
Authors: Weglarz-Tomczak Ewelina , Rijlaarsdam Demi J. , Tomczak Jakub M. , Brul Stanley
Published: September 2020

Cancer cell metabolism is dependent on cell-intrinsic factors like genetics, and cell-extrinsic factors like nutrient availability. In this context, understanding how these two aspects interact and how diet influences cellular metabolism is important for developing personalized treatment. In order to achieve this goal, genome-scale metabolic models (GEMs) are used, however, genetics and nutrient availability are rarely considered together. Here, we propose an integrated metabolic profiling, a framework that allows to enrich GEMs with metabolic gene expression data and information about nutrients. First, the RNA-seq is converted into Reaction Activity Score (RAS) to further scale reaction bounds. Second, nutrient availability is converted to Maximal Uptake Rate (MUR) to modify exchange reactions in a GEM. We applied our framework to the human osteosarcoma cell line (U2OS). Osteosarcoma is a common and primary malignant form of bone cancer with poor prognosis, and, as indicated in our study, a glutamine-dependent type of cancer.
B Cell Division Capacity in Germinal Centers Depends on Myc Transcript Stabilization Through m6A mRNA Methylation and IGF2BP3 Functions
Authors: Grenov Amalie C. , Moss Lihee , Edelheit Sarit , Cordiner Ross , Schmiedel Dominik , Biram Adi , Hanna Jacob H , Jensen Torben H , Schwartz Schraga , Shulman Ziv
Published: September 2020

Long-lasting immunity from pathogens depends on the generation of protective antibodies through the germinal center (GC) reaction. The Myc gene produces highly short-lived transcripts which are essential for generation of high-affinity antibodies. mRNA lifetime is regulated by N6-methyladenosine (m6A)-modification of mRNAs through METTL3 activity; however, the role of this machinery in the GC remains unclear. Here, we find that m6A-modification of mRNAs is required for GC maintenance through Myc mRNA stabilization by the atypical m6A-interactor, IGF2BP3. MYC expression, activation of MYC transcriptional programs and cell-cycle progression were diminished in METTL3-deficient GC B cells. METTL3 attenuated Myc-transcript decay and overexpression of MYC in METTL3-deficient GC B cells restored the GC reaction. IGF2BP3 which was induced by CD40-signaling, reinforced MYC expression and MYC-related gene programs in GC B cells. Our findings explain how GC responses are maintained through regulation of Myc-transcript lifetime and expose new targets for manipulation in MYC-driven lymphoma.

One Sentence Summary

Germinal centers depend on the m6A-machinery
cytomapper: an R/Bioconductor package for visualisation of highly multiplexed imaging data
Authors: Eling Nils , Damond Nicolas , Hoch Tobias , Bodenmiller Bernd
Published: September 2020

Highly multiplexed imaging technologies enable spatial profiling of dozens of biomarkersin situ. Standard data processing pipelines quantify cell-specific features and generate object segmentation masks as well as multi-channel images. Therefore, multiplexed imaging data can be visualised across two layers of information: pixel-intensities represent the spatial expression of biomarkers across an image while segmented objects visualise cellular morphology, interactions and cell phenotypes in their microenvironment.

Here we describecytomapper, a computational tool that enables visualisation of pixel- and cell-level information obtained by multiplexed imaging. The package is written in the statistical programming language R, integrates with the image and single-cell analysis infrastructure of the Bioconductor project, and allows visualisation of single to hundreds of images in parallel. Usingcytomapper, expression of multiple markers is displayed as composite images, segmentation masks are coloured based on cellular features, and selected cells can be outlined in images based on their cell type, among other functions. We illustrate the utility ofcytomapperby analysing 100 images obtained by imaging mass cytometry from a cohort of type 1 diabetes patients and healthy individuals. In addition,cytomapperincludes a Shiny application that allows hierarchical gating of cells based on marker expression and visualisation of selected cells in corresponding images. Together,cytomapperoffers tools for diverse image and single-cell visualisation approaches and supports robust cell phenotyping via gating.
Therapeutic assessment of targeting ASNS combined with L-Asparaginase treatment in solid tumors and investigation of resistance mechanisms
Authors: Apfel Verena , Begue Damien , Cordo Valentina , Holzer Laura , Martinuzzi Laetitia , Buhles Alexandra , Kerr Grainne , Barbosa Ines , Naumann Ulrike , Piquet Michelle , Ruddy David , Weiss Andreas , Ferretti Stephane , Almeida Reinaldo , Bonenfant Debora , Tordella Luca , Galli Giorgio G.
Published: September 2020

Asparagine deprivation by L-Asparaginase (L-ASNase) is an effective therapeutic strategy in Acute Lymphoblastic Leukemia, with resistance occurring due to upregulation of ASNS, the only human enzyme synthetizing Asparagine1. L-Asparaginase efficacy in solid tumors is limited by dose-related toxicities2. Large-scale loss of function genetic in vitro screens identified ASNS as a cancer dependency in several solid malignancies3,4. Here we evaluate the therapeutic potential of targeting ASNS in melanoma cells. While we confirm in-vitro dependency on ASNS silencing, this is largely dispensable for in vivo tumor growth, even in face of asparagine deprivation, prompting us characterize such resistance mechanism to devise novel therapeutic strategies. Usingex vivoquantitative proteome and transcriptome profiling, we characterize the compensatory mechanism elicited by ASNS knockout melanoma cells allowing their survival. Mechanistically, a genome-wide CRISPR screen revealed that such resistance mechanism is elicited by a dual axis: GCN2-ATF4 aimed at restoring amino acids levels and MAPK-BCLXL to promote survival. Importantly, pharmacological inhibition of such nodes synergizes with L-Asparaginase-mediated Asparagine deprivation in ASNS deficient cells suggesting novel potential therapeutic combinations in melanoma.
Genomic selection to optimize doubled haploid-based hybrid breeding in maize
Authors: Li Jinlong , Cheng Dehe , Guo Shuwei , Yang Zhikai , Chen Ming , Chen Chen , Jiao Yanyan , Li Wei , Liu Chenxu , Zhong Yu , Qi Xiaolong , Yang Jinliang , Chen Shaojiang
Published: September 2020

Crop improvement, as a long-term endeavor, requires continuous innovations in technique from multiple perspectives. Doubled haploid (DH) technology for pure inbred production, which shaves years off of the conventional selfing approach, has been widely used for breeding. However, the final success rate ofin vivomaternal DH production is determined by four factors: haploids induction, haploids identification, chromosome doubling, and successful selfing of the fertile haploid plants to produce DH seeds. Traits in each of these steps, if they can be accurately predicted using genomic selection methods, will help adjust the DH production protocol and simplify the logistics and save costs. Here, a hybrid population (N=158) was generated based on an incomplete half diallel design using 27 elite inbred lines. These hybrids were induced to create F1-derived haploid families. The hybrid materials, as well as the 27 inbreds, the inbred-derived haploids (N=200), and the F1-derived haploids (N=5,000) were planted in the field to collect four DH-production traits, three yield-related traits, and three developmental traits. Quantitative genetics analysis suggested that in both diploids and haploid families, most of the developmental traits showed high heritability, while the DH-production and developmental traits exhibited intermediate levels of heritability. By employing different genomic selection models, our results showed that the prediction accuracy ranged from 0.52 to 0.59 for the DH-production traits, 0.50 to 0.68 for the yield-related traits, and 0.44 to 0.87 for the developmental traits. Further analysis using index selection achieved the highest prediction accuracy when considering both DH production efficiency and the agronomic trait performance. Furthermore, the long-term responses through simulation confirmed that index selection would increase the genetic gain for targeted agronomic traits while maintaining the DH production efficiency. Therefore, our study provides an optimization strategy to integrate GS technology for DH-based hybrid breeding.
Genomic asymmetry of theBrassica napusseed: Epigenetic contributions of DNA methylation and small RNAs to subgenome bias
Authors: Ziegler Dylan J. , Khan Deirdre , Pulgar-Vidal Nadège , Parkin Isobel A.P. , Robinson Stephen J. , Belmonte Mark F.
Published: September 2020

Polyploidy has predominated the genetic history of the angiosperms, and allopolyploidy is known to have contributed to the vast speciation of flowering plants.Brassica napus, one of the world’s most important oilseeds, is one such polyploid species originating from the interspecific hybridization ofBrassica rapa(An) andBrassica oleracea(Cn). Nascent amphidiploids must balance progenitor genomes during reproduction, though the role of epigenetic regulation in subgenome maintenance is unknown. The seed is the pivotal developmental transition into the new sporophytic generation and as such undergoes substantial epigenetic modifications. We investigated subgenome bias between the Anand Cnsubgenomes as well as across syntenic regions by profiling DNA methylation and siRNAs characteristic ofB. napusseed development. DNA methylation and siRNA accumulation were prevalent in the Cnsubgenome and most pronounced early during seed morphogenesis. Hypermethylation during seed maturation was most pronounced on non-coding elements, including promoters, repetitive elements, and siRNAs. Methylation on siRNA clusters was more prevalent in syntenic regions of the Cnsubgenome and implies selective silencing of genomic loci of the seed. Together, we find compelling evidence for the asymmetrical epigenetic regulation of the Anand Cnsubgenomes ofBrassica napusacross seed development.
Global Importance Analysis: An Interpretability Method to Quantify Importance of Genomic Features in Deep Neural Networks
Authors: Koo Peter K. , Majdandzic Antonio , Ploenzke Matthew , Anand Praveen , Paul Steffan B.
Published: September 2020

Deep neural networks have demonstrated improved performance at predicting the sequence specificities of DNA- and RNA-binding proteins compared to previous methods that rely onk-mers and position weight matrices. To gain insights into why a DNN makes a given prediction, model interpretability methods, such as attribution methods, can be employed to identify motif-like representations along a given sequence. Because explanations are given on an individual sequence basis and can vary substantially across sequences, deducing generalizable trends across the dataset and quantifying their effect size remains a challenge. Here we introduce global importance analysis (GIA), a model interpretability method that quantifies the population-level effect size that putative patterns have on model predictions. GIA provides an avenue to quantitatively test hypotheses of putative patterns and their interactions with other patterns, as well as map out specific functions the network has learned. As a case study, we demonstrate the utility of GIA on the computational task of predicting RNA-protein interactions from sequence. We first introduce a convolutional network, we call ResidualBind, and benchmark its performance against previous methods on RNAcompete data. Using GIA, we then demonstrate that in addition to sequence motifs, ResidualBind learns a model that considers the number of motifs, their spacing, and sequence context, such as RNA secondary structure and GC-bias.
Clostridium difficilebinary toxin (CDT) is recognized by the TLR2/6 heterodimer to induce an NF-κB response
Authors: Simpson Morgan , Frisbee Alyse , Kumar Pankaj , Schwan Carsten , Aktories Klaus , Petri William A.
Published: September 2020

Clostridioides difficileinfection (CDI) represents a significant burden on the health care system, one that is exacerbated by the emergence of binary toxin (CDT)-producing hypervirulentC. difficilestrains. Previous work from our lab has shown that TLR2 recognizes CDT to induce inflammation. Here we explore the interactions of CDT with TLR2 and the impact on host immunity during CDI. We found that the TLR2/6 heterodimer, not TLR2/1, is responsible for CDT recognition, and that gene pathways including NF-κB and MAPK downstream of TLR2/6 are upregulated in mice with intact TLR2/6 signaling during CDI.
Retinal circuits driving a non-image forming visual behavior
Authors: Beier Corinne , Bocchero Ulisse , Zhang Zhijing , Jin Nange , Massey Stephen C. , Ribelayga Christophe P. , Martemyanov Kirill , Hattar Samer , Pahlberg Johan
Published: September 2020

Outer retinal circuits that drive non-image forming vision in mammals are unknown. Rods and cones signal light increments and decrements to the brain through the ON and OFF pathways, respectively. Although their contribution to image-forming vision is known, the contributions of the ON and OFF pathway to the pupillary light response (PLR), a non-image forming behavior, are unexplored. Here we use genetically modified mouse lines, to comprehensively define the outer retinal circuits driving the PLR. The OFF pathway, which mirrors the ON pathway in image-forming vision, plays no role in the PLR. We found that rods use the primary rod pathway to drive the PLR at scotopic light levels. At photopic light levels, the primary and secondary rod pathways drive normal PLR. Importantly, we find that cones are unable to compensate for rods. Thus, retinal circuit dynamics allow rods to drive the PLR across a wide range of light intensities.
Lateralized decrease of parvalbumin+cells in the somatosensory cortex of ASD models is correlated with unilateral tactile hypersensitivity
Authors: Deemyad Tara , Puig Stephanie , Papale Andrew , Qi Hang , LaRocca Gregory M , Aravind Deepthi , LaNoce Emma , Urban Nathaniel N
Published: September 2020

Inhibitory control of excitatory networks contributes to cortical functions. Increasing evidence indicates that parvalbumin expressing (PV+) basket cells (BC) are a major player in maintaining the balance between excitation (E) and inhibition (I) in the cortex. Disruption of E/I balance in cortical networks is believed to be a hallmark of autism spectrum disorders (ASD) and may contribute to sensory alterations seen in ASD. Here, we report a lateralized decrease in the number of PV+BCs in L2/3 of the somatosensory cortex in the dominant hemisphere of adult Shank3-/-and Cntnap2-/-mouse models of ASD. The dominant hemisphere was identified during a reaching task to establish each animal’s dominant forepaw. Double labeling with anti-PV antibody and a biotinylated lectin (i.e., VVA) showed that the number of BCs was not different but rather, some BCs did not express detectable levels of PV (PV-), resulting in an elevated number of PV-VVA+basket cells. This lateralized reduction was not observed in the number of interneurons from the other two major groups that express somatostatin or the serotonergic receptor 5HT3a. Finally, we showed that dominant hind paws had higher mechanical sensitivity (i.e., lower mechanical thresholds measured with von Frey test) but no difference in thermal sensitivity (measured with Hargreaves test) when compared to the other hind paw. This mechanical hypersensitivity in the dominant paw correlated with the decrease in the number of PV+interneurons and reduced PV expression in the corresponding cortex. Together, these results suggest that the sensory hypersensitivity in ASD could be due to decreased inhibitory inputs to the dominant somatosensory cortex.
Repeated Decision Stumping Distils Simple Rules from Single Cell Data
Authors: Croydon Veleslavov Ivan A. , Stumpf Michael P.H.
Published: September 2020

Here we introduce repeated decision stumping, to distill simple models from single cell data. We develop decision trees of depth one – hence ‘stumps’ – to identify in an inductive manner, gene products involved in driving cell fate transitions, and in applications to published data we are able to discover the key-players involved in these processes in an unbiased manner without prior knowledge. The approach is computationally efficient, has remarkable predictive power, and yields robust and statistically stable predictors: the same set of candidates is generated by applying the algorithm to different subsamples of the data.
Neonatal enteropathogenicEscherichia coliinfection disrupts microbiota-gut-brain axis signaling
Authors: Hennessey Carly , Barboza Mariana , Brust-Mascher Ingrid , Knotts Trina A , Sladek Jessica A. , Pusceddu Matteo M , Stokes Patricia , Rabasa Gonzalo , Honeycutt Mackenzie , Walsh Olivia , Reardon Colin , Gareau Mélanie G.
Published: September 2020

Background

Diarrheal diseases are a leading cause of death in children under age five worldwide. Repeated early life exposures to diarrheal pathogens can result in co-morbidities including stunted growth and cognitive deficits suggesting an impairment in the microbiota-gut-brain (MGB) axis.

Methods

Neonatal C57BL/6 mice were infected with EPEC (strain e2348/69; ΔescV [T3SS mutant]), or vehicle (LB broth) via orogastric gavage (105CFU) at post-natal day (P7). Behavior (novel object recognition [NOR] task, light/dark [L/D] box, and open field test [OFT]), intestinal physiology (Ussing chambers), and the microbiota (16S Illumina sequencing) were assessed in adulthood (6-8 weeks).

Results

Neonatal infection of mice with EPEC impaired recognition memory (NOR task), coupled with increased neurogenesis (Ki67 and doublecortin immunostaining) and neuroinflammation (increased microglia activation [Iba1]) in adulthood. Intestinal pathophysiology was characterized by increased secretory state (short circuit current; Isc) and permeability (conductance; FITC-dextran flux) in the ileum and colon of neonatally EPEC-infected mice, along with increased expression of pro-inflammatory cytokines (Tnfα, Il12, Il6) and pattern recognition receptors (Nlr, Tlr). Finally, neonatal EPEC infection caused significant dysbiosis of the gut microbiota, including decreased Firmicutes, in adulthood.

Conclusions

Together these findings demonstrate that infection in early life can significantly impair the MGB axis in adulthood.
Metagenomic sequencing to detect respiratory viruses in persons under investigation for COVID-19
Authors: Babiker Ahmed , Bradley Heath L. , Stittleburg Victoria D. , Key Autum , Kraft Colleen S. , Waggoner Jesse J. , Piantadosi Anne
Published: September 2020

We used metagenomic next-generation sequencing (mNGS) to assess the frequencies of alternative viral infections in SARS-CoV-2 RT-PCR negative persons under investigations (PUIs) (n=30) and viral co-infections in SARS-CoV-2 RT-PCR positive PUIs (n=45). mNGS identified both co-infections and alternative viral infections that were not detected by routine clinical workup.
Adherence to COVID-19 pandemic prescribed recommendations, source of information and lockdown psychological impact of Nigeria social media users
Authors: Bolarinwa Obasanjo Afolabi , Olagunju Olalekan , Babalola Tesleem
Published: September 2020

Background

COVID-19 is a highly infectious viral disease that has spread to over one hundred and eight countries, including Nigeria. Countries across the globe have been implementing preventive measures towards curbing the spread and impact of the virus. Thus, the present study was aimed at assessing compliance to prescribe preventive recommendations, the psychological effect of lockdown, and the source of information among Nigeria social media users.

Methods

This research implemented an online cross-sectional survey using an unidentified online Google based questionnaire to elicit required information from potential respondents via social media channels such as WhatsApp, Twitter, Instagram, Telegram and Facebook. On these forums, an external link with google based questionnaire was shared with Nigerians social media users to participate from 1st to 31st April 2020 and we had 1,131 respondents who participated in the survey.

Results

Age and respondents’ scientific or non-scientific backgrounds were the socio-demographic variables associated with respondents having psychological challenges as P<0.05. However, none of the socio-demographic variables of the respondents were associated with compliance with the recommendations as P>0.05. Also, most (63.4%) of the respondents were stressed by the feelings associated with the COVID-19 pandemic, as the expected majority (80.1%) sources information about the epidemics through social media platforms.

Conclusion

Given numerous uncertainties surrounding the global COVID-19 pandemics, there is a need to continuously increase awareness through various media and ensure that people are highly complying with the preventive measures being put in place by relevant authorities. Also, palliative measures should be put in place to reduce the psychological impact of the pandemic.
Evaluation of Safety and Immunogenicity of an Adjuvanted, TH-1 Skewed, Whole Virion InactivatedSARS-CoV-2 Vaccine - BBV152
Authors: Ganneru Brunda , Jogdand Harsh , Dharam Vijaya Kumar , Molugu Narasimha Reddy , Prasad Sai D , Vellimudu Srinivas , Ella Krishna M , Ravikrishnan Rajaram , Awasthi Amit , Jose Jomy , Rao Panduranga , Kumar Deepak , Ella Raches , Abraham Priya , Yadav Pragya , Sapkal Gajanan N , Shete Anita , Desphande Gururaj Rao , Mohandas Sreelekshmy , Basu Atanu , Gupta Nivedita , Vadrevu Krishna Mohan
Published: September 2020

We report the development and evaluation of safety and immunogenicity of a whole virion inactivated SARS-COV-2 vaccine (BBV152), adjuvanted with aluminium hydroxide gel (Algel), or a novel TLR7/8 agonist adsorbed Algel. We used a well-characterized SARS-CoV-2 strain and an established vero cell platform to produce large-scale GMP grade highly purified inactivated antigen, BBV152. Product development and manufacturing were carried out in a BSL-3 facility. Immunogenicity was determined at two antigen concentrations (3μg and 6μg), with two different adjuvants, in mice, rats, and rabbits. Our results show that BBV152 vaccine formulations generated significantly high antigen-binding and neutralizing antibody titers, at both concentrations, in all three species with excellent safety profiles. The inactivated vaccine formulation containing TLR7/8 agonist adjuvant-induced Th1 biased antibody responses with elevated IgG2a/IgG1 ratio and increased levels of SARS-CoV-2 specific IFN-γ+ CD4 T lymphocyte response. Our results support further development for Phase I/II clinical trials in humans.
Newly regenerated axons through a cell-containing biomaterial scaffold promote reorganization of spinal circuitry and restoration of motor functions with epidural electrical stimulation
Authors: Siddiqui Ahad M. , Islam Riazul , Cuellar Carlos A. , Silvernail Jodi L. , Knudsen Bruce , Curley Dallece E. , Strickland Tammy , Manske Emilee , Suwan Parita T , Latypov Timur , Akhmetov Nafis , Zhang Shuya , Summer Priska , Nesbitt Jarred J. , Chen Bingkun K. , Grahn Peter J. , Madigan Nicolas N. , Yaszemski Michael J. , Windebank Anthony J. , Lavrov Igor
Published: September 2020

We report the effect of newly regenerated neural fibers via bioengineered scaffold on reorganization of spinal circuitry and restoration of motor functions with electrical epidural stimulation (EES) after spinal transection (ST). Restoration across multiple modalities was evaluated for 7 weeks after ST with implanted scaffold seeded with Schwann cells, producing neurotrophic factors and with rapamycin microspheres. Gradual improvement in EES-facilitated stepping was observed in animals with scaffolds, although, no significant difference in stepping ability was found between groups without EES. Similar number of regenerated axons through the scaffolds was found in rats with and without EES-enabled training. Re-transection through the scaffold at week 6, reduced EES-enabled motor function, remaining higher compared to rats without scaffolds. The combination of scaffolds and EES-enabled training demonstrated synaptic changes below the injury. These findings indicate that sub-functional connectivity with regenerated across injury fibers can reorganize of sub-lesional circuitry, facilitating motor functions recovery with EES.
The effects of multi-day rTMS and cardiorespiratory fitness on working memory and local GABA concentration
Authors: Hendrikse Joshua , Thompson Sarah , Suo Chao , Yücel Murat , Rogasch Nigel C. , Coxon James P.
Published: September 2020

Working memory (WM) refers to the capacity to temporarily retain and manipulate finite amounts of information; a critical process in complex behaviours such as reasoning, comprehension, and learning. This cognitive function is supported by a parietal-prefrontal network and linked to the activity of key neurotransmitters, such as gamma-aminobutyric acid (GABA). Impairments in WM are seen in a range of psychiatric and neurological disorders, and there are currently no effective treatments. In this study, we analysed secondary outcome measures from a trial investigating the effects of multi-day rTMS on cognition. Participants received four days of 20 Hz rTMS to an individualised region of left parietal cortex in one week, and an individualised region of pre-supplementary motor area (pre-SMA) in a separate week. We assessed changes to WM function before and after each week of stimulation (N = 39), and changes to GABA concentration before and after stimulation in week one using MR spectroscopy (N = 18 per stimulation condition). We hypothesised that parietal rTMS would enhance WM and alter GABA concentration at the site of stimulation, but this was not observed. Instead, we report some evidence of improved WM function following the first week of pre-SMA rTMS stimulation, and a generalised increase in GABA concentration across both parietal and pre-SMA voxels following pre-SMA rTMS. Additionally, we found that higher cardiorespiratory fitness was associated with greater WM improvement following pre-SMA stimulation. This study does not support the use of parietal multi-day rTMS for the enhancement of working memory. In contrast, the results suggest that increasing cardiorespiratory fitness may provide a novel approach to enhance the effects of pre-SMA rTMS on cognition.
Cytosolic sequestration of spatacsin by Protein Kinase A and 14-3-3 proteins
Authors: Cogo Susanna , Tomkins James E. , Vavouraki Nikoleta , Giusti Veronica , Forcellato Federica , Franchin Cinzia , Tessari Isabella , Arrigoni Giorgio , Cendron Laura , Manzoni Claudia , Civiero Laura , Lewis Patrick A. , Greggio Elisa
Published: September 2020

Mutations in SPG11, encoding spatacsin, constitute the major cause of autosomal recessive Hereditary Spastic Paraplegia (HSP) with thinning of the corpus callosum. Previous studies showed that spatacsin orchestrates cellular traffic events through the formation of a coat-like complex and its loss of function results in lysosomal and axonal transport impairments. However, the upstream mechanisms that regulate spatacsin trafficking are unknown. Here, using proteomics and CRISPR/Cas9-mediated tagging of endogenous spatacsin, we identified a subset of 14-3-3 proteins as physiological interactors of spatacsin. The interaction is modulated by Protein Kinase A (PKA)-dependent phosphorylation of spatacsin at Ser1955, which initiates spatacsin trafficking from the plasma membrane to the intracellular space. Our study provides novel insight in understanding spatacsin physio-pathological roles with mechanistic dissection of its associated pathways.
A new model of spinal cord injury by cryoapplication: Morphodynamics of histological changes of the spinal cord lesion
Authors: Telegin George B. , Minakov Alexey N. , Chernov Aleksandr S. , Kazakov Vitaly A. , Кalabina Elena A. , Belogurov Alexey A. , Konovalov Nikolay A. , Gabibov Aleksandr G
Published: September 2020

Up to 500,000 people worldwide suffer from spinal cord injuries (SCI) annually, according to the WHO. Animal models are essential for searching novel methodological guidelines and therapeutic agents for SCI treatment. We developed an original model of posttraumatic spinal cord glial scar in rats using cryoapplication. The method is based on cryodestruction of spinal cord tissue with liquid nitrogen. Thirty six male SD linear rats of SPF category were included in this experimental study. A T13 unilateral hemilaminectomy was performed with an operating microscope, as it was extremely important not to penetrate the dura mater, and liquid nitrogen was applied into the bone defect for one minute. The animals were euthanized at various intervals ranging from 1 to 60 days after inducing cryogenic trauma, their Th12-L1 vertebrae were removed “en bloc” and the segment of the spinal cord exposed to the cryoapplicator was carefully separated for histological examination. The study results demonstrated that cryoapplication of liquid nitrogen, provoking a local temperature of approximately minus 20°C, produced a highly standardized transmural defect which extended throughout the dorsoventral arrangement of the spinal cord and had an “hour-glass” shape. During the entire study period (1-60 post-injury days), the glial scarring process and the spinal cord defect were located within the surgically approached vertebral space (Th13). Unlike other available experimental models of SCI (compression, contusion, chemical, etc.), the present option is characterized by a minimal invasiveness (the hemilaminectomy is less than 1 mm wide), high precision and consistency. Also, there was a low interanimal variability in histological lesions and dimensions of the produced defect. The original design of cryoapplicator used in the study played a major role in achieving these results. The original technique of high-precision cryoapplication for inducing consistent morphodynamic glial scarring could facilitate a better understanding of the self-recovery processes of injured spinal cord and would be helpful for proposing new platforms for the development of therapeutic strategies.
Adaptive dating and fast proposals: revisiting the phylogenetic relaxed clock model
Authors: Douglas Jordan , Zhang Rong , Bouckaert Remco
Published: September 2020

Uncorrelated relaxed clock models enable estimation of molecular substitution rates across lineages and are widely used in phylogenetics for dating evolutionary divergence times. In this article we delved into the internal complexities of the relaxed clock model in order to develop efficient MCMC operators for Bayesian phylogenetic inference. We compared three substitution rate parameterisations, introduced an adaptive operator which learns the weights of other operators during MCMC, and we explored how relaxed clock model estimation can benefit from two cutting-edge proposal kernels: the AVMVN and Bactrian kernels. This work has produced an operator scheme that is up to 65 times more efficient at exploring continuous relaxed clock parameters compared with previous setups, depending on the dataset. Finally, we explored variants of the standard narrow exchange operator which are specifically designed for the relaxed clock model. In the most extreme case, this new operator traversed tree space 40% more efficiently than narrow exchange. The methodologies introduced are adaptive and highly effective on short as well as long alignments. The results are available via the open source optimised relaxed clock (ORC) package for BEAST 2 under a GNU licence (https://github.com/jordandouglas/ORC).

Author summary

Biological sequences, such as DNA, accumulate mutations over generations. By comparing such sequences in a phylogenetic framework, the evolutionary tree of lifeforms can be inferred. With the overwhelming availability of biological sequence data, and the increasing affordability of collecting new data, the development of fast and efficient phylogenetic algorithms is more important than ever. In this article we focus on the relaxed clock model, which is very popular in phylogenetics. We explored how a range of optimisations can improve the statistical inference of the relaxed clock. This work has produced a phylogenetic setup which can infer parameters related to the relaxed clock up to 65 times faster than previous setups, depending on the dataset. The methods introduced adapt to the dataset during computation and are highly efficient when processing long biological sequences.
Molecular evidence for the hybrid origin ofCryptocoryne ×purpureaRidl. nothovar.purpurea(Araceae)
Authors: Rosazlina Rusly , Jacobsen Niels , Ørgaard Marian , Othman Ahmad Sofiman
Published: September 2020

Natural hybridization has been considered a source of taxonomic complexity inCryptocoryne. A combined study of DNA sequencing data from internal transcribed spacer (ITS) of nuclear ribosomal DNA andtrnK-matKregion of chloroplast DNA was used to identify the parents ofCryptocoryneputative hybrids from Peninsular Malaysia. Based on the morphological intermediary and sympatric distribution, the plants were tentatively identified as the hybridCryptocoryne ×purpureanothovar.purpurea;plants were pollen sterile and had long been considered to be hybrids, possibly between two related and co-existing species,C. cordatavar. cordataandC. griffithii. TheC. ×purpureanothovar.purpureastatus was independently confirmed by the presence of an additive ITS sequence pattern from these two parental species in hybrid individuals. Analysis of the chloroplasttrnK-matKsequences showed that the hybridization is bidirectional with the putative hybrids sharing identical sequences fromC. cordatavar. cordataandC. griffithii, indicating that both putative parental species had been the maternal parent in different accessions.
Fish harvesting advice under climate change: a risk-equivalent empirical approach
Authors: Duplisea Daniel E. , Roux Marie-Julie , Hunter Karen L. , Rice Jake
Published: September 2020

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The rate of climate change (CC) has accelerated to the point where it now affects the mid-to long-term sustainability of fishing strategies. Therefore, it is important to consider practical and effective ways to incorporate CC into fisheries advice so that the advice can be considered conditioned to CC. We developed a quantitative model to characterise the empirical relationship between a variable affected by climate and fish production. We then used model projections as a foundation for a risk analysis of CC effects on harvesting of Greenland halibutReinhardtius hippoglossoidesin the Gulf of St Lawrence, Canada. The risk-based approach quantified a) the relative change in risk of a status quo fishing strategy under various CC scenarios, and b) the change in fishery exploitation rates required to achieve a management objective over a specified time period at a level of risk considered acceptable (risk equivalent fishery exploitation advice). This empirical approach can be used to develop risk-based advice for any other external variable that affects stock production in addition to climate-related variables and it can be applied in most situations where there is an index of stock biomass and fisheries catch. Shifting the focus from process-based understanding of the responses of fish stocks to CC to quantification of how CC-contributed uncertainty can alter the risks associated with different fishing strategies and/or management options, can ensure timely delivery of robust scientific advice for fisheries under non-stationary environmental conditions.
Individual differences in honey bee behavior enabled by plasticity in brain gene regulatory networks
Authors: Jones Beryl M. , Rao Vikyath D. , Gernat Tim , Jagla Tobias , Cash-Ahmed Amy , Rubin Benjamin E. R. , Comi Troy J. , Bhogale Shounak , Husain Syed S. , Blatti Charles , Middendorf Martin , Sinha Saurabh , Chandrasekaran Sriram , Robinson Gene E.
Published: September 2020

Understanding the regulatory architecture of phenotypic variation is a fundamental goal in biology, but connections between gene regulatory network (GRN) activity and individual differences in behavior are poorly understood. We characterized the molecular basis of behavioral plasticity in queenless honey bee (Apis mellifera) colonies, where individuals engage in both reproductive and non-reproductive behaviors. Using high-throughput behavioral tracking, we discovered these colonies contain a continuum of phenotypes, with some individuals specialized for either egg-laying or foraging and “generalists” that perform both. Brain gene expression and chromatin accessibility profiles were correlated with behavioral variation, with generalists intermediate in behavior and molecular profiles. Models of brain GRNs constructed for individuals revealed that transcription factor (TF) activity was highly predictive of behavior, and behavior-associated regulatory regions had more TF motifs. These results provide new insights into the important role played by brain GRN plasticity in the regulation of behavior, with implications for social evolution.
Relative matching using low coverage sequencing
Authors: Petter Ella , Schweiger Regev , Shahino Bar , Shor Tal , Aker Malka , Almog Lior , Weissglas-Volkov Daphna , Naveh Yoav , Navon Oron , Carmi Shai , Li Jeremiah H. , Berisa Tomaz , Pickrell Joseph K. , Erlich Yaniv
Published: September 2020

Finding familial relatives using DNA has multiple applications, in genetic genealogy, population genetics, and forensics. So far, most relative matching algorithms rely on detecting identity-by-descent (IBD) segments with high quality genotype data. Recently, low coverage sequencing (LCS) has received growing attention as a promising cost-effective method to ascertain genomic information. However, with higher error rates, it is unclear whether existing IBD detection can work on LCS datasets. Here, we developed and tested a framework for relative matching using sequencing with 1× coverage (1×LCS). We started by exploring the error characteristics of this method compared to array data. Our results show that after some optimization 1×LCS can exhibit the same genotyping discordance rates as the discordance between two array platforms. Using this observation, we developed a hybrid framework for relative matching and tuned this framework with >2,700 pairs of confirmed genealogical relatives that were genotyped using heterogenous datasets. We then obtained array and 1×LCS on 19 samples and use our framework to find relatives in a database of over 3 million individuals. The total length of shared segments obtained by 1×LCS was virtually indistinguishable to genotyping arrays for matches with a total sharing >200cM (second cousins or closer). For more distant relatives, as long as those were detected by both technologies, the total length obtained by LCS and by genotyping arrays was highly correlated, with no evidence of over- or underestimation. Taken together, our results show that 1×LCS can be a valid alternative to arrays for relative matching, opening the possibility for further democratization of genomic data.
Natural sensory context drives diverse brain-wide activity duringC. elegansmating
Authors: Susoy Vladislav , Hung Wesley , Witvliet Daniel , Whitener Joshua E. , Wu Min , Graham Brett J. , Zhen Mei , Venkatachalam Vivek , Samuel Aravinthan D.T.
Published: September 2020

Natural goal-directed behaviors often involve complex sequences of many stimulus-triggered components. Understanding how brain circuits organize such behaviors requires mapping the interactions between an animal, its environment, and its nervous system. Here, we use continuous brain-wide neuronal imaging to study the full performance of mating by theC. elegansmale. We show that as each mating unfolds in its own sequence of component behaviors, the brain operates similarly between instances of each component, but distinctly between different components. When the full sensory and behavioral context is taken into account, unique roles emerge for each neuron. Functional correlations between neurons are not fixed, but change with behavioral dynamics. From the contribution of individual neurons to circuits, our study shows how diverse brain-wide dynamics emerge from the integration of sensory perception and motor actions within their natural context.