bluuebunny/crossref_metadata_2025 huggingface dataset:
Genotyping by sequencing for identification and mapping of QTLs for bioenergy-related traits in sweet sorghum
Authors: Teingtham Kanokwan , Braun David M. , Dweikat Ismail
Published: June 2020

Sweet sorghum (Sorghum bicolorL. Moench) is a promising bioenergy crop. To increase the productivity of this crop, marker-assisted breeding will be important to advance genetic improvement of sweet sorghum. The objective of the present study was to identify quantitative trait loci (QTLs) associated with bioenergy-related traits in sweet sorghum. We used 188 F7recombinant inbred lines (RILs) derived from a cross between sweet sorghum (Wray) and grain sorghum (Macia). The RILs and their parental lines were grown at two locations in 2012 and 2013. Genotyping-by-sequencing analysis of the RILs allowed the construction of a map with 979 single nucleotide polymorphisms. Using the inclusive composite interval mapping of additive QTLs, major QTLs for flowering time and head moisture content were detected on chromosome 6, and explained 29.45% and 20.65% of the phenotypic variances (PVE), respectively. Major QTLs for plant height (29.51% PVE) and total biomass yield (16.46% PVE) were detected on chromosome 7, and QTLs for stem diameter (9.43% PVE) and 100 seed weight (22.97% PVE) were detected on chromosome 1. A major QTL for brix (39.92% PVE) and grain yield (49.14%) PVE co-localized on chromosome 3, was detected consistently across four environments, and is closely associated with a SWEET sugar transporter gene. Additionally, several other QTLs for brix identified in this study or reported previously were found to be associated with sugar transporter genes. The identified QTLs in this study will help to further understand the underlying genes associated with bioenergy-related traits and could be used for development of molecular markers for marker-assisted selection.
Differential role of cytosolic Hsp70s in longevity assurance and protein quality control
Authors: Andersson Rebecca , Eisele-Bürger Anna Maria , Hanzén Sarah , Vielfort Katarina , Öling David , Eisele Frederik , Johansson Gustav , Gustafsson Tobias , Kvint Kristian , Nyström Thomas
Published: June 2020

70 kDa heat shock proteins (Hsp70) are essential chaperones of the protein quality control network; vital for cellular fitness and longevity. The four cytosolic Hsp70’s in yeast, Ssa1-4, are thought to be functionally redundant but the absence of Ssa1 and Ssa2 causes a severe reduction in cellular reproduction and accelerates replicative aging. In our efforts to identify which Hsp70 activities are most important for longevity assurance, we systematically investigated the capacity of Ssa4 to carry out the different activities performed by Ssa1/2 by overproducing Ssa4 in cells lacking these Hsp70 chaperones. We found that Ssa4, when overproduced in cells lacking Ssa1/2, rescued growth, mitigated aggregate formation, restored spatial deposition of aggregates into protein inclusions, and promoted protein degradation. In contrast, Ssa4 overproduction in the Hsp70 deficient cells failed to restore the recruitment of the disaggregase Hsp104 to misfolded/aggregated proteins, to fully restore clearance of protein aggregates, and to bring back the formation of the nucleolus-associated aggregation compartment. Exchanging the nucleotide-binding domain of Ssa4 with that of Ssa1 suppressed this ‘defect’ of Ssa4. Interestingly, Ssa4 overproduction extended the short lifespan ofssa1Δssa2Δ mutant cells to a lifespan comparable to, or even longer than, wild type cells, demonstrating that Hsp104-dependent aggregate clearance is not a prerequisite for longevity assurance in yeast.

AUTHOR SUMMARY

All organisms have proteins that network together to stabilize and protect the cell throughout its lifetime. One of these types of proteins are the Hsp70s (heat shock protein 70). Hsp70 proteins take part in folding other proteins to their functional form, untangling proteins from aggregates, organize aggregates inside the cell and ensure that damaged proteins are destroyed. In this study, we investigated three closely related Hsp70 proteins in yeast; Ssa1, 2 and 4, in an effort to describe the functional difference of Ssa4 compared to Ssa1 and 2 and to answer the question: What types of cellular stress protection are necessary to reach a normal lifespan? We show that Ssa4 can perform many of the same tasks as Ssa1 and 2, but Ssa4 doesn’t interact in the same manner as Ssa1 and 2 with other types of proteins. This leads to a delay in removing protein aggregates created after heat stress. Ssa4 also cannot ensure that misfolded proteins aggregate correctly inside the nucleus of the cell. However, this turns out not to be necessary for yeast cells to achieve a full lifespan, which shows us that as long as cells can prevent aggregates from forming in the first place, they can reach a full lifespan.
Subsurface carbon monoxide oxidation capacity revealed through genome-resolved metagenomics of a carboxydotroph
Authors: Mu Andre , Thomas Brian C. , Banfield Jillian F. , Moreau John W.
Published: June 2020

Microbial communities play important roles in the biogeochemical cycling of carbon in the Earth’s deep subsurface. Previously, we demonstrated changes to the microbial community structure of a deep aquifer (1.4 km) receiving 150 tons of injected supercritical CO2(scCO2) in a geosequestration experiment. The observed changes support a key role in the aquifer microbiome for the thermophilic CO-utilising anaerobeCarboxydocella,which decreased in relative abundance post-scCO2injection. Here, we present results from more detailed metagenomic profiling of this experiment, with genome resolution of the native carboxydotrophicCarboxydocella.We demonstrate a switch in CO-oxidation potential byCarboxydocellathrough analysis of its carbon monoxide dehydrogenase (CODH) gene before and after the geosequestration experiment. We discuss the potential impacts of scCO2on subsurface flow of carbon and electrons from oxidation of the metabolic intermediate carbon monoxide (CO).

Originality-Significance Statement

The research conducted in this study is associated with one of the world’s largest demonstrations of carbon geosequestration – The Cooperative Research Centre for Greenhouse Gas Technologies Otway Project (Victoria, Australia). Our results expand the ecology of CO-utilising microbes to include the terrestrial deep subsurface through genome-resolved metagenomics of an aquifer-native carboxydotroph.
A molecular pore spans the double membrane of the coronavirus replication organelle
Authors: Wolff Georg , Limpens Ronald W.A.L. , Zevenhoven-Dobbe Jessika C. , Laugks Ulrike , Zheng Shawn , de Jong Anja W. M. , Koning Roman I. , Agard David A. , Grünewald Kay , Koster Abraham J. , Snijder Eric J. , Bárcena Montserrat
Published: June 2020

Coronavirus genome replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored micro-environment for viral RNA synthesis in the infected cell. However, it is unclear how newly synthesized genomes and mRNAs can travel from these sealed replication compartments to the cytosol to ensure their translation and the assembly of progeny virions. Here, using cellular electron cryo-microscopy, we unveiled a molecular pore complex that spans both membranes of the double-membrane vesicle and would allow export of RNA to the cytosol. A hexameric assembly of a large viral transmembrane protein was found to form the core of the crown-shaped complex. This coronavirus-specific structure likely plays a critical role in coronavirus replication and thus constitutes a novel drug target
Evolutionary dynamics of bipartite begomoviruses revealed by complete genome analysis
Authors: Xavier César A.D. , Godinho Márcio T. , Mar Talita B. , Ferro Camila G. , Sande Osvaldo F.L. , Silva José C. , Ramos-Sobrinho Roberto , Nascimento Renato N. , Assunção Iraildes , Lima Gaus S.A. , Lima Alison T.M. , Zerbini F.Murilo
Published: June 2020

Several key evolutionary events marked the evolution of geminiviruses, culminating with the emergence of bipartite genomes represented by viruses classified in the genusBegomovirus. This genus represents the most abundant group of multipartite viruses, contributing significantly to the observed abundance of multipartite species in the virosphere. Although aspects related to virus-host interactions and evolutionary dynamics have been extensively studied, the bipartite nature of these viruses has been little explored in evolutionary studies. We performed a parallel evolutionary analysis of the DNA-A and DNA-B components of New World begomoviruses. A total of 239 full-length DNA-B sequences obtained in this study, combined with 292 DNA-A and 76 DNA-B sequences retrieved from GenBank, were analyzed. The results indicate that the DNA-A and DNA-B respond differentially to evolutionary processes, with the DNA-B being more permissive to variation and more prone to recombination than the DNA-A. Although a clear geographic segregation was observed for both components, differences in the genetic structure between DNA-A and DNA-B were also observed, with cognate components belonging to distinct genetic clusters. DNA-B coding regions evolve under the same selection pressures than DNA-A coding regions. Together, our results indicate an interplay between reassortment and recombination acting at different levels across distinct subpopulations and components.
Actomyosin forces and the energetics of red blood cell invasion by the malaria parasitePlasmodium falciparum
Authors: Blake Thomas C. A. , Haase Silvia , Baum Jake
Published: June 2020

All symptoms of malaria disease are associated with the asexual blood stages of development, involving cycles of red blood cell (RBC) invasion and egress by thePlasmodiumspp. merozoite. Merozoite invasion is rapid and is actively powered by a parasite actomyosin motor. The current accepted model for actomyosin force generation envisages arrays of parasite myosins, pushing against short actin filaments connected to the external milieu that drive the merozoite forwards into the RBC. InPlasmodium falciparum, the most virulent human malaria species, Myosin A (PfMyoA) is critical for parasite replication. However, the precise function of PfMyoA in invasion, its regulation, the role of other myosins and overall energetics of invasion remain unclear. Here, we developed a conditional mutagenesis strategy combined with live video microscopy to probe PfMyoA function and that of the auxiliary motor PfMyoB in invasion. By imaging conditional mutants with increasing defects in force production, based on disruption to a key PfMyoA phospho-regulation site, the absence of the PfMyoA essential light chain, or complete motor absence, we define three distinct stages of incomplete RBC invasion. These three defects reveal three energetic barriers to successful entry: RBC deformation (pre-entry), mid-invasion initiation, and completion of internalisation, each requiring an active parasite motor. In defining distinct energetic barriers to invasion, these data illuminate the mechanical challenges faced in this remarkable process of protozoan parasitism, highlighting distinct myosin functions and identifying potential targets for preventing malaria pathogenesis.
A Thermodynamic Model of Mesoscale Neural Field Dynamics: Derivation and Linear Analysis
Authors: Qin Y. , Maurer A.P. , Sheremet A.
Published: June 2020

Motivated by previous research suggesting that mesoscopic collective activity has the defining characteristics of a turbulent system, we postulate a thermodynamic model based on the fundamental assumption that the activity of a neuron is characterized by two distinct stages: a sub-threshold stage, described by the value of mean membrane potential, and a transitional stage, corresponding to the firing event. We therefore distinguish between two types of energy: the potential energy released during a spike, and the internal kinetic energy that triggers a spike. Formalizing these assumptions produces a system of integro-differential equations that generalizes existing models [Wilson and Cowan, 1973, Amari, 1977], with the advantage of providing explicit equations for the evolution of state variables. The linear analysis of the system shows that it supports single- or triple-point equilibria, with the refractoriness property playing a crucial role in the generation of oscillatory behavior. In single-type (excitatory) systems this derives from the natural refractory state of a neuron, producing “refractory oscillations” with periods on the order of the neuron refractory period. In dual-type systems, the inhibitory component can provide this functionality even if neuron refractory period is ignored, supporting mesoscopic-scale oscillations at much lower activity levels. Assuming that the model has any relevance for the interpretation of LFP measurements, it provides insight into mesocale dynamics. As an external forcing, theta may play a major role in modulating key parameters of the system: internal energy and excitability (refractoriness) levels, and thus in maintaining equilibrium states, and providing the increased activity necessary to sustain mesoscopic collective action. Linear analysis suggest that gamma oscillations are associated with the theta trough because it corresponds to higher levels of forced activity that decreases the stability of the equilibrium state, facilitating mesoscopic oscillations.
Biomimetic system design for engineering biofidelic 3-D respiratory tissuesin vitro
Authors: Poon C. , Zhang M. , Boughton P. , Hong A. , Ruys A.
Published: June 2020

Objective

The structural and functional complexity of the respiratory system present significant challenges to capturing conditions vital for maintaining phenotypic cellular functions in vitro. Here we report a unique tissue engineering system that enables respiratory constructs to be cultured under physiological loading at an air-liquid interface (ALI).

Methods

The system consists of a porous poly-e-caprolactone scaffold mounted in a well insert, which articulates via magnetic coupling with a linear actuator device to strain attached scaffolds through a sterile barrier. For proof of concept, NCI-H460 human carcinoma cells were seeded on scaffold inserts which were subjected to 5-15% cyclic tensile strain at 0.2Hz within a six well plate. The dynamic constructs were cultured at an ALI in a standard incubator for up to 10 days along with unstimulated (static) ALI and static submerged control groups.

Results

High (near-100%) cell seeding efficiency was achieved within the scaffold-strain device. Both dynamic and static ALI groups yielded higher cell densities compared to the submerged control for all time points. Distinctly different patterns in cellular growth and behaviour between dynamic air-liquid interface and conventional static submerged culture groups were revealed by nuclei staining, where the actuated group displayed more uniform cellular distribution throughout the construct compared to both static controls.

Conclusion

Air-liquid interface culture and physiological strain are important for engineering respiratory tissue models.

Significance

The system described allows scalable and replicable culture of 3-D tissue engineered respiratory models under biologically-relevant conditions.
Patients’ accounts of living with and managing Inflammatory Bowel Disease in rural Southern New Zealand: a qualitative study
Authors: Richard Lauralie , Noller Geoff , Derrett Sarah , Sullivan Trudy , Doolan-Noble Fiona , McCombie Andrew , Schultz Michael , Ho Christine , Stokes Tim
Published: June 2020

Objective

To explore how adults living with Inflammatory Bowel Disease (IBD) in rural New Zealand manage their condition and engage with health care providers.

Design

Qualitative exploratory design with semi-structured interviews analysed thematically.

Setting and participants

Interviews were conducted with 18 people living with IBD in the Otago region of the South Island.

Results

Five important constructs were identified: 1. Journey to confirming and accepting diagnosis; 2. Importance of the relationship with the health care team; 3. Support from others; 4. Learning how to manage IBD; and 5. Care at a distance - experiences of rurality. Pathways to confirming diagnosis involved two contrasting journeys: a long and slow process where diagnosis remained unclear for a prolonged period, and a more acute process where diagnosis typically came as a shock. Central to the acceptance process was acknowledging the chronicity of the condition, which involved feelings of grief but also the fear of judgement and stigma. Building a strong relationship with the specialist was central to medical management, particularly in the initial stage following diagnosis. Support from others was critical, enabling participants to progress through acceptance of the disease and developing confidence in its everyday management. Participants shared different strategies on how to manage IBD, describing a “trial and error” process of “finding what’s right” at different stages of the condition. Managing IBD rurally involved challenges of access to specialist care, with perceptions of delayed referrals and concerns about disparities in specialist access compared to urban counterparts. Rural living also had financial implications - cost of time and cost of mobilising resources for long travels to the urban centre for treatments.

Conclusions

Findings from this study provide a rich understanding of the complex health journeys of people living with IBD and the challenges of managing the condition rurally.

STRENGTHS AND LIMITATIONS OF THIS STUDY
Machine Learning Prediction Models for Chronic Kidney Disease using National Health Insurance Claim Data in Taiwan
Authors: Krishnamurthy Surya , Kapeleshh KS , Dovgan Erik , Luštrek Mitja , Gradišek Piletič Barbara , Srinivasan Kathiravan , Li Yu-Chuan , Gradišek Anton , Syed-Abdul Shabbir
Published: June 2020

Background and Objective

Chronic kidney disease (CKD) represent a heavy burden on the healthcare system because of the increasing number of patients, high risk of progression to end-stage renal disease, and poor prognosis of morbidity and mortality. The aim of this study is to develop a machine-learning model that uses the comorbidity and medication data, obtained from Taiwan's National Health Insurance Research Database, to forecast whether an individual will develop CKD within the next 6 or 12 months, and thus forecast the prevalence in the population.

Methods

A total of 18,000 people with CKD and 72,000 people without CKD diagnosis along with the past two years of medication and comorbidity data matched by propensity score were used to build a predicting model. A series of approaches were tested, including Convoluted Neural Networks (CNN). 5-fold cross-validation was used to assess the performance metrics of the algorithms.

Results

Both for the 6 month and 12-month models, the CNN approach performed best, with the AUROC of 0.957 and 0.954, respectively. The most prominent features in the tree-based models were identified, including diabetes mellitus, age, gout, and medications such as sulfonamides, angiotensins which had an impact on the progression of CKD.

Conclusions

The model proposed in this study can be a useful tool for the policy-makers helping them in predicting the trends of CKD in the population in the next 6 to 12 months. Information provided by this model can allow closely monitoring the people with risk, early detection of CKD, better allocation of resources, and patient-centric management
Nitrogen dioxide exposures from LPG stoves in a cleaner-cooking intervention trial
Authors: Kephart Josiah L , Fandiño-Del-Rio Magdalena , Williams Kendra N , Malpartida Gary , Lee Alexander , Steenland Kyle , Naeher Luke P. , Gonzales Gustavo F. , Chiang Marilu , Checkley William , Koehler Kirsten ,   CHAP trial Investigators
Published: June 2020

Background

Liquefied petroleum gas (LPG) stoves have been promoted in low- and middle-income countries (LMICs) as a clean energy alternative to biomass burning cookstoves.

Objective

We sought to characterize kitchen area concentrations and personal exposures to nitrogen dioxide (NO2) within a randomized controlled trial in the Peruvian Andes. The intervention included the provision of an LPG stove and continuous fuel distribution with behavioral messaging to maximize compliance.

Methods

We measured 48-hour kitchen area NO2 concentrations at high temporal resolution in homes of 50 intervention participants and 50 control participants longitudinally within a biomass-to-LPG intervention trial. We also collected 48-hour mean personal exposures to NO2 among a subsample of 16 intervention and 9 control participants. We monitored LPG and biomass stove use continuously throughout the trial.

Results

In 367 post-intervention 24-hour kitchen area samples of 96 participants’ homes, geometric mean (GM) highest hourly NO2 concentration was 138 ppb (geometric standard deviation [GSD] 2.1) in the LPG intervention group and 450 ppb (GSD 3.1) in the biomass control group. Post-intervention 24-hour mean NO2 concentrations were a GM of 43 ppb (GSD 1.7) in the intervention group and 77 ppb (GSD 2.0) in the control group. Kitchen area NO2 concentrations exceeded the WHO indoor hourly guideline an average of 1.3 hours per day among LPG intervention participants. GM 48-hour personal exposure to NO2 was 5 ppb (GSD 2.4) among 35 48-hour samples of 16 participants in the intervention group and 16 ppb (GSD 2.3) among 21 samples of 9 participants in the control group.

Discussion

In a biomass-to-LPG intervention trial in Peru, kitchen area NO2 concentrations were substantially lower within the LPG intervention group compared to the biomass-using control group. However, within the LPG intervention group, 69% of 24-hour kitchen area samples exceeded WHO indoor annual guidelines and 47% of samples exceeded WHO indoor hourly guidelines. Forty-eight-hour NO2 personal exposure was below WHO indoor annual guidelines for most participants in the LPG intervention group, and we did not measure personal exposure at high temporal resolution to assess exposure to cooking-related indoor concentration spikes. Further research is warranted to understand the potential health risks of LPG-related NO2 emissions and inform current campaigns which promote LPG as a clean-cooking option.
Care Giver’s Experiences of Having a Child with Hydrocephalus: A Phenomenological Study at Ruharo Mission Hospital
Authors: Kyarimpa Racheal , Muramuzi Dan , Muhwezi Talbert
Published: June 2020

Background

Hydrocephalus is a long-term neurologic condition, normally identified in early childhood, where there is excessive fluid in the ventricular system within the brain which results into enlargement of the head to an abnormal size. The most common cause of hydrocephalus in most patient population is infection (over 60%) typically meningitis. In Uganda, it is estimated that about 1000 to 2000 new cases of hydrocephalus occur every year with 60 percent of these are reportedly attributed to neonatal infections. The general objective was to explore care givers‘ experiences of living with a child having hydrocephalus.

Methods

The phenomenological descriptive study involved fifteen respondents who were purposively selected. The in-depth interviews were conducted with the aid of an interview guide and a tape recorder. Transcribed interviews were analyzed using the thematic approach.

Results

Care givers were experiencing financial problems, psychological problems, lack of social support and cultural constraints and stigma associated with hydrocephalus. The care givers experiences were full of life changes and coping strategies, and they used both problem and emotion focused coping strategies to deal with the challenges as compassionate and responsive care was illustrated by the participants.

Conclusion

The study discovered that having a child with hydrocephalus is challenging and frustrating in terms of financial, physical, social, and psychological experience. Therefore, these findings are essential for counselling care givers, families and communities affected by hydrocephalus. In this context, attention should be targeted to families and communities to reduce stigma and isolation faced by the affected.
A Digital Therapeutic Intervention for Smoking Cessation in Adult Smokers: Randomized Controlled Trial
Authors: Webb Jamie , Peerbux Sarrah , Smittenaar Peter , Siddiqui Sarim , Sherwani Yusuf , Ahmed Maroof , MacRae Hannah , Puri Hannah , Bhalla Sangita , Majeed Azeem
Published: June 2020

Background

Tobacco smoking remains the leading cause of preventable death and disease worldwide. Digital interventions delivered through smartphones offer a promising alternative to traditional methods, but little is known about their effectiveness.

Objective

Our objective was to test the effectiveness of Quit Genius, a novel digital therapeutic intervention for smoking cessation.

Methods

A two-arm, single-blinded, parallel-group randomized controlled trial design was used. Participants were recruited via referrals from primary care practices and social media advertisements in the UK. 556 Adult smokers (aged ≥18 years), smoking at least five cigarettes a day for the past year were recruited. 530 were included for the final analysis. Participants were randomized to one of two interventions. Treatment consisted of a digital therapeutic intervention for smoking cessation consisting of a smartphone application delivering cognitive behavioral therapy content, one-to-one coaching, craving tools and tracking capabilities. The control intervention was Very Brief Advice along the Ask, Advise, Act model. All participants were offered nicotine replacement therapy for three months. A random half of each arm was assigned a carbon monoxide (CO) device for biochemical verification. Outcomes were self-reported via phone or online. The primary outcome was self-reported 7-day point prevalence abstinence at 4-weeks post quit date.

Results

556 participants were randomized (treatment n=277, control n=279). The intention-to-treat analysis included 530 participants (n=265 in each arm; 11 excluded for randomization before trial registration, and 15 for protocol violations at baseline visit). By the quit date (an average 16 days after randomization) 89% (236/265) of those in the treatment arm were still actively engaged. At the time of primary outcome, 74% (196) of participants were still engaging with the app. At 4-weeks post-quit date, 45% (118) of participants in the treatment arm had not smoked in the preceding 7-days, compared to 29% (76) in control (risk ratio 1.55, 1.23-1.96, P = .0002; intention-to-treat, N=530). Self-reported 7-day abstinence agreed with CO measurement (CO <10 ppm) in 96% of cases (80/83) where CO readings were available. No harmful effects of the intervention were observed.

Conclusions

The Quit Genius digital therapeutic intervention is a superior treatment in achieving smoking cessation four weeks post quit date compared to very brief advice.

Trial Registration

The trial was registered in the ISRCTN database on December 18, 2018 (https://www.isrctn.com/ISRCTN65853476).
An Epidemic Model SIPHERD and its application for prediction of the spread of COVID-19 infection in India
Authors: Mahajan Ashutosh , Solanki Ravi , Sivadas Namitha
Published: June 2020

After originating from Wuhan, China, in late 2019, with a gradual spread in the last few months, COVID-19 has become a pandemic crossing 9 million confirmed positive cases and 450 thousand deaths. India is not only an overpopulated country but has a high population density as well, and at present, a high-risk nation where COVID-19 infection can go out of control. In this paper, we employ a compartmental epidemic model SIPHERD for COVID-19 and predict the total number of confirmed, active and death cases, and daily new cases. We analyze the impact of lockdown and the number of tests conducted per day on the prediction and bring out the scenarios in which the infection can be controlled faster. Our findings indicate that increasing the tests per day at a rapid pace (10k per day increase), stringent measures on social-distancing for the coming months and strict lockdown in the month of July all have a significant impact on the disease spread.
Impact of the Use of a WhatsApp-based Group Chat for Sharing Emergency Department Access-Block Data on Overcrowding and Census in a Low-Resource Emergency Department in Kigali, Rwanda
Authors: Nkeshimana Menelas , Uwineza Christine , Pousson Amelia Y , Cattermole Giles N
Published: June 2020

In Low & Middle Income Countries (LMICs), hospitals often face serious communication issues that threaten to paralyze the process of healthcare provision. The Centre Hospitalier Universitaire de Kigali (CHUK) is located in the middle of a vibrant city of Kigali, and is often overwhelmed by a high number of referred patients from its catchment area, and those brought in by emergency evacuation ambulance system (SAMU). The facility has no interdepartmental landline communication network, which would be ideal to connect the inpatient services to the emergency room in order to fasten the care process. Using WhatsApp-based Group Chat for sharing the real-time caseloads, the number of patients boarding the emergency room has significantly improved (dropping from 38.1 +-7.1 to 28 +-6.5, p<0.001), although the overall length of stay in the emergency room has remained high (3.37 +-0.61 days), mainly due to other co-factors such as the availability of specialized staff (i.e. neurosurgeon) and uninterrupted imaging services (i.e. computer tomography scans).
Genetically informed precision drug repurposing for lung function and implications for respiratory infection
Authors: Reay William R. , Shair Sahar I. El , Geaghan Michael P. , Riveros Carlos , Holliday Elizabeth G. , McEvoy Mark A. , Hancock Stephen , Peel Roseanne , Scott Rodney J. , Attia John R. , Cairns Murray J.
Published: June 2020

Impaired lung function is associated with significant morbidity and mortality. Restrictive and obstructive lung disorders are a large contributor to decreased lung function, as well as the acute impact of infection. Measures of pulmonary function are heritable, and thus, we sought to utilise genomics to propose novel drug repurposing candidates which could improve respiratory outcomes. Lung function measures were found to be genetically correlated with metabolic and hormone traits which could be pharmacologically modulated, with a causal effect of increased fasting glucose on diminished lung function supported by latent causal variable models and Mendelian randomisation. We developed polygenic scores for lung function specifically within pathways with known drug targets to prioritise individuals who may benefit from particular drug repurposing opportunities, accompanied by transcriptome-wide association studies to identify drug-gene interactions with potential lung function increasing modes of action. These drug repurposing candidates were further considered relative to the host-viral interactome of three viruses with associated respiratory pathology (SARS-CoV2, influenza, and human adenovirus). We uncovered an enrichment amongst glycaemic pathways of human proteins which putatively interact with virally expressed SARS-CoV2 proteins, suggesting that antihyperglycaemic agents may have a positive effect both on lung function and SARS-CoV2 progression.
Detection of SARS-CoV-2 in ascitic fluid: a case of viral peritonitis?
Authors: Passarelli Victor C. , Perosa Ana H. , Luna Luciano , Conte Danielle D. , Nascimento Oliver A. , Ota-Arakaki Jaquelina , Bellei Nancy
Published: June 2020

SARS Coronavirus-2 detection in different clinical specimens, including serum and stool, has raised important insights about its dynamics and pathogenesis, but some details remain to be understood.

In that respect, disrupt viral control seen in immunocompromising conditions can help unveil pathogenetic mechanisms and characterize new Coronavirus Disease-19 immunological and clinical aspects in general.

We herein report a case of cirrhosis decompensation with ascites due to COVID-19 and unprecedented detection of SARS-CoV-2 in ascitic fluid, hence a possible acute viral peritonitis, as well as in serum, leading to a fatal disseminated infection.
Genomic and multi-tissue proteomic integration for understanding the biology of disease and other complex traits
Authors: Yang Chengran , Farias Fabiana G. , Ibanez Laura , Sadler Brooke , Fernandez Maria Victoria , Wang Fengxian , Bradley Joseph L. , Eiffert Brett , Bahena Jorge A. , Budde John P. , Li Zeran , Dube Umber , Sung Yun Ju , Mihindukulasuriya Kathie A. , Morris John C. , Fagan Anne , Perrin Richard J. , Benitez Bruno , Rhinn Herve , Harari Oscar , Cruchaga Carlos
Published: June 2020

Expression quantitative trait loci (eQTL) mapping has successfully resolved some genome-wide association study (GWAS) loci for complex traits1–6. However, there is a need for implementing additional “omic” approaches to untangle additional loci and provide a biological context for GWAS signals. We generated a detailed landscape of the genomic architecture of protein levels in multiple neurologically relevant tissues (brain, cerebrospinal fluid (CSF) and plasma), by profiling thousands of proteins in a large and well-characterized cohort. We identified 274, 127 and 32 protein quantitative loci (pQTL) for CSF, plasma and brain respectively. We demonstrated that cis-pQTL are more likely to be shared across tissues but trans-pQTL are tissue-specific. Between 78% to 87% of pQTL are not eQTL, indicating that protein levels have a different genetic architecture than gene expression. By combining our pQTL with Mendelian Randomization approaches we identified potential novel biomarkers and drug targets for neurodegenerative diseases including Alzheimer disease and frontotemporal dementia. In the context of personalized medicine, these results highlight the need for implementing additional functional genomic approaches beyond gene expression in order to understand the biology of complex traits, and to identify novel biomarkers and potential drug targets for those traits.
Implementation-independent representation for deep convolutional neural networks and humans in processing faces
Authors: Song Yiying , Qu Yukun , Xu Shan , Liu Jia
Published: June 2020

Deep convolutional neural networks (DCNN) nowadays can match and even outperform human performance in challenging complex tasks. However, it remains unknown whether DCNNs achieve human-like performance through human-like processes; that is, do DCNNs use similar internal representations to achieve the task as humans? Here we applied a reverse-correlation method to reconstruct the internal representations when DCNNs and human observers classified genders of faces. We found that human observers and a DCNN pre-trained for face identification, VGG-Face, showed high similarity between their “classification images” in gender classification, suggesting similar critical information utilized in this task. Further analyses showed that the similarity of the representations was mainly observed at low spatial frequencies, which are critical for gender classification in human studies. Importantly, the prior task experience, which the VGG-Face was pre-trained for processing faces at the subordinate level (i.e., identification) as humans do, seemed necessary for such representational similarity, because AlexNet, a DCNN pre-trained to process objects at the basic level (i.e., categorization), succeeded in gender classification but relied on a completely different representation. In sum, although DCNNs and humans rely on different sets of hardware to process faces, they can use a similar representation, possibly from similar prior task experiences, to achieve the same computation goal. Therefore, our study provides the first empirical evidence supporting the hypothesis of implementation-independent representation.
Task-irrelevant visual forms facilitate covert and overt spatial selection
Authors: Bogadhi Amarender R. , Buonocore Antimo , Hafed Ziad M.
Published: June 2020

Covert and overt spatial selection behaviors are guided by both visual saliency maps derived from early visual features as well as priority maps reflecting high-level cognitive factors. However, whether mid-level perceptual processes associated with visual form recognition contribute to covert and overt spatial selection behaviors remains unclear. We hypothesized that if peripheral visual forms contribute to spatial selection behaviors, then they should do so even when the visual forms are task-irrelevant. We tested this hypothesis in male and female human subjects as well as in male macaque monkeys performing a visual detection task. In this task, subjects reported the detection of a supra-threshold target spot presented on top of one of two peripheral images, and they did so with either a speeded manual button press (humans) or a speeded saccadic eye movement response (humans and monkeys). Crucially, the two images, one with a visual form and the other with a partially phase-scrambled visual form, were completely irrelevant to the task. In both manual (covert) and oculomotor (overt) response modalities, and in both humans and monkeys, response times were faster when the target was congruent with a visual form than when it was incongruent. Importantly, incongruent targets were associated with almost all errors, suggesting that forms automatically captured selection behaviors. These findings demonstrate that mid-level perceptual processes associated with visual form recognition contribute to covert and overt spatial selection. This indicates that neural circuits associated with target selection, such as the superior colliculus, may have privileged access to visual form information.

Significance statement

Spatial selection of visual information either with (overt) or without (covert) foveating eye movements is critical to primate behavior. However, it is still not clear whether spatial maps in sensorimotor regions known to guide overt and covert spatial selection are influenced by peripheral visual forms. We probed the ability of humans and monkeys to perform overt and covert target selection in the presence of spatially congruent or incongruent visual forms. Even when completely task-irrelevant, images of visual objects had a dramatic effect on target selection, acting much like spatial cues used in spatial attention tasks. Our results demonstrate that traditional brain circuits for orienting behaviors, such as the superior colliculus, likely have privileged access to visual object representations.
Performance ofBracon brevicornis(Wesmael) on twoSpodopteraspecies and application as potential biocontrol agent against fall armyworm
Authors: Ghosh Enakshi , Varshney Richa , Venkatesan Radhika
Published: June 2020

Successful pest management using parasitoids requires careful evaluation of host-parasitoid interactions. Here, we report the performance of larval ecto-parasitoid wasp,Bracon brevicornis(Wesmael) on important agricultural pests,Spodoptera litura(Fabricius) andS. frugiperda(J.E. Smith). Biology ofB. brevicorniswas studied on different host instars under laboratory and cage setup. In no-choice assay, the parasitoid development was highest on fifth instarS. lituralarvae as the wasp laid ∼253 eggs with 62% hatching, 76% pupae formation and 78% adult emergence. Similarly, these parameters were highest on fifth instarS. frugiperdalarvae (293 eggs, 57% hatching, 80% pupae formation, 70% adult emergence). In two-choice assay,B. brevicornispreferred fourth or fifth over third instar larvae of both hosts. Successful parasitism depends on host paralysis and suppression of host immunity.B. brevicornisinteraction downregulated cellular immunity of both hosts as shown by reduced hemocyte viability and spreading. The percent parasitism rate ofB. brevicorniswas unaltered in the presence of host plant,Zea maysin cage study. 76 and 84% parasitism was observed on fifth instar larvae ofS. lituraandS. frugiperda, respectively. We evaluated the performance ofB. brevicornisas a biocontrol agent onS. frugiperdain maize field. Our results show 54% average reduction in infestation after release ofB. brevicornis. Taken together, we report the performance ofB. brevicornison important insect pests for the first time in laboratory and field conditions. Our findings indicate thatB. brevicornisis a promising candidate for integrated pest management.

Key messages

We have evaluated the instar preference and performance ofB. brevicornisas a potential biocontrol agent for two serious pests,Spodoptera lituraandS. frugiperda.

Fifth instar larva was most suitable forB. brevicornisdevelopment irrespective of the host species.B. brevicornisattack induced permanent paralysis and down-regulated cellular immunity of both hosts.

Our field experiment confirmedB. brevicornisas a promising parasitoid for controllingS. frugiperda, a highly invasive pest of growing concern.
Higher pharyngeal epithelial gene expression of Angiotensin-Converting Enzyme-2 in upper respiratory infection patients
Authors: Zhang Mingjiao , Du Lingyan , Faleti Oluwasijibomi Damola , Huang Jing , Xiao Gang , Lyu Xiaoming
Published: June 2020

We analyzed the expression of ACE2 in pharyngeal epithelium and examined its relationship with clinical features and serological parameters in the upper respiratory infection (URI) patients. The expression of ACE2 were significantly higher in URI patients than in healthy controls individuals, and positively correlated with age and body temperature.
Chronic Kidney Disease Prediction Using Neural Approach
Authors: Dutta Shawni , Bandyopadhyay Samir Kumar
Published: June 2020

All over the world, chronic kidney disease (CKD) is a serious public health condition that needs to be detected in advance so that costly end-stage treatments like dialysis, kidney transplantations can be avoided. Neural network model and 10-fold cross-validation methodology under a single platform in proposed as well as implemented in order to classify patients with CKD. This will assist medical care fields so that counter measures can be suggested. The performance of proposed classifier is justified against other baseline classifiers such as Support Vector Machine, K-Nearest Neighbours, Decision tree and Gradient Boost classifier. Experimental results conclude that the performance of neural network with 10-fold cross-validation method reaches promising accuracy of 98.25%, f1-score of 0.98, and kappa score of 0.96 and MSE of 0.0175.
A single nucleotide change underlies the genetic assimilation of a plastic trait
Authors: Vigne Paul , Gimond Clotilde , Ferrari Céline , Vielle Anne , Hallin Johan , Pino-Querido Ania , Mouridi Sonia El , Frøkjær-Jensen Christian , Boulin Thomas , Teotónio Henrique , Braendle Christian
Published: June 2020

Genetic assimilation – the evolutionary process by which an ancestral environmentally sensitive phenotype is made constitutive – is a fundamental concept in biology. Its evolutionary relevance is debated, and our understanding of its prevalence, and underlying genetics and molecular mechanisms, is poor. Matricidal hatching is an extreme form of maternal provisioning induced by adverse conditions, which varies amongCaenorhabditis eleganspopulations. We identified wild isolates, sampled from natural populations across multiple years and locations, that express a derived state of near-constitutive matricidal hatching. A single amino acid change inkcnl-1, encoding a small-conductance calcium-activated potassium channel subunit, explains most of this variation. A gain-of-function mutation altering the S6 transmembrane domain causes inappropriate activation of the K+channel, leading to reduced vulval muscle excitability, and thus reduced expulsion of embryos, irrespective of environment. Using reciprocal allelic replacements, we show that this amino acid change is sufficient to induce constitutive matricidal hatching whilst re-establishing the ancestral protein abolishes matricidal hatching and restores egg-laying, thereby doubling lifetime reproductive fitness under benign conditions. While highly deleterious in the laboratory, experimental evolution showed that KNCL-1(V530L) is maintained under fluctuating resource availability. Selection on a single point mutation can therefore underlie the genetic assimilation of an ancestrally plastic trait with drastic life-history consequences.
2,2′-(Disulfanediyl)dibenzoic acid N,N-dimethylformamide monosolvate: crystal structure, Hirshfeld surface analysis and computational study
Authors: Tan Sang Loon , Tiekink Edward R. T.
Published: June 2020

The title 1:1 solvate, C14H10O4S2·C3H7NO, features a twisted molecule of 2,2′-dithiodibenzoic acid (DTBA), with the central C—S—S—C torsion angle being −88.57 (6)°, and a molecule of dimethylformamide (DMF). The carboxylic acid groups are, respectively, close to co-planar and twisted with respect to the benzene rings to which they are connected as seen in the CO2/C6 torsion angles of 1.03 (19) and 7.4 (2)°. Intramolecular, hypervalent S←O interactions are noted [S...O = 2.6140 (9) and 2.6827 (9) Å]. In the crystal, four-molecule aggregates are formed via DTBA-O—H...O(DMF) and DTBA-O—H...O(DTBA) hydrogen bonding, the latter via an eight-membered {...OHCO}2 homosynthon. These are linked into supramolecular layers parallel to (011) via benzene-C—H...O(DTBA) and DTBA-C=O...π(benzene) interactions, with the connections between these, giving rise to a three-dimensional architecture, being of the type benzene-C—H...π(benzene). An analysis of the calculated Hirshfeld surfaces indicates, in addition to the aforementioned intermolecular contacts, the presence of stabilizing interactions between a benzene ring and a quasi-π-system defined by O—H...O hydrogen bonds between a DTBA dimer, i.e. the eight-membered {...OCOH}2 ring system, and between a benzene ring and a quasi-π(OCOH...OCH) system arising from the DTBA-O—H...O(DMF) hydrogen bond. The inter-centroid separations are 3.65 and 3.49 Å, respectively.