bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drosophila melanogaster females prioritise dietary sterols for producing high quality eggs
Authors: Zanco Brooke , Rapley Lisa , Johnstone Joshua N , Dedman Amy , Mirth Christen K , Sgrò Carla M , Piper Matthew DW 
Published: June 2021

AbstractLimiting calories or specific nutrients without malnutrition, otherwise known as dietary restriction (DR), has been shown to extend lifespan across a broad range of taxa. Our recent findings in Drosophila melanogaster show that supplementing flies on macronutrient-rich diets with additional cholesterol can extend lifespan to the same extent as DR. Macronutrient-rich diets drive high levels of egg production and in doing so deplete the mothers of somatic sterols that are essential for survival. Thus, DR may be beneficial for lifespan because it reduces egg production which in turn reduces the mother’s demand for sterols. If this is true, mothers must be prioritising their available sterols, whether from the diet or from their own bodies, to sustain high quality egg production. To test this, we measured the quality of eggs laid by mothers fed either cholesterol-sufficient or cholesterol-depleted diets. We found that even when the mother’s diet was completely devoid of cholesterol, high quality egg production persisted. Furthermore, we show that sterol-supplemented flies with long lives continue to lay high quality eggs that give rise to healthy offspring. Thus, in our assays, long life does not require a fecundity cost.
Federated analysis of BRCA1 and BRCA2 variation in a Japanese cohort
Authors: Casaletto James , Parsons Michael , Markello Charles , Iwasaki Yusuke , Momozawa Yukihide , Spurdle Amanda B. , Cline Melissa 
Published: June 2021

SummaryMore than 40% of the germline variants in ClinVar today are variants of uncertain significance (VUS). These variants remain unclassified in part because the patient-level data needed for their interpretation is siloed. Federated analysis can overcome this problem by “bringing the code to the data”: analyzing the sensitive patient-level data computationally within its secure home institution and providing researchers with valuable insights from data that would not otherwise be accessible. We tested this principle with a federated analysis of breast cancer clinical data at RIKEN, derived from the BioBank Japan repository. We were able to analyze these data within RIKEN’s secure computational framework, without the need to transfer the data, gathering evidence for the interpretation of several variants. This exercise represents an approach to help realize the core charter of the Global Alliance for Genomics and Health (GA4GH): to responsibly share genomic data for the benefit of human health.
RT-QuIC amplification of CWD prions in winter ticks (Dermacentor albipictus) collected from North American elk (Cervus canadensis) in a CWD-endemic area
Authors: Haley NJ , Henderson DM , Senior K , Miller M , Donner R 
Published: June 2021

AbstractChronic wasting disease (CWD) is a progressive and fatal spongiform encephalopathy of deer and elk species, caused by a misfolded variant of the normal prion protein. Horizontal transmission of the misfolded CWD prion between animals is thought to occur through shedding in saliva and other forms of excreta. The role of blood in CWD transmission is less clear, though infectivity has been demonstrated in various blood fractions. Blood-feeding insects, including ticks, are known vectors for a range of bacterial and viral infections in animals and humans, though to date there has been no evidence for their involvement in prion disease transmission. In the present study, we evaluated winter ticks (Dermacentor albipictus) collected from 136 North American elk (Cervus canadensis) in a CWD-endemic area for evidence of CWD prion amplification using the real time quaking-induced conversion assay (RT-QuIC). Although 30 elk were found to be CWD-positive (22%) postmortem, amplifiable prions were found in just a single tick collected from an elk in advanced stages of CWD infection, with some evidence for prions in ticks collected from elk in mid-stage infection. These findings suggest that further investigation of ticks as reservoirs for prion disease may be warranted.ImportanceThis study reports the first finding of detectable levels of prions linked to chronic wasting disease in a tick collected from a clinically infected elk. Using the real time quaking-induced conversion assay (RT-QuIC), evidence of amplifiable CWD prions was also found in ticks collected from elk in earlier stages of disease. Observed levels were at the lower end of our detection limits, though our findings suggest that additional research evaluating ticks collected from animals in late-stage disease may be warranted to further evaluate the role of ticks as potential vectors of chronic wasting disease.
Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-related Mental Disorders (MIND-Set): a cross-sectional comorbidity study from an RDoC perspective
Authors: van Eijndhoven Philip F.P. , Collard Rose M. , Vrijsen Janna N. , Geurts Dirk G.M. , Arias-Vasquez Alejandro , Schellekens Arnt F.A. , van den Munckhof Eva , Brolsma Sophie C.A. , Duyser Fleur A. , Bergman M. Annemiek , van Oort Jasper , Tendolkar Indira , Schene Aart H. 
Published: June 2021

AbstractBackgroundIt is widely acknowledged that comorbidity between psychiatric disorders is common. Shared and diverse underpinnings of psychiatric disorders cannot be systematically understood on the basis of symptom-based categories of mental disorders, which map poorly onto pathophysiological mechanisms. In the MIND-Set study, we make use of current concepts of comorbidity that transcend the current diagnostic categories. We test this approach to psychiatric problems in patients with frequently occurring psychiatric disorders and their comorbidities (excluding psychosis). The main objective of the MIND-Set project is to determine the shared and specific mechanisms of neurodevelopmental and stress-related psychiatric disorders at different observational levels.MethodsThis is an observational, cross-sectional study. Data from different observational levels as defined in the research domain criteria (RDoC; genetics, physiology, neuropsychology, system level neuroimaging, behavior, self-report and experimental neurocognitive paradigms) are collected over four time points. Included are adult (≥ 18 years), non-psychotic, psychiatric patients with a clinical diagnosis of a stress-related disorder (mood disorder, anxiety disorder and/or addiction disorder) and/or a neurodevelopmental disorder (ASD and/or ADHD). Individuals with no current or past psychiatric diagnosis are included as controls. Data collection started in June 2016 with the aim to include a total of 650 patients and 150 healthy controls by 2021. The data collection procedure includes online questionnaires and three subsequent sessions with 1) Standardized clinical examination, physical examination, and blood sampling; 2) Psychological constructs, neuropsychological tests, and biological marker sampling; 3) Neuroimaging measures.DiscussionThe MIND-Set study enables us to investigate the mechanistic underpinnings of non-psychotic psychiatric disorders transdiagnostically. We will identify both shared and disorder-specific markers at different observational levels that can be used as targets for future diagnostic and treatment approaches.
Insect-specific viruses regulate vector competence in Aedes aegypti mosquitoes via expression of histone H4
Authors: Olmo Roenick P. , Todjro Yaovi M. H. , Aguiar Eric R. G. R. , de Almeida João Paulo P. , Armache Juliana N. , de Faria Isaque J. S. , Ferreira Flávia V. , Silva Ana Teresa S. , de Souza Kátia P. R. , Vilela Ana Paula P. , Tan Cheong H. , Diallo Mawlouth , Gaye Alioune , Paupy Christophe , Obame-Nkoghe Judicaël , Visser Tessa M. , Koenraadt Constantianus J. M. , Wongsokarijo Merril A. , Cruz Ana Luiza C. , Prieto Mariliza T. , Parra Maisa C. P. , Nogueira Maurício L. , Avelino-Silva Vivian , Mota Renato N. , Borges Magno A. Z. , Drumond Betânia P. , Kroon Erna G. , Sedda Luigi , Marois Eric , Imler Jean-Luc , Marques João T. 
Published: June 2021

AbstractAedes aegypti and Aedes albopictus are major mosquito vectors for arthropod-borne viruses (arboviruses) such as dengue (DENV) and Zika (ZIKV) viruses. Mosquitoes also carry insect-specific viruses (ISVs) that may affect the transmission of arboviruses. Here, we analyzed the global virome in urban Aedes mosquitoes and observed that two insect-specific viruses, Phasi Charoen-like virus (PCLV) and Humaita Tubiacanga virus (HTV), were the most prevalent in A. aegypti worldwide except for African cities, where transmission of arboviruses is low. Spatiotemporal analysis revealed that presence of HTV and PCLV led to a 200% increase in the chances of having DENV in wild mosquitoes. In the laboratory, we showed that HTV and PCLV prevented downregulation of histone H4, a previously unrecognized proviral host factor, and rendered mosquitoes more susceptible to DENV and ZIKV. Altogether, our data reveals a molecular basis for the regulation of A. aegypti vector competence by highly prevalent ISVs that may impact how we analyze the risk of arbovirus outbreaks.
Quantification of Antisense Oligonucleotides by Splint Ligation and Quantitative Polymerase Chain Reaction
Authors: Shin Minwook , Krishnamurthy Pranathi Meda , Watts Jonathan K. 
Published: June 2021

AbstractReliable detection and quantification of antisense oligonucleotides (ASOs) in experimental and clinical specimens is essential to understand the biological function of novel oligonucleotide-based therapeutics. In this study, we describe a method to detect and quantify ASOs in biological samples, whereby the ASO acts as a splint to direct the ligation of complementary probes and quantitative real-time PCR was used to monitor ligation products. Low levels of 2′-O-MOE gapmer ASO in serum, liver, kidney, lung, heart, muscle, and brain tissues can be detected over a 6-log linear range for detection using this method. This method allows quantification of various types of chemically modified ASOs, including PS linkage, 2′-OMe, 2′-O-MOE, locked nucleic acid (LNA), and siRNA. This method does not require probe modifications, and can be performed using standard laboratory equipment; making it a fast, sensitive, and reliable technique that can be widely applied. This detection method may find potential applications in detection of therapeutic oligonucleotides in biological samples.
Sustained post-developmental T-bet expression is critical for the maintenance of type one innate lymphoid cells in vivo
Authors: Schroeder J-H , Roberts LB , Meissl K , Lo JW , Hromadová D , Hayes K , Zabinski T , Read E , Heliodoro C Moreira , Reis R , Howard JK , Grencis RK , Neves J F , Strobl B , Lord GM 
Published: June 2021

ABSTRACTInnate lymphoid cells (ILC) play a significant role in the intestinal immune response and T-bet+ CD127+ group 1 cells (ILC1) have been linked to the pathogenesis of human inflammatory bowel disease (IBD). However, the functional importance of ILC1 in the context of an intact adaptive immune response has been controversial. In this report we demonstrate that induced depletion of T-bet using a Rosa26-Cre-ERT2 model resulted in the loss of intestinal ILC1, pointing to a post-developmental requirement of T-bet expression for these cells. In contrast, neither colonic lamina propria (cLP) ILC2 nor cLP ILC3 abundance were altered upon induced deletion of T-bet. Mechanistically, we report that STAT1 or STAT4 are not required for intestinal ILC1 development and maintenance. Mice with induced deletion of T-bet and subsequent loss of ILC1 were protected from the induction of severe colitis in vivo. Hence, this study provides support for the clinical development of an IBD treatment based on ILC1 depletion via targeting T-bet or its downstream transcriptional targets.
A marginal habitat, but not a sink: Ecological genetics reveal a diversification hotspot for marine invertebrates in the brackish Baltic Sea
Authors: Geburzi Jonas C. , Heuer Nele , Homberger Lena , Kabus Jana , Moesges Zoe , Ovenbeck Kira , Brandis Dirk , Ewers-Saucedo Christine 
Published: June 2021

AbstractAimEnvironmental gradients have emerged as important barriers structuring populations and species distributions. We set out to test whether a strong salinity gradient from marine to brackish, represented in a marginal northern European sea, should be considered a diversification hotspot or a population sink, and to identify life history traits that correlate with either evolutionary trajectory.LocationThe Baltic Sea, the North Sea and their transition zone.MethodsWe accumulated mitochondrial cytochrome oxidase subunit 1 sequence data and data on the distribution, salinity tolerance and life history for 28 species belonging to the Cnidaria, Crustacea, Echinodermata, Mollusca, Polychaeta and Gastrotricha, including seven non-native species. We calculated measures of genetic diversity and differentiation across the environmental gradient, coalescent times and migration rates between North and Baltic Sea populations, and analysed correlations between genetic and life history data.ResultsThe majority of investigated species is either genetically differentiated and/or is adapted to the lower salinity conditions of the Baltic Sea. Moreover, the species exhibiting population structure have a range of patterns of genetic diversity in comparison to the North Sea, from lower in the Baltic Sea to higher in the Baltic Sea, or equally diverse in North and Baltic Sea.Main conclusionsOur results indicate that the Baltic Sea should be considered a diversification hotspot: The diversity of genetic patterns points towards independent trajectories in the Baltic compared to the North Sea. At the same time, we found limited evidence for the traditional scenario of the Baltic Sea as a population sink with lower diversity and strong gene flow. The North Sea - Baltic Sea region provides a unique setting to study evolutionary adaptation during colonization processes at different stages by jointly considering native and non-native species.
Carboxypeptidase E is efficiently secreted and internalized via lysosomes
Authors: Armoza-Eilat Shir , Caspi Michal , Shomron Olga , Hirschberg Koret , Rosin-Arbesfeld Rina 
Published: June 2021

ABSTRACTCarboxypeptidase E (CPE) a key factor in the biosynthesis of most peptide hormones and neuropeptides, is predominantly expressed in endocrine tissues and the nervous system. This highly conserved enzyme cleaves the C-terminal basic residues of the peptide precursors to generate their bioactive form. CPE is a secreted protein; however, the Intracellular pathways leading to its secretion are still obscure. We combined live-cell microscopy and molecular analysis to examine the intracellular distribution and secretion dynamics of fluorescently tagged CPE. CPE was found to be a soluble luminal protein as it traffics from the ER via the Golgi apparatus to lysosomes. Moreover, CPE is efficiently secreted and reinternalized to lysosomes of neighboring cells. The C-terminal amphipathic helix of CPE is essential for its efficient targeting to, and secretion from lysosomes. Fluorescence resonance energy transfer demonstrated that CPE and its substrate neuropeptide Y (NPY) interact in the Golgi apparatus and Immunoprecipitation analysis demonstrated that both CPE and NPY are co-secreted. The implications of the well-defined CPE intra and extracellular routes are discussed.
The ciliary gene INPP5E confers dorsal telencephalic identity to human cortical organoids by negatively regulating Sonic Hedgehog signalling
Authors: Schembs Leah , Willems Ariane , Hasenpusch-Theil Kerstin , Cooper James D. , Whiting Katie , Burr Karen , Bøstrand Sunniva M.K. , Selvaraj Bhuvaneish T. , Chandran Siddharthan , Theil Thomas 
Published: June 2021

SUMMARYDefects in primary cilia, cellular antennas that controls multiple intracellular signalling pathways, underlie several neurodevelopmental disorders, but how cilia control essential steps in human brain formation remains elusive. Here, we show that cilia are present on the apical surface of radial glial cells in human foetal forebrain. Interfering with cilia signalling in human organoids by mutating the INPP5E gene leads to the formation of ventral telencephalic cell types instead of cortical progenitors and neurons. INPP5E mutant organoids also showed increased SHH signalling and cyclopamine treatment partially rescued this ventralisation. In addition, ciliary expression of SMO was increased and the integrity of the transition zone was compromised. Overall, these findings establish the importance of primary cilia for dorsal/ventral patterning in human corticogenesis, indicate a tissue specific role of INPP5E as a negative regulator of SHH signalling and have implications for the emerging roles of cilia in the pathogenesis of neurodevelopmental disorders.
Generative replay for compositional visual understanding in the prefrontal-hippocampal circuit
Authors: Schwartenbeck Philipp , Baram Alon , Liu Yunzhe , Mark Shirley , Muller Timothy , Dolan Raymond , Botvinick Matthew , Kurth-Nelson Zeb , Behrens Timothy 
Published: June 2021

AbstractUnderstanding the visual world is a constructive process. Whilst a frontal-hippocampal circuit is known to be essential for this task, little is known about the associated neuronal computations. Visual understanding appears superficially distinct from other known functions of this circuit, such as spatial reasoning and model-based planning, but recent models suggest deeper computational similarities. Here, using fMRI, we show that representations of a simple visual scene in these brain regions are relational and compositional – key computational properties theorised to support rapid construction of hippocampal maps. Using MEG, we show that rapid sequences of representations, akin to replay in spatial navigation and planning problems, are also engaged in visual construction. Whilst these sequences have previously been proposed as mechanisms to plan possible futures or learn from the past, here they are used to understand the present. Replay sequences form constructive hypotheses about possible scene configurations. These hypotheses play out in an optimal order for relational inference, progressing from predictable to uncertain scene elements, gradually constraining possible configurations, and converging on the correct scene configuration. Together, these results suggest a computational bridge between apparently distinct functions of hippocampal-prefrontal circuitry, and a role for generative replay in constructive inference and hypothesis testing.
Whole-cell cryo-electron tomography of cultured and primary eukaryotic cells on micropatterned TEM grids
Authors: Sibert Bryan S. , Kim Joseph Y. , Yang Jie E. , Wright Elizabeth R. 
Published: June 2021

ABSTRACTWhole-cell cryo-electron tomography (cryo-ET) is a powerful technique that can provide nanometer-level resolution of biological structures within the cellular context and in a near-native frozen-hydrated state. It remains a challenge to culture or adhere cells on TEM grids in a manner that is suitable for tomography while preserving the physiological state of the cells. Here, we demonstrate the versatility of micropatterning to direct and promote growth of both cultured and primary eukaryotic cells on TEM grids. We show that micropatterning is compatible with and can be used to enhance studies of host-pathogen interactions using respiratory syncytial virus infected BEAS-2B cells as an example. We demonstrate the ability to use whole-cell tomography of primary Drosophila neuronal cells to identify organelles and cytoskeletal stuctures in cellular axons and the potential for micropatterning to dramatically increase throughput for these studies. During micropatterning, cell growth is targeted by depositing extra-cellular matrix (ECM) proteins within specified patterns and positions on the foil of the TEM grid while the other areas remain coated with an anti-fouling layer. Flexibility in the choice of surface coating and pattern design make micropatterning broadly applicable for a wide range of cell types. Micropatterning is useful for studies of structures within individual cells as well as more complex experimental systems such as host-pathogen interactions or differentiated multi-cellular communities. Micropatterning may also be integrated into many downstream whole-cell cryo-ET workflows including correlative light and electron microscopy (cryo-CLEM) and focused-ion beam milling (FIB-SEM).
Confronting assumptions about prey selection by lunge‐feeding whales using a process‐based model
Authors: Chenoweth Ellen M. , Boswell Kevin M. , Friedlaender Ari S. , McPhee Megan V. , Burrows Julia A. , Heintz Ron A. , Straley Jan M. 
Published: June 2021

Abstract

The relative energetic benefits of foraging on one type of prey rather than another are not easily measured, particularly for large free‐ranging predators. Nonetheless, assumptions about preferred and alternative prey are frequently made when predicting how a predator may impact its environment, adapt to environmental change or interact with human activities.

We developed and implemented a process‐based model to investigate the potential energetic benefit (PEB) of in situ foraging opportunities in rorqual whales. The model integrates and evaluates the energetic importance of measured prey patch characteristics (prey distribution, energy content and predator avoidance) and predator characteristics (morphometrics, foraging tactics and feeding rates). We applied the model to test the assumption that hatchery‐released juvenile salmon are an ‘easy meal’ for humpback whales compared to more common prey: herring and krill.

In 11 out of the 13 foraging situations considered, whales were found to be feeding in a manner where net energy gain was greater than the energetic costs of non‐foraging swimming. Humpback whale PEB for hatchery‐released juvenile salmon fell within the range of the PEB for krill and herring but varied by species, from relatively high PEB for chum salmon to relatively low for coho salmon. Our model provides behavioural insight as well, indicating that shallow feeding may be more important for reducing energy expenditure through slower lunge speeds than for increasing prey capture. The model also provides a means of identifying prey patch characteristics, with prey aggregation playing the largest role in determining PEB despite being a poor overall proxy for PEB, supporting the use of the complex model framework.

Modelling approaches are especially valuable where they can use reasonable assumptions to substitute for lack of reliable observations, thereby integrating a range of interacting factors into a single framework. Additionally, because process‐based models can be used to make predictions outside the range of previously observed conditions, they will be increasingly useful in a changing climate.

A free Plain Language Summary can be found within the Supporting Information of this article.