Miracle-dz/UniFAR-FTUs huggingface dataset:
Operationalizing climate risk in a global warming hotspot

There has been a proliferation of climate change vulnerability assessments of species, yet possibly due to their limited reproducibility, scalability, and interpretability, their operational use in applied decision-making remains paradoxically low. We use a newly developed Climate Risk Index for Biodiversity to evaluate the climate vulnerability and risk for ∼2,000 species across three ecosystems and 90 fish stocks in the northwest Atlantic Ocean, a documented global warming hotspot. We found that harvested and commercially valuable species were at significantly greater risk of exposure to hazardous climate conditions than non-harvested species, and emissions mitigation disproportionately reduced their projected exposure risk and cumulative climate risk. Of the 90 fish stocks we evaluated, 41% were at high climate risk, but this proportion dropped to 25% under emissions mitigation. Our structured framework demonstrates how climate risk can be operationalized to support short- and long-term fisheries objectives to enhance marine fisheries’ climate readiness and resilience.
“FDA-approved carbonic anhydrase inhibitors reduce Amyloid β pathology and improve cognition, by ameliorating cerebrovascular health and glial fitness”

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder with no effective cure. Cerebrovascular and neurovascular pathology are early and causal hallmarks of AD, where cerebral amyloid angiopathy (CAA), the deposition of amyloid β (Aβ) at the cerebral vasculature, is present in about 90% of cases. Our previous work has uncovered the protective effect of carbonic anhydrase (CA) inhibition against Aβ-mediated mitochondrial dysfunction, production of reactive oxygen species (ROS) and apoptosis in vascular, glial and neuronal cells in culture. Here, we tested for the first time in a transgenic model of AD and cerebrovascular amyloidosis, the TgSwDI mice, a therapeutic regimen employing the FDA-approved CA inhibitors (CAIs), methazolamide (MTZ) and acetazolamide (ATZ). These drugs are used in humans for glaucoma, high altitude sickness, and other disorders, and can cross the blood-brain barrier. We found that both CAIs were non- toxic, significantly reduced cerebral amyloidosis, vascular, microglial and astrocytic Aβ accumulation, and ameliorated cognition. MTZ and ATZ treatment prevented caspase-3 activation in endothelial cells, microglia and astrocytes, reverted capillary constriction and microhemorrhages, reduced gliosis, and induced glial pro-clearance pathways, which are likely responsible for the reduction of Aβ deposition. Notably, we unveiled a critical new druggable target, revealing that the mitochondrial isozyme CA-VB is specifically upregulated in TgSwDI mouse brains, as well as in human brains of CAA and AD (with CAA) patients. Importantly, Aβ challenge induced CA-VB overexpression in human cerebral endothelial cells, and CA-VB silencing, mimicking CAIs effects, reduced Aβ-mediated endothelial apoptosis. This work paves the way for the application of CAIs in clinical trials for AD and CAA and uncovers CA-VB as a mediator of cerebral amyloid toxicity.
Coupling of oxytocin and cholecystokinin pathways in the hypothalamus is required for gut-to-brain homeostatic feeding control

Oxytocin-expressing paraventricular hypothalamic neurons (PVNOT neurons) integrate afferent signals from the gut including cholecystokinin (CCK) to adjust whole-body energy homeostasis. However, the molecular underpinnings by which PVNOT neurons orchestrate gut-to-brain feeding control remain unclear. Here, we show that mice undergoing selective ablation of PVNOT neurons fail to reduce food intake in response to CCK and develop hyperphagic obesity on chow diet. Notably, exposing wildtype mice to a high-fat/high-sugar (HFHS) diet recapitulates this insensitivity towards CCK, which is linked to diet-induced transcriptional and electrophysiological aberrations specifically in PVNOT neurons. Restoring OT pathways in DIO mice via chemogenetics or polypharmacology sufficiently re-establishes CCK’s anorexigenic effects. Lastly, by single-cell profiling, we identify a specialized PVNOT neuronal subpopulation with increased κ-opioid signaling under HFHS diet, which restrains their CCK-evoked activation. In sum, we here document a novel (patho)mechanism by which PVNOT signaling uncouples a gut-brain satiation pathway under obesogenic conditions.
The dual role of a multi-heme cytochrome in methanogenesis: MmcA is important for energy conservation and carbon metabolism in Methanosarcina acetivorans

Methanogenic archaea belonging to the Order Methanosarcinales conserve energy using an electron transport chain (ETC). In the genetically tractable strain Methanosarcina acetivorans, ferredoxin donates electrons to the ETC via the Rnf (Rhodobacter nitrogen fixation) complex. The Rnf complex in M. acetivorans, unlike its counterpart in Bacteria, contains a multiheme c-type cytochrome (MHC) subunit called MmcA. Early studies hypothesized MmcA is a critical component of Rnf, however recent work posits that the primary role of MmcA is facilitating extracellular electron transport. To explore the physiological role of MmcA, we characterized M. acetivorans mutants lacking either the entire Rnf complex (Δrnf) or just the MmcA subunit (ΔmmcA). Our data show that MmcA is essential for growth during acetoclastic methanogenesis but neither Rnf nor MmcA are required for methanogenic growth on methylated compounds. On methylated compounds, the absence of MmcA alone leads to a more severe growth defect compared to a Rnf deletion likely due to different strategies for ferredoxin regeneration that arise in each strain. Transcriptomic data suggest that the ΔmmcA mutant might regenerate ferredoxin by upregulating the cytosolic Wood-Ljundahl pathway for acetyl-CoA synthesis, whereas the Δrnf mutant may repurpose the F420 dehydrogenase complex (Fpo) to regenerate ferredoxin coupled to proton translocation. Beyond energy conservation, the deletion of Rnf or MmcA leads to some shared and some unique transcriptional changes in methyltransferase genes and regulatory proteins. Overall, our study provides systems-level insights into the non-overlapping roles of the Rnf bioenergetic complex and the associated MHC, MmcA. Importance Methane is a greenhouse gas that is ten times more potent than carbon dioxide and efforts to curb emissions are crucial to meet climate goals. Methane emissions primarily stem from the metabolic activity of microorganisms called methanogenic archaea (methanogens). The electron transport chain (ETC) in methanogens that belong to the Order Methanosarcinales has been the focus of many in vitro studies to date, but the endogenous functions of the bioenergetic complexes that comprise the ETC have rarely been investigated. In this study, we use genetic techniques to functionally characterize the Rnf bioenergetic complex and the associated multi-heme c-type cytochrome MmcA in the model methanogen, Methanosarcina acetivorans. Our results show that MmcA and Rnf have shared and unique roles in the cell, and that, contrary to current knowledge, M. acetivorans has the capacity to induce at least two alternative pathways for ferredoxin regeneration in the absence of a functional Rnf complex.
Inference of selective sweep parameters through supervised learning

A selective sweep occurs when positive selection drives an initially rare allele to high population frequency. In nature, the precise parameters of a sweep are seldom known: How strong was positive selection? Did the sweep involve only a single adaptive allele (hard sweep) or were multiple adaptive alleles at the locus sweeping at the same time (soft sweep)? If the sweep was soft, did these alleles originate from recurrent new mutations (RNM) or from standing genetic variation (SGV)? Here, we present a method based on supervised machine learning to infer such parameters from the patterns of genetic variation observed around a given sweep locus. Our method is trained on sweep data simulated with SLiM, a fast and flexible framework that allows us to generate training data across a wide spectrum of evolutionary scenarios and can be tailored towards the specific population of interest. Inferences are based on summary statistics describing patterns of nucleotide diversity, haplotype structure, and linkage disequilibrium, which are estimated across systematically varying genomic window sizes to capture sweeps across a wide range of selection strengths. We show that our method can accurately infer selection coefficients in the range 0.01 < s < 100 and classify sweep types between hard sweeps, RNM soft sweeps, and SGV soft sweeps with accuracy 69 % to 95 % depending on sweep strength. We also show that the method infers the correct sweep types at three empirical loci known to be associated with the recent evolution of pesticide resistance in Drosophila melanogaster. Our study demonstrates the power of machine learning for inferring sweep parameters from present-day genotyping samples, opening the door to a better understanding of the modes of adaptive evolution in nature. Author summary Adaptation often involves the rapid spread of a beneficial genetic variant through the population in a process called a selective sweep. Here, we develop a method based on machine learning that can infer the strength of selection driving such a sweep, and distinguish whether it involved only a single adaptive variant (a so-called hard sweep) or several adaptive variants of independent origin that were simultaneously rising in frequency at the same genomic position (a so-called soft selective sweep). Our machine learning method is trained on simulated data and only requires data sampled from a single population at a single point in time. To address the challenge of simulating realistic datasets for training, we explore the behavior of the method under a variety of testing scenarios, including scenarios where the history of the population of interest was misspecified. Finally, to illustrate the accuracy of our method, we apply it to three known sweep loci that have contributed to the evolution of pesticide resistance in Drosophila melanogaster.
Free-Standing Multilayer Films as Growth Factor Reservoirs for Future Wound Dressing Applications

Chronic skin wounds place a high burden on patients and health care systems. The use of angiogenic and mitogenic growth factors (GF) can facilitate the healing but GF are quickly inactivated by the wound environment if added exogenously. Here, free-standing multilayer films (FSF) are fabricated from chitosan (CHI) and alginate (ALG) as opposing polyelectrolytes in an alternating manner using layer-by-layer technique (LbL). One hundred bilayers form an about 450 µm thick, detachable free-standing film (N-FSF) that is subsequently crosslinked by either ethyl (dimethylaminopropyl) carbodiimide (EDC) combined with N-hydroxysuccinimide (NHS) (E-FSF) or genipin (G-FSF). The characterization of swelling, oxygen permeability and crosslinking density shows reduced swelling and oxygen permeability for both crosslinked films compared to N-FSF. Loading of fibroblast growth factor 2 (FGF2) into the films results in a sustained release of GF from crosslinked in comparison to N-FSF. Biocompatibility studies in vitro with human dermal fibroblasts (HDF) cultured underneath the films demonstrate increased cell growth and cell migration for all films with and without FGF2. Especially G-FSF loaded with FGF2 greatly increases cell proliferation and migration. In vivo biocompatibility studies by subcutaneous implantation in mice show that E-FSF causes a strong inflammatory response while G-FSF is of high biocompatibility. N-FSF also represents a biocompatible film but shows early degradation. All FSF possess antibacterial properties against gram+ and gram-bacteria demonstrated by an agar diffusion disc assay. In summary, FSF made of ALG and CHI crosslinked with genipin can act as a reservoir for the sustained release of FGF2, possessing high biocompatibility in vitro and in vivo. Moreover, G-FSF promotes growth and migration of HDF and has antibacterial properties which makes it an interesting candidate for bioactive wound dressings.
Molecular and spatial profiling of the paraventricular nucleus of the thalamus

The paraventricular nucleus of the thalamus (PVT) is known to regulate various cognitive and behavioral processes. However, while functional diversity among PVT circuits has often been linked to cellular differences, the molecular identity and spatial distribution of PVT cell types remain unclear. To address this gap, here we used single nucleus RNA sequencing (snRNA-seq) and identified five molecularly distinct PVT neuronal subtypes in the mouse brain. Additionally, multiplex fluorescent in situ hybridization of top marker genes revealed that PVT subtypes are organized by a combination of previously unidentified molecular gradients. Lastly, comparing our dataset with a recently published single-cell sequencing atlas of the thalamus yielded novel insight into the PVT’s connectivity with the cortex, including unexpected innervation of auditory and visual areas. This comparison also revealed that our data contains a largely non-overlapping transcriptomic map of multiple midline thalamic nuclei. Collectively, our findings uncover previously unknown features of the molecular diversity and anatomical organization of the PVT and provide a valuable resource for future investigations.
Fractionating distraction: how past- and future-relevant distractors influence integrated decisions

Many everyday tasks require us to integrate information from multiple steps to make a decision. Dominant accounts of flexible cognition suggest that we are able to navigate such complex tasks by attending to each step in turn, yet few studies measure how we direct our attention to immediate and future task steps. Here, we used a two-step task to test whether participants are sensitive to information that is currently irrelevant, but will be relevant in a future task step. Participants viewed two displays in sequence, each containing two superimposed moving dot clouds of different colours. Participants attended to one cued target colour in each display and reported the average direction of the two target dot clouds. In a subset of trials, we presented a “decoy” distractor: the second target colour appeared as the distractor in the first display. We regressed behavioural responses on the dot clouds’ motion directions to track how this future-relevant “decoy” distractor influenced participants’ reporting of the average target direction. We compared the influence of decoy distractors to never-relevant, recently relevant, and globally relevant distractor baselines. Across four experiments, we found that responses reflected what was immediately relevant, as well as the broader historical relevance of the distractors. However, relevance for a future task step did not reliably influence attention. We propose that attention in multi-step tasks is shaped by what has been relevant in the current setting, and by the immediate demands of each task step. Public Significance Our everyday functioning depends on our ability to piece together information to make coherent decisions. Understanding how we efficiently select and integrate goal-relevant information is critical if we wish to anticipate how decision-making can go wrong, whether because of fatigue, mental load, or illness. This study shows that decisions in multi-step tasks reflect two distinct processes: narrow focus on what is relevant in each step, alongside broader awareness of what has been relevant in this setting.
Genetic variation in correlated regulatory region of Immunity

Studying the interplay between genetic variation, epigenetic changes and regulation of gene expression in immune cells is important to understand the modification of cellular states in various conditions, including immune diseases. Here, we built cis maps of regulatory regions with coordinated activity – Cis Regulatory Domains (CRDs) – in neutrophils, monocytes and T cells. For this, we leveraged (i) whole-genome sequencing (WGS), (ii) chromatin immunoprecipitation sequencing (ChIP-seq), (iii) DNA methylation (450k arrays), and (iv) transcriptional profiles (RNA-seq) from the BLUEPRINT consortium, for up to 200 individuals. Our study uncovers 9287, 7666 and 5480 histone CRDs (hCRDs) and 6053, 6112, 5701 methyl CRDs (mCRDs) in monocytes, neutrophils and T-cells, respectively. We discovered 15294 hCRD-gene and 6185 mCRD-gene associations (5% FDR). Only 33% of hCRD-gene associations and 37% of mCRD-gene associations were shared between cell-types, revealing the dynamic nature of regulatory interactions and how similarly located regulatory regions modulate the activity of different genes on different cell types. We mapped Quantitative Trait Loci associated with CRD activity (CRD-QTLs) and found that 89% and 70% of these hCRDs and mCRDs are under genetic control highlighting the importance of genetic variation to study the coordination of cellular regulatory programs. We found CRD-QTLs to be enriched in celltype-specific transcription factor binding sites, such as SPI1, STAT3, RFX1, SOX4, ATF3 for neutrophils and monocytes and TCF4 and BCL11A for T-cells, in line with the Human protein Atlas. We integrated PCHi-C data, which showed that most significant associations discovered within gene-CRD associations and co-expressed genes associated with the same CRD, involving large genomic distances, tend to happen between genomic regions in close spatial proximity. Finally, we mapped trans regulatory associations between CRDs, which enabled the discovery of 207 trans-eQTLs across cell types. Overlapping our hits with trans eQTLs from eQTLGen Consortium meta-analysis in whole blood revealed 52 trans-eQTLs shared between the two studies. Overall, we show that mapping functional regulatory units using population genomics data allows discovering important mechanisms in the regulation of gene expression in immune cells and gain a greater understanding of cell-type specific regulatory mechanisms of immunity.
Stepwise recombination suppression around the mating-type locus in the fungus Schizothecium tetrasporum (Ascomycota, Sordariales)

Recombination is often suppressed at sex-determining loci in plants and animals, and at self-incompatibility or mating-type loci in plants and fungi. In fungal ascomycetes, recombination suppression around the mating-type locus is associated with pseudo-homothallism, i.e., the production of self-fertile dikaryotic sexual spores carrying the two opposite mating types. This has been well studied in two species complexes from different families of Sordariales: Podospora anserina and Neurospora tetrasperma. However, it is unclear whether this intriguing convergent association holds in other species. We show here that Schizothecium tetrasporum, a fungus from a third family in the order Sordariales, also produces mostly self-fertile dikaryotic spores carrying the two opposite mating types. This was due to a high frequency of second meiotic division segregation at the mating-type locus, indicating the occurrence of a single and systematic crossing-over event between the mating-type locus and the centromere, as in P. anserina. The mating-type locus has the typical Sordariales organization, plus a MAT1-1-1 pseudogene in the MAT1-2 haplotype. High-quality genome assemblies of opposite mating types and segregation analyses revealed a suppression of recombination in a region of 1.3 Mb around the mating-type locus. We detected three evolutionary strata, displaying a stepwise extension of recombination suppression, but no rearrangement or transposable element accumulation in the non-recombining region. Our findings indicate a convergent evolution of self-fertile dikaryotic sexual spores across multiple ascomycete fungi. The particular pattern of meiotic segregation at the mating-type locus was associated with recombination suppression around this locus, that had extended stepwise. This association is consistent with a recently proposed mechanism of deleterious allele sheltering through recombination suppression around a permanently heterozygous locus. AUTHOR SUMMARY Recombination allows faster adaptation and the purging of deleterious mutation but is often paradoxically lacking in sex chromosomes. It has been recently recognized that recombination can also be suppressed on fungal mating-type chromosomes, but the evolutionary explanation and the proximal mechanism of this phenomenon remain unclear. By studying here the sexual biology of a poorly studied mold living in rabbit dung, we reveal a striking convergence in three distant fungal lineages of an independently evolved association between the production of self-fertile sexual spores (carrying two nuclei with opposite mating types), a particular segregation of the mating-type locus and the lack of recombination on mating-type chromosomes, having evolved stepwise. Such a convergent association suggests causal relationships and will contribute to unveil the evolutionary causes of recombination suppression. Graphical summary
Performance analysis of single EWMA controller subject to metrology delay under dynamic models

ABSTRACT This article mainly focuses on analyzing the performance of a closed-loop system where a single exponentially weighted moving average controller (SEWMA) subject to metrology delay is applied to regulate a semiconductor manufacturing process that exhibits input–output dynamics. Based on the Hurwitz stability criterion, the sufficient and necessary conditions for the stability of the closed-loop system are established. Based on these, it is convenient to study the effect of metrology delay on the feasible region of the weighting factor in the SEWMA controller. Later, under the stability condition, the asymptotical properties of the SEWMA controller are discussed and the performance of the closed-loop control system is analyzed in terms of the asymptotical variation and the transient deviation in the presence of several typical types of process stochastic disturbance. Then an optimization model is built to find the appropriate weighting factor to reduce the overall variation of the process output during production. Finally, extensive simulations are carried out to demonstrate the validity of our theoretical analysis in the context of chemical–mechanical planarization process.
Wideband circularly polarized antenna array using sequential phase feed structure and U‐shaped radiating patch elements for S‐band applications

In this article, a 2 × 2 circular polarized (CP) antenna array, which is using sequential rotation (SR) technique in feeding network, has been introduced. The feeding network uses two 90° arcs and several rectangular lines with the same width. The length of these elements is multiple of λg/4 to produce 90° phase difference in 4 outputs of feeding network. By connecting the patch elements to the feeding network, which have been surrounded with radiating patch elements, design of 2 × 2 patch array has been completed. This array antenna with an incomplete ground which helps to have a better impedance matching, has been caused to reach a wider axial ratio (AR) and impedance bandwidth. The prototype of the proposed antenna array is built to validate the antenna performance. By using these techniques, a common bandwidth of 1.15 GHz has been achieved for impedance bandwidth (S11 < 10 dB) and AR bandwidth (AR < 3 dB) and 7.5 dBi maximum gain. In addition, the gain is more than 4 dBi in desired frequency range. According to the frequency range of 2.8‐3.95 GHz, the proposed antenna is suitable for S‐band applications.