Miracle-dz/UniFAR-FTUs huggingface dataset:
Epidermal activation of Hedgehog signaling establishes an immunosuppressive microenvironment in basal cell carcinoma by modulating skin immunity

Genetic activation of Hedgehog (HH)/GLI signaling causes basal cell carcinoma (BCC), a very frequent non-melanoma skin cancer. Small molecule targeting of the essential HH effector Smoothened (SMO) proved an efficient medical therapy of BCC, although lack of durable responses and frequent development of drug resistance pose major challenges to anti-HH treatments. In light of the recent breakthroughs in cancer immunotherapy, we analyzed in detail the possible immunosuppressive mechanisms in HH/GLI-induced BCC. Using a genetic mouse model of BCC, we identified profound differences in the infiltration of BCC lesions with cells of the adaptive and innate immune system. Epidermal activation of HH/GLI led to an accumulation of immunosuppressive regulatory T cells, and to an increased expression of immune checkpoint molecules including PD-1/PD-L1. Anti-PD1 monotherapy, however, did not reduce tumor growth, presumably due to the lack of immunogenic mutations in common BCC mouse models, as shown by whole-exome sequencing. BCC lesions also displayed a marked infiltration with neutrophils, the depletion of which unexpectedly promoted BCC growth. The results provide a comprehensive survey of the immune status of murine BCC and provide a basis for the design of efficacious rational combination treatments. This study also underlines the need for predictive immunogenic mouse models of BCC to evaluate in vivo the efficacy of immunotherapeutic strategies.
Is there an impact of behaviour on trapping migratory invasive sea lamprey (Petromyzon marinus)?

Trapping is used to control a variety of invasive species; however, trap encounter and entrance can vary betweenand within-species depending on consistent individual differences in behaviour. We develop a framework for testing how consistent differences in behaviour might be related to trapping a migratory species. We tested whether adult migrating sea lamprey display consistent individual differences in two behaviours, boldness (measured as exit time from an enclosure) and activity (measured as the proportion of time spent moving), and whether these differences were related to trap entrance or timing. We predicted that bolder and more active individuals would migrate sooner and be more likely to be caught in a trap. We also predicted that early in the migration phenology, trapped individuals would not differ in behaviour from untrapped individuals, but later in the migration phenology, trapped individuals would be bolder and more active. We determined that sea lamprey exhibit consistent individual differences in boldness and activity but found no evidence that these differences were related to migratory timing or trap capture A greater understanding of how individual differences in behaviour influence trapping could help improve the management of invasive species by allowing for a better estimation of population size and provide insight into how to target different behavioural types.
Landscape use by two opossums is shaped by habitat preferences rather than by competitive interactions

Given the phylogenetic proximity and similar morphology of opossums (Didelphis spp.), they are good models to study factors that facilitate or impede coexistence of syntopic species and to better understand how landscape changes affect species distributions and habitat use. For this purpose, we used single-species and two-species occupancy models using records of D. albiventris, considered the dominant species, and D. aurita from a camera-trap survey conducted in an agricultural and conservation landscape in the Atlantic Forest of Argentina. We evaluated which factors determined the probability of species occurrence: habitat preferences or interspecific relationships. We also estimated the overlap in daily activity patterns between species, and evaluated changes in D. aurita activity in response to the occupancy probability of D. albiventris. Didelphis aurita had higher occupancy probabilities in the continuous native forest, whereas D. albiventris had higher occupancy probabilities in fragmented forests with less complex and more open vegetation structure, and greater proximity to buildings. Both opossums were almost absent in pine plantations. Results of the co-occurrence models and the overlap in diel activity suggest that D. aurita is not avoiding D. albiventris. Occurrences of these two opossums most probably reflect different adaptations by each species to different habitats, and competitive interactions seem to play a minor role in shaping their current distributions. Didelphis albiventris may be replacing D. aurita mainly as a result of changing environmental conditions, which become unfavorable to the latter but promote the creation of new habitat for the former.
Chromosome-scale de novo assembly and phasing of a Chinese indigenous pig genome

Chinese indigenous pigs differ significantly from Western commercial pig breeds in phenotypic and genomic characteristics. Thus, building a high-quality reference genome for Chinese indigenous pigs is pivotal to exploring gene function, genome evolution and improving genetic breeding in pigs. Here, we report an ultrahigh-quality phased chromosome-scale genome assembly for a male Luchuan pig, a representative Chinese domestic breed, by generating and combining data from PacBio Sequel reads, Illumina paired-end reads, high-throughput chromatin conformation capture and BioNano optical map. The primary assembly is ∼ 2.58 Gb in size with contig and scaffold N50s of 18.03 Mb and 140.09 Mb, respectively. Comparison between primary assembly and alternative haplotig reveals numerous haplotype-specific alleles, which provide a rich resource to study the allele-specific expression, epigenetic regulation, genome structure and evolution of pigs. Gene enrichment analysis indicates that the Luchuan-specific genes are predominantly enriched in Gene Ontology terms for phosphoprotein phosphatase activity, signaling receptor activity and phosphatidylinositol binding. We provide clear molecular evolutionary evidence that the divergence time between Luchuan and Duroc pigs is dated back to about 1.7 million years ago. Meanwhile, Luchuan exhibits fewer events of gene family expansion and stronger gene family contraction than Duroc. The positively selected genes (PSGs) in Luchuan pig significantly enrich for protein tyrosine kinase activity, microtubule motor activity, GTPase activator activity and ubiquitin-protein transferase activity, whereas the PSGs in Duroc pig enrich for G-protein coupled receptor activity. Overall, our findings not only provide key benchmark data for the pig genetics community, but also pave a new avenue for utilizing porcine biomedical models to study human health and diseases.
64-OR: Postprandial Effects of Endogenous Glucose-Dependent Insulinotropic Polypeptide in Type 2 Diabetes

The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) is released from the small intestine following meal ingestion and potentiates glucose-stimulated insulin secretion. Exogenous GIP has a poor insulinotropic effect in patients with type 2 diabetes (T2D). We investigated postprandial effects of endogenous GIP in patients with T2D using the GIP receptor antagonist, GIP(3-30)NH2. In a randomized, double-blinded, placebo-controlled, cross-over study, 10 patients with T2D (mean±SD; HbA1c 6.9±3.2%; BMI 32.5±4.8 kg/m2) received 250-minute infusions of GIP(3-30)NH2 (1,200 pmol/kg/min) or placebo (saline) during two separate standardized liquid meal tests. Compared with placebo, GIP(3-30)NH2 infusion caused lower postprandial insulin (Δ%±SD; -19±15%, P=0.010) and C-peptide (-14±21%, P=0.021) responses (area under the curve) but had no effect on plasma glucagon (P=0.580) or glucose excursions (P=0.692). Postprandial inhibition of bone resorption (assessed by carboxy-terminal collagen crosslinks) was ∼50% lower during GIP(3-30)NH2 infusion compared with placebo (P=0.005; Figure 1). In conclusion, endogenous GIP slightly reduced postprandial insulin secretion with no effect on postprandial glucagon or glucose concentrations in patients with T2D. In contrast, endogenous GIP was a major determinant of postprandial suppression of bone resorption in these patients. Disclosure S. Stensen: None. L.S. Gasbjerg: Stock/Shareholder; Self; Antag Therapeutics. L.S. Krogh: None. A.H. Sparre-Ulrich: Other Relationship; Self; Antag Therapeutics. K. Skov-Jeppesen: None. M. Jensen: Employee; Self; Antag Therapeutics. B. Hartmann: None. T. Vilsboll: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. M.M. Rosenkilde: Consultant; Self; Antag Therapeutics. M.B. Christensen: None. F.K. Knop: Advisory Panel; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi. Consultant; Self; Amgen Inc., Carmot Therapeutics, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker9s Bureau; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Norgine, Novo Nordisk A/S. Funding Novo Nordisk Foundation; European Foundation for the Study of Diabetes
Attention to rhythms: sensory-specific constrained sampling of temporal regularities

That attention is a fundamentally rhythmic process has recently received abundant empirical evidence. The essence of temporal attention, however, is to flexibly focus in time. Whether this function is hampered by an underlying rhythmic mechanism is unknown. In six interrelated experiments, we behaviourally quantify the sampling capacities of periodic temporal attention during auditory or visual perception. We reveal the presence of limited attentional capacities, with an optimal sampling rate of ~1.4 Hz in audition and ~0.7 Hz in vision. Investigating the motor contribution to temporal attention, we show that it scales with motor rhythmic precision, maximal at ~1.7 Hz. Critically, the motor modulation is beneficial to auditory but detrimental to visual temporal attention. These results are captured by a computational model of coupled oscillators, that reveals the underlying structural constraints governing the temporal alignment between motor and attention fluctuations.
Species-specific secretion of ESX-5 type VII substrates is determined by the linker 2 of EccC5

Type VII secretion systems (T7SSs) are used by mycobacteria to translocate a wide range of effector proteins across their diderm cell envelope. These systems, also known as ESX systems, have crucial roles for the viability and/or virulence of mycobacterial pathogens, including Mycobacterium tuberculosis and the fish pathogen Mycobacterium marinum. We previously observed species-specificity in the secretion of the PE_PGRS proteins by the ESX-5 system [1], in that the M. tuberculosis ESX-5 system was unable to fully complement an M. marinum esx-5 mutant. In this study, we established that the responsible factor for this is the central membrane ATPase EccC5, which has three nucleotide binding domains (NBDs). By creating chimeric M. marinum/M. tuberculosis EccC5 constructs, we observed that PE_PGRS secretion is mediated only in the presence of an EccC5 containing the cognate linker 2, irrespective of the origin of the EccC5 backbone. This region is responsible for linking the first two NBDs and for keeping the first NBD in an inhibited state. Notably, this region is disordered in a EccC crystal structure and is particularly extended in EccC proteins of the different ESX-5 systems. These results indicate that this region is involved in species-specific substrate recognition and might therefore be an additional substrate recognition site of EccC5.
BUSCA NÃO SUPERVISIONADA DE PADRÕES POR TÉCNICAS DE AGRUPAMENTO CLÁSSICA E NEBULOSA

Clustering analysis is one of techniques of knowledge discovery in databases (KDD), providing an effective way to identify patterns and relationships in complex data and to form hypotheses about their structure. When used as a data analysis tool in the branch of Zootechny, as in dairy farming, broadens its field of research and allows the pattern discovery that supports prediction and/or decision making for the sustainability of production systems. This study aims to identify cattle clusters with different phenotypic characteristics in relation to milk production. The phenotype or observed value of a certain trait depends on genetic value of the individual, environment in which it is produced and their interactions. In another words, it is influenced by genotype and environment in an additive and independent way. Therefore, one must to take into account these three factors in the analysis of potential phenotypic variations within the same environment, most likely due to genotypic issues and/or different responses of the genotype-environment interaction; as well as the potential variations due to the environment changing. The environmental factor considered was the diet used in animal nutrition. The results showed associations between different types of diets regarding to the productive performance of the cows, which consequently can generate practical implications, such as cost reductions in dairy cattle feeding and nutrition. In addition, they also allowed identifying well-defined clusters of cows with different productive performances, which may be useful for genetic evaluations, aiming at generating of genetically superior heifers for milk production. The clustering methods used were K-Means and Fuzzy C-Means.
Acetylcholine acts on songbird premotor circuitry to invigorate vocal output

Acetylcholine is well-understood to enhance cortical sensory responses and perceptual sensitivity in aroused or attentive states. Yet little is known about cholinergic influences on motor cortical regions. Here we use the quantifiable nature of birdsong to investigate how acetylcholine modulates the cortical (pallial) premotor nucleus HVC and shapes vocal output. We found that dialyzing the cholinergic agonist carbachol into HVC increased the pitch, amplitude, tempo and stereotypy of song, similar to the natural invigoration of song that occurs when males direct their songs to females. These carbachol-induced effects were associated with increased neural activity in HVC and occurred independently of basal ganglia circuitry. Moreover, we discovered that the normal invigoration of female-directed song was also accompanied by increased HVC activity and was attenuated by blocking muscarinic acetylcholine receptors. These results indicate that, analogous to its influence on sensory systems, acetylcholine can act directly on cortical premotor circuitry to adaptively shape behavior.
Deer Indirectly Alter the Reproductive Strategy and Operational Sex Ratio of an Unpalatable Forest Perennial

Environmental conditions impose restrictions and costs on reproduction. Multiple reproductive options exist when increased reproductive costs drive plant populations toward alternative reproductive strategies. Using 4 years of demographic data across a deer impact gradient, where deer alter the abiotic environment, we parameterize a size-dependent integral projection model for a sexually labile and unpalatable forest perennial to investigate the demographic processes driving differentiation in the operational sex ratio (OSR) of local populations. In addition to a relative increase in asexual reproduction, our results illustrate that nontrophic indirect effects by overabundant deer on this perennial result in delayed female sex expression to unsustainably large plant sizes and lead to more pronounced plant shrinkage following female sex expression, effectively increasing the cost of reproduction. Among plants of reproductive age, increased deer impact decreases the size-dependent probability of flowering and reduces reproductive consistency over time. This pattern in sex expression skews populations toward female-biased OSRs at low deer impact sites and male-biased OSRs at intermediate and high deer impact sites. While this shift toward a male-biased OSR may ameliorate pollen limitation, it also decreases the effective population size when coupled with increased asexual reproduction. The divergence of reproductive strategies and reduced lifetime fitness in response to indirect deer impacts illustrate the persistent long-term effects of overabundant herbivores on unpalatable understory perennials.
Comments on the diet of Phyllostomid bats (Chiroptera) in a subtropical dry forest in central Honduras

ABSTRACT Leaf-nose or Phyllostomid bats represent the most diverse family of mammals referring to feeding habits, including frugivory. Species of this family have a wide range of food habits. However, there is scarce information about the specific diet per species in Honduras. We studied the feces of seven Phyllostomid bat species captured in a subtropical dry forest in Ciudad Universitaria (CU-UNAH) from 2015 to 2017. The alimentary patterns observed on the community of Phyllostomid bats does not follow the core plant hypothesis. Nevertheless, new records to the diet of Phyllostomid bats in Honduras, and to their general diet are proportionated.
Genetic diversity of Herpetospermum caudigerum (Ser.) Baill using AFLP and chloroplast microsatellites

Abstract Herpetospermum caudigerum (Ser.) Baillis is an endangered species found in high altitude regions of Tibet in China. In this work, its genetic diversity and genetic structure were investigated based on nuclear and chloroplast DNA. A total of 426 fragments were scored using 10 amplified fragment length polymorphism (AFLP) primer combinations, and from these, 256 fragments (60.7%) were polymorphic and could differentiate these populations. The dendrogram revealed that populations from different altitude have rich genetic diversities (Ht = 0.156, Hs = 0.111, Gst = 0.287 and Nm = 1.618). The averages of the number of alleles (Na), effective number of alleles (Ne), Nei’s genetic diversity (H) and Shannon’s index (I) were 1.352, 1.188, 0.111 and 0.168, respectively. In addition, 5 P03-trnL-trnF-300 haplotypes and 3 P02-trnL-trnF-396 haplotypes were identified among the 4 populations, and 7 haplotypes were identified based on the combined fragments. The non-coding region P03-trnL-trnF-300 exhibited higher polymorphisms with the number of haplotypes, the abundant haplotype (gene) diversity and the nucleotide diversity. Tajima’s test showed that all Tajima’s D values were statistically significant at P < 0.05, indicating that natural selection has an effect on mutations in these fragments. Our results from H. caudigerum cpDNA indicated a high genetic diversity fixation index (Fst = 0.968) and showed greater genetic differentiation among populations (96.7%, P < 0.01) than analysis of nDNA (63.72%, P < 0.01). These results could lay the foundation for further understanding and conservation of H. caudigerum germplasm resources.
The many faces of synapsid cranial allometry

Abstract. Previous studies of cranial shape have established a consistent interspecific allometric pattern relating the relative lengths of the face and braincase regions of the skull within multiple families of mammals. In this interspecific allometry, the facial region of the skull is proportionally longer than the braincase in larger species. The regularity and broad taxonomic occurrence of this allometric pattern suggests that it may have an origin near the base of crown Mammalia, or even deeper in the synapsid or amniote forerunners of mammals. To investigate the possible origins of this allometric pattern, we used geometric morphometric techniques to analyze cranial shape in 194 species of nonmammalian synapsids, which constitute a set of successive outgroups to Mammalia. We recovered a much greater diversity of allometric patterns within nonmammalian synapsids than has been observed in mammals, including several instances similar to the mammalian pattern. However, we found no evidence of the mammalian pattern within Therocephalia and nonmammalian Cynodontia, the synapsids most closely related to mammals. This suggests that the mammalian allometric pattern arose somewhere within Mammaliaformes, rather than within nonmammalian synapsids. Further investigation using an ontogenetic series of the anomodont Diictodon feliceps shows that the pattern of interspecific allometry within anomodonts parallels the ontogenetic trajectory of Diictodon. This indicates that in at least some synapsids, allometric patterns associated with ontogeny may provide a “path of least resistance” for interspecific variation, a mechanism that we suggest produces the interspecific allometric pattern observed in mammals.
The complete chloroplast genome characterization and phylogenetic analysis of Canarium album

Abstract Canarium album is one of the precious and characteristic fruit trees of China. In this study, we first presented the complete chloroplast genome of C. album by using BGISEQ-500 sequencing. Its complete chloroplast genome is 163,140 bp in size, containing a pair of inverted repeat regions of 30,729 bp, a large single copy region of 87,748 bp and a small single copy region of 13,934 bp. The chloroplast genome contains 117 unique genes, including 83 protein coding genes, 30 tRNA and 4 rRNA genes. Phylogenetic analysis based on complete chloroplast genomes indicated that C. album was closest to Boswellia sacra.
Crumbs organizes the transport machinery by regulating apical levels of PI(4,5)P2 in Drosophila

An efficient vectorial intracellular transport machinery depends on a well-established apico-basal polarity and is a prerequisite for the function of secretory epithelia. Despite extensive knowledge on individual trafficking pathways, little is known about the mechanisms coordinating their temporal and spatial regulation. Here, we report that the polarity protein Crumbs is essential for apical plasma membrane phospholipid-homeostasis and efficient apical secretion. Through recruiting βHeavy-Spectrin and MyosinV to the apical membrane, Crumbs maintains the Rab6-, Rab11- and Rab30-dependent trafficking and regulates the lipid phosphatases Pten and Ocrl. Crumbs knock-down results in increased apical levels of PI(4,5)P2 and formation of a novel, Moesin- and PI(4,5)P2-enriched apical membrane sac containing microvilli-like structures. Our results identify Crumbs as an essential hub required to maintain the organization of the apical membrane and the physiological activity of the larval salivary gland.
A Survey of Virginia Vineyards Revealed High Incidences of Grapevine Rupestris Stem Pitting-Associated Virus, Grapevine Red Blotch Virus, and Two Mealybug Species

We investigated the prevalence of viruses infecting grapevines in Virginia, identity of disease vectors, and potential factors affecting virus incidence. Tested viruses were grapevine leafroll-associated virus (GLRaV-1 and -4), grapevine fleck virus (GFkV), grapevine virus A (GVA), grapevine virus B (GVB), grapevine rupestris stem pitting-associated virus (GRSPaV), tomato ringspot virus (ToRSV), grapevine vein clearing virus (GVCV), grapevine red blotch virus (GRBV), and grapevine Pinot gris virus (GPGV). We documented wide distributions of GRSPaV (54%) and GRBV (24%) and common occurrences of grape (Pseudococcus maritimus) and Gill’s (Ferrisia gilli) mealybugs among vineyards. This is the first report of GLRaV-1, GLRaV-4, GVA, GVB, GRSPaV, and obscure mealybug (Pseudococcus viburni) in Virginia. We also documented significant association (P ≤ 0.05) of the presence of mealybugs and GVA and GVB. With younger vines, significantly lower incidences were found for viruses that were listed (i.e., tested for a certification) by the Foundation Planting Service’s and the National Clean Plant Network’s grape programs. On the other hand, there was a lack of the age effect on incidence of GRSPaV and GRBV, which were not listed until recently. These results suggest the importance of clean plant material and vector management for grapevine virus disease management in Virginia.