bluuebunny/crossref_metadata_2025_split huggingface dataset:
A gut-derived hormone switches dietary preference after mating in Drosophila
Authors: Malita Alina , Kubrak Olga , Koyama Takashi , Ahrentløv Nadja , Halberg Kenneth V. , Texada Michael J. , Nagy Stanislav , Rewitz Kim 
Published: March 2022

AbstractAnimals must adapt their dietary choices to meet their nutritional needs. How these needs are detected and translated into nutrient-specific appetites that drive food-choice behaviors is poorly defined. Here, we show that the enteroendocrine cells (EECs) of the adult female Drosophila midgut sense nutrients and in response release neuropeptide F (NPF), an ortholog of mammalian NPY-family gut-brain hormones. Gut-derived NPF acts via effects on glucagon-like adipokinetic hormone (AKH) signaling to induce sugar satiety and to drive hunger for protein-rich food, and on adipose tissue to promote storage of ingested nutrients. Suppression of gut NPF leads to overconsumption of dietary sugar while decreasing intake of protein-rich yeast. Furthermore, we show a female-specific function of gut-derived NPF in the suppression of AKH signaling after mating. This induces a dietary switch that promotes preference for protein-containing food to support reproduction. Together, our findings suggest that the gut NPF-AKH axis regulates appetite that drives specific food choices to ensure homeostatic consumption of nutrients, providing insight into the hormonal mechanisms that underlie nutrient-specific hungers.
Comprehensive analysis of cis- and trans-acting factors affecting Break-Induced Replication
Authors: Uribe-Calvillo Tannia , Maestroni Laetitia , Marsolier Marie-Claude , Khadaroo Basheer , Arbiol Christine , Schott Jonathan , Llorente Bertrand 
Published: March 2022

AbstractBreak-induced replication (BIR) is a highly mutagenic eukaryotic homologous DNA recombination pathway that repairs one-ended DNA double strand breaks such as broken DNA replication forks and eroded telomeres. While searching for cis-acting factors regulating BIR efficiency, we found that BIR efficiency is the highest close to chromosome ends. The variations of BIR efficiency as a function of the length of DNA to replicate can be described as a combination of two decreasing exponential functions, a property in line with repeated cycles of strand invasion, elongation and dissociation that characterize BIR. Interestingly, the apparent processivity of BIR depends on the length of DNA already synthesized. BIR is more susceptible to disruption during the synthesis of the first ∼35-40 kb of DNA than later, notably when the template chromatid is being transcribed or heterochromatic. Finally, we show that the Srs2 helicase promotes BIR from both telomere proximal and telomere distal regions in diploid cells but only from telomere proximal sites in haploid cells. Altogether, we bring new light on the factors impacting a last resort DNA repair pathway.
Deep networks may capture biological behaviour for shallow, but not deep, empirical characterizations
Authors: Neri Peter 
Published: March 2022

AbstractWe assess whether deep convolutional networks (DCN) can account for a most fundamental property of human vision: detection/discrimination of elementary image elements (bars) at different contrast levels. The human visual process can be characterized to varying degrees of ‘depth’, ranging from percentage of correct detections to detailed tuning and operating characteristics of the underlying perceptual mechanism. We challenge deep networks with the same stimuli/tasks used with human observers and apply equivalent characterization of the stimulus-response coupling. In general, we find that popular DCN architectures do not account for signature properties of the human process. For shallow depth of characterization, some variants of network-architecture/training-protocol produce human-like trends; however, richer empirical descriptors expose glaring discrepancies. These results urge caution in assessing whether neural networks do or do not capture human behaviour: ultimately, our ability to assess ‘success’ in this area can only be as good as afforded by the depth of behavioural characterization against which the network is evaluated. We propose a novel set of metrics/protocols that impose stringent constraints on the evaluation of DCN behaviour as adequate approximation of biological processes.
A comprehensive single-cell expression atlas of human AML leukemia-initiating cells unravels the contribution of HIF pathway and its therapeutic potential
Authors: Velasco-Hernandez Talia , Trincado Juan L. , Vinyoles Meritxell , Closa Adria , Gutiérrez-Agüera Francisco , Molina Oscar , Rodríguez-Cortez Virginia C , Petazzi Paolo , Beneyto-Calabuig Sergi , Velten Lars , Romecin Paola , Casquero Raquel , Abollo-Jiménez Fernando , Díaz de la Guardia Rafael , Lorden Patricia , Bataller Alex , Lapillonne Helene , Stam Ronald W , Vives Susana , Torrebadell Montserrat , Fuster Jose Luis , Bueno Clara , Eyras Eduardo , Heyn Holger , Menéndez Pablo 
Published: March 2022

AbstractRelapse remains a major challenge in the clinical management of acute myeloid leukemia (AML), and is driven by rare therapy-resistant leukemia-initiating stem cells (LSCs) that reside in specific bone marrow niches. Hypoxia signaling keeps cells in a quiescent and metabolically relaxed state, desensitizing them to chemotherapy. This suggests the hypothesis that hypoxia contributes to AML-LSC function and chemoresistance and is a therapeutic target to sensitize AML-LSCs to chemotherapy. Here, we provide a comprehensive single-cell expression atlas (119,000 cells) of AML cells and AML-LSCs in paired diagnostic-relapse samples from risk-stratified patients with AML. The HIF/hypoxia pathway is attenuated in AML-LSCs compared with differentiated AML cells, but is enhanced when compared with healthy hematopoietic cells. Accordingly, chemical inhibition cooperates with standard-of-care chemotherapy to impair leukemogenesis, substantially eliminating AML-LSCs. These findings support the HIF pathway as a stem cell regulator in human AML, and reveal avenues for combinatorial targeted and chemotherapy-based approaches to specifically eliminate AML-LSCs.
Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies Against Delta and Omicron in Mice
Authors: van Vuren Petrus Jansen , McAuley Alexander J. , Kuiper Michael J. , Singanallur Nagendrakumar B. , Bruce Matthew P. , Riddell Shane , Goldie Sarah , Mangalaganesh Shruthi , Chahal Simran , Drew Trevor W. , Blasdell Kim R. , Tachedjian Mary , Caly Leon , Druce Julian D. , Ahmed Shahbaz , Khan Mohammad Suhail , Malladi Sameer Kumar , Singh Randhir , Pandey Suman , Varadarajan Raghavan , Vasan Seshadri S. 
Published: March 2022

AbstractAs existing vaccines fail to completely prevent COVID-19 infections or community transmission, there is an unmet need for vaccines that can better combat SARS-CoV-2 variants of concern (VOC). We have previously developed highly thermo-tolerant monomeric and trimeric receptor binding domain derivatives that can withstand 100°C for 90 minutes and 37°C for four weeks, and help eliminate cold chain requirements. We show that mice immunised with these vaccine formulations elicit high titres of antibodies that neutralise SARS-CoV-2 variants VIC31 (with Spike: D614G mutation), Delta and Omicron (BA.1.1) VOC. Compared to VIC31, there was an average 14.4-fold reduction in neutralisation against BA.1.1 for the three monomeric antigen-adjuvant combinations, and 16.5-fold reduction for the three trimeric antigen-adjuvant combinations; the corresponding values against Delta were 2.5 and 3.0. Our findings suggest that monomeric formulations are suitable for the upcoming Phase I human clinical trials, and that there is potential for increasing efficacy with vaccine matching to improve responses against emerging variants. These findings are consistent with in silico modelling and AlphaFold predictions which show that while oligomeric presentation can be generally beneficial, it can make important epitopes inaccessible, and also carries the risk of eliciting unwanted antibodies against the oligomerisation domain.
Follicle cell contact maintains main body axis polarity in theDrosophila melanogasteroocyte
Authors: Milas Ana , de-Carvalho Jorge , Telley Ivo A. 
Published: March 2022

AbstractInDrosophila melanogasterthe anterior-posterior body axis is maternally established and governed by differential localization of partitioning defective (Par) proteins within the oocyte. At mid-oogenesis, Par-1 accumulates at the posterior end of the oocyte while Par-3/Bazooka is excluded there but maintains its localization along the remaining oocyte cortex. This mutual exclusion leads to a polarized microtubule network and accumulation of posterior determinantoskarlater in oogenesis. Reciprocal biochemical interactions between Par proteins can explain their cortical exclusion and domain formation – for example, Par-1 excludes Par-3 by phosphorylation. However, past studies have proposed the need for somatic cells at the posterior end to initiate oocyte polarization by providing a trigger signal. To date, despite modern screening approaches and genetic manipulation, neither the molecular identity nor the nature of the signal is known. Here, we provide the first evidence that mechanical contact of posterior follicle cells (PFCs) with the oocyte cortex causes the posterior exclusion of Bazooka and maintains oocyte polarity. We show that Bazooka prematurely accumulates exclusively where posterior follicle cells have been mechanically detached or ablated. This occurs before Par-1 is removed suggesting that phosphorylation of Bazooka by Par-1 is not sufficient to maintain Bazooka exclusion in the absence of PFC contact. Furthermore, we provide evidence that PFC contact maintains Par-1 andoskarlocalization and microtubule cytoskeleton polarity in the oocyte. Our observations suggest that cell-cell contact mechanics modulates Par protein binding sites at the oocyte cortex.
Mechanosensory Systems and Sensory Integration MediateC. elegansNegative Gravitaxis
Authors: Ackley Caroline , Washiashi Lindsey , Ziaei Kajbaf Neda , Krishnamurthy Ruchira , Sun Zhenxuan , Duong Vivian , Choe Kaylin , Lane Elijah , Wood Cricket , Smith Eleanor , Pellegrini Giulia , Sherwin Mark , Joshi Pradeep , Rothman Joel H. 
Published: March 2022

AbstractThe ability to sense Earth’s gravitational pull is essential for orientation, navigation, and proprioception in many organisms. We report here thatC. elegansexhibits pronounced negative gravitaxis, or movement away from the Earth’s center, independent of orientation of the geomagnetic field. This behavior is antagonized by light and electromagnetic fields, suggesting that it is integrated with other sensory inputs. We found that MEC-5/7/12, and TRPA-1, but not MEC-4/10 DEG/ENaC channels or other proteins involved in gentle touch transduction, are essential for negative gravitaxis, suggesting that the sensory system for detecting and responding to gravity is separable from touch sensation. We also found that the PVD neurons but not touch receptor neurons (TRNs) are required for this behavior. These findings implicate an interconnected mechanism for gravity sensation involving an ion channel that is also present in the mammalian vestibular system, suggesting possible homology in gravity sensing across animal phylogeny.
The Endoplasmic Reticulum Membrane Complex Promotes Proteostasis of GABAAReceptors
Authors: Whittsette Angela , Wang Ya-Juan , Mu Ting-Wei 
Published: March 2022

ABSTRACTThe endoplasmic reticulum membrane complex (EMC) plays a critical role in the biogenesis of tail-anchored and a subset of multi-pass membrane proteins in the endoplasmic reticulum. However, due to the nearly exclusive expression of neurotransmitter-gated ion channels in the central nervous system, the role of the EMC in their biogenesis is not well understood. In this study, we demonstrated that the EMC positively regulates the surface trafficking and thus function of endogenous γ-aminobutyric acid (GABAA) receptors, the primary inhibitory ion channels in the mammalian brain. Further, among ten EMC subunits, EMC3 and EMC6 have the most prominent effects, indicating a subunit-specific contribution. EMC3 and EMC6 show endogenous interactions with major neuroreceptors, which depends on their transmembrane domains. Overexpression of EMC3 and EMC6 is sufficient to restore the function of epilepsy-associated GABAAreceptor variants, suggesting that operating EMC has the potential to ameliorate neurological diseases associated with protein conformational defects.In briefThe multi-subunit EMC serves as an insertase for a subset of membrane proteins and enables their biogenesis in the endoplasmic reticulum. However, the subunit-specific effect of the EMC on multi-pass neuroreceptors is not well understood. Whittsette et al. demonstrate that EMC3 and EMC6 interact with GABAAreceptors and positively regulate their trafficking and function.HighlightsEMC3 and EMC6 positively regulate the function of endogenous GABAAreceptors.The EMC interacts with major endogenous neuroreceptors.The interaction between EMC and GABAAreceptors depends on the EMC transmembrane domains.Overexpressing the EMC is sufficient to restore the function of pathogenic GABAAreceptor variants.
Eukaryotic initiation factor 2α kinases regulate virulence functions, stage conversion, and the stress response in Entamoeba invadens
Authors: Walters Heather A. , Welter Brenda H. , Orobio-Hurtado Ronny , Moss Harrison C. , Villano Martha A. , Sullivan William J. , Temesvari Lesly A. 
Published: March 2022

AbstractEntamoeba histolytica is a protozoan parasite that causes amoebic dysentery and liver abscess. This pathogen possesses a two-stage life cycle consisting of an environmentally stable cyst and a pathogenic amoeboid trophozoite. Since infection is acquired by ingestion of cysts from contaminated food and water, this parasite is prevalent in underdeveloped countries. A reptilian pathogen, Entamoeba invadens, which can encyst in culture, has long-served as a surrogate to study stage conversion. In the host, the Entamoebae must manage stress including nutrient deprivation and host immune pressure. In many systems, the stress response is characterized by down-regulation of translation, which is initiated by the phosphorylation of eukaryotic initiation factor-2 alpha (eIF2α). In mammalian cells, this phosphorylation is carried out by a family of eIF2α kinases. A canonical eIF2α translational control system exists in the Entamoebae; however, no eIF2α kinases have been characterized. In this study, we identified two eIF2α kinases in E. invadens, EiIF2K-A and EiIF2K-B. Their identity as eIF2α kinases was validated using a heterologous yeast system. We used an RNAi Trigger-mediated silencing system to reduce expression of EiIF2K-A, which also reduced expression of EiIF2K-B. Parasites with decreased kinase expression exhibited decreased phosphorylation of eIF2α and increased sensitivity to oxidative stress. Diminished kinase expression also correlates with an increased rate of encystation, a decreased the rate of excystation, and an increase in several virulence functions, erythrophagocytosis and adhesion to host cells. Taken together, these data suggest that EiIF2K-A and EiIF2K-B are authentic eIF2α kinases that may regulate the Entamoeba stress response.ImportanceEntamoeba histolytica is a human pathogen that causes dysentery and affects millions of people worldwide. This parasite possesses a two-stage life cycle: an environmentally stable cyst and the pathogenic trophozoite. Cysts are ingested from contaminated food and water; thus, this parasite in prevalent in underdeveloped countries. Current therapies commonly cause adverse side effects; therefore, new treatments are needed. In the host, Entamoeba experiences stress brought on, in part, by the host immune system. Understanding stage conversion and the stress response of this pathogen may lead to new drug therapies. Using the model organism, E. invadens, we identified two kinases, similar to those involved in stress and stage conversion in other systems. We determined that these kinases may regulate the oxidative stress response, stage conversion, and virulence. This work is significant as it will inform future studies on the life cycle and pathogenicity of the Entamoeba species.
Immunogenicity of an Ad26-based SARS-CoV-2 Omicron Vaccine in Naïve Mice and SARS-CoV-2 Spike Pre-immune Hamsters
Authors: Swart Maarten , de Wilde Adriaan , Schmit-Tillemans Sonja , Verspuij Johan , Daal Chenandly , Choi Ying , Perkasa Aditya , Kourkouta Eleni , Tahiri Issam , Mulders Michel , Gil Ana Izquierdo , Muchene Leacky , Juraszek Jarek , Vellinga Jort , Custers Jerome , Bos Rinke , Schuitemaker Hanneke , Wegmann Frank , Roozendaal Ramon , Kuipers Harmjan , Zahn Roland 
Published: March 2022

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant sparked concern due to its fast spread and the unprecedented number of mutations in the spike protein that enables it to partially evade spike-based COVID-19 vaccine-induced humoral immunity. In anticipation of a potential need for an Omicron spike-based vaccine, we generated an Ad26 vector encoding an Omicron (BA.1) spike protein (Ad26.COV2.S.529). Ad26.COV2.S.529 encodes for a prefusion stabilized spike protein, similar to the current COVID-19 vaccine Ad26.COV2.S encoding the Wuhan-Hu-1 spike protein. We verified that spike expression by Ad26.COV2.S.529 was comparable to Ad26.COV2.S. Immunogenicity of Ad26.COV2.S.529 was then evaluated in naïve mice and SARS-CoV-2 Wuhan-Hu-1 spike pre-immunized hamsters. In naïve mice, Ad26.COV2.S.529 elicited robust neutralizing antibodies against SARS-CoV-2 Omicron (BA.1) but not to SARS-CoV-2 Delta (B.1.617.2), while the opposite was observed for Ad26.COV2.S. In pre-immune hamsters, Ad26.COV2.S.529 vaccination resulted in robust increases in neutralizing antibody titers against both SARS-CoV-2 Omicron (BA.1) and Delta (B.1.617.2), while Ad26.COV2.S vaccination only increased neutralizing antibody titers against the Delta variant. Our data imply that Ad26.COV2.S.529 can both expand and boost a Wuhan-Hu-1 spike-primed humoral immune response to protect against distant SARS-CoV-2 variants.
Misinterpreting the horseshoe effect in neuroscience
Authors: Proix Timothée , Perich Matthew G. , Milekovic Tomislav 
Published: March 2022

ABSTRACTDimensionality reduction methods are frequently used to analyze high-dimensional activity of cortical neuron populations during behavior. The resulting oscillatory trajectories that consistently emerge from this analysis have been interpreted as a signature of latent dynamical systems. Here, we show that these oscillatory trajectories necessarily result from applying dimensionality reduction methods on recordings that approximately exhibit continuous variation in time, regardless of whether or not the recorded system incorporates latent dynamics.
Seasonal changes in membrane structure and excitability in central neurons of goldfish (Carassius auratus) under constant environmental conditions
Authors: Country Michael W. , Haase Kristina , Blank Katrin , Canez Carlos R. , Roberts Joshua A. , Campbell Benjamin F.N. , Smith Jeffrey C. , Pelling Andrew E. , Jonz Michael G. 
Published: March 2022

ABSTRACTSeasonal modifications in the structure of cellular membranes occur as an adaptive measure to withstand exposure to prolonged environmental change. Little is known about whether such changes may occur independently of external cues, such as photoperiod or temperature, or how they may impact the central nervous system (CNS). We compared membrane properties of central neurons isolated from the retina of goldfish (Carassius auratus), an organism well-adapted to extreme environmental change, during the summer and winter months. Goldfish were maintained in a facility under constant environmental conditions throughout the year. Analysis of whole-retina phospholipid composition using mass spectrometry-based lipidomics revealed a two-fold increase in phosphatidylethanolamine species during the winter, suggesting an increase in cell membrane fluidity. Atomic force microscopy was used to produce localized, nanoscale-force deformation of neuronal membranes. Measurement of Young’s modulus indicated increased membrane stiffness (or decreased elasticity) in neurons isolated during the winter. Voltage-clamp electrophysiology was used to assess physiological changes in neurons between seasons. Winter neurons displayed a hyperpolarized reversal potential (Vrev) and a significantly lower input resistance (Rin) compared to summer neurons. This was indicative of a decrease in membrane excitability during the winter. Subsequent measurement of intracellular Ca2+ activity using Fura-2 microspectrofluorometry confirmed a reduction in action potential activity, including duration and action potential profile, in neurons isolated during the winter. These studies demonstrate chemical and biophysical changes that occur in central neurons of goldfish throughout the year without exposure to seasonal cues, and suggest a novel mechanism of seasonal regulation of CNS activity.SUMMARY STATEMENTCentral neurons isolated from the retina of goldfish held under constant environmental conditions undergo seasonal changes in membrane structure and excitability.
Widespread hybridization between invasive bleak (Alburnus alburnus) and native Iberian chubs (Squalius spp.): a neglected threat
Authors: Morgado-Santos M , Curto M , Alexandre CM , Alves MJ , Gante HF , Gkenas C , Medeiros JP , Pinheiro PJ , Almeida PR , Magalhães MF , Ribeiro F 
Published: March 2022

ABSTRACTHybridization between native and exotic species is a major conservation issue. In Iberian rivers, which are simultaneously among the most invaded and diverse ecosystems, harboring a high proportion of endemic fishes, this issue is becoming highly concerning. To date, hybridization has been reported to occur between the invasive bleak Alburnus alburnus and the endemic chubs Squalius alburnoides and S. pyrenaicus, in some scattered locations. However, the bleak is increasingly spreading in the region, potentially increasing the risks of hybridization with these and other Squalius species. To gather a more comprehensive picture on the current extension of hybridization, we compiled and mapped records on hybrids between bleak and chubs collected by multiple research teams in different ongoing projects in the Portuguese territory, and genetically assessed the hybrid identity of specimens in an area of sympatry between bleak and S. carolitertii, using nuclear and mitochondrial markers. We found that hybridization with bleak is widespread in several Portuguese river basins and involves at least three endemic chubs, S. alburnoides, S. pyrenaicus and S. carolitertii. This may have serious consequences, including not only waste of reproductive effort and damage of genetic integrity, but also putative shifts on the reproductive dynamics of the Squalius system, which includes endemic hybrids, reproducing sexually and nonsexually. Hybridization should be recognized as a significant impact of biological invasions, and we recommend that future studies should characterize the fitness of hybrids and their ecological and genetic interactions with parental Iberian fish, to elucidate effective conservation measures.