Miracle-dz/UniFAR-FTUs huggingface dataset:
Benthic foraminiferal faunas associated with cold‐water coral environments in the North Atlantic realm

Surface benthic foraminiferal assemblages associated with cold‐water coral mounds and reefs from the Irish margin and Norwegian shelf (North‐east Atlantic) are for the first time compared quantitatively. Results indicate that the considered sites share a common assemblage, dominated by elevated epibenthic and distinct infaunal species. This surface assemblage is typical of environments that are subject to strong bottom‐water turbulence with enhanced food availability. It provides a benchmark for comparison with fossil benthic foraminiferal assemblages from past cold‐water coral environments. Similar to macrofaunal and megafaunal communities, surface benthic foraminiferal diversity is higher on reefs and mounds than in surrounding off‐mound/off‐reef sediments. Benthic foraminiferal diversity is highest within the living coral macrohabitat, possibly as a result of enhanced availability and variety of food sources, and ecological niche separation. Indeed, living coral generally thrives on the summits or flanks of reefs and mounds where food availability is most important. The second part discusses the use of fossil benthic foraminiferal assemblages as palaeoceanographic proxies from past cold‐water coral environments. The overview of previous observations demonstrates that benthic foraminifera are valuable tools to reconstruct past bottom‐water oxygenation, bottom‐water currents and surface productivity, all of which are key environmental variables controlling cold‐water coral growth. Moreover, the advantages of a detailed investigation of benthic foraminiferal assemblages within cold‐water coral environments are compared to other palaeoceanographic proxies. This study highlights that benthic foraminiferal assemblages are an often overlooked proxy within cold‐water coral environments, despite yielding valuable information.
Cardiovascular Safety of Antifracture Medications in Patients With Osteoporosis: A Narrative Review of Evidence From Randomized Studies

Osteoporosis and cardiovascular (CV) disease share common risk factors and pathophysiology. Low bone mineral density (BMD) and fractures appear to increase the risk for multiple CV diseases. Equally, prevalent CV disease appears to predispose to bone loss and increase fracture rates. This relationship has naturally provoked the hypothesis that stopping bone loss may result in some CV benefit. Secondary analyses of safety and adverse event data from many randomized controlled trials (RCTs) have attempted to clarify this putative association. Recently, the discontinuation of odanacatib (anti‐cathepsin K monoclonal antibody) over stroke concerns and the imbalance in ischemic events in romosozumab‐treated (anti‐sclerostin monoclonal antibody) women compared to bisphosphonate‐treated women, has provided further justification to better characterize potential CV benefits and harms of osteoporosis medications. This review delves into the seminal, and other major RCTs of osteoporosis medications and, using both published data and additional information provided on trial registration pages, examines the evidence for CV safety and harms of these medications. Accepted and emerging “off‐target” effects are explored for validity, biological plausibility, and clinical importance. A brief research agenda is provided to stimulate the next wave of clinical development and CV understanding of osteoporosis medications. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Insula to mPFC Reciprocal Connectivity Differentially Underlies Novel Taste Neophobic Response and Learning

To survive in an ever-changing environment, animals must detect and learn salient information. The anterior insular cortex (aIC) and medial prefrontal cortex (mPFC) are heavily implicated in salience and novelty processing, and specifically, the processing of taste sensory information. Here, we examined the role of aIC-mPFC reciprocal connectivity in novel taste neophobia and memory formation, in mice. Using pERK and neuronal intrinsic properties as markers for neuronal activation, and retrograde AAV (rAAV) constructs for connectivity, we demonstrate a correlation between aIC-mPFC activity and novel taste experience. Furthermore, by expressing inhibitory chemogenetic receptors in these projections, we show that aIC-to-mPFC activity is necessary for both taste neophobia and its attenuation. However, activity within mPFC-to-aIC projections is essential only for the neophobic reaction but not for the learning process. These results provide an insight into the cortical circuitry needed to detect, react to- and learn salient stimuli, a process critically involved in psychiatric disorders.
Functional characterisation of the Nep1-like protein effectors of the necrotrophic pathogen - Alternaria brassicae

Alternaria brassicae is an important necrotrophic pathogen that infects the Brassicaceae family. Alternaria brassicae, like other necrotrophs, also secretes various proteinaceous effectors and metabolites that cause cell death to establish itself in the host. However, there has been no systematic study of A. brassicae effectors and their roles in pathogenesis. The availability of the genome sequence of A. brassicae in public domain has enabled the search for effectors and their functional characterisation. Nep1-like proteins are a superfamily of proteins that induce necrosis and ethylene biosynthesis. They have been reported from a variety of microbes including bacteria, fungi, and oomycetes. In this study, we identified two NLPs from A. brassicae viz. AbrNLP1 and AbrNLP2 and functionally characterised them. Although both AbrNLPs were found to be secretory in nature, they localised differentially inside the plant. AbrNLP2 was found to induce necrosis in both host and nonhost species, while AbrNLP1 could not induce necrosis in both species. Additionally, AbrNLP2 was shown to induce pathogen-associated molecular pattern (PAMP)-triggered immunity in both host and nonhost species. Overall, our study indicates that AbrNLPs are functionally and spatially (subcellular location) distinct and may play different but important roles during the pathogenesis of A. brassicae.
Stable Isotope Tracing in vivo Reveals A Metabolic Bridge Linking the Microbiota to Host Histone Acetylation

The gut microbiota influences host epigenetics by fermenting dietary fiber into butyrate. Although butyrate could promote histone acetylation by inhibiting histone deacetylases, it may also undergo oxidation to acetyl-CoA, a necessary cofactor for histone acetyltransferases. Here, we find that epithelial cells from germ-free mice harbor a loss of histone H4 acetylation across the genome except at promoter regions. Using stable isotope tracing in vivo with 13C-labeled fiber, we demonstrate that the microbiota supplies carbon for histone acetylation. Subsequent metabolomic profiling revealed hundreds of labeled molecules and supported a microbial contribution to host fatty acid metabolism, which declined in response to colitis and correlated with reduced expression of genes involved in fatty acid oxidation. These results illuminate the flow of carbon from the diet to the host via the microbiota, disruptions to which may affect energy homeostasis in the distal gut and contribute to the development of colitis.
Feeding effects on liver mitochondrial bioenergetics of Boa constrictor (Serpentes: Boidae)

Snakes are interesting examples of overcoming energy metabolism challenges as many species can endure long periods without feeding, and their eventual meals are of reasonably large sizes, thus exhibiting dual extreme adaptations. Consequently, metabolic rate increases considerably to attend to the energetic demand of digestion, absorption and, protein synthesis. These animals should be adapted to transition from these two opposite states of energy fairly quickly, and therefore we investigated mitochondrial function plasticity in these states. Herein we compared liver mitochondrial bioenergetics of the boid snake Boa constrictor during fasting and after meal intake. We fasted the snakes for 60 days, then we fed a subgroup with 30% of their body size and evaluated their maximum postprandial response. We measured liver respiration rates from permeabilized tissue and isolated mitochondria, and from isolated mitochondria, we also measured Ca2+ retention capacity, the release of H2O2, and NAD(P) redox state. Mitochondrial respiration rates were maximized after feeding, reaching until 60% increase from fasting levels when energized with complex I-linked substrates. Interestingly, fasting and fed snakes exhibited similar respiratory control ratios and citrate synthase activity. Furthermore, we found no differences in Ca2+ retention capacity, indicating no increase in susceptibility to mitochondrial permeability transition pore (PTP), or redox state of NAD(P), although fed animals exhibited increases in the release of H2O2. Thus, we conclude that liver mitochondria from B. constrictor snakes increase the maintenance costs during the postprandial period and quickly improve the mitochondrial bioenergetics capacity without compromising the redox balance.
Direct neuronal reprogramming by temporal identity factors

Temporal identity factors are sufficient to reprogram developmental competence of neural progenitors, but whether they could also reprogram the identity of fully differentiated cells is unknown. To address this question, we designed a conditional gene expression system combined with genetic lineage tracing that allows rapid screening of potential reprogramming factors in the mouse retina. Using this assay, we report that co-expression of the early temporal identity transcription factor Ikzf1, together with Ikzf4, another Ikaros family member, is sufficient to directly convert adult Müller glial cells into neuron-like cells in vivo, without inducing a proliferative progenitor state. scRNA-seq analysis shows that the reprogrammed cells share some transcriptional signatures with both cone photoreceptors and bipolar cells. Furthermore, we show that co-expression of Ikzf1 and Ikzf4 can reprogram mouse embryonic fibroblasts to induced neurons by remodeling chromatin and promoting a neuronal gene expression program. This work uncovers general neuronal reprogramming properties for temporal identity factors in differentiated cells, opening new opportunities for cell therapy development.
Quantitative Separation of Graphene Oxide Nanoribbon by Froth Flotation

Froth flotation was employed for quantitative separation of graphene oxide nanoribbon (GONR) from its solution. The effects of GONR concentration, pH, and cetyltrimethyl ammonium bromide (CTAB) concentration on GONR separation were studied through a Box–Behnken experimental design method. F value of 176.47, coefficient of determination of 0.9969, adjusted R2 of 0.9912, and coefficient of variation of 4.09%, explored by means of analysis of variance, implied the satisfactory adjustment of the obtained quadratic model. The results indicated that low GONR and high CTAB concentration at low pH were ideal for maximum separation by flotation. GRAPHICAL ABSTRACT
Increased frequency of recurrent in-frame deletions in new expanding lineages of SARS CoV-2 reflects immune selective pressure

Most of the attention in the surveillance of evolution of SARS-CoV-2 has been centered on single nucleotide substitutions in the spike glycoprotein. We show that in-frame deletions (IFDs) also play a significant role in the evolution of viral genome. The percentage of genomes and lineages with IFDs is growing rapidly and they co-occur independently in multiple lineages, including emerging variants of concerns. IFDs distribution is correlated with spike mutations associated with immune escape and concentrated in proteins involved in interactions with the host immune system. Structural analysis suggests that IFDs remodel viral proteins’ surfaces at common epitopes and interaction interfaces, affecting the virus’ interactions with the immune system. We hypothesize that the increased frequency of IFDs is an adaptive response to elevated global population immunity. Summary Monitoring of SARS-CoV-2 genome evolution uncovers increased frequency and non-random distribution of in-frame deletions in recently emerged lineages.
Aberrant motor contagion of emotions in psychopathy and high-functioning autism

Psychopathy and autism are both associated with aberrant social interaction and communication, yet only psychopaths are markedly antisocial and violent. Here we compared the functional neural alterations underlying these two different phenotypes with distinct patterns of socioemotional difficulties. We studied 19 incarcerated male offenders with high psychopathic traits, 20 males with high-functioning autism and 19 age-matched healthy controls. All groups underwent functional magnetic resonance imaging while they viewed dynamic happy, angry and disgust facial expressions or listened to laughter and crying sounds. Psychopathy was associated with reduced somatomotor responses to almost all expressions, while subjects with autism demonstrated less marked and emotion-specific alterations in the somatomotor area. These data suggest that psychopathy and autism involve both common and distinct functional alterations in the brain networks involved in socioemotional processing.
CXCL17 is an endogenous inhibitor of CXCR4 via a novel mechanism of action

CXCL17 is the most recently described chemokine. It is principally expressed by mucosal tissues, where it facilitates chemotaxis of monocytes, dendritic cells, and macrophages and has antimicrobial properties. CXCL17 is also implicated in the pathology of inflammatory disorders and progression of several cancers, as well as being highly upregulated during viral infections of the lung. However, the exact role of CXCL17 in health and disease is largely unknown, mainly due to a lack of known molecular targets mediating CXCL17 functional responses. Using a range of bioluminescence resonance energy transfer (BRET) based assays, here we demonstrate that CXCL17 inhibits CXCR4-mediated signalling and ligand binding. Moreover, CXCL17 interacts with neuropillin-1, a VEGFR2 co-receptor. Additionally, we find CXCL17 only inhibits CXCR4 ligand binding in intact cells and demonstrate that this effect is mimicked by known glycosaminoglycan binders, surfen and protamine sulfate. This indicates that CXCL17 inhibits CXCR4 by a unique mechanism of action that potentially requires the presence of a glycosaminoglycan containing accessory protein. Altogether, our results reveal that CXCL17 is an endogenous inhibitor of CXCR4 and represents an important discovery in our understanding of the (patho) physiological functions of CXCL17 and regulation of CXCR4 signalling.
The Cl--channel TMEM16A controls the generation of cochlear Ca2+ waves and promotes the refinement of auditory brainstem networks

Before hearing onset (postnatal day 12 in mice), inner hair cells (IHC) spontaneously fire action potentials thereby driving pre-sensory activity in the ascending auditory pathway. The rate of IHC action potential bursts is modulated by inner supporting cells (ISC) of Kölliker’s organ through the activity of the Ca2+ activated Cl- channel TMEM16A. Here we show that conditional deletion of Tmem16a in mice disrupts the generation of Ca2+ waves within Kölliker’s organ, reduces the burst firing activity and the frequency-selectivity of auditory brainstem neurons in the medial nucleus of the trapezoid body (MNTB), and also impairs the refinement of MNTB projections to the lateral superior olive (LSO). These results reveal the importance of the activity of Kölliker’s organ for the refinement of central auditory connectivity. In addition, our study suggests a mechanism for the generation of Ca2+ waves, which may also apply to other tissues expressing TMEM16A.
The Dilemma Of Disobedience: An ERP study

The present experiment aimed at investigating the decision-making and the associated event-related potentials (ERPs) of subordinates under hierarchical pressure. Participants (N = 33) acted as UAV operators and had to decide to crash their defective drone either on a civilian site killing all civilians present on the site or on a military site destroying military material but preventing any human losses. While in the no-command condition, participants decided according to their own preferences, in the command condition they were ordered to protect the military material at the expense of civilians for undisclosed strategic reasons. The results revealed that in the no-command condition participants almost always crashed the drone on the military site (96%), whereas in the command condition they chose to obey orders and sacrifice civilians to protect the military material 33% of the time. In the command condition, participants were longer to make their decisions, mobilizing greater attentional and cognitive resources (i.e., greater P300 responses) to resolve the conflict between their internal moral values and the orders they were given (i.e., greater N200 responses) than in the no-command condition, where they automatically applied the “you shall not kill” rule. Participants also showed a greater negative affective response (i.e., greater P260 amplitudes) after choosing to disobey than to obey orders. This result suggests that disobeying authority could be perceived as a greater moral violation than obeying and sacrificing civilians, suggesting that individuals may sometimes choose to obey malevolent authority to avoid the negative affective reaction triggered by disobedience.
Precise optical control of gene expression in C. elegans using genetic code expansion and Cre recombinase

Synthetic strategies for optically controlling gene expression may enable the precise spatiotemporal control of genes in any combination of cells that cannot be targeted with specific promoters. We develop an efficient genetic code expansion system in C. elegans and use it to create a photo-activatable Cre recombinase. We laser-activate Cre in single neurons within a bilaterally symmetric pair to selectively switch on expression of a loxP controlled optogenetic channel in the targeted neuron. We use the system to dissect, in freely moving animals, the individual contributions of the mechanosensory neurons PLML/PLMR to the C. elegans touch response circuit, revealing distinct and synergistic roles for these neurons. We thus demonstrate how genetic code expansion and optical targeting can be combined to break the symmetry of neuron pairs and dissect behavioural outputs of individual neurons that cannot be genetically targeted.
Association Analysis of Candidate Variants in Admixed Brazilian Patients With Genetic Generalized Epilepsies

Genetic generalized epilepsies (GGEs) include well-established epilepsy syndromes with generalized onset seizures: childhood absence epilepsy, juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), myoclonic absence epilepsy, epilepsy with eyelid myoclonia (Jeavons syndrome), generalized tonic–clonic seizures, and generalized tonic–clonic seizures alone. Genome-wide association studies (GWASs) and exome sequencing have identified 48 single-nucleotide polymorphisms (SNPs) associated with GGE. However, these studies were mainly based on non-admixed, European, and Asian populations. Thus, it remains unclear whether these results apply to patients of other origins. This study aims to evaluate whether these previous results could be replicated in a cohort of admixed Brazilian patients with GGE. We obtained SNP-array data from 87 patients with GGE, compared with 340 controls from the BIPMed public dataset. We could directly access genotypes of 17 candidate SNPs, available in the SNP array, and the remaining 31 SNPs were imputed using the BEAGLE v5.1 software. We performed an association test by logistic regression analysis, including the first five principal components as covariates. Furthermore, to expand the analysis of the candidate regions, we also interrogated 14,047 SNPs that flank the candidate SNPs (1 Mb). The statistical power was evaluated in terms of odds ratio and minor allele frequency (MAF) by the genpwr package. Differences in SNP frequencies between Brazilian and Europeans, sub-Saharan African, and Native Americans were evaluated by a two-proportion Z-test. We identified nine flanking SNPs, located on eight candidate regions, which presented association signals that passed the Bonferroni correction (rs12726617; rs9428842; rs1915992; rs1464634; rs6459526; rs2510087; rs9551042; rs9888879; and rs8133217; p-values <3.55e–06). In addition, the two-proportion Z-test indicates that the lack of association of the remaining candidate SNPs could be due to different genomic backgrounds observed in admixed Brazilians. This is the first time that candidate SNPs for GGE are analyzed in an admixed Brazilian population, and we could successfully replicate the association signals in eight candidate regions. In addition, our results provide new insights on how we can account for population structure to improve risk stratification estimation in admixed individuals.
Feasibility of Fiber Reinforcement Within Magnetically Actuated Soft Continuum Robots

Soft continuum manipulators have the potential to replace traditional surgical catheters; offering greater dexterity with access to previously unfeasible locations for a wide range of interventions including neurological and cardiovascular. Magnetically actuated catheters are of particular interest due to their potential for miniaturization and remote control. Challenges around the operation of these catheters exist however, and one of these occurs when the angle between the actuating field and the local magnetization vector of the catheter exceeds 90°. In this arrangement, deformation generated by the resultant magnetic moment acts to increase magnetic torque, leading to potential instability. This phenomenon can cause unpredictable responses to actuation, particularly for soft, flexible materials. When coupled with the inherent challenges of sensing and localization inside living tissue, this behavior represents a barrier to progress. In this feasibility study we propose and investigate the use of helical fiber reinforcement within magnetically actuated soft continuum manipulators. Using numerical simulation to explore the design space, we optimize fiber parameters to enhance the ratio of torsional to bending stiffness. Through bespoke fabrication of an optimized helix design we validate a single, prototypical two-segment, 40 mm × 6 mm continuum manipulator demonstrating a reduction of 67% in unwanted twisting under actuation.