Miracle-dz/UniFAR-FTUs huggingface dataset:
Self-Administration of entactogen psychostimulants dysregulates GABA and Kappa Opioid Receptor signaling in the central nucleus of the amygdala of female Wistar rats

Male rats escalate intravenous self-administration of entactogen psychostimulants, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxymethamphetamine (MDMA) under extended access conditions, as with typical psychostimulants. Here, we investigated whether female rats escalate self-administration of methylone, 3,4-methylenedioxypentedrone (pentylone), and MDMA and then studied consequences of MDMA and pentylone self-administration on GABAA receptor and kappa opioid receptor (KOR) signaling in the central nucleus of the amygdala (CeA), a brain area critically dysregulated by extended access self-administration of alcohol or cocaine. Adult female Wistar rats were trained to self-administer methylone, pentylone, MDMA (0.5 mg/kg/infusion), or saline-vehicle using a fixed-ratio 1 response contingency in 6-hour sessions (long-access: LgA) followed by progressive ratio (PR) dose-response testing. The effects of pentylone-LgA, MDMA-LgA and saline on basal GABAergic transmission (miniature postsynaptic inhibitory currents, mIPSCs) and the modulatory role of KOR at CeA GABAergic synapses were determined in acute brain slices using whole-cell patch-clamp. Methylone-LgA and pentylone-LgA rats similarly escalated their drug intake (both obtained more infusions compared to MDMA-LgA rats) however, pentylone-LgA rats reached higher breakpoints in PR tests. At the cellular level, baseline CeA GABA transmission was markedly elevated in pentylone-LgA and MDMA-LgA rats compared to saline-vehicle. Specifically, pentylone-LgA was associated with increased CeA mIPSC frequency (GABA release) and amplitude (postsynaptic GABAA receptor function), while mIPSC amplitudes (but not frequency) was larger in MDMA-LgA rats compared to saline rats. In addition, pentylone-LgA and MDMA-LgA profoundly disrupted CeA KOR signaling such as both KOR agonism (1mM U50488) and KOR antagonism (200nM nor-binaltorphimine) decreased mIPSC frequency suggesting recruitment of non-canonical KOR signaling pathways. This study confirms escalated self-administration of entactogen psychostimulants under LgA conditions in female rats which is accompanied by increased CeA GABAergic inhibition and altered KOR signaling. Collectively, our study suggests that CeA GABA and KOR mechanisms play a critical role in entactogen self-administration like those observed with escalation of alcohol or cocaine self-administration.
Express Arm Responses Appear Bilaterally on Upper-limb Muscles in an Arm Choice Reaching Task

When required, humans can generate very short latency reaches towards visual targets, like catching a falling cellphone. During such rapid reaches, express arm responses are the first wave of upper limb muscle recruitment, occurring ~80-100 ms after target appearance. There is accumulating evidence that express arm responses arise from signaling along the tecto-reticulo-spinal tract, but the involvement of the reticulo-spinal tract has not been well-studied. Since the reticulospinal tract projects bilaterally, we studied whether express arm responses would be generated bilaterally. Human participants (n = 14; 7 female) performed visually guided reaches in a modified emerging target paradigm where either arm could intercept the target. We recorded electromyographic activity bilaterally from the pectoralis major muscle. Our analysis focused on target locations where participants reached with the right arm on some trials, and the left arm on others. In support of the involvement of the reticulospinal tract, express arm responses persisted bilaterally regardless of which arm reached to the target. The latency and magnitude of the express arm response did not depend on whether the arm was chosen to reach or not. However, on the reaching arm, the magnitude of the express arm response was correlated to the level of anticipatory activity. The bilateral generation of express arm responses supports the involvement of the reticulo-spinal tract. We surmise that the correlation between anticipatory activity and the magnitude of express arm responses on the reaching arm arises from convergence of cortically-derived signals with a parallel subcortical pathway mediating the express arm response. New and Noteworthy Express arm responses have been proposed to arise from the tecto-reticulo-spinal tract originating within the superior colliculus, but the involvement of the reticulo-spinal tract has not been well studied. Here, we show these responses appear bilaterally in a task where either arm can reach to a newly appearing stimulus. Our results suggest that the most rapid visuomotor transformations for reaching are performed by a subcortical pathway.
γ-TuRCs are required for asymmetric microtubule nucleation from the somatic Golgi of Drosophila neurons

Microtubules are polarised polymers nucleated by multi-protein γ-tubulin ring complexes (γ-TuRCs). Within neurons, microtubule polarity is plus-end-out in axons and mixed or minus-end-out in dendrites. Previously we showed that within the soma of Drosophila sensory neurons γ-tubulin localises asymmetrically to Golgi stacks, Golgi-derived microtubules grow asymmetrically towards the axon, and growing microtubule plus-ends are guided towards the axon and restricted from entering dendrite in a Kinesin-2-dependent manner (Mukerjee et al., 2020). Here we show that depleting γ-TuRCs perturbs the direction of microtubule growth from the Golgi stacks, consistent with a model for asymmetric microtubule nucleation involving γ-TuRCs and other nucleation-promoting factors. We also directly observe microtubule turning along microtubule bundles and show that depleting APC, proposed to link Kinesin-2 to plus ends, reduces microtubule turning and increases plus end growth into dendrites. These results support a model of asymmetric nucleation and guidance within the neuronal soma that helps establish and maintain overall microtubule polarity.
Influence of High Energy Diet and Polygenic Predisposition for Obesity on Postpartum Health in Rat Dams

It is estimated that 30% of pregnant women worldwide are overweight or obese, which leads to adverse health effects for both the mother and child. Women with obesity during pregnancy are at higher risk for developing both metabolic and mental disorders, such as diabetes and depression. Numerous studies have used rodent models of maternal obesity to understand its consequences on the offspring, yet characterization of changes in the dams is rare, and most rodent models rely solely on a high fat diet to induce maternal obesity, without regarding genetic propensity for obesity. Here we present the influence of both peripartum high energy diet (HE) and obesity-proneness on maternal health using selectively-bred diet-resistant (DR) and diet-induced obese (DIO) rat dams. Outbred Sprague-Dawley rats were selected and bred according to their propensity to gain weight. From F1 onward, dams consuming a HE diet displayed higher body weight gain during pregnancy, and HE diet had a strong effect on meal patterns. Sensitivity to the hormone amylin was preserved during pregnancy, regardless of diet. After several rounds of selective breeding, dams from generation F3 were assessed for their postpartum physiology and behaviors. We observed strong diet and phenotype effects on gestational weight gain, with DIO-HE dams gaining 119% more weight than DR-chow. A high-resolution analysis of maternal behaviors on postpartum day 2 (P2) did not detect main effects of diet or phenotype, but a subset of DIO dams showed decreased pup-related behaviors. During a sucrose preference test (SPT) on P14, all DR dams consumed at least 70% sucrose, while a subset of DIO dams preferred water. In generation F6/F7 dams, effects on gestational weight gain persisted, and we observed a main effect of phenotype of SPT, with DIO-chow dams showing the lowest sucrose preference. Both DIO and DR dams consuming HE diet had severe postpartum liver lipidosis and exhibited reduced leptin sensitivity in the arcuate nucleus at the time of pup-weaning. These data demonstrate that both diet and genetic obesity-proneness have consequences on maternal health.
Learning in Convolutional Neural Networks Accelerated by Transfer Entropy

Recently, there is a growing interest in applying Transfer Entropy (TE) in quantifying the effective connectivity between artificial neurons. In a feedforward network, the TE can be used to quantify the relationships between neuron output pairs located in different layers. Our focus is on how to include the TE in the learning mechanisms of a Convolutional Neural Network (CNN) architecture. We introduce a novel training mechanism for CNN architectures which integrates the TE feedback connections. Adding the TE feedback parameter accelerates the training process, as fewer epochs are needed. On the flip side, it adds computational overhead to each epoch. According to our experiments on CNN classifiers, to achieve a reasonable computational overhead–accuracy trade-off, it is efficient to consider only the inter-neural information transfer of the neuron pairs between the last two fully connected layers. The TE acts as a smoothing factor, generating stability and becoming active only periodically, not after processing each input sample. Therefore, we can consider the TE is in our model a slowly changing meta-parameter.
Engineering SnS2 nanosheet assemblies for enhanced electrochemical lithium and sodium ion storage

The reversible electrochemical storage of Li+ and Na+ ions is the operating basis of secondary lithium-ion and sodium-ion batteries. In recent years, there has been rapid growth in the search for appropriate electrode materials. Nevertheless, the development of host materials for active and durable electrochemical storage of both Li+ and Na+ ions remain challenging. In this study, we report a facile solvothermal method to prepare hierarchical assemblies of thin SnS2 nanosheets in N-methyl-2-pyrrolidone. The as-prepared product has an expanded layered structure due to the presence of organic intercalates. Mild annealing restores the normal 2H-SnS2 phase with the hierarchical architecture preserved. When annealed SnS2 was evaluated as the anode material of lithium-ion batteries, it exhibited large capacity in excess of 1200 mA h g−1 and decent short-term cycling stability. It was further coated with a thin carbon layer as the physical and electrical reinforcement, which led to a much improved cycle life at both low and high current rates. Moreover, carbon coated SnS2 also demonstrated a large capacity (∼600 mA h g−1) and decent cycling stability as the anode material of sodium-ion batteries.
The Use of a Length-Structured Multispecies Model Fitted Directly to Data in Near-Real Time as a Viable Tool for Advice

Fish communities are multispecies assemblages, so ideally multispecies models should be used directly for assessing this resource. However, progress in this direction has been slow, partly because these models are often more complex and take longer to fit, rendering them too slow to demonstrate near-real-time utility, and thus creating a perception that they are opaque to stakeholders. In this study we implemented a multispecies assessment for the Irish Sea, fitting a model of eight key stocks directly to catch and survey data. Two novel features of our approach allowed the multispecies model to be fitted within a few hours. Firstly, by using size-based theory and life-history invariants to specify many of the required properties of stocks, we reduced the number of general parameters that needed to be fitted directly to a more manageable 25. Secondly, by using state-of-the-art fitting methods, we found acceptable solutions quickly enough to provide assessments within the timescale of an advisory meeting. The outcomes were compared with the standard single species assessments of the same eight species. Model fits were generally good for either catch or at least one of the surveys, but not for all data sources at the same time, illustrating the challenges of fitting multiple stocks to different data sources simultaneously. Estimates of SSB and F agreed qualitatively with the assessments for most stocks with the exception of whiting. Estimates of natural mortality showed modest year to year variability, suggesting that single species assessments may be appropriate for short term tactical management. This method shows great promise for making multispecies assessments as a complement to existing assessments because of the rapid turnaround time and ability to respond at meetings to the requests of stakeholders. In addition, because these models avoid our current dependence on existing single species models they can be used to provide boundary conditions in natural mortality for standard assessment models and check for internal consistency in the assessment process. Furthermore, they are easily accessible because they are based upon freely available code.
Lactic Acid Bacteria – A Promising Tool for Controlling Chicken Campylobacter Infection

Since 2005, campylobacteriosis has been the most common zoonotic disease in Europe. The main reservoir of pathogenic Campylobacter strains is broilers, which makes raw and undercooked poultry meat two major sources of disease. Infection in chicken flocks is most often asymptomatic, despite a high level of colonization reaching 106–109cfu/g in animal ceca. It is widely believed that controlling the level of colonization of the birds’ digestive tract by pathogenic strains is a good way to increase food safety. Many treatments have been proposed to combat or at least reduce the level of colonization in animals reservoirs: probiotics, bacteriophages, vaccines, and anti-Campylobacter bacteriocins. This review focuses on the effects of Campylobacter infection on the chicken microbiome and colonization control strategies using probiotics (mostly lactic acid bacteria, LAB), which are live microorganisms included in the diet of animals as feed additives or supplements. Probiotics are not only an alternative to antibiotics, which were used for years as animal growth promoters, but they also constitute an effective protective barrier against excessive colonization of the digestive system by pathogenic bacteria, including Campylobacter. Moreover, one of the many beneficial functions of probiotics is the ability to manipulate the host’s microbiota. Recently, there have also been some promising attempts to use lactic acid bacteria as a delivery system of oral vaccine against Campylobacter. Recombinant LAB strains induce primarily a mucosal immune response against foreign antigens, accompanied by at most a low-level immune response against carrier strains. Since the main barrier against the invasion of pathogens in the gastrointestinal tract is the intestinal mucosal membrane, the development of effective oral vaccines to protect animals against enteric infection is very reasonable.
Sirtuin Modulators in Cellular and Animal Models of Human Diseases

Sirtuins use NAD+ to remove various acyl groups from protein lysine residues. Through working on different substrate proteins, they display many biological functions, including regulation of cell proliferation, genome stability, metabolism, and cell migration. There are seven sirtuins in humans, SIRT1-7, each with unique enzymatic activities, regulatory mechanisms, subcellular localizations, and substrate scopes. They have been indicated in many human diseases, including cancer, neurodegeneration, microbial infection, metabolic and autoimmune diseases. Consequently, interests in development of sirtuin modulators have increased in the past decade. In this brief review, we specifically summarize genetic and pharmacological modulations of sirtuins in cancer, neurological, and cardiovascular diseases. We further anticipate this review will be helpful for scrutinizing the significance of sirtuins in the studied diseases.
Effect of microabsorption on the determination of amorphous content via powder X-ray diffraction

Powder X-ray diffraction has become a routine procedure for the quantification of phases in mixtures. The most common method for this measurement is the Rietveld method, which generally returns the relative weight percentages of the crystalline components within the mixture. However, in many instances, it is also desirable to obtain an estimate of the amorphous content of a sample. There are several methods that may be used for this measurement and their accuracy has been assessed previously with a number of ideal, synthetic mixtures. Many samples, especially in the mineralogy sphere, are far from ideal and contain multiple phases of varying absorption contrast. This creates a microabsorption problem which affects the accuracy of the determination of both the crystalline and amorphous components. This paper assesses commonly used methods of amorphous determination with a series of synthetic samples designed to create a considerable microabsorption problem.
Muscle-Bone Crosstalk in Chronic Obstructive Pulmonary Disease

Sarcopenia and osteoporosis are common musculoskeletal comorbidities of chronic obstructive pulmonary disease (COPD) that seriously affect the quality of life and prognosis of the patient. In addition to spatially mechanical interactions, muscle and bone can also serve as endocrine organs by producing myokines and osteokines to regulate muscle and bone functions, respectively. As positive and negative regulators of skeletal muscles, the myokines irisin and myostatin not only promote/inhibit the differentiation and growth of skeletal muscles, but also regulate bone metabolism. Both irisin and myostatin have been shown to be dysregulated and associated with exercise and skeletal muscle dysfunction in COPD. During exercise, skeletal muscles produce a large amount of IL-6 which acts as a myokine, exerting at least two different conflicting functions depending on physiological or pathological conditions. Remarkably, IL-6 is highly expressed in COPD, and considered to be a biomarker of systemic inflammation, which is associated with both sarcopenia and bone loss. For osteokines, receptor activator of nuclear factor kappa-B ligand (RANKL), a classical regulator of bone metabolism, was recently found to play a critical role in skeletal muscle atrophy induced by chronic cigarette smoke (CS) exposure. In this focused review, we described evidence for myokines and osteokines in the pathogenesis of skeletal muscle dysfunction/sarcopenia and osteoporosis in COPD, and proposed muscle-bone crosstalk as an important mechanism underlying the coexistence of muscle and bone diseases in COPD.
Conserved Mechanism of Bicarbonate-Induced Sensitization of CatSper Channels in Human and Mouse Sperm

To fertilize an egg, mammalian sperm must undergo capacitation in the female genital tract. A key contributor to capacitation is the calcium (Ca2+) channel CatSper, which is activated by membrane depolarization and intracellular alkalinization. In mouse epididymal sperm, membrane depolarization by exposure to high KCl triggers Ca2+ entry through CatSper only in alkaline conditions (pH 8.6) or after in vitro incubation with bicarbonate (HCO3–) and bovine serum albumin (capacitating conditions). However, in ejaculated human sperm, membrane depolarization triggers Ca2+ entry through CatSper in non-capacitating conditions and at lower pH (< pH 7.4) than is required in mouse sperm. Here, we aimed to determine the mechanism(s) by which CatSper is activated in mouse and human sperm. We exposed ejaculated mouse and human sperm to high KCl to depolarize the membrane and found that intracellular Ca2+ concentration increased at pH 7.4 in sperm from both species. Conversely, intracellular Ca2+ concentration did not increase under these conditions in mouse epididymal or human epididymal sperm. Furthermore, pre-incubation with HCO3– triggered an intracellular Ca2+ concentration increase in response to KCl in human epididymal sperm. Treatment with protein kinase A (PKA) inhibitors during exposure to HCO3– inhibited Ca2+ concentration increases in mouse epididymal sperm and in both mouse and human ejaculated sperm. Finally, we show that soluble adenylyl cyclase and increased intracellular pH are required for the intracellular Ca2+ concentration increase in both human and mouse sperm. In summary, our results suggest that a conserved mechanism of activation of CatSper channels is present in both human and mouse sperm. In this mechanism, HCO3– in semen activates the soluble adenylyl cyclase/protein kinase A pathway, which leads to increased intracellular pH and sensitizes CatSper channels to respond to membrane depolarization to allow Ca2+ influx. This indirect mechanism of CatSper sensitization might be an early event capacitation that occurs as soon as the sperm contact the semen.
Characterising the Phenotypic Diversity of Antigen-Specific Memory B Cells Before and After Vaccination

The diversity of B cell subsets and their contribution to vaccine-induced immunity in humans are not well elucidated but hold important implications for rational vaccine design. Prior studies demonstrate that B cell subsets distinguished by immunoglobulin (Ig) isotype expression exhibit divergent activation-induced fates. Here, the antigen-specific B cell response to tetanus toxoid (TTd) booster vaccination was examined in healthy adults, using a dual-TTd tetramer staining flow cytometry protocol. Unsupervised analyses of the data revealed that prior to vaccination, IgM-expressing CD27+ B cells accounted for the majority of TTd-binding B cells. 7 days following vaccination, there was an acute expansion of TTd-binding plasmablasts (PB) predominantly expressing IgG, and a minority expressing IgA or IgM. Frequencies of all PB subsets returned to baseline at days 14 and 21. TTd-binding IgG+ and IgA+ memory B cells (MBC) exhibited a steady and delayed maximal expansion compared to PB, peaking in frequencies at day 14. In contrast, the number of TTd-binding IgM+IgD+CD27+ B cells and IgM-only CD27+ B cells remain unchanged following vaccination. To examine TTd-binding capacity of IgG+ MBC and IgM+IgD+CD27+ B cells, surface TTd-tetramer was normalised to expression of the B cell receptor-associated CD79b subunit. CD79b-normalised TTd binding increased in IgG+ MBC, but remained unchanged in IgM+IgD+CD27+ B cells, and correlated with the functional affinity index of plasma TTd-specific IgG antibodies, following vaccination. Finally, frequencies of activated (PD-1+ICOS+) circulating follicular helper T cells (cTFH), particularly of the CXCR3-CCR6- cTFH2 cell phenotype, at their peak expansion, strongly predicted antigen-binding capacity of IgG+ MBC. These data highlight the phenotypic and functional diversity of the B cell memory compartment, in their temporal kinetics, antigen-binding capacities and association with cTFH cells, and are important parameters for consideration in assessing vaccine-induced immune responses.