Hanleylohse1104

Across human cultures, conversations are regulated by temporal and social rules. The universality of conversational rules suggests possible biological bases and encourages comparisons with the communicative interactions of nonhuman animals. Unexpectedly, few studies have focused on other great apes despite evidence of proto-conversational rules in monkeys, thus preventing researchers from drawing conclusions on potential evolutionary origins of this behaviour. A previous study showed however that western lowland gorillas engage in soft call interactions that seem temporally- and socially-ruled. Indeed, interactions occurred mainly between individuals close in age who followed a preset response delay, thus preventing call overlap. Here, we experimentally investigated the presence of these rules in a captive gorilla group, using a violation-of-expectation paradigm. Head orientation responses suggest that the respect of response delay matters to subjects, but the importance of the interlocutors' age proximity appeared less clear. The intensity of the response varied with subjects' age in a context-dependent way, supporting a possible role of learning. Our findings support the growing number of studies highlighting the importance of vocal turn-taking in animals and a possible sociogenesis of this ability. The capacity to "converse" might have been a key step in the co-evolution of communication and complex sociality.Although the fighting behaviour in gamecocks has evolved because of artificial selection, it is unknown whether the selection for aggressiveness affects neurotransmitter levels in the avian central nervous system. We sought to identify the source and origin of this trait. We collected the brain samples from 6 female Shamo gamecocks and 5 Shaver Brown chickens (control; bred for egg production). The midbrain levels of norepinephrine (NE) were significantly higher in Shamo gamecocks (P = 0.0087) than in the controls. Moreover, alleles encoding adrenergic receptors differed between the breeds in terms of response to NE. Gene mutations specific to Shamo and potentially associated with fighting behaviour were in sites T440N of ADRα1D; V296I of ADRα2A; and T44I, Q232R, and T277M of ADRβ2. The evolutionary analysis indicated that the ADRβ2 (T44I and Q232R) mutations were heritable in all Galliformes, whereas the T440N mutation of ADRα1D and V296I mutations of ADRα2A were unique to Shamo and originated by artificial selection. A high NE level may confer a selective advantage by enabling gamecocks to be aggressive and pain tolerant. Therefore, the strong fighting behaviour of Shamo has resulted from a combination of naturally inherited and mutant genes derived by artificial selection.Three-dimensional (3D) in vitro models of human skeletal muscle mimic aspects of native tissue structure and function, thereby providing a promising system for disease modeling, drug discovery or pre-clinical validation, and toxicity testing. Widespread adoption of this research approach is hindered by the lack of easy-to-use platforms that are simple to fabricate and that yield arrays of human skeletal muscle micro-tissues (hMMTs) in culture with reproducible physiological responses that can be assayed non-invasively. Here, we describe a design and methods to generate a reusable mold to fabricate a 96-well platform, referred to as MyoTACTIC, that enables bulk production of 3D hMMTs. All 96-wells and all well features are cast in a single step from the reusable mold. Non-invasive calcium transient and contractile force measurements are performed on hMMTs directly in MyoTACTIC, and unbiased force analysis occurs by a custom automated algorithm, allowing for longitudinal studies of function. Characterizations of MyoTACTIC and resulting hMMTs confirms the capability of the device to support formation of hMMTs that recapitulate biological responses. We show that hMMT contractile force mirrors expected responses to compounds shown by others to decrease (dexamethasone, cerivastatin) or increase (IGF-1) skeletal muscle strength. Since MyoTACTIC supports hMMT long-term culture, we evaluated direct influences of pancreatic cancer chemotherapeutics agents on contraction competent human skeletal muscle myotubes. A single application of a clinically relevant dose of Irinotecan decreased hMMT contractile force generation, while clear effects on myotube atrophy were observed histologically only at a higher dose. This suggests an off-target effect that may contribute to cancer associated muscle wasting, and highlights the value of the MyoTACTIC platform to non-invasively predict modulators of human skeletal muscle function.Feather waste is the highest protein-containing resource in nature and is poorly reused. Bioconversion is widely accepted as a low-cost and environmentally benign process, but limited by the availability of safe and highly efficient feather degrading bacteria (FDB) for its industrial-scale fermentation. Excessive focuses on keratinase and limited knowledge of other factors have hindered complete understanding of the mechanisms employed by FDB to utilize feathers and feather cycling in the biosphere. Streptomyces sp. SCUT-3 can efficiently degrade feather to products with high amino acid content, useful as a nutrition source for animals, plants and microorganisms. Using multiple omics and other techniques, we reveal how SCUT-3 turns on its feather utilization machinery, including its colonization, reducing agent and protease secretion, peptide/amino acid importation and metabolism, oxygen consumption and iron uptake, spore formation and resuscitation, and so on. This study would shed light on the feather utilization mechanisms of FDBs.Treatment paradigms for patients with upper tract urothelial carcinoma (UTUC) are typically extrapolated from studies of bladder cancer despite their distinct clinical and molecular characteristics. The advancement of UTUC research is hampered by the lack of disease-specific models. Here, we report the establishment of patient derived xenograft (PDX) and cell line models that reflect the genomic and biological heterogeneity of the human disease. Models demonstrate high genomic concordance with the corresponding patient tumors, with invasive tumors more likely to successfully engraft. Treatment of PDX models with chemotherapy recapitulates responses observed in patients. Analysis of a HER2 S310F-mutant PDX suggests that an antibody drug conjugate targeting HER2 would have superior efficacy versus selective HER2 kinase inhibitors. In sum, the biological and phenotypic concordance between patient and PDXs suggest that these models could facilitate studies of intrinsic and acquired resistance and the development of personalized medicine strategies for UTUC patients.Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); however, causal inference remains uncertain. Oxyphenisatin price Here, we use bacterial DNA sequencing from serially collected vaginal samples from a cohort of 87 adolescent and young women aged 16-26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus-dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies.The naked mole-rat is a subterranean rodent, approximately the size of a mouse, renowned for its exceptional longevity (>30 years) and remarkable resistance to cancer. To explore putative mechanisms underlying the cancer resistance of the naked mole-rat, we investigated the regulation and function of the most commonly mutated tumor suppressor, TP53, in the naked mole-rat. We found that the p53 protein in naked mole-rat embryonic fibroblasts (NEFs) exhibits a half-life more than ten times in excess of the protein's characterized half-life in mouse and human embryonic fibroblasts. We determined that the long half-life of the naked mole-rat p53 protein reflects protein-extrinsic regulation. Relative to mouse and human p53, a larger proportion of naked mole-rat p53 protein is constitutively localized in the nucleus prior to DNA damage. Nevertheless, DNA damage is sufficient to induce activation of canonical p53 target genes in NEFs. Despite the uniquely long half-life and unprecedented basal nuclear localization of p53 in NEFs, naked mole-rat p53 retains its canonical tumor suppressive activity. Together, these findings suggest that the unique stabilization and regulation of the p53 protein may contribute to the naked mole-rat's remarkable resistance to cancer.The diagnostic procedure for upper aerodigestive tract (UADT) tumours is by white light endoscopy (WLE) combined with biopsy. However, WLE has difficulty identifying minute epithelial changes which hinders early diagnosis. Storz Professional Image Enhancement System (SPIES) is designed to enhance the visualization of microvasculature on the mucosal surface and detect any epithelial changes. In this study, we aimed to evaluate the use of Ni endoscopic classification with SPIES endoscopy in the detection of UADT tumours. Fifty-nine patients with suspected UADT tumours underwent WLE followed by SPIES endoscopy. All the tumours were biopsied and sent for histopathological examination (HPE). The kappa index (κ) was used to evaluate the agreement between the methods. The level of agreement between SPIES using Ni classification and HPE showed almost perfect agreement as compared to moderate agreement between WLE and HPE. The sensitivity and specificity for WLE and HPE were 77.5% and 84.2% respectively with positive predictive value (PPV) of 91.2% and negative predictive value (NPV) of 64%. The sensitivity and specificity for SPIES endoscopy using Ni classification and HPE were 97.5% and 94.7% respectively with PPV of 97.5% and NPV of 94.7%. SPIES endoscopy using Ni classification is a valid tool for earlier tumour detection.In contrast to the vast majority of reptiles, the skulls of adult crown birds are characterized by a high degree of integration due to bone fusion, e.g., an ontogenetic event generating a net reduction in the number of bones. To understand this process in an evolutionary context, we investigate postnatal ontogenetic changes in the skulls of crown bird and non-avian theropods using anatomical network analysis (AnNA). Due to the greater number of bones and bone contacts, early juvenile crown birds have less integrated skulls, resembling their non-avian theropod ancestors, including Archaeopteryx lithographica and Ichthyornis dispars. Phylogenetic comparisons indicate that skull bone fusion and the resulting modular integration represent a peramorphosis (developmental exaggeration of the ancestral adult trait) that evolved late during avialan evolution, at the origin of crown-birds. Succeeding the general paedomorphic shape trend, the occurrence of an additional peramorphosis reflects the mosaic complexity of the avian skull evolution.