bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic resistance in clinical isolates of Escherichia coli non-producer of Extended Spectrum Betalactamases (ESBL), obtained from urine cultures in patients with urinary tract infection
Authors: Villegas Jorge Angel Almeida , Rodriguez Mariana Islas , Estrada Iris Mellolzy , Rodriguez Miriam Deyanira , Muñoz María Carolina Erazo , Rodriguez Silvia Patricia
Published: August 2020

Objective

To identify strains of Escherichia coli that do not produce Extended Spectrum Betalactamases (ESBL) in urine cultures and to evaluate the patterns of resistance to certain antibiotics used in clinical practice as treatments of choice in the Toluca Valley of Mexico.

Method

155 urine samples were obtained from people in the Toluca Valley, Mexico under necessary hygiene conditions. 100ml used to identify the pathogen and its resistance patterns were collected from each sample, using an automated Walkaway method.

Result

19 strains of non-ESBL-producing Escherichia coli were obtained, of which 68.42% showed resistance to ampicillin and tetracycline, 47.36% resistance to trimethoprim with sulfamethoxazole, 26.31% for levofloxacin, ciprofloxacin, ceftriaxone, and resistance of 21 % with ampicillin and sulbactam. 100% sensitivity for amikacin, tigecycline and carbapenems.

Conclusion

Antibiotic resistance represents a major health problem, as the present study shows, ampicillin is a drug of choice for urinary tract infection produced by Eschericha coli, but in the Toluca Valley the resistance to this antibiotic is 68.42% In non-ESBL producing strains, high resistance patterns are also shown for quinolones, tetracycline and trimethoprim with sulfamethoxazole.
Boosting SARS-CoV-2 qRT-PCR detection combining pool sample strategy and mathematical modeling
Authors: Correa Isadora Alonso , Rodrigues Tamires de Souza , Queiroz Alex , Nascimento Leon de França , Wolff Thiago , Akamine Rubens Nobumoto , Kuriyama Sergio Noboru , da Costa Luciana Jesus , Fidalgo-Neto Antonio Augusto
Published: August 2020

qRT-PCR is the gold standard technique available for SARS-CoV-2 detection. However, the long test run time and costs associated with this type of molecular testing are a challenge in the actual pandemic scenario. Due to high testing demand, pooling sample strategy is an interesting approach to allow cost savings. We aim to evaluate pooling tests in experimental procedures, as well as perform in silico statistical modeling analysis validated with specimen samples obtained from a mass testing program of Industry Federation of the State of Rio de Janeiro (Brazil). Although the sensitivity reduction in samples pooled with 32 individuals was observed, the high-test sensitivity is maintained even when 16 and 8 samples were pooled. The in silico analysis showed high-cost savings in populations with positive rates lower than 15.0% according to the pool size. This data was validated with the results obtained in our mass testing program: statistical modeling predicted a cost saving of 48.0%, which in practice, was 51.5%, already considering the expenditures with pool sampling that were analyzed individually. Our data confirmed that mathematical modeling is a powerful strategy to improve the pooling approach for SARS-CoV-2 mass testing around the world while maintaining high sensitivity and robustness.
Prevalence and associated factors of burnout in allied healthcare professionals in a tertiary hospital in Singapore
Authors: Teo Yao Hao , Xu Jordan Thet Ke , Ho Cowan , Leong Jui Min , Tan Benjamin Kye Jyn , Tan Elisabeth Ker Hsuen , Goh Wei-An , Neo Elson , Chua Jonathan Yu Jing , Ng Sean Jun Yi , Cheong Julia Jie Yi , Hwang Jeff Yi-Fu , Lim See Ming , Soo Thomas , Sng Judy Gek Khim , Yi Siyan
Published: August 2020

Objective

To explore the prevalence of burnout, factors associated with burnout, and barriers to seeking psychological help among allied health professionals in Singapore.

Design

Cross-sectional study.

Setting

A tertiary hospital in Singapore.

Participants

Allied health professionals.

Primary outcome measure

Burnout measured by using Maslach Burnout Inventory (MBI-HSS)

Results

In total, 328 participants completed the questionnaire. The prevalence of burnout was 67.4%. A majority of the respondents were female (83.9%), Singaporean (73.5%), aged 40 years and below (84.2%), and of Chinese ethnicity (79.9%). In the multiple logistic regression model, burnout was negatively associated with being in the age groups of 31 to 40 (AOR 0.39, 95% CI 0.16–0.93) and ≥40 years (AOR 0.30, 95% CI 0.10–0.87) and a low workload burden (AOR 0.35, 95% CI 0.23–0.52). Burnout was positively associated with a longer work experience of 3 to 5 years (AOR 5.27, 95% CI 1.44–20.93) and more than five years (AOR 4.24; 95% CI 1.16–16.79). Among the 190 participants who completed the PBPT, barriers to seeking psychological help shown to be significantly associated with burnout were a ‘lack of motivation’ and ‘time constraints’ (p< 0.01).

Conclusions

This study shows a high prevalence of burnout and identifies its associated factors among Singapore’s allied health professionals. The findings revealed the urgency of addressing burnout in allied health professionals and the need for effective interventions to reduce burnout. Concurrently, proper consideration of the barriers to seeking help is warranted to improve allied health professionals’ mental wellbeing.

Strengths and limitations of this study

This study is the first to show a high prevalence of burnout and identify its associated

We used validated scales, including Maslach Burnout Inventory, Areas of Worklife Survey, and Perceived Barriers to Psychological Treatment.

Limitations of the study included the cross-sectional design, the low response rate, the potential social desirability bias, and the limited generalizability.

This study did not cover factors associated with burnout in previous studies, including the increasing computerization of practices and the participants’ personality traits.
The Development of a Care Home Data Platform in Scotland: Insights from the Care Home Innovation Partnership, Lothian
Authors: Johnston Lucy , Hockley Jo , Henderson David AG , Shenkin Susan D
Published: August 2020

Care homes collect a large amount of data about their residents, and the care provided, but there is a lack of consistency in how this information is collected. There is also a need to minimise the burden of data collection on staff, ensure information informs and supports person-centred care, and that this data is then of use to regulatory agencies, policy makers and researchers.

We examined the data collected in six Care Homes in Lothian, Scotland. We extracted the meta-data collected, cross-referenced definitions and assessed the degree of current harmonisation between individual care homes and with data sets currently in use in Scotland and internationally. We interviewed the care home managers to identify data collection processes, views and experiences of current data availability, gaps, access and issues of capacity and capability in relation to data management and analytics.

Our work has illustrated the scale of the data collected by care homes, the varied formats and heterogeneity of scope and definition. The inventory of 15 core data items that emerged, serves to expose in detail the foundations of care home data sets. The groundwork illuminated the heterogeneity in tools and assessments used to generate the data and the way in which the data is to be used, affects how it is specified and frequency of collection. By making known the reality of how and why care home data is collected, we can understand better the nuances of each individual data item that collectively create a data platform. We make four recommendations for the development of a national care home data platform.
Transcriptional Profiling of Identified Neurons in Leech
Authors: Heath-Heckman Elizabeth , Yoo Shinja , Winchell Christopher , Pellegrino Maurizio , Angstadt James , Lammardo Veronica B. , Bautista Diana , De-Miguel Francisco F. , Weisblat David
Published: August 2020

While leeches in the genusHirudohave long been models for neurobiology, the molecular underpinnings of nervous system structure and function in this group remain largely unknown. To begin to bridge this gap, we performed RNASeq on pools of identified neurons of the central nervous system (CNS): sensory T (touch), P (pressure) and N (nociception) neurons; neurosecretory Retzius cells; and ganglia from which these four cell types had been removed. Bioinformatic analyses identified 2,812 putative genes whose expression differed significantly among the samples. These genes clustered into 7 groups which could be associated with one or more of the identified cell types. We verified predicted expression patterns throughin situhybridization on whole CNS ganglia, and found that orthologous genes were for the most part similarly expressed in a divergent leech genus, suggesting evolutionarily conserved roles for these genes. Transcriptional profiling allowed us to identify candidate phenotype-defining genes from expanded gene families. Thus, we identified one of eight hyperpolarization-activated cyclic-nucleotide gated (HCN) channels as a candidate for mediating the prominent sag current in P neurons, and found that one of five inositol triphosphate receptors (IP3Rs), representing a sub-family of IP3Rs absent from vertebrate genomes, is expressed with high specificity in T cells. We also identified one of twopiezogenes, two of ~65deg/enacgenes, and one of at least 16transient receptor potential(trp) genes as prime candidates for involvement in sensory transduction in the three distinct classes of leech mechanosensory neurons.
KG-COVID-19: a framework to produce customized knowledge graphs for COVID-19 response
Authors: Reese Justin , Unni Deepak , Callahan Tiffany J. , Cappelletti Luca , Ravanmehr Vida , Carbon Seth , Fontana Tommaso , Blau Hannah , Matentzoglu Nicolas , Harris Nomi L. , Munoz-Torres Monica C. , Robinson Peter N. , Joachimiak Marcin P. , Mungall Christopher J.
Published: August 2020

Integrated, up-to-date data about SARS-CoV-2 and coronavirus disease 2019 (COVID-19) is crucial for the ongoing response to the COVID-19 pandemic by the biomedical research community. While rich biological knowledge exists for SARS-CoV-2 and related viruses (SARS-CoV, MERS-CoV), integrating this knowledge is difficult and time consuming, since much of it is in siloed databases or in textual format. Furthermore, the data required by the research community varies drastically for different tasks - the optimal data for a machine learning task, for example, is much different from the data used to populate a browsable user interface for clinicians. To address these challenges, we created KG-COVID-19, a flexible framework that ingests and integrates biomedical data to produce knowledge graphs (KGs) for COVID-19 response. This KG framework can also be applied to other problems in which siloed biomedical data must be quickly integrated for different research applications, including future pandemics.

BIGGER PICTURE

An effective response to the COVID-19 pandemic relies on integration of many different types of data available about SARS-CoV-2 and related viruses. KG-COVID-19 is a framework for producing knowledge graphs that can be customized for downstream applications including machine learning tasks, hypothesis-based querying, and browsable user interface to enable researchers to explore COVID-19 data and discover relationships.
A toolkit for studyingVarroagenomics and transcriptomics: Preservation, extraction, and sequencing library preparation
Authors: Hasegawa Nonno , Techer Maeva , Mikheyev Alexander S.
Published: August 2020

Background

The honey bee parasite,Varroa destructor, is a leading cause of honey bee population declines. In addition to being an obligate ectoparasitic mite,Varroacarries several viruses that infect honey bees and act as the proximal cause of colony collapses. Nevertheless, until recently, studies ofVarroahave been limited by the paucity of genomic tools. Lab- and field-based methods exploiting such methods are still nascent. This study developed a set of methods for preservingVarroaDNA and RNA from the field to the lab and processing them into sequencing libraries. We performed preservation experiments in whichVarroamites were immersed in TRIzol, RNAlater, and absolute ethanol for preservation periods up to 21 days post-treatment to assess DNA and RNA integrity.

Results

For both DNA and RNA, mites preserved in TRIzol and RNAlater at room temperature degraded within 10 days post-treatment. Mites preserved in ethanol at room temperature and 4°C remained intact through 21 days.Varroamite DNA and RNA libraries were created and sequenced for ethanol preserved samples, 15 and 21 days post-treatment. All DNA sequences mapped to theV. destructorgenome at above 95% on average, while RNA sequences mapped toV. destructor, but also sometimes to high levels of the deformed-wing virus and to various organisms.

Conclusion

Ethanolic preservation of field-collected mites is inexpensive and simple, and allows them to be shipped and processed successfully in the lab for a wide variety of sequencing applications. It appears to preserve RNA from bothVarroaand at least some of the viruses it vectors.
Evaluation of pneumococcal serotyping in nasopharyngeal carriage isolates by latex agglutination, whole genome sequencing (PneumoCaT) and DNA microarray in a high pneumococcal carriage prevalence population in Malawi
Authors: Swarthout Todd D. , Gori Andrea , Bar-Zeev Naor , Kamng’ona Arox W. , Mwalukomo Thandie S. , Bonomali Farouck , Nyirenda Roseline , Brown Comfort , Msefula Jacquline , Everett Dean , Mwansambo Charles , Gould Katherine , Hinds Jason , Heyderman Robert S. , French Neil
Published: August 2020

Background

Accurate assessment of the serotype distribution associated with pneumococcal colonization and disease is essential for the evaluation and formulation of pneumococcal vaccines and informing vaccine policy.

Methods

We evaluated pneumococcal serotyping concordance between latex agglutination, PneumoCaT by whole genome sequencing (WGS) and DNA microarray using samples from community carriage surveillance in Blantyre, Malawi. Nasopharyngeal swabs were collected, following WHO recommendations, between 2015 and 2017, using stratified random sampling among study populations. Participants included healthy children 3–6 years old (PCV13 vaccinated as part of EPI), healthy children 5–10 years (age-ineligible for PCV13), and HIV-infected adults (18–40yrs) on ART. For phenotypic serotyping we used a 13-valent latex kit (SSI, Denmark). For genomic serotyping we applied PneumoCaT pipeline to whole genome sequence libraries. For molecular serotyping by microarray we used the BUGS Bioscience DNA microarray.

Results

1347 samples were analysed. Concordance was 90.7% (95% CI: 89.0–92.2) between latex and PneumoCaT; 95.2% (93.9–96.3) between latex and microarray; and 96.6% (95.5–97.5) between microarray and PneumoCaT. By detecting carried vaccine serotype (VT) pneumococcus in low relative abundance (median 8%), microarray increased VT detection by 31.5% compared to latex serotyping.

Conclusion

All three serotyping methods were highly concordant in identifying dominant serotypes. Latex serotyping is accurate in identifying vaccine-serotypes and requires the least expertise and resources for field-implementation and analysis. However, WGS, which adds population structure, and microarray, which adds multiple-serotype carriage, should be considered at regional reference laboratories while investigating the importance of VT in low relative abundance in transmission and disease.
Hyperlocal Variation in Soil Iron and Rhizosphere Microbiome Determines Disease Development in Amenity Turfgrass
Authors: Chou Ming-Yi , Shrestha Smita , Rioux Renee , Koch Paul
Published: August 2020

Dollar spot, caused by the fungal pathogenClarireedia spp., is an economically important disease of amenity turfgrass in temperate climates worldwide. This disease often occurs in a highly variable manner, even on a local scale with relatively uniform environmental conditions. The objective of this study was to investigate mechanisms behind this local variation, focusing on contributions of the soil and rhizosphere microbiome. Turfgrass, rhizosphere, and bulk soil samples were taken from within a 256 m2area of healthy turfgrass, transported to a controlled environment chamber, and inoculated withC. jacksonii. Bacterial communities were profiled targeting the 16s rRNA gene, and 16 different soil chemical properties were assessed. Despite their initial uniform appearance, the samples differentiated into highly susceptible and moderately susceptible groups following inoculation in the controlled environment chamber. The highly susceptible samples harbored a unique rhizosphere microbiome with lower relative abundance of antibiotic-producing bacterial taxa and higher predicted abundance of genes associated with xenobiotic biodegradation pathways. In addition, stepwise regression revealed that bulk soil iron content was the only significant soil characteristic that positively regressed with decreased dollar spot susceptibility during the peak disease development stage. These findings suggest that localized variation in soil iron induces the plant to select for a particular rhizosphere microbiome that alters the disease outcome. More broadly, further research in this area may indicate how plot-scale variability in soil properties can drive variable plant disease development through alterations in the rhizosphere microbiome.

IMPORTANCE

Dollar spot is the most economically important disease of amenity turfgrass, and more fungicides are applied targeting dollar spot than any other turfgrass disease. Dollar spot symptoms are small (3-5 cm), circular patches that develop in a highly variable manner within plot-scale even under seemingly uniform conditions. The mechanism behind this variable development is unknown. This study observed that differences in dollar spot development over a 256 m2area were associated with differences in bulk soil iron concentration and correlated with a particular rhizosphere microbiome. These findings provide important clues for understanding the mechanisms behind the highly variable development of dollar spot, which may offer important clues for innovative control strategies. Additionally, these results also suggest that small changes in soil properties can alter plant activity and hence the plant-associated microbial community which has important implications for a broad array of important agricultural and horticultural plant pathosystems.
In-depth blood proteome profiling analysis revealed distinct functional characteristics of plasma proteins between severe and non-severe COVID-19 patients
Authors: Park Joonho , Kim Hyeyoon , Kim So Yeon , Kim Yeonjae , Lee Jee-Soo , Seong Moon-Woo , Han Dohyun
Published: August 2020

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over ten million patients worldwide. Although most coronavirus disease 2019 (COVID-19) patients have a good prognosis, some develop severe illness. Markers that define disease severity or predict clinical outcome need to be urgently developed as the mortality rate in critical cases is approximately 61.5%. In the present study, we performed indepth proteome profiling of undepleted plasma from eight COVID-19 patients. Quantitative proteomic analysis using the BoxCar method revealed that 91 out of 1,222 quantified proteins were differentially expressed depending on the severity of COVID-19. Importantly, we found 76 proteins, previously not reported, which could be novel prognostic biomarker candidates. Our plasma proteome signatures captured the host response to SARS-CoV-2 infection, thereby highlighting the role of neutrophil activation, complement activation, platelet function, and T cell suppression as well as proinflammatory factors upstream and downstream of interleukin-6, interleukin-1B, and tumor necrosis factor. Consequently, this study supports the development of blood biomarkers and potential therapeutic targets to aid clinical decision-making and subsequently improve prognosis of COVID-19.
Characterization of histone inheritance patterns in theDrosophilafemale germline
Authors: Kahney Elizabeth W. , Sohn Lydia , Viets-Layng Kayla , Johnston Robert , Chen Xin
Published: August 2020

Stem cells have the unique ability to undergo asymmetric division which produces two daughter cells that are genetically identical, but commit to different cell fates. The loss of this balanced asymmetric outcome can lead to many diseases, including cancer and tissue dystrophy. Understanding this tightly regulated process is crucial in developing methods to treat these abnormalities. Here, we report that produced from aDrosophilafemale germline stem cell asymmetric division, the two daughter cells differentially inherit histones at key genes related to either maintaining the stem cell state or promoting differentiation, but not at constitutively active or silenced genes. We combined histone labeling with DNA Oligopaints to distinguish old versus new histone distribution and visualize their inheritance patterns at single-gene resolution in asymmetrically dividing cellsin vivo. This strategy can be widely applied to other biological contexts involving cell fate establishment during development or tissue homeostasis in multicellular organisms.
Diapause regulation in newly invaded environments: termination timing allows matching novel climatic constraints in the box tree moth, Cydalima perspectalis (Lepidoptera: Crambidae)
Authors: Poitou Laura , Bras Audrey , Pineau Patrick , Lorme Philippe , Roques Alain , Rousselet Jérôme , Auger-Rozenberg Marie-Anne , Laparie Mathieu
Published: August 2020

The association between indirect environmental cues that modulate insect diapause and the actual stressors is by no means granted when a species encounters new environments. The box tree moth, Cydalima perspectalis, is an Asian pest whose rapid invasion in Europe cause considerable economic and ecological impacts. Larvae enter a winter diapause induced by photoperiod in both native and invaded ranges, but factors that trigger the return to an active phase are still unknown. Yet, identifying them is crucial to understand how diapause end synchronizes with the end of the winter stress encountered in Europe. To test whether activity resumption is regulated by thermal and/or photoperiodic thresholds, or additive effects between these factors often involved in diapause termination, diapausing caterpillars from an invaded area were exposed to crossed treatments at the laboratory. The evolution of diapause rate was monitored over time and compared to that of nearby field sites invaded. A strong positive effect of increasing temperature was found on the rate and dynamics of diapause termination, whereas no compelling effect of photoperiod appeared. Resuming development directly when main stressors fade, not in response to indirect photoperiodic cues that could be mismatched outside native areas, likely contributes to the good match observed between diapause and the new climates this pest encountered in the invaded range.
Region-level Epimutation Rates inArabidopsis thaliana
Authors: Denkena Johanna , Johannes Frank , Colomé-Tatché Maria
Published: August 2020

Failure to maintain DNA methylation patterns during plant development can occasionally give rise to so-called ‘spontaneous epimutations’. These stochastic methylation changes are sometimes heritable across generations and thus accumulate in plant genomes over time. Recent evidence indicates that spontaneous epimutations have a major role in shaping patterns of methylation diversity in plant populations. Using single CG dinucleotides as units of analysis, previous work has shown that the epimutation rate is several orders of magnitude higher than the genetic mutation rate. While these large rate differences have obvious implications for understanding genome-methylome co-evolution, the functional relevance of single CG methylation changes remains questionable. In contrast to single CG, solid experimental evidence has linked methylation gains and losses in larger genomic regions with transcriptional variation and heritable phentoypic effects. Here we show that such region-level changes arise stochastically at about the same rate as those at individual CG sites, are only marginal dependent on region size and cytosine density, but strongly dependent on chromosomal location. We also find consistent evidence that region-level epimutations are not restricted to CG contexts but also frequently occur in non-CG regions at the genome-wide scale. Taken together, our results support the view that many differentially methylated regions (DMRs) in natural populations originate from epimutational events and may not be effectively tagged by proximal SNPs. This possibility reinforces the need for epigenome-wide association studies (EWAS) in plants as away to identify the epigenetic basis of adaptive traits.
Erythroid precursors and progenitors suppress adaptive immunity and get invaded by SARS-CoV-2
Authors: Shahbaz Shima , Xu Lai , Osman Mohammad , Sligl Wendy , Shields Justin , Joyce Michael , Tyrrell Lorne , Oyegbami Olaide , Elahi Shokrollah
Published: August 2020

SARS-CoV-2 infection is associated with lower blood oxygen levels even in patients without hypoxia requiring hospitalization. This discordance illustrates the need for a more unifying explanation as to whether SARS-CoV-2 directly or indirectly affects erythropoiesis. Here we show significantly enriched CD71+ erythroid precursors/progenitors in the blood circulation of COVID-19 patients that have distinctive immunosuppressive properties. A subpopulation of abundant erythroid cells, CD45+CD71+cells, co-express ACE2, TMPRSS2, CD147, CD26 and these can be infected with SARS-CoV-2. In turn, pre-treatment of erythroid cells with dexamethasone significantly diminished ACE2/TMPRSS2 expression and subsequently reduced their infectivity with SARS-CoV-2. Taken together, pathological abundance of erythroid cells might reflect stress erythropoiesis due to the invasion of erythroid progenitors by SARS-CoV-2. This may provide a novel insight into the impact of SARS-CoV-2 on erythropoiesis and hypoxia seen in COVID-19 patients.
Arabidopsis Myosin XIK Interacts with the Exocyst Complex to Facilitate Vesicle Tethering during Exocytosis
Authors: Zhang Weiwei , Huang Lei , Zhang Chunhua , Staiger Christopher J.
Published: August 2020

Myosin motors are essential players in secretory vesicle trafficking and exocytosis in yeast and mammalian cells; however, similar roles in plants remain a matter for debate, at least for diffusely-growing cells. Here, we demonstrate that Arabidopsis (Arabidopsis thaliana) myosin XIK, via its globular tail domain (GTD), participates in the vesicle tethering step of exocytosis through direct interactions with the exocyst complex. Specifically, myosin XIK GTD bound directly to the SEC5B subunit of exocyst in vitro and functional fluorescently-tagged XIK colocalized with multiple exocyst subunits at plasma membrane (PM)-associated stationary foci. Moreover, genetic and pharmacological inhibition of myosin XI activity reduced the frequency and lifetime of stationary exocyst complexes at the PM. By tracking single exocytosis events of cellulose synthase (CESA) complexes (CSCs) with high spatiotemporal resolution imaging and pair-wise colocalization analysis of myosin XIK, exocyst subunits and CESA6, we demonstrated that XIK associates with secretory vesicles earlier than exocyst and is required for the recruitment of exocyst to the PM tethering site. This study reveals an important functional role for myosin XI in secretion and provides new insights about the dynamic regulation of exocytosis in plants.
Trophic shift and the origin of birds
Authors: Wu Yonghua
Published: August 2020

Birds are characterized by evolutionary specializations of both locomotion (e.g., flapping flight) and digestive system (toothless, crop, and gizzard), while the potential selection pressures responsible for these evolutionary specializations remain unclear. Here we used a recently developed molecular phyloecological method to reconstruct the diets of the ancestral archosaur and of the common ancestor of living birds (CALB). Our results showed that the ancestral archosaur exhibited a predominant Darwinian selection of protein and fat digestion and absorption, whereas the CALB showed a marked enhanced selection of carbohydrate and fat digestion and absorption, suggesting a trophic shift from carnivory to herbivory (fruit, seed, and/or nut-eater) at the archosaur-to-bird transition. The evolutionary shift of the CALB to herbivory may have essentially made them become a low-level consumer and, consequently, subject to relatively high predation risk from potential predators such as gliding maniraptorans, from which birds descended. Under the relatively high predation pressure, ancestral birds with gliding capability may have then evolved not only flapping flight as a possible anti-predator strategy against gliding predatory maniraptorans but also the specialized digestive system as an evolutionary tradeoff of maximizing foraging efficiency and minimizing predation risk. Our results suggest that the powered flight and specialized digestive system of birds may have evolved as a result of their tropic shift-associated predation pressure.
A thermal trade-off between viral production and degradation drives phytoplankton-virus population dynamics
Authors: Demory David , Weitz Joshua S. , Baudoux Anne-Claire , Touzeau Suzanne , Simon Natalie , Rabouille Sophie , Sciandra Antoine , Bernard Olivier
Published: August 2020

Marine viruses interact with their microbial hosts in dynamic environments shaped by variations in abiotic factors, including temperature. However, the impacts of temperature on viral infection of phytoplankton are not well understood. Here we coupled mathematical modeling with experimental datasets to explore the effect of temperature on threeMicromonas-prasinovirus pairs. Our model shows the negative consequences of high temperatures on infection and suggests a temperature-dependent threshold between viral production and degradation. Modeling long-term dynamics in environments with different average temperatures revealed the potential for long-term host-virus coexistence, epidemic free, or habitat loss states. Hence, we generalized our model to global sea surface temperature of present and future seas and show that climate change may influence virus-host dynamics differently depending on the virus-host pair. Our study suggests that temperature-dependent changes in the infectivity of virus particles may lead to shifts in virus-host habitats in warmer oceans, analogous to projected changes in the habitats of macro- and micro-organisms.
A Large-scale Comparison of Cortical and Subcortical Structural Segmentation Methods in Alzheimer’s Disease: a Statistical Approach
Authors: Zamani Jafar , Sadr Ali , Javadi Amir-Homayoun
Published: August 2020

Background

Alzheimer’s disease (AD) is a neurodegenerative disease that leads to anatomical atrophy, as evidenced by magnetic resonance imaging (MRI). Automated segmentation methods are developed to help with the segmentation of different brain areas. However, their reliability has yet to be fully investigated. To have a more comprehensive understanding of the distribution of changes in AD, as well as investigating the reliability of different segmentation methods, in this study we compared volumes of cortical and subcortical brain segments, using automated segmentation methods in more than 60 areas between AD and healthy controls (HC).

Methods

A total of 44 MRI images (22 AD and 22 HC, 50% females) were taken from the minimal interval resonance imaging in Alzheimer’s disease (MIRIAD) dataset. HIPS, volBrain, CAT and BrainSuite segmentation methods were used for the subfields of hippocampus, and the rest of the brain.

Results

While HIPS, volBrain and CAT showed strong conformity with the past literature, BrainSuite misclassified several brain areas. Additionally, the volume of the brain areas that successfully discriminated between AD and HC showed a correlation with mini mental state examination (MMSE) scores. The two methods of volBrain and CAT showed a very strong correlation. These two methods, however, did not correlate with BrainSuite.

Conclusion

Our results showed that automated segmentation methods HIPS, volBrain and CAT can be used in the classification of AD and HC. This is an indication that such methods can be used to inform researchers and clinicians of underlying mechanisms and progression of AD.
Thyroid hormone regulates proximodistal identity in the fin skeleton
Authors: Hu Yinan , Harper Melody , Acosta Benjamin , Donahue Joan , Bui Hoa , Lee Hyungwoo , Nguyen Stacy , McMenamin Sarah
Published: August 2020

Across the ∼30,000 species of ray-finned fish, fins show incredible diversity in overall shape and in the patterning of the supportive bony rays. Fin length mutant zebrafish have provided critical insights into the developmental pathways that regulate relative fin size. However, the processes that govern skeletal patterning along the proximodistal axis of the fin have remained less well understood. Here, we show that thyroid hormone regulates proximodistal identity of fin rays, distalizing gene expression profiles, morphogenetic processes during outgrowth, and ultimate morphology of the fin. This role for thyroid hormone in specifying proximodistal identity appears conserved between development and regeneration, in all the fins, and between species. We demonstrate that proximodistal identity is regulated independently from pathways that determine size, and we show that modulating proximodistal patterning relative to growth can recapitulate the spectrum of fin ray diversity found in nature.
Respiratory complex and tissue lineage drive mutational patterns in the tumor mitochondrial genome
Authors: Gorelick Alexander N. , Kim Minsoo , Chatila Walid K. , La Konnor , Hakimi A. Ari , Taylor Barry S. , Gammage Payam A. , Reznik Ed
Published: August 2020

Mitochondrial DNA (mtDNA) encodes essential protein subunits and translational machinery for four distinct complexes of oxidative phosphorylation (OXPHOS). Using repurposed whole-exome sequencing data, we demonstrate that pathogenic mtDNA mutations arise in tumors at a rate comparable to the most common cancer driver genes. We identify OXPHOS complexes as critical determinants shaping somatic mtDNA mutation patterns across tumor lineages. Loss-of-function mutations accumulate at an elevated rate specifically in Complex I, and often arise at specific homopolymeric hotspots. In contrast, Complex V is depleted of all non-synonymous mutations, suggesting that mutations directly impacting ATP synthesis are under negative selection. Both common truncating mutations and rarer missense alleles are associated with a pan-lineage transcriptional program, even in cancer types where mtDNA mutations are comparatively rare. Pathogenic mutations of mtDNA are associated with substantial increases in overall survival of colorectal adenocarcinoma patients, demonstrating a clear functional relationship between genotype and phenotype. The mitochondrial genome is therefore frequently and functionally disrupted across many cancers, with significant implications for patient stratification, prognosis and therapeutic development.
Post-interval EEG activity is related to task-goals in temporal discrimination
Authors: Bueno Fernanda D. , Cravo André M.
Published: August 2020

Studies investigating the neural mechanisms of time perception often measure brain activity while participants perform a temporal task. However, several of these studies are based exclusively on tasks in which time is relevant, making it hard to dissociate activity related to decisions about time from other task-related patterns. In the present study, human participants performed a temporal or color discrimination task of visual stimuli. Participants were informed which magnitude they would have to judge before or after presenting the two stimuli (S1 and S2) in different blocks. Our behavioral results showed, as expected, that performance was better when participants knew beforehand which magnitude they would judge. Electrophysiological data (EEG) was analyzed using Linear Discriminant Contrasts (LDC) and a Representational Similarity Analysis (RSA) approach to investigate whether and when information about time and color was encoded. During the presentation of S1, we did not find consistent differences in EEG activity as a function of the task. On the other hand, during S2, we found that temporal and color information was encoded in a task-relevant manner. Taken together, our results suggest that task goals strongly modulate decision-related information in EEG activity.
ABbs5mouse model reveals pituitary cilia contributions to developmental abnormalities
Authors: Bentley Melissa R. , Engle Staci E. , Haycraft Courtney J. , Andersen Reagan S. , Croyle Mandy J. , Clearman Kelsey R. , Rains Addison B. , Berbari Nicolas F. , Yoder Bradley K.
Published: August 2020

Primary cilia are critical sensory and signaling compartments present on most mammalian cell types. These specialized structures require a unique signaling protein composition relative to the rest of the cell to carry out their functions. Defects in ciliary structure and signaling result in a broad group of disorders collectively known as ciliopathies. One ciliopathy, Bardet-Biedl Syndrome (BBS; OMIM 209900), presents with diverse clinical features, many of which are attributed to defects in ciliary signaling during both embryonic development and postnatal life. For example, patients exhibit obesity, polydactyly, hypogonadism, developmental delay, and skeletal abnormalities along with sensory and cognitive deficits, but for many of these phenotypes it is uncertain which are developmental in origin. A subset of BBS proteins assembles into the BBSome complex, which is responsible for mediating transport of membrane proteins into and out of the cilium, establishing it as a sensory and signaling hub. Here we describe two new mouse models for BBS resulting from a congenital null and conditional allele ofBbs5.Bbs5null mice develop a complex phenotype including craniofacial defects, skeletal shortening, ventriculomegaly, infertility, and pituitary anomalies. Utilizing the conditional allele, we show that the male fertility defects, ventriculomegaly, and pituitary abnormalities are only found whenBbs5is mutated prior to P7 indicating a developmental origin. In contrast, mutation ofBbs5results in obesity independent of the age ofBbs5loss. Compared to other animal models of BBS,Bbs5mutant mice exhibit pathologies that suggest a specialized role for Bbs5 in ciliary function.
Endothelial Barrier Function is co-regulated at Vessel Bifurcations by Fluid Forces and Sphingosine-1-Phosphate
Authors: Akbari Ehsan , Spychalski Griffin B. , Menyhert Miles M. , Rangharajan Kaushik K. , Prakash Shaurya , Song Jonathan W.
Published: August 2020

Sphingosine-1-phosphate (S1P) is a blood-borne bioactive lipid mediator of endothelial barrier function. Prior studies have implicated mechanical stimulation due to intravascular laminar shear stress in co-regulating S1P signaling in endothelial cells (ECs). Yet, vascular networksin vivoconsist of vessel bifurcations, and this geometry produces hemodynamic forces that are distinct from laminar shear stress. However, the role of these forces at vessel bifurcations in regulating S1P-dependent endothelial barrier function is not known. In this study, we implemented a microfluidic platform that recapitulates the flow dynamics of vessel bifurcations within situquantification of the permeability of microvessel analogues. Co-application of S1P with impinging bifurcated fluid flow, which was characterized by approximately zero shear stress and 38 dyn cm-2stagnation pressure at the vessel bifurcation point, promotes vessel stabilization. Similarly, co-treatment of carrier-free S1P with 3 dyn cm-2laminar shear stress is also protective of endothelial barrier function. Moreover, it is shown that vessel stabilization due to laminar shear stress, but not bifurcated fluid flow, is dependent on S1P receptor 1 or 2 signaling. Collectively, these findings demonstrate the endothelium-protective function of fluid forces at vessel bifurcations and their involvement in coordinating S1P-dependent regulation of vessel permeability.
Hexosamine biosynthetic pathway integrates circadian and metabolic signals to regulate daily rhythms in protein O-linked N-acetylglucosaminylation
Authors: Liu Xianhui , Blaženović Ivana , Contreras Adam J. , Pham Thu M. , Tabuloc Christine A. , Li Ying H. , Ji Jian , Fiehn Oliver , Chiu Joanna C.
Published: August 2020

The integration of circadian and metabolic signals is essential for maintaining robust circadian rhythms and ensuring efficient metabolism and energy use. UsingDrosophilaas an animal model, we showed that cellular protein O-linked N-acetylglucosaminylation (O-GlcNAcylation) exhibits robust 24-hour rhythm and is a key post-translational mechanism that regulates circadian physiology. We observed strong correlation between protein O-GlcNAcylation rhythms and clock-controlled feeding-fasting cycles, suggesting that O-GlcNAcylation rhythms are primarily driven by nutrient input. Interestingly, daily O-GlcNAcylation rhythms were severely dampened when we subjected flies to time-restricted feeding (TRF) at unnatural feeding time. This suggests the presence of a clock-regulated buffering mechanism that prevents excessive O-GlcNAcylation at non-optimal times of the day-night cycle. We found that this buffering mechanism is mediated by glutamine-fructose-6-phosphate amidotransferase (GFAT) activity, which is regulated through integration of circadian and metabolic signals. Finally, we generated a mathematical model to describe the key factors that regulate daily O-GlcNAcylation rhythm.
Genetics of mouse behavioral and peripheral neural responses to sucrose
Authors: Lin Cailu , Inoue Masashi , Li Xia , Bosak Natalia P. , Ishiwatari Yutaka , Tordoff Michael G. , Beauchamp Gary K. , Bachmanov Alexander A. , Reed Danielle R.
Published: August 2020

Mice of the C57BL/6ByJ (B6) strain have higher consumption of, and stronger peripheral neural responses to, sucrose solution than do mice of the 129P3/J (129) strain. To identify quantitative trait loci (QTLs) responsible for this strain difference and evaluate the contribution of peripheral taste responsiveness to individual differences in sucrose intake, we produced an intercross (F2) of 627 mice, measured their sucrose consumption in two-bottle choice tests, recorded the electrophysiological activity of the chorda tympani nerve elicited by sucrose in a subset of F2mice, and genotyped the mice with DNA markers distributed in every mouse chromosome. We confirmed a sucrose consumption QTL (Scon2, or Sac) on mouse chromosome (Chr) 4, harboring theTas1r3gene, which encodes the sweet taste receptor subunit T1R3 and affects both behavioral and neural responses to sucrose. For sucrose consumption, we also detected five new main-effect QTLsScon6(Chr2),Scon7(Chr5),Scon8(Chr8),Scon3(Chr9) and a sex-specific QTLScon9(Chr15), and an interacting QTL pairScon4(Chr1)and Scon3(Chr9). No additional QTLs for the taste nerve responses to sucrose were detected besides the previously known one on Chr4 (Scon2). Identification of the causal genes and variants for these sucrose consumption QTLs may point to novel mechanisms beyond peripheral taste sensitivity that could be harnessed to control obesity and diabetes.
Chronic oxytocin-driven alternative splicing of CRFR2α induces anxiety
Authors: Winter Julia , Meyer Magdalena , Berger Ilona , Peters Sebastian , Royer Melanie , Bianchi Marta , Stang Simone , Langgartner Dominik , Reber Stefan O. , Kuffner Kerstin , Schmidtner Anna K. , Hartmann Finn , Bludau Anna , Bosch Oliver J. , Slattery David A. , van den Burg Erwin H. , Neumann Inga D. , Jurek Benjamin
Published: August 2020

Recently, oxytocin (OXT) has generated considerable interest as potential treatment for psychiatric disorders, including general anxiety disorder or autism spectrum disorder. Therefore, knowledge on the involved molecular processes downstream of OXT receptor (OXTR) activation is indispensable. We reveal that alternative splicing of corticotropin releasing factor receptor 2α (CRFR2α) parallels increased anxiety-like behavior following chronic OXT treatment, contrasting the well-known anxiolysis of acute OXT. In detail, chronic OXT shifts the splicing ratio between membrane-bound (mCRFR2α) and soluble CRFR2α (sCRFR2α) in favor of the latter via ERK1/2-MEF2A signaling. Targeted manipulations ofCrfr2αsplicing mimic the effect of chronic OXT, confirming its role in the regulation of anxiety-like behavior. Furthermore, chronic OXT triggers cytoplasmic distribution and extracellular release of sCRFR2α into the cerebrospinal fluid, with sCRFR2α levels positively correlating with anxiety-like behavior. Concluding, the dichotomy between anxiolytic mCRFR2α and anxiogenic sCRFR2α is the basis for the deleterious effects of chronic OXT on anxiety.

Graphical Abstract
Intranasal Administration of Functionalized Soot Particles Disrupts Olfactory Sensory Neuron Progenitor Cells in the Neuroepithelium
Authors: Norwood Jordan N. , Gharpure Akshay P. , Kumal Raju , Turner Kevin L. , Pistone Lauren Ferrer , Vander Wal Randy , Drew Patrick J.
Published: August 2020

Exposure to air pollution has been linked to the development of neurodegenerative diseases and anosmia, but the underlying mechanism is not known. Additionally, the loss of olfactory function often precedes the onset of neurodegenerative diseases. Chemical ablation of olfactory sensory neurons blocks the drainage of cerebrospinal fluid (CSF) through the cribriform plate and alters normal CSF production and/or circulation. Damage to this drainage pathway could contribute to the development of neurodegenerative diseases and could link olfactory sensory neuron health and neurodegeneration. Here, we investigated the impact of intranasal treatment of combustion products (laboratory-generated soots) and their oxygen functionalized derivatives on mouse olfactory sensory neurons, olfactory nerve cell progenitors, and the behavior of the mouse. We found that after a month of every-other-day intranasal treatment of soots, there was minimal effect on olfactory sensory neuron anatomy or exploratory behavior in the mouse. However, oxygen-functionalized soot caused a large decrease in globose basal cells, which are olfactory progenitor cells. These results suggest that exposure to air pollution damages the olfactory neuron progenitor cells, and could lead to decreases in the number of olfactory neurons, potentially disrupting CSF drainage.