Miracle-dz/UniFAR-FTUs huggingface dataset:
Query to reference single-cell integration with transfer learning

Large single-cell atlases are now routinely generated with the aim of serving as reference to analyse future smaller-scale studies. Yet, learning from reference data is complicated by batch effects between datasets, limited availability of computational resources, and sharing restrictions on raw data. Leveraging advances in machine learning, we propose a deep learning strategy to map query datasets on top of a reference called single-cell architectural surgery (scArches, https://github.com/theislab/scarches). It uses transfer learning and parameter optimization to enable efficient, decentralized, iterative reference building, and the contextualization of new datasets with existing references without sharing raw data. Using examples from mouse brain, pancreas, and whole organism atlases, we showcase that scArches preserves nuanced biological state information while removing batch effects in the data, despite using four orders of magnitude fewer parameters compared to de novo integration. To demonstrate mapping disease variation, we show that scArches preserves detailed COVID-19 disease variation upon reference mapping, enabling discovery of new cell identities that are unseen during training. We envision our method to facilitate collaborative projects by enabling the iterative construction, updating, sharing, and efficient use of reference atlases.
Comparative analysis of the molecular mechanism of resistance to vapendavir across a panel of picornavirus species

Vapendavir is a rhino/enterovirus inhibitor that targets a hydrophobic pocket in the viral capsid. Drug-resistant variants were selected in vitro. Mutations in the drug-binding pocket in VP1 (C199R/Y in hRV14; I194F in PV1; M252L and A156T in EV-D68), typical for this class of compounds, were identified. We also observed mutations that are located outside the pocket (K167E in EV-D68 and G149C in hRV2) and that contribute to the resistant phenotype. Remarkably, the G149C substitution made the replication of human rhinovirus 2 dependent on the presence of vapendavir. Our data suggest that vapendavir binding to the capsid of the dependent isolate may be required to stabilize the viral particle and to allow efficient dissemination of the virus. Our results demonstrate that vapendavir-resistant pheno- and genotypes of clinically relevant picornavirus species are more complex than generally believed.
Increased alcohol self-administration following exposure to the predator odor TMT in high stress-reactive female rats

Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid. Additionally, individual differences in response to stress suggest resilient and susceptible populations. The current study exposed male and female Long Evans rats to the synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) to examine individual differences in stress-reactive behaviors (digging and immobility) and whether these differences could predict lasting consequences of TMT and increases in alcohol drinking. Male and female Long Evans rats were trained on operant alcohol self-administration. After 9 sessions, rats underwent exposure to TMT or water (Control) in a distinct context. 6 days after TMT exposure, rats underwent re-exposure to the TMT-paired context (without TMT), and a series of behavioral assessments (acoustic startle, zero maze, light/dark box), after which rats resumed alcohol self-administration. Rats were divided into two TMT-subgroups using a ratio of digging and immobility behavior during TMT exposure: TMT-subgroup 1 (low digging/immobility ratio) and TMT-subgroup 2 (high digging/immobility ratio). Digging/immobility ratio scores predicted elevated corticosterone levels during TMT exposure and reactivity during context re-exposure in males and females (TMT-subgroup 2), as well as elevated corticosterone levels after context re-exposure and hyperarousal behavior in females (TMT-subgroup 1). Furthermore, TMT stress reactivity predicted increases in alcohol self-administration, specifically in females. These data show that stress-reactivity can predict lasting behavioral changes which may lead to a better understanding of increases in alcohol drinking following stress in females and that individual differences in stress-reactive behaviors using TMT may be helpful to understand resilience/susceptibility to the lasting consequences of stress. Highlights Exposure to the predator odor TMT produces distinct behavioral phenotypes in male and female rats Male and female high stress reactive rats show enhanced reactivity to the TMT-paired context Stress-reactivity during TMT predicts increases in alcohol self-administration, in females Stress-reactivity may help to understand resilience/susceptibility and impact on alcohol drinking
MULTIDIRECTIONAL ASSESSMENT OF BONE STRUCTURE INCLUDING RADIOISOTOPIC ANALYSIS IN PERIMENOPAUSAL WOMEN.

Objective In postmenopausal period, changes in bone turnover markers (BTM), vitamin D3, cytokines and parathyroid hormone (PTH) are frequently observed. The study was to assess bone mineral density (BMD) and bone metabolism index (IBM) in the perimenopausal women. Design years 2013-2014. Subjects and Methods One hundred and thirteen women were divided into four groups: group I (35 not menstruating 50 - 60 years old with osteoporosis), II (23 not menstruating 50 - 60 years old without osteoporosis), III (30 menstruating 40 - 49 years old with osteoporosis), IV (25 menstruating 40 - 49 years old without osteoporosis). The following parameters were measured: IL-1β, IL-6, TNF-α, hormone oestradiol (E2), PTH, FSH, TSH, calcium (Ca2+), phosphates (P), alkaline phosphatase (bALP), C-terminal telopeptide of type I collagen alpha 1 chain (α1CTX), osteocalcin (OC), BMD, IBM. Results IBM and BMD were significantly lower in premenopausal than in postmenopausal women. The concentration of OC, CTX, 25OH D3 and PTH levels differed significantly between group I vs. II, group I vs. III and group II vs. IV. Conclusions The levels of BTM, D3, PTH differed significantly between groups. This study demonstrated that bone metabolism depended mainly on processes related with menopause state and changes in D3, PTH and cytokines levels.
Leave no stone unturned: The hidden potential of carbon and nitrogen cycling by novel, highly adapted Thaumarchaeota in the Atacama Desert hyperarid core

The hyperarid core of the Atacama Desert is an extremely harsh environment previously thought to be colonized by only a few heterotrophic bacterial species. In addition, carbon and nitrogen cycling in these highly oligotrophic ecosystems are poorly understood. Here we genomically resolved a novel genus of Thaumarchaeota, Ca. Nitrosodesertus, found below boulders of the Atacama hyperarid core, and used comparative genomics to analyze their pangenome and site-specific adaptations. Their genomes contain genes for ammonia oxidation and the 3-hydroxypropionate/4-hydroxybutyrate carbon fixation pathway, indicating a chemolithoautotrophic lifestyle. Ca. Nitrosodesertus possesses the capacity for tolerating extensive environmental stress highlighted by the presence of genes against oxidative stress, DNA damage and genes for the formation of biofilms. These features are likely responsible for their dominance in samples with extremely low water content across three different boulder fields and eight different boulders. Genome-specific adaptations of the genomes included the presence of additional genes for UV resistance, heavy metal transporters, multiple types of ATP synthases, and divergent genes for aquaporins. Our results suggest that Thaumarchaeota mediate important carbon and nitrogen cycling in the hyperarid core of the Atacama and are part of its continuous and indigenous microbiome.
The Energetic Cost of Parasitism in Isopods

Abstract: Assessment of the energetic costs of parasitism is central to understanding the role of parasites in their hosts' foodwebs, but few studies have directly measured these costs. This study demonstrates that infection with the acanthocephalan parasite Acanthocephalus tehlequahensis causes a significant and direct energetic cost to its freshwater isopod intermediate host Ceacidotea communis at both individual and population levels. Bomb calorimetry was used to measure energy (kj·m-2·y-1) allocated to host growth, reproduction, and respiration in infected and uninfected isopods and to parasite tissue in infected isopods. Infected isopod individuals allocated ∼21% of their net production energy to parasite growth, and they were larger (length), consumed more leaf detritus, and lost significantly more energy to respiration than uninfected controls (P ≤ 0.05). They also allocated proportionally less energy to tissue growth, allocated zero energy to reproduction, and were less efficient at converting energy into isopod biomass when compared to uninfected controls (P ≤ 0.05). In the field, isopod populations were surveyed monthly for a year. The parasite had a mean infection prevalence in the stream of 30.19% ± 8.31 SE with a mean intensity of 1.12 ± 0.39 SE parasites/host in the population, and based on this infection rate, it is estimated that ∼6.7% of total production energy of the isopod population (infected and uninfected) is diverted towards the parasite. Nomenclature: Say, 1818; Oetinger & Buckner, 1976.
Extratubular Polymerized Uromodulin Induces Leukocyte Recruitment and Inflammation In Vivo

Uromodulin (UMOD) is produced and secreted by tubular epithelial cells. Secreted UMOD polymerizes (pUMOD) within the lumen, where it regulates salt transport and protects the kidney from bacteria and stone formation. Under various pathological conditions, pUMOD accumulates within the tubular lumen and reaches extratubular sites where it may interact with renal interstitial cells. Here, we investigated the potential of extratubular pUMOD to act as a damage associated molecular pattern (DAMP) molecule thereby creating local inflammation. We found that intrascrotal and intraperitoneal injection of pUMOD induced leukocyte recruitment in vivo and led to TNF-α secretion by F4/80 positive macrophages. Additionally, pUMOD directly affected vascular permeability and increased neutrophil extravasation independent of macrophage-released TNF-α. Interestingly, pUMOD did not directly upregulate adhesion molecules on endothelial cells and did not directly activate β2 integrins on neutrophils. In obstructed neonatal murine kidneys, we observed extratubular UMOD accumulation with tubular atrophy and leukocyte infiltrates. Finally, we found extratubular UMOD deposits associated with peritubular leukocyte infiltration in kidneys from patients with inflammatory kidney diseases. Taken together, we identified extratubular pUMOD as a strong inducer of leukocyte recruitment, underlining its critical role in mounting an inflammatory response in various kidneys pathologies.
A Possible Inductive Mechanism for Magnetogenetics

Reports of genetically conferred sensitivity to magnetic stimuli have preceded plausible mechanistic explanations. Frequently, these experiments rely on a fusion of ferritin with a transient receptor potential vanniloid channel protein, speculating associated mechanical or thermal cues. However, it has been argued compellingly that the small magnetic moment of ferritin precludes these possibilities. Here, we offer an alternative hypothesis based on stochastic resonance that does not require appreciable interaction of ferritin with the applied field. Rather, we suggest that ferritin might act merely as a localized source of high frequency inductive noise on the membrane. When combined with externally applied time-varying fields, this noise might help surmount the activation threshold of endogenous voltage-gated ion channels. To explore this concept, we use the stochastic Landau-Lifshitz-Gilbert equation to model magnetization dynamics and compare the magnetic field noise resulting from ferritin and from a 15 nm magnetite particle.
Neural tube closure requires the endocytic receptor Lrp2 and its functional interaction with intracellular scaffolds

ABSTRACT Pathogenic mutations in the endocytic receptor LRP2 in humans are associated with severe neural tube closure defects (NTDs) such as anencephaly and spina bifida. Here, we have combined analysis of neural tube closure in mouse and in the African Clawed Frog Xenopus laevis to elucidate the etiology of Lrp2-related NTDs. Lrp2 loss of function impaired neuroepithelial morphogenesis, culminating in NTDs that impeded anterior neural plate folding and neural tube closure in both model organisms. Loss of Lrp2 severely affected apical constriction as well as proper localization of the core planar cell polarity (PCP) protein Vangl2, demonstrating a highly conserved role of the receptor in these processes, which are essential for neural tube formation. In addition, we identified a novel functional interaction of Lrp2 with the intracellular adaptor proteins Shroom3 and Gipc1 in the developing forebrain. Our data suggest that, during neurulation, motifs within the intracellular domain of Lrp2 function as a hub that orchestrates endocytic membrane removal for efficient apical constriction, as well as PCP component trafficking in a temporospatial manner. Highlighted Article: Analysis of neurulation in mouse and Xenopus reveals novel roles for Lrp2-mediated endocytosis in orchestrating apical constriction and planar cell polarity essential for neural tube closure.
Integrated aqueous humor ceRNA and miRNA–TF–mRNA network analysis reveals potential molecular mechanisms governing primary open-angle glaucoma pathogenesis

Primary open-angle glaucoma (POAG) is the leading cause of blindness globally, which develops through complex and poorly understood biological mechanisms. Herein, we conducted an integrated bioinformatics analysis of extant aqueous humor (AH) gene expression datasets in order to identify key genes and regulatory mechanisms governing POAG progression. We downloaded AH gene expression datasets (GSE101727 and GSE105269) corresponding to healthy controls and POAG patients from the Gene Expression Omnibus. We then identified mRNAs, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) that were differentially expressed (DE) between control and POAG patients. DEmRNAs and DElncRNAs were then subjected to pathway enrichment analyses, after which a protein-protein interaction (PPI) network was generated. This network was then expanded to establish lncRNA-miRNA-mRNA and miRNA-transcription factor(TF)-mRNA networks. In total, the GSE101727 dataset was used to identify 2746 DElncRNAs and 2208 DEmRNAs, while the GSE105269 dataset was used to identify 45 DEmiRNAs. We ultimately constructed a competing endogenous RNA (ceRNA) network incorporating 37, 5, and 14 of these lncRNAs, miRNAs and mRNAs, respectively. The proteins encoded by these 14 hub mRNAs were found to be significantly enriched for activities that may be linked to POAG pathogenesis. In addition, we generated a miRNA-TF-mRNA regulatory network containing 2 miRNAs (miR-135a-5p and miR-139-5p), 5 TFs (TGIF2, TBX5, HNF1A, TCF3, and FOS) and 5 mRNAs (SHISA7, ST6GAC2, TXNIP, FOS, and DCBLD2). The SHISA7, ST6GAC2, TXNIP, FOS, and DCBLD2 genes that may be viable therapeutic targets for the prevention or treatment of POAG, and regulated by the TFs (TGIF2, HNF1A, TCF3, and FOS).
Aerobic cometabolic degradation of cis- and trans- dichloroethene by a consortium of bacteria isolated from contaminated sites in Africa

Biodegradation of dichloroethenes (DCEs) to innocuous products such as ethene and carbondioxide is often a limiting factor in the use of reductive dechlorination as an approach for the remediation of chloroethene-contaminated sites. In this study, the effect of some water-soluble, non-toxic and nonflammable substrates on the biodegradation of DCEs by a mixed culture of aerobic bacteria isolated from contaminated sites in Africa was investigated. A general increase of 2.13 ‐ 22.18% and 0.39 ‐ 12.61% in the amount of cis- and trans-DCE degraded, respectively, was observed in the presence of the different primary substrates. Glucose had the most significant effect resulting in 91.68% removal of cis-DCE and 86.98% removal of trans-DCE after 7 days. These values corresponded to 22.18 and 12.61% above the amount of cis- and trans-DCE degraded, respectively, in the absence of primary substrates. Results from this study indicate that the biodegradation of both compounds is enhanced by cometabolism. This finding is significant for active bioremediation systems, since the addition of these substrates to groundwater has several advantages over other cometabolic electron donors presently in use.
Human Argonaute2 and Argonaute3 are catalytically activated by different lengths of guide RNA

RNA interfering is a eukaryote-specific gene silencing by 20∼23-nucleotide (nt) microRNAs and small interfering RNAs that recruit Argonaute proteins to complementary RNAs for degradation. In humans, Argonaute2 (AGO2) has been known as the only slicer while Argonaute3 (AGO3) barely cleaves RNAs. Therefore, the intrinsic slicing activity of AGO3 remains controversial and a long-standing question. Here, we report 14-nt 3′ end-shortened variants of let-7a, miR-27a, and specific miR-17–92 families that make AGO3 an extremely competent slicer, increasing target cleavage up to ∼82-fold in some instances. These RNAs, named cleavage-inducing tiny guide RNAs (cityRNAs), conversely lower the activity of AGO2, demonstrating that AGO2 and AGO3 have different optimum guide lengths for target cleavage. Our study sheds light on the role of tiny guide RNAs.
A comparison of the immune profile of commercial broiler strains when raised on marginal and high protein diets

A study was conducted to compare the immunocompetence of four commercial broiler strains (Ross 3F8, Ross x Cobb, Ross 308 and Cobb x Cobb (CC)) that were fed either a marginal protein diet (D1) or a high protein diet (D2) for the starter and finisher diets, respectively. Strain CC showed comparatively higher and more persistent antibody titers against sheep red blood cells (SRBC) (P < 0.0182) as well as higher macrophage phagocytic function for SRBC uptake (P = 0.0118) than the other strains. The Ross 308 strain had significantly greater cell mediated immune response, as measured by T-lymphocyte proliferation response to phytohemagglutinin-P (PHA-P), P < 0.04) and Concanavalin-A (Con-A) (P < 0.0281), as well as for the chemotaxis response to formyl-met-leu-phe (P < 0.0019) than the other strains. The diet effect was variable for monocyte-macrophage functions, but birds on the high protein diets showed higher cell- mediated response than the birds on the low protein diets when measured by Con-A and PHA-P responses. An interaction between strains and diets was seen for antibody response with the Ross 308 showing higher titers on D1 while the CC had greater antibody response when raised on D2. These results suggest that genetic differences exist between various commercial broiler chicken lines for cell mediated, humoral and innate immune responses. Furthermore, dietary protein levels appear to influence the immune response levels of broiler chickens but the response obtained varies by strain. The results of these studies imply that immunocompetence is genetically controlled, and, therefore some measures of immunocompetence could be considered as a selection criterion while selecting for performance traits.
Wing-pattern-specific effects of experience on mating behavior in Heliconius melpomene butterflies

Many animals have the ability to learn, and some taxa have shown learned mate preference. This learning may be important for speciation in some species. The butterfly Heliconius melpomene is a model system for several areas of research, including hybridization, mate selection, and speciation, partially due to its widespread diversity of wing patterns. It remains unclear whether these butterflies can learn to prefer certain mates and if social experience shapes realized mating preferences. Here we test whether previous experience with a female influences male mate preference for two different H. melpomene subspecies, H. m. malleti and H. m. rosina. We conducted no-choice behavioral assays to determine if latency to court and whether males courted (vs no courtship) differed between naïve males and males with previous exposure to a young, sexually mature, virgin female. To test whether assortative courtship preference is learned in H. melpomene, males were either paired with a female who shared their phenotype or one who did not. Naïve H. m. malletti males courted assortatively, while naïve H.m. rosina males did not. Experienced H. m. malleti males reduced their courting relative to naïve males, suggesting that social experience with a sexually mature female that does not result in copulation may be perceived as a negative experience. In contrast, experienced H. m. rosina males exhibited similar courting rates to naïve H. m. rosina males. Our results suggest that social experience can influence male mating behavior in H. melpomene and that behavioral plasticity may differ across populations in this species.
A pentameric protein ring with novel architecture is required for herpesviral packaging

Genome packaging in large double-stranded DNA viruses requires a powerful molecular motor to force the viral genome into nascent capsids. This process appears mechanistically similar in two evolutionarily distant viruses, the herpesviruses and the tailed bacteriophages, which infect different kingdoms of life. While the motor and mechanism as a whole are thought to be conserved, accessory factors that influence packaging are divergent and poorly understood, despite their essential roles. An accessory factor required for herpesviral packaging is encoded by ORF68 in the oncogenic virus Kaposi’s sarcoma-associated herpesvirus (KSHV), whose homolog in Epstein Barr Virus (EBV) is BFLF1. Here, we present structures of both KSHV ORF68 and EBV BFLF1, revealing that these proteins form a highly similar homopentameric ring. The central channel of this ring is positively charged, and we demonstrate that this region of KSHV ORF68 binds double-stranded DNA. Mutation of individual positively charged residues within but not outside the channel ablates DNA binding, and in the context of KSHV infection these mutants fail to package the viral genome or produce progeny virions. Thus, we propose a model in which ORF68 facilitates the transfer of newly replicated viral genomes to the packaging motor.
Genetic diversity and population structure of ridge gourd (Luffa acutangula) accessions in a Tropical Asian collection using DArTseq based SNP markers

This study explored a germplasm consisting of 112 Luffa acutangula (ridge gourd) accessions originating from Thailand, Vietnam, China, Philippines, Indonesia, USA, Bangladesh and Laos for an analysis of the population structure and underlying genetic diversity using 2,834 DArTseq based SNPs. STRUCTURE analysis (ΔK at K=6) allowed us to group the accessions into six populations that corresponded well with the unrooted phylogenetic tree and Principle coordinate analyses. The phylogenetic tree differentiated the accessions into groups according to their passport geographic origin. STRUCTURE also revealed collection locations of the accessions for each cluster, demonstrating that genotypes of the ridge gourds were admixed at places nearby their regions of origin. AMOVA based on STRUCTURE clustering showed a higher variation within a population (87.17%) than AMOVA groups based on country of origin (84.94%). We also observed significant results in which a higher degree of genetic differentiation between populations according to the Phi statistics based on STRUCTURE clustering (0.128) rather than by country of germplasm collection (0.079). The clusters generated by STRUCTURE assigned characteristic fruit shape and length to each cluster grouping. The ample genetic diversity found in the L. acutangula germplasm can be utilized in ridge gourd breeding programs to help meet the demands of consumers (reduced bitterness) and aid farmers through breeding lines resistant to plant viruses.