bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACT70 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 SUMMARYAll 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

SummaryMicrobial 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 StatementThe 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.
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

ABSTRACTSeveral 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

SummaryAll 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

ABSTRACTMotivated 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

AbstractObjectiveThe 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).MethodsThe 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.ResultsHigh (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.ConclusionAir-liquid interface culture and physiological strain are important for engineering respiratory tissue models.SignificanceThe 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

ABSTRACTObjectiveTo explore how adults living with Inflammatory Bowel Disease (IBD) in rural New Zealand manage their condition and engage with health care providers.DesignQualitative exploratory design with semi-structured interviews analysed thematically.Setting and participantsInterviews were conducted with 18 people living with IBD in the Otago region of the South Island.ResultsFive 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.ConclusionsFindings 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

ABSTRACTBackground and ObjectiveChronic 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.MethodsA 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.ResultsBoth 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.ConclusionsThe 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

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

AbstractBackgroundHydrocephalus 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.MethodsThe 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.ResultsCare 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.ConclusionThe 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

AbstractBackgroundTobacco 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.ObjectiveOur objective was to test the effectiveness of Quit Genius, a novel digital therapeutic intervention for smoking cessation.MethodsA 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.Results556 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.ConclusionsThe Quit Genius digital therapeutic intervention is a superior treatment in achieving smoking cessation four weeks post quit date compared to very brief advice.Trial RegistrationThe trial was registered in the ISRCTN database on December 18, 2018 (https://www.isrctn.com/ISRCTN65853476).