Miracle-dz/UniFAR-FTUs huggingface dataset:
Population genetic analysis of Ophidiomyces ophidiicola, the causative agent of snake fungal disease, indicates recent introductions to the USA

Snake fungal disease (SFD; ophidiomycosis), caused by the pathogen Ophidiomyces ophidiicola (Oo), has been documented in wild snakes in North America and Eurasia, and is considered an emerging disease in the eastern USA. However, a lack of historical disease data has made it challenging to determine whether Oo is a recent arrival to the USA or whether SFD emergence is due to other factors. Here, we examined the genomes of 82 Oo strains to determine the pathogen’s history in the eastern USA. Oo strains from the USA formed a clade (Clade II) distinct from European strains (Clade I), and molecular dating indicated that these clades diverged too recently (∼2,000 years ago) for transcontinental dispersal of Oo to have occurred via natural snake movements across Beringia. A lack of nonrecombinant intermediates between clonal lineages in Clade II indicates that Oo has actually been introduced multiple times to North America from an unsampled source population, and molecular dating indicates that several of these introductions occurred within the last few hundred years. Molecular dating also indicated that the most common Clade II clonal lineages have expanded recently in the USA, with time of most recent common ancestor mean estimates ranging from 1985-2007 CE. The presence of Clade II in captive snakes worldwide demonstrates a potential mechanism of introduction and highlights that additional incursions are likely unless action is taken to reduce the risk of pathogen translocation and spillover into wild snake populations.
Measuring plant diversity in a two-stage sampling design by Bayesian updated relative abundances

The two-stage sampling design provides good local estimates of both the number of plant species and the relative abundances. However, it is a problem to calculate Hill diversity indices at the local scale, because some of the species found in the large plot are not present in the small plot and such species should then incorrectly be weighted with zero relative abundance. A new method for calculating local Hill diversity indices from species richness and relative abundances data is therefore needed. We suggest to replace the local relative abundances with Bayesian updated relative abundance estimates, where the prior probability distribution of the relative abundances are empirically estimated from all plots of the same habitat types. The method is applied on Danish Nardus grasslands.
Bipartite recruitment of PCH2 and COMET to the synaptonemal complex drives chromosome axis reconstruction leading to crossover restriction

Chromosome axis-associated HORMA domain proteins (HORMADs), e.g., ASY1 in Arabidopsis, are crucial for meiotic recombination. ASY1, as other HORMADs, is assembled on the axis at early meiosis and depleted when homologous chromosomes synapse. Puzzlingly, both processes are catalyzed by AAA+ ATPase PCH2 together with its cofactor COMET. Here, we show that the ASY1 remodeling complex is temporally and spatially differently assembled. While PCH2 and COMET appear to directly interact in the cytoplasm in early meiosis, PCH2 is recruited by the transverse filament protein ZYP1 and brought to the ASY1-bound COMET assuring the timely removal of ASY1 during chromosome synapsis. Since we found that the PCH2 homolog TRIP13 also binds to the ZYP1 homolog SYCP1 in mouse, we postulate that this mechanism is conserved among eukaryotes. Deleting the PCH2 binding site of ZYP1 led to a failure of ASY1 removal. Interestingly, the placement of one obligatory crossover per homologous chromosome pair, compromised by ZYP1 depletion, is largely restored in this engineered zyp1 allele suggesting that crossover assurance is promoted by synapsis. In contrast, the engineered zyp1 allele, similar to the zyp1 null mutant, showed elevated type I crossover numbers indicating that PCH2-mediated eviction of ASY1 from the axis restricts crossover formation.
A cellular and molecular analysis of SoxB-driven neurogenesis in a cnidarian

Neurogenesis is the generation of neurons from stem cells, a process that is regulated by SoxB transcription factors (TFs) in many animals. Although the roles of these TFs are well understood in bilaterians, how their neural function evolved is unclear. Here, we use Hydractinia symbiolongicarpus, a member of the early-branching phylum Cnidaria, to provide insight into this question. Using a combination of mRNA in situ hybridization, transgenesis, gene knockdown, transcriptomics, and in-vivo imaging, we provide a comprehensive molecular and cellular analysis of neurogenesis during embryogenesis, homeostasis, and regeneration in this animal. We show that SoxB genes act sequentially. Stem cells expressing Piwi1 and Soxb1, which have a broad developmental potential, become neural progenitors that express Soxb2 before differentiating into mature neural cells. Knockdown of SoxB genes resulted in complex defects in embryonic neurogenesis. Hydractinia neural cells differentiate while migrating from the aboral to the oral end of the animal, but it is unclear whether migration per se or exposure to different microenvironments is the main driver of their fate determination. Our data constitute a rich resource for studies aiming at addressing this question, which is at the heart of understanding neurological disorders in all animals, including humans.
Forest refuge areas and carbon emissions from tropical deforestation in the 21st century

Tropical forests are disappearing at an alarming rate due to human activities. Here, we provide spatial models of deforestation in 92 countries covering all the tropical moist forests in the world. Our models confirm the effectiveness of protected areas in displacing deforestation and the negative impact of roads and landscape fragmentation on forest conservation in the tropics. Using our models, we derive high-resolution pantropical maps of the deforestation risk and future forest cover for the 21st century under a “business-as-usual” scenario based on the deforestation rates observed in the 2010s. Although under this scenario, large areas of tropical moist forest should remain in the heart of the Amazon, in the Congo Basin, and in New Guinea in 2100, 48% (39–56%) of all forest cover is expected to disappear during the course of the 21st century, and many countries will have lost all their forests by 2100. The remaining forests will be highly fragmented and located in remote places. As future deforestation will concern forests with higher aboveground carbon stocks, annual carbon emissions associated with tropical deforestation are expected to increase by +0.161 Pg/yr (+35%) between the 2010s and the 2090s. 1
Cell size and shape regulation of E. coli determines surface area scaling with volume

The scaling of surface area and volume of cells has widespread consequences for cell physiology, growth and adaptation. While the surface area increases with volume as SA ~ Vγ the scaling exponent for proportional growth maintaining the shape and aspect is γ ~ 2/3 or 0.66. However most well-studied cellular systems deviate from this standard exponent. At the same time, a mechanism that could predict the biological or physical basis of these scaling relations remains unclear. Here, we quantify the surface area scaling with volume of Escherichia coli cells with varying growth rates and under different conditions and find the scaling exponent varies from γ ~ 0.7 to 0.9. A model of uncorrelated statistical variation of cell lengths and widths can reproduce the exponent observed in experiment. Average values of length and width on the other hand results in an impression of ‘ideal’ geometric scaling, as reported in some studies. Experimental data however suggests that E. coli cell width is strongly correlated with length and a model of saturation best explains the observations. We hypothesize this model of cell size and shape regulation could serve the function of optimizing flux of nutrients, within the constraints of the cell division machinery.
TFAP2 paralogs facilitate chromatin access for MITF at pigmentation genes but inhibit expression of cell-cell adhesion genes independently of MITF

In developing melanocytes and in melanoma cells, multiple paralogs of the Activating-enhancer-binding Protein 2 family of transcription factors (TFAP2) contribute to expression of genes encoding pigmentation regulators, but their interaction with Microphthalmia transcription factor (MITF), a master regulator of these cells, is unclear. Supporting the model that Tfap2 facilitates MITF’s ability to activate expression of pigmentation genes, single-cell seq analysis of zebrafish embryos revealed that pigmentation genes are only expressed in the subset of mitfa- expressing cells that also express Tfap2 paralogs. To test this model in SK-MEL-28 melanoma cells we deleted the two TFAP2 paralogs with highest expression, TFAP2A and TFAP2C, creating TFAP2 knockout (TFAP2-KO) cells. We then assessed gene expression, chromatin accessibility, binding of TFAP2A and of MITF, and the chromatin marks H3K27Ac and H3K27Me3 which are characteristic of active enhancers and silenced chromatin, respectively. Integrated analyses of these datasets indicate TFAP2 paralogs directly activate enhancers near genes enriched for roles in pigmentation and proliferation, and directly repress enhancers near genes enriched for roles in cell adhesion. Consistently, compared to WT cells, TFAP2-KO cells proliferate less and adhere to one another more. TFAP2 paralogs and MITF co-operatively activate a subset of enhancers, with the latter necessary for MITF binding and chromatin accessibility. By contrast, TFAP2 paralogs and MITF do not appear to co-operatively inhibit enhancers. These studies reveal a mechanism by which TFAP2 profoundly influences the set of genes activated by MITF, and thereby the phenotype of pigment cells and melanoma cells.
The Geobattery Concept: A Geothermal Circular Heat Network for the Sustainable Development of Near Surface Low Enthalpy Geothermal Energy to Decarbonise Heating

Decarbonisation of heating represents a major challenge in efforts to reach Net Zero carbon emissions, especially for countries that rely heavily on the combustion of carbon-based fossil fuels to meet heating demand such as the United Kingdom. In this paper we explore the use of near surface low enthalpy geothermal energy accessed via commercial and domestic heat pump technology. These resources may become increasingly important in decarbonisation efforts but, while they are renewable, their sustainability is contingent on appropriate management. Here, we introduce a new geothermal circular heat network concept, known as a “geobattery,” which redistributes recyclable heat from emitters to users via elevated permeability pathways in the subsurface and offers a platform to manage shallow geothermal resources. If successfully implemented the concept has the potential to provide low carbon, resilient, low-cost heating that is sustainable both in terms of heat pump performance and the shallow geothermal resource. We demonstrate the concept based on the cooling requirements of a case study data centre with existing high energy use and the potential to inject the generated heat into elevated permeability pathways in the shallow subsurface. We show that thermal recharge under these conditions has the potential to arrest subsurface temperature declines associated with closely spaced borehole heat exchangers, ensure the long-term sustainability of shallow geothermal resources for generations to come, and play an important role in the decarbonisation of heating.
Disrupting AMPK-Glycogen Binding in Mice Increases Carbohydrate Utilization and Reduces Exercise Capacity

The AMP-activated protein kinase (AMPK) is a central regulator of cellular energy balance and metabolism and binds glycogen, the primary storage form of glucose in liver and skeletal muscle. The effects of disrupting whole-body AMPK-glycogen interactions on exercise capacity and substrate utilization during exercise in vivo remain unknown. We used male whole-body AMPK double knock-in (DKI) mice with chronic disruption of AMPK-glycogen binding to determine the effects of DKI mutation on exercise capacity, patterns of whole-body substrate utilization, and tissue metabolism during exercise. Maximal treadmill running speed and whole-body energy utilization during submaximal running were determined in wild type (WT) and DKI mice. Liver and skeletal muscle glycogen and skeletal muscle AMPK α and β2 subunit content and signaling were assessed in rested and maximally exercised WT and DKI mice. Despite a reduced maximal running speed and exercise time, DKI mice utilized similar absolute amounts of liver and skeletal muscle glycogen compared to WT. DKI skeletal muscle displayed reduced AMPK α and β2 content versus WT, but intact relative AMPK phosphorylation and downstream signaling at rest and following exercise. During submaximal running, DKI mice displayed an increased respiratory exchange ratio, indicative of greater reliance on carbohydrate-based fuels. In summary, whole-body disruption of AMPK-glycogen interactions reduces maximal running capacity and skeletal muscle AMPK α and β2 content and is associated with increased skeletal muscle glycogen utilization. These findings highlight potential unappreciated roles for AMPK in regulating tissue glycogen dynamics and expand AMPK’s known roles in exercise and metabolism.
Non-Invasive Evaluation of Cerebral Hemodynamic Changes After Surgery in Adult Patients With Moyamoya Using 2D Phase-Contrast and Intravoxel Incoherent Motion MRI

Objective To explore the feasibility of 2D phase-contrast MRI (PC-MRI) and intravoxel incoherent motion (IVIM) MRI to assess cerebrovascular hemodynamic changes after surgery in adult patients with moyamoya disease (MMD). Methods In total, 33 patients with MMD who underwent 2D PC-MRI and IVIM examinations before and after surgery were enrolled. Postsurgical changes in peak and average velocities, average flow, forward volume, and the area of superficial temporal (STA), internal carotid (ICA), external carotid (ECA), and vertebral (VA) arteries were evaluated. The microvascular perfusion status was compared between the hemorrhage and non-hemorrhage groups. Results The peak velocity, average flow, forward volume, area of both the ipsilateral STA and ECA, and average velocity of the ipsilateral STA were increased (p < 0.05). The average flow and forward volume of both the ipsilateral ICA and VA and the area of the ipsilateral VA were increased (p < 0.05). The peak velocity, average velocity, average flow and forward volume of the contralateral STA, and the area of the contralateral ICA and ECA were also increased (p < 0.05), whereas the area of the contralateral VA was decreased (p < 0.05). The rf value of the ipsilateral anterior cerebral artery (ACA) supply area was increased (p < 0.05) and more obvious in the non-hemorrhage group (p < 0.05). Conclusion Two-dimensional PC-MRI and IVIM may have the potential to non-invasively evaluate cerebrovascular hemodynamic changes after surgery in patients with MMD. An improvement in the microvascular perfusion status is more obvious in patients with ischemic MMD than in patients with hemorrhagic MMD.
Clinical Implications of Heart Rate Control in Heart Failure With Atrial Fibrillation: Multi-Center Prospective Observation Registry (CODE-AF Registry)

Background Atrial fibrillation (AF) is treated by heart rate (HR) control. However, the optimal HR target in AF patients with heart failure (HF) remains unclear. To evaluate the clinical implication of the resting HR in AF patients with HF accompanied by preserved, mid-range, or reduced ejection fraction (HFpEF, HFmrEF, or HFrEF, respectively). Methods Echocardiographic data from June 2016 to April 2020 in a prospective, multicenter, observational registry from 11,104 patients were analyzed. The follow-up duration was 2.2 years. The main outcome was composite of death and hospitalization. We categorized patients according to the HF type and resting HR: ≤ 60 bpm, 61–80 bpm, 81–110 bpm, and >110 bpm. Results A total of 1,421 patients were enrolled in the study: 582 in the HFpEF group, 506 in the HFmrEF group, and 333 in the HFrEF group. The patients had a mean age of 69 ± 11 years and consisted of 872 (61.4%) men. Primary endpoint rates among HFpEF patients with 60 < HR ≤ 110 bpm were lower than those with HR ≤ 60 bpm (61–80 bpm group: hazard ratio, 0.66; 95% CI, 0.46–0.94; p = 0.021; 81–110 bpm group: hazard ratio, 0.60; 95% CI, 0.40–0.90; p = 0.013). Especially, HFpEF patients with HR 81–110 bpm had a lower incidence of hospitalization caused by HF aggravation than those with other HR strata (HR ≤ 80bpm strata or HR >110 bpm strata). In HFmrEF and HFrEF patients, the survival rates did not differ significantly among patients in the three groups with HR ≤ 110 bpm. Moreover, the event rates increased significantly in HFmrEF patients with HR >110 bpm (hazard ratio, 1.91; 95% CI, 1.16-3.14, p = 0.011). Conclusion In patients with AF and HFpEF, the resting HR has U-shaped associations with the overall primary endpoint. A lower or higher resting HR is associated with increased cardiovascular outcomes, especially in patients with HFpEF and AF.
Sexual Dysfunctions in Patients Receiving Opioid Agonist Treatment and Heroin-Assisted Treatment Compared to Patients in Private Practice—Identifying Group Differences and Predictors

Background and Aims Sexual dysfunctions (SDs) show a marked impact on a person’s general wellbeing. Several risk-factors like physical and mental illnesses as well as alcohol and tobacco use have to date been identified to contribute to the occurrence of SDs. The impact of opioid-agonist treatment (OAT) on SDs remains unclear, with some studies demonstrating an improvement after methadone maintenance treatment (MMT) initiation. However, no studies on the prevalence and predictors of SDs in heroin-assisted treatment (HAT) exist to date. Methods A cross-sectional study was conducted with patients from a MMT center (n = 57) and a center specializing in HAT (n = 47). A control group of patients with mild transient illnesses (n = 67) was recruited from a general practitioner (GP). The International Index of Erectile Function, the Female Sexual Function Index, as well as measurements for psychological distress, depressive state, nicotine dependence, and high-risk alcohol use were employed. Patients also completed a self-designed questionnaire on help-seeking behavior regarding sexual health. Mann-Whitney-U tests and chi-square tests were performed for group comparisons and binary logistic regression models were calculated. Results Twenty-five percent of the GP sample (n = 17), 70.2% (n = 40) of the MMT sample, and 57.4% (n = 27) of the HAT sample suffered from SDs at the time of study conduction. OAT patients differed significantly from GP patients in depressive state, high-risk alcohol use, nicotine dependence, and psychological distress. Age, depressive state, and opioid dependence predicted the occurrence of SDs in the total sample. No differences between OAT and GP patients were found regarding help-seeking behavior. Discussion Age, depressive state, and opioid dependence predicted the occurrence of SDs in the total sample. It remains unclear whether SDs are caused by opioid intake itself or result from other substance-use related lifestyle factors, that were not controlled for in this study. A lack of help-seeking behavior was observed in our sample, underlining the importance of clinicians proactively inquiring about the sexual health of their patients. Conclusion The high prevalence of SDs observed in MMT does not differ from the prevalence in HAT. Clinicians should actively inquire about their patients’ sexual health in GP and OAT centers alike.
Identification of Immune-Related Gene Signature and Prediction of CeRNA Network in Active Ulcerative Colitis

Background Ulcerative colitis (UC) is an inflammatory disease of the intestinal mucosa, and its incidence is steadily increasing worldwide. Intestinal immune dysfunction has been identified as a central event in UC pathogenesis. However, the underlying mechanisms that regulate dysfunctional immune cells and inflammatory phenotype remain to be fully elucidated. Methods Transcriptome profiling of intestinal mucosa biopsies were downloaded from the GEO database. Robust Rank Aggregation (RRA) analysis was performed to identify statistically changed genes and differentially expressed genes (DEGs). Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore potential biological mechanisms. CIBERSORT was used to evaluate the proportion of 22 immune cells in biopsies. Weighted co-expression network analysis (WGCNA) was used to determine key module-related clinical traits. Protein-Protein Interaction (PPI) network and Cytoscape were performed to explore protein interaction network and screen hub genes. We used a validation cohort and colitis mouse model to validate hub genes. Several online websites were used to predict competing endogenous RNA (ceRNA) network. Results RRA integrated analysis revealed 1838 statistically changed genes from four training cohorts (adj. p-value < 0.05). GSEA showed that statistically changed genes were enriched in the innate immune system. CIBERSORT analysis uncovered an increase in activated dendritic cells (DCs) and M1 macrophages. The red module of WGCNA was considered the most critical module related to active UC. Based on the results of the PPI network and Cytoscape analyses, we identified six critical genes and transcription factor NF-κB. RT-PCR revealed that andrographolide (AGP) significantly inhibited the expression of hub genes. Finally, we identified XIST and three miRNAs (miR-9-5p, miR-129-5p, and miR-340-5p) as therapeutic targets. Conclusions Our integrated analysis identified four hub genes (CXCL1, IL1B, MMP1, and MMP10) regulated by NF-κB. We further revealed that AGP decreased the expression of hub genes by inhibiting NF-κB activation. Lastly, we predicted the involvement of ceRNA network in the regulation of NF-κB expression. Collectively, our results provide valuable information in understanding the molecular mechanisms of active UC. Furthermore, we predict the use of AGP and small RNA combination for the treatment of UC.
Biophysical responses of Santa Inês and crossbred Santa Inês-Dorper (F1) ewes to a hot environment

This study aimed to evaluate the biophysical responses of Santa Ines ewes and crossbred Santa Ines-Dorper ewes in a hot environment. Physiological parameters were measured: rectal temperature, respiratory rate, coat surface temperature, skin surface temperature, and heart rate. Biophysical parameters were also calculated: heat exchanges by cutaneous convection and radiation, as well as heat storage and thermal conduction in fleece. Throughout the collection period, meteorological variables were similarly monitored. The statistical design was completely randomized in a factorial 2 x 2 (two genotypes and two shifts). According to meteorological variables, the afternoon shift introduced itself with greater heat stress compared with the morning shift. The effect of interaction between genotypes and shifts for respiratory rate, rectal temperature, skin surface temperature, and hair coat surface temperature showed that genotypes exhibit different physiological behavior under similar heat stress situations. Heart rate had the effect of two sources of variation. As for the biophysical parameters, radiation and conduction exchanges in fleece presenting with the shift effect. Heat storage was slightly higher in Santa Ines ewes than in their crossbred Santa Ines-Dorper ewes. It was therefore concluded that crossbred ewes use physiological mechanisms more vigorously to perform heat exchanges, similar to Santa Ines ewes, which have become more adapted to a hot environment.