bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct survival, growth lag, and ribosomal RNA degradation kinetics during long-term starvation for carbon or phosphate
Authors: Himeoka Yusuke , Gummesson Bertil , Sørensen Michael A. , Svenningsen Sine Lo , Mitarai Namiko 
Published: September 2020

AbstractStationary phase is the general term for the state a bacterial culture reaches when no further increase in cell number occurs due to the exhaustion of nutrients in the growth medium. Depending on the type of nutrient that is first depleted, the metabolic state of the stationary phase cells may vary greatly, and the subsistence strategies that best support cell survival may differ. As ribosomes play a central role in bacterial growth and energy expenditure, ribosome preservation is a key element of such strategies. To investigate the degree of ribosome preservation during long-term starvation, we compared the dynamics of ribosomal RNA (rRNA) levels of carbon-starved and phosphorus-starvedEscherichia colicultures for up to 28 days. The starved cultures’ contents of full-length 16S and 23S rRNA decreased exponentially and phosphorus starvation resulted in much more rapid rRNA degradation than carbon starvation. Bacterial survival kinetics were also quantified over the starvation period. Upon replenishment of the nutrient in question, carbon-starved cells resumed growth faster than cells starved for phosphate for the equivalent amount of time, and for both conditions, the lag time increased with the starvation time. While these results are in accordance with the hypothesis that cells with a larger ribosome pool recover more readily upon replenishment of nutrients, we also observed that the lag time kept increasing with increasing starvation time, also when the amount of rRNA per viable cell remained constant.ImportanceBacteria grow exponentially consuming nutrients, and then starve until the next nutrient is added. To elucidate the survival kinetics of the cells under starvation, we performed month-long, carbon and phosphorus starvation experiments ofEscherichia colimonitoring ribosomal RNA levels and survival of the cells. The starved cultures’ concentration of ribosomal RNA dropped exponentially with time, and the speed of degradation was much quicker under the phosphorus starvation than the carbon starvation. We have also quantified the lag time, i.e., the time needed to resume growth when the starved cells are transferred into fresh media. The observation revealed that the lag time increases with starvation time and the phosphorus starvation has a greater impact on the increase of the lag time.
VisualizingBorrelia burgdorferiinfection using a small molecule imaging probe
Authors: Sell Madeline G , Alcorta David A. , Padilla Andrew E. , Nollner Dakota W. , Hasenkampf Nicole R. , Lambert Havard S. , Embers Monica E. , Spector Neil L. 
Published: September 2020

AbstractIn vivodiagnostic imaging of bacterial infections is currently reliant on targeting their metabolic pathways, an ineffective method to identify microbial species with low metabolic activity. Here we establish HS-198 as a small molecule-fluorescent conjugate that selectively targets the highly conserved bacterial protein, HtpG (High temperature protein G), withinB. burgdorferi, the bacteria responsible for Lyme Disease. We describe the use of HS-198 to target morphologic forms ofB. burgdorferiin both the logarithmic growth phase and the metabolically dormant stationary phase. Furthermore, in a murine infection model, systemically injected HS-198 identifiedB. burgdorferias revealed by imaging in post necropsy tissue sections. These findings demonstrate how small molecule probes directed at conserved bacterial protein targets can function to identify the microbe using non-invasive imaging and potentially as scaffolds to deliver antimicrobial agents to the pathogen.
Diagnosing Chronic Obstructive Airway Disease: a diagnostic accuracy study of a smartphone delivered algorithm combining patient-reported symptoms and cough analysis for use in acute care consultations
Authors: Porter Paul , Brisbane Joanna , Abeyratne Udantha , Bear Natasha , Wood Javan , Peltonen Vesa , Della Phill , Purdie Fiona , Smith Claire , Claxton Scott 
Published: September 2020

ABSTRACTBackgroundRapid and accurate diagnosis of Chronic Obstructive Pulmonary Disease (COPD) is problematic in acute-care settings, particularly in the presence of infective comorbidities.ObjectiveThe aim of this study was to develop a rapid, smartphone-based algorithm for the detection of COPD, in the presence or absence of acute respiratory infection, and then evaluate diagnostic accuracy on an independent validation set.MethodsSubjects aged 40-75 years with or without symptoms of respiratory disease who had no chronic respiratory condition apart from COPD, chronic bronchitis or emphysema, were recruited into the study. The algorithm analysed 5 cough sounds and 4 patient-reported clinical symptoms, providing a diagnosis in less than 1 minute. Clinical diagnoses were determined by a specialist physician using all available case notes, including spirometry where available.ResultsThe algorithm demonstrated high percent agreement (PA) with clinical diagnosis for COPD in the total cohort (n=252, Positive PA=93.8%, Negative PA=77.0%, AUC=0.95); in subjects with pneumonia or infective exacerbations of COPD (n=117, PPA=86.7%, NPA=80.5%, AUC=0.93) and in subjects without an infective comorbidity (n=135, PPA=100.0%, NPA=74.0%, AUC=0.97.) In those who had their COPD confirmed by spirometry (n=229), PPA = 100.0% and NPA = 77.0%, AUC=0.97.ConclusionsThe algorithm demonstrates high agreement with clinical diagnosis and rapidly detects COPD in subjects presenting with or without other infective lung illnesses. The algorithm can be installed on a smartphone to provide bedside diagnosis of COPD in acute care settings, inform treatment regimens and identify those at increased risk of mortality due to seasonal or other respiratory ailments.
Detecting sleep in free-living conditions without sleep-diaries: a device-agnostic, wearable heart rate sensing approach
Authors: Perez-Pozuelo Ignacio , Posa Marius , Spathis Dimitris , Westgate Kate , Wareham Nicholas , Mascolo Cecilia , Brage Søren , Palotti Joao 
Published: September 2020

AbstractThe rise of multisensor wearable devices offers a unique opportunity for the objective inference of sleep outside laboratories, enabling longitudinal monitoring in large populations. To enhance objectivity and facilitate cross-cohort comparisons, sleep detection algorithms in free-living conditions should rely on personalized but device-agnostic features, which can be applied without laborious human annotations or sleep diaries. We developed and tested a heart rate-based algorithm that captures inter- and intra-individual sleep differences, does not require human input and can be applied in free-living conditions. The algorithm was evaluated across four study cohorts using different research- and consumer-grade devices for over 2,000 nights. Recording periods included both 24-hour free-living and conventional lab-based night-only data. Our method was systematically optimized and evaluated against polysomnography (PSG) and sleep diaries and compared to sleep periods produced by accelerometry-based angular change algorithms. Against sleep diaries, the algorithm yielded a mean squared error (MSE) of 0.04 to 0.06 and a total sleep time deviation of -2.70 (±5.74) and 12.80 (±3.89) minutes, respectively. When evaluated with PSG lab studies, the MSE ranged between 0.06 and 0.11 yielding a time deviation between -29.07 and -55.04 minutes. Our findings suggest that the heart rate-based algorithm can reliably and objectively infer sleep under longitudinal, free-living conditions, independent of the wearable device used. This represents the first open-source algorithm that can infer sleep using heart rate signals without actigraphy or diary annotations.
Quantifying Inaccuracies in Modeling COVID-19 Pandemic within a Continuous Time Picture
Authors: Bâldea Ioan 
Published: September 2020

AbstractTypically, mathematical simulation studies on COVID-19 pandemic forecasting are based on deterministic differential equations which assume that both the number (n) of individuals in various epidemiological classes and the time (t) on which they depend are quantities that vary continuous. This picture contrasts with the discrete representation ofnandtunderlying the real epidemiological data reported in terms daily numbers of infection cases, for which a description based on finite difference equations would be more adequate. Adopting a logistic growth framework, in this paper we present a quantitative analysis of the errors introduced by the continuous time description. This analysis reveals that, although the height of the epidemiological curve maximum is essentially unaffected, the positionobtained within the continuous time representation is systematically shifted backwards in time with respect to the positionpredicted within the discrete time representation. Rather counterintuitively, the magnitude of this temporal shiftis basically insensitive to changes in infection rateκ. For a broad range ofκvalues deduced from COVID-19 data at extreme situations (exponential growth in time and complete lockdown), we found a rather robust estimateτ≃ −2.65 day−1. Being obtained without any particular assumption, the present mathematical results apply to logistic growth in general without any limitation to a specific real system.
Beneficial and harmful outcomes of tocilizumab in severe COVID-19: a systematic review and meta-analysis
Authors: Rubio-Rivas Manuel , Mora-Luján Jose María , Montero Abelardo , Homs Narcís A. , Rello Jordi , Corbella Xavier 
Published: September 2020

ABSTRACTObjectivesPending for randomized control trials, the use of tocilizumab (TCZ) in COVID-19 remains controversial. We performed a systematic review and meta-analysis to investigate the effect on clinical outcomes of TCZ to treat severe COVID-19.MethodsFrom 1 January to 21 August 2020, we searched PubMed (via MEDLINE), Scopus, and medRxiv repository databases for observational studies in any language reporting efficacy and safety of TCZ use in hospitalized adults with COVID-19. Independent and dually data extraction and quality assessment were performed.ResultsOf 57 eligible studies, 27 controlled and 30 not. The overall included patients were 8,128: 4,021 treated with TCZ, in addition to standard of care (SOC), and 4,107 only receiving SOC. The pooled mortality was lower in the TCZ-group, with a relative risk (RR) of 0.73 (95%CI 0.57-0.93; p=0.010). TCZ-treated patients were transferred to the intensive care unit (ICU) in a higher proportion, but ICU mortality was lower than in the control group. Conversely, a higher proportion of TCZ-treated patients developed secondary infections after TCZ use.ConclusionsTCZ seems beneficial in preventing in-hospital mortality in severe, non-critically ill COVID-19 patients. However, patients receiving TCZ appear to be at higher risk for secondary infections, especially those admitted to ICU.
Optimized iLID membrane anchors for local optogenetic protein recruitment
Authors: Natwick Dean E. , Collins Sean R. 
Published: September 2020

AbstractOptogenetic protein dimerization systems are powerful tools to investigate the biochemical networks that cells use to make decisions and coordinate their activities. These tools, including the improved Light-Inducible Dimer (iLID) system, offer the ability to selectively recruit components to subcellular locations, such as micron-scale regions of the plasma membrane. In this way, the role of individual proteins within signaling networks can be examined with high spatiotemporal resolution. Currently, consistent recruitment is limited by heterogeneous optogenetic component expression, and spatial precision is diminished by protein diffusion, especially over long timescales. Here, we address these challenges within the iLID system with alternative membrane anchoring domains and fusion configurations. Using live cell imaging and mathematical modeling, we demonstrate that the anchoring strategy affects both component expression and diffusion, which in turn impact recruitment strength, kinetics, and spatial dynamics. Compared to the commonly used C-terminal iLID fusion, fusion proteins with large N-terminal anchors show stronger local recruitment, slower diffusion of recruited components, and efficient recruitment over wider gene expression ranges. We also define guidelines for component expression regimes for optimal recruitment for both cell-wide and subcellular recruitment strategies. Our findings highlight key sources of imprecision within light-inducible dimer systems and provide tools that allow greater control of subcellular protein localization across diverse cell biological applications.SignificanceOptogenetic light-inducible dimer systems, such as iLID, offer the ability to examine cellular signaling networks on second timescales and micrometer spatial scales. Confined light stimulation can recruit proteins to subcellular regions of the plasma membrane, and local signaling effects can be observed. Here, we report alternative iLID fusion proteins that display stronger and more spatially confined membrane recruitment. We also define optogenetic component expression regimes for optimal recruitment and show that slow-diffusing iLID proteins allow more robust recruitment in cell populations with heterogenous expression. These tools should improve the spatiotemporal control and reproducibility of optogenetic protein recruitment to the plasma membrane.
Spatial heterogeneity in resources alters selective dynamics inDrosophila melanogaster
Authors: Wilson Audrey E , Siddiqui Ali , Dworkin Dr. Ian 
Published: September 2020

AbstractEnvironmental features can alter the behaviours and phenotypes of organisms and populations evolving within them including the dynamics between natural and sexual selection. Experimental environmental manipulation, particularly when conducted in experiments where the dynamics of the purging of deleterious alleles are compared, has demonstrated both direct and indirect effects on the strength and direction of selection. However, many of these experiments are conducted with fairly simplistic environments when it is not always clear how or why particular forms of spatial heterogeneity may influence behaviour or selection. UsingDrosophila melanogaster, we tested three different spatial environments designed to determine if spatial constraint of critical resources influences the efficiency of natural and sexual selection. We conducted two allele purging experiments to 1) assess the effects of these spatial treatments on the selective dynamics of six recessive mutations, and 2) determine how these dynamics changed when sexual selection was relaxed and the spatial area was reduced. We found that allele purging dynamics depended on spatial environment, however the patterns of purging rates between the environments differed across distinct deleterious mutations. We also found that for two of the mutations, the addition of sexual selection increased the purging rate.
Vapur: A Search Engine to Find Related Protein - Compound Pairs in COVID-19 Literature
Authors: Köksal Abdullatif , Dönmez Hilal , Özçelik Rıza , Ozkirimli Elif , Özgür Arzucan 
Published: September 2020

AbstractCoronavirus Disease of 2019 (COVID-19) created dire consequences globally and triggered an intense scientific effort from different domains. The resulting publications created a huge text collection in which finding the studies related to a biomolecule of interest is challenging for general purpose search engines because the publications are rich in domain specific terminology. Here, we present Vapur: an online COVID-19 search engine specifically designed to find related protein - chemical pairs. Vapur is empowered with a relation-oriented inverted index that is able to retrieve and group studies for a query biomolecule with respect to its related entities. The inverted index of Vapur is automatically created with a BioNLP pipeline and integrated with an online user interface. The online interface is designed for the smooth traversal of the current literature by domain researchers and is publicly available athttps://tabilab.cmpe.boun.edu.tr/vapur/.
Structural and Functional Brain-wide Alterations in A350V IQSEC2 Mutant Mice Displaying Autistic-like Behavior
Authors: Lichtman Daniela , Bergmann Eyal , Kavushansky Alexandra , Cohen Nadav , Levy Nina S. , Levy Andrew P. , Kahn Itamar 
Published: September 2020

AbstractIQSEC2 is an X-linked gene which is associated with autism spectrum disorder (ASD), intellectual disability and epilepsy. IQSEC2 is a postsynaptic density protein, localized on excitatory synapses as part of the NMDA receptor complex and is suggested to play a role in AMPA receptor trafficking and mediation of long-term depression. Here, we present brain-wide structural volumetric and functional connectivity characterization in a novel mouse model with a missense mutation in the IQ domain of IQSEC2 (A350V). Using high-resolution structural and functional MRI, we show that animals with the A350V mutation display increased whole-brain volume which was further found to be specific to the cortex and hippocampus. Moreover, using a data-driven approach we demonstrate that A350V mice present alterations in structure–function relations of the frontal, auditory, and visual networks. Examination of these alterations revealed an increase in functional connectivity between the anterior cingulate cortex and the dorsomedial striatum. We also show that corticostriatal functional connectivity is correlated with individual variability in social behavior only in A350V mice, as assessed using the three–chamber social preference test. Our results at the systems-level bridge the impact of previously reported changes in AMPA receptor trafficking to network-level disruption and impaired social behavior. Further, the A350V mouse model recapitulates similarly reported brain-wide changes in other ASD mouse models, with substantially different cellular-level pathologies that nonetheless result in similar brain-wide alterations, suggesting that novel therapeutic approaches in ASD that result in systems-level rescue will be relevant to IQSEC2 mutations.Significance StatementSeveral recent studies have characterized the changes in the organization of brain networks in animal models of autism spectrum disorders (ASD). Here we assessed the effect of an A350V missense mutation in the IQSEC2 gene, which is associated with ASD, on brain-wide functional connectivity and its relation to social behavior deficits in A350V mice relative to controls. We found that the A350V IQSEC2 model results in disrupted functional connectivity of the anterior cingulate cortex and the dorsomedial striatum. Critically, disrupted increased corticostriatal functional connectivity is predictive of individual variability in social interaction only in A350V mice implicating this pathway in the pathophysiology of the A350V IQSEC2 mutation.
High-content analysis and Kinetic Image Cytometry identify toxic and epigenotoxic effects of HIV antiretrovirals on human iPSC-neurons and primary neural precursor cells
Authors: Smith Alyson S. , Ankam Soneela , Farhy Chen , Fiengo Lorenzo , Basa Ranor C.B. , Gordon Kara L. , Martin Charles T. , Terskikh Alexey V. , Jordan-Sciutto Kelly L. , Price Jeffrey H. , McDonough Patrick M. 
Published: September 2020

AbstractDespite viral suppression due to combination antiretroviral therapy (cART), HIV-associated neurocognitive disorders (HAND) continue to affect half of people with HIV, suggesting that certain antiretrovirals (ARVs) may contribute to HAND. We examined the effects of nucleoside/nucleotide reverse transcriptase inhibitors tenofovir disproxil fumarate (TDF) and emtricitabine (FTC) and the integrase inhibitors dolutegravir (DTG) and elvitegravir (EVG) on viability, structure, and function of glutamatergic neurons (a subtype of CNS neuron involved in cognition) derived from human induced pluripotent stem cells (hiPSC-neurons), and primary human neural precursor cells (hNPCs), which are responsible for neurogenesis. Using automated digital microscopy and image analysis (high content analysis, HCA), we found that DTG, EVG, and TDF decreased hiPSC-neuron viability, neurites, and synapses after seven days of treatment. Analysis of hiPSC-neuron calcium activity using Kinetic Image Cytometry (KIC) demonstrated that DTG and EVG also decreased the frequency and magnitude of intracellular calcium transients. Longer ARV exposures and simultaneous exposure to multiple ARVs increased the magnitude of these neurotoxic effects. Using the Microscopic Imaging of Epigenetic Landscapes (MIEL) assay, we found that TDF decreased hNPC viability and changed the distribution of histone modifications that regulate chromatin packing, suggesting that TDF may reduce neuroprogenitor pools important for CNS development and maintenance of cognition in adults. This study establishes human preclinical assays that can screen potential ARVs for CNS toxicity to develop safer cART regimens and HAND therapeutics.
Developmental plasticity of texture discrimination following early vision loss in the marsupialMonodelphis domestica
Authors: Ramamurthy Deepa L. , Dodson Heather K. , Krubitzer Leah A. 
Published: September 2020

ABSTRACTBehavioral strategies that depend on sensory information are not immutable; rather they can be shaped by the specific sensory context in which animals develop. This behavioral plasticity depends on the remarkable capacity for the brain to reorganize in response to alterations in the sensory environment, particularly when changes in sensory input occur at an early age. To study this phenomenon, we utilize the short-tailed opossum, a marsupial that has been a valuable animal model to study developmental plasticity due to the extremely immature state of its nervous system at birth. Previous studies in opossums have demonstrated that removal of retinal inputs early in development results in profound alterations to cortical connectivity and functional organization of visual and somatosensory cortex; however, behavioral consequences of this plasticity are not well understood. We trained early blind (EB) and sighted control (SC) opossums to perform a two-alternative forced choice texture discrimination task. Whisker trimming caused an acute deficit in discrimination accuracy for both EB and SC animals indicating that they primarily used a whisker-based strategy to guide choices based on tactile cues – though performance recovered in days, suggesting a shift to the use of other body parts when whiskers were absent. Mystacial whiskers were important for performance in both groups; however, genal whiskers only contributed to performance in EB animals. EB opossums significantly outperformed SC opossums in discrimination accuracy, being more sensitive to textural differences by ~75 μm smaller. Our results support behavioral compensation following early blindness using tactile inputs, especially the whisker system.