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To evaluate the expression of core molecular clock genes/proteins in penile cavernous tissue from healthy male subjects and to determine whether their expression has circadian variation. Corpus cavernosum biopsy samples were obtained from 10 healthy males with penile deviation or fracture who underwent surgical intervention during the day and night. The daytime group (n=5) underwent corpus cavernosum tissue sampling during zeitgeber time (ZT) 8-12, while the nighttime group (n=5) underwent sampling during ZT 20-24. The expression and localization of BMAL1, CLOCK, PER1, PER2, PER3, CRY1, and CRY2 proteins were analyzed using immunohistochemistry and quantified using H-score analysis. RT-qPCR analysis was performed to assess the expression of core molecular clock genes in the corpus cavernosum tissue of 5 additional daytime patients. The expression of core molecular clock proteins was detected in vascular endothelial cells (VECs) and smooth muscle cells (SMCs) in corpus cavernosum during daytime and nighttime. BMAL1 exhibited the most significant nuclear expression during daytime in both cell types, whereas its expression decreased significantly at night. In VECs, a significant decrease in the nuclear expression of CRY1 was observed at night. In SMCs, a significant decrease in the cytoplasmic expression of PER3 was observed at night. The expression patterns of the core molecular clock genes were ascertained through a RT-qPCR analysis. Our research provides compelling evidence that core molecular clock genes are distinctly expressed in penile tissue in humans. Furthermore, we observed the expression of molecular clock proteins within the VECs and SMCs of the corpus cavernosum, with BMAL1 being the most prominently expressed. The discovery of core molecular clock genes in penile tissue, as well as proteins within the SMCs and VECs of the corpus cavernosum, introduces the potential significance of the molecular clock mechanism in the physiology of penile erection.

Aim: Niche theory proposes that increases in species richness along an environmental gradient are associated with a packing of species inside the niche space or an expansion of the niche space. We test whether and under what conditions an increase in bird species richness along a gradient of resource availability is associated with an expansion or packing of the niche as measured based on traits related to resource use. Location: Global. Time period: Current. Major taxa studied: Birds. Methods: We measured birds’ realized niche space as the standardized departure between observed total trait range and its null expectation (functional richness: SES.FRic) in 12,188 cells worldwide. We first correlated both species richness and this measurement along the global net primary productivity (NPP) gradient using linear regressions. Second, we investigated the nonstationarity of the species richness–NPP relationship with Lee’s bivariate correlation, a measure of the spatial association of two variables. We then assessed the number of cells exhibiting a significant positive species richness–NPP association and a significant negative or positive SES.FRic. Third, we assessed whether species of species-rich assemblages occur within or outside the niche space of species-poor assemblages. Results: At a global scale, we found that species richness and SES.FRic increased with NPP. We also showed that cells with a significant positive association between species richness and NPP exhibited niche packing (1,699 assemblages out of 12,188) more than niche expansion (five assemblages). Niche packing was associated with complex biomes such as tropical rain forests. Finally, by showing that species in species-rich assemblages predominantly occur within the niche space of species-poor assemblages, we showed that the increase in SES.FRic with NPP contributed little to the increase in species richness. Main conclusion: Although niche volume increases with species richness along an NPP gradient, we confirmed that niche packing is the pattern most associated with the species richness–NPP relationship at a global scale.

Aim: To assess contemporary and historical determinants of taxonomic and ecological trait turnover in birds worldwide. We tested whether taxonomic and trait turnover (1) are structured by regional bioclimatic conditions, (2) increase in relationship with topographic heterogeneity and environmental turnover and change according to current and historical environmental conditions, and (3) decrease with human impact. Major Taxa: Birds. Location: Global. Methods: We used computationally efficient algorithms to map the taxonomic and trait turnover of 8,040 terrestrial bird assemblages worldwide, based on a grid with 110 km 3 110 km resolution overlaid on the extent-of-occurrence maps of 7,964 bird species, and nine ecological traits reflecting six key aspects of bird ecology (diet, habitat use, thermal preference, migration, dispersal and body size). We used quantile regression and model selection to quantify the influence of biomes, environment (temperature, precipitation, altitudinal range, net primary productivity, Quaternary temperature and precipitation change) and human impact (human influence index) on bird turnover. Results: Bird taxonomic and trait turnover were highest in the north African deserts and boreal biomes. In the tropics, taxonomic turnover tended to be higher, but trait turnover was lower than in other biomes. Taxonomic and trait turnover exhibited markedly different or even opposing relationships with climatic and topographic gradients, but at their upper quantiles both types of turnover decreased with increasing human influence. Main conclusions: The influence of regional, environmental and anthropogenic factors differ between bird taxonomic and trait turnover, consistent with an imprint of niche conservatism, environmental filtering and topographic barriers on bird regional assemblages. Human influence on these patterns is pervasive and demonstrates global biotic homogenization at a macroecological scale. K E Y W O R D S Anthropocene, beta diversity, biogeographical legacies, biotic homogenization, functional diversity, life-history traits, regional assemblages 1190 |

Polysaccharide utilization loci (PUL) within the genomes of resident human gut Bacteroidetes are central to the metabolism of the otherwise indigestible complex carbohydrates known as \"dietary fiber.\" However, functional characterization of PUL lags significantly behind sequencing efforts, which limits physiological understanding of the human-bacterial symbiosis. In particular, the molecular basis of complex polysaccharide recognition, an essential prerequisite to hydrolysis by cell surface glycosidases and subsequent metabolism, is generally poorly understood. Here, we present the biochemical, structural, and reverse genetic characterization of two unique cell surface glycan-binding proteins (SGBPs) encoded by a xyloglucan utilization locus (XyGUL) from Bacteroides ovatus, which are integral to growth on this key dietary vegetable polysaccharide. Biochemical analysis reveals that these outer membrane-anchored proteins are in fact exquisitely specific for the highly branched xyloglucan (XyG) polysaccharide. The crystal structure of SGBP-A, a SusD homolog, with a bound XyG tetradecasaccharide reveals an extended carbohydrate-binding platform that primarily relies on recognition of the beta-glucan backbone. The unique, tetra-modular structure of SGBP-B is comprised of tandem Ig-like folds, with XyG binding mediated at the distal C-terminal domain. Despite displaying similar affinities for XyG, reverse-genetic analysis reveals that SGBP-B is only required for the efficient capture of smaller oligosaccharides, whereas the presence of SGBP-A is more critical than its carbohydrate-binding ability for growth on XyG. Together, these data demonstrate that SGBP-A and SGBP-B play complementary, specialized roles in carbohydrate capture by B. ovatus and elaborate a model of how vegetable xyloglucans are accessed by the Bacteroidetes. IMPORTANCE The Bacteroidetes are dominant bacteria in the human gut that are responsible for the digestion of the complex polysaccharides that constitute \"dietary fiber.\" Although this symbiotic relationship has been appreciated for decades, little is currently known about how Bacteroidetes seek out and bind plant cell wall polysaccharides as a necessary first step in their metabolism. Here, we provide the first biochemical, crystallographic, and genetic insight into how two surface glycan-binding proteins from the complex Bacteroides ovatus xyloglucan utilization locus (XyGUL) enable recognition and uptake of this ubiquitous vegetable polysaccharide. Our combined analysis illuminates new fundamental aspects of complex polysaccharide recognition, cleavage, and import at the Bacteroidetes cell surface that may facilitate the development of prebiotics to target this phylum of gut bacteria.

The administration of modified immune cells (MIC) before kidney transplantation led to specific immunosuppression against the allogeneic donor and a significant increase in regulatory B lymphocytes. We wondered how this approach affected the continued clinical course of these patients. Ten patients from a phase I clinical trial who had received MIC infusions prior to kidney transplantation were retrospectively compared to 15 matched standard-risk recipients. Follow-up was until year five after surgery. The 10 MIC patients had an excellent clinical course with stable kidney graft function, no donor-specific human leukocyte antigen antibodies (DSA) or acute rejections, and no opportunistic infections. In comparison, a retrospectively matched control group receiving standard immunosuppressive therapy had a higher frequency of DSA (log rank = 0.046) and more opportunistic infections (log rank = 0.033). Importantly, MIC patients, and in particular the four patients who had received the highest cell number 7 days before surgery and received low immunosuppression during follow-up, continued to show a lack of anti-donor T lymphocyte reactivity and high CD19 CD24 CD38 transitional and CD19 CD24 CD27 memory B lymphocytes until year five after surgery. MIC infusions together with reduced conventional immunosuppression were associated with good graft function during five years of follow-up, no DSA development and no opportunistic infections. In the future, MIC infusions might contribute to graft protection while reducing the side effects of immunosuppressive therapy. However, this approach needs further validation in direct comparison with prospective controls. https://clinicaltrials.gov/, identifier NCT02560220 (for the TOL-1 Study). EudraCT Number: 2014-002086-30.

Alien species can be damaging to native biodiversity, human well‐being and the economy. Identifying the complete range of impacts they cause, and the ways that these impacts are connected, may inform the prioritisation of management actions to mitigate impacts. Using datasets on the biodiversity impacts and monetary costs (damage and management costs) of alien birds, we aimed to establish whether species with the most severe biodiversity impacts also had the highest costs; whether types of biodiversity impact were associated with high costs; and whether specific factors associated with alien species are linked to both damaging biodiversity impacts and high costs. We identified a positive relationship between a specific type of biodiversity impact (predation) and costs, possibly because predation by alien birds can be severely damaging to native species and therefore attracts management actions. However, predation impacts are likely to occur more frequently and to be easier to identify than some other impact mechanisms such as hybridisation and transmission of diseases, and they are therefore likely to be more frequently managed and hence to have costs. We identified a specific species characteristic (generalism) to be associated with severe biodiversity impacts and high costs, probably because generalist species have greater opportunity to cause impacts, whether they be on biodiversity or the economy, or both. We also found widely distributed alien birds to be associated with high costs, probably because these species also have greater opportunity to cause impacts. Management interventions that prevent the introduction of both predatory and generalist alien bird species, or that reduce their geographic distribution at early stages of invasions, may have significant biodiversity and economic benefits. Read the free Plain Language Summary for this article on the Journal blog. Les espèces exotiques envahissantes peuvent nuire à la biodiversité indigène, au bien‐être des humains et à l'économie. L'identification de l'ensemble des impacts qu'elles provoquent et de la manière dont ces impacts sont liés peut permettre de hiérarchiser les mesures de gestion visant à atténuer ces impacts. En utilisant des ensembles de données sur les impacts sur la biodiversité et les coûts monétaires (dommages et coûts de gestion) des oiseaux exotiques, nous avons cherché à établir si les espèces ayant les impacts les plus importants sur la biodiversité avaient également les coûts les plus élevés ; si certains types d'impacts étaient associés à des coûts élevés ; et si des facteurs spécifiques associés aux espèces exotiques étaient liés à la fois à des dommages sur la biodiversité et à des coûts élevés. Nous avons identifié une relation positive entre un type spécifique d'impact sur la biodiversité (la prédation) et les coûts, peut‐être parce que la prédation par les oiseaux exotiques peut être très préjudiciable aux espèces indigènes et nécessite donc des mesures de gestion. Cependant, les impacts de la prédation sont susceptibles de se produire plus fréquemment et d'être plus faciles à identifier que d'autres mécanismes d'impact tels que l'hybridation et la transmission de maladies, et ils sont donc susceptibles d'être gérés plus fréquemment, et donc d'entraîner des coûts. Nous avons identifié une caractéristique spécifique des espèces (le généralisme) comme étant associée à des impacts forts sur la biodiversité et à des coûts élevés, probablement parce que les espèces généralistes ont plus de possibilités de causer des impacts, que ce soit sur la biodiversité ou sur l'économie, ou sur les deux. Nous avons également constaté que les oiseaux exotiques largement répandus étaient associés à des coûts élevés, probablement aussi parce que ces espèces ont plus de chances d'avoir un impact. Les interventions de gestion qui peuvent avoir les plus forts avantages en termes de biodiversité et d'économie sont ceux qui préviennent l'introduction d'espèces d'oiseaux exotiques prédatrices et généralistes, ou qui réduisent leur distribution géographique aux premiers stades des invasions. Read the free Plain Language Summary for this article on the Journal blog.

We show that if Σ is an embedded least area (area minimizing) plane in ℍ3 whose asymptotic boundary is a simple closed curve with at least one smooth point, then Σ is properly embedded in ℍ3.

Background The increasing interest in camel milk (CM) worldwide in recent years has increased the need for studies on the properties of CM, which is relatively less studied than other species. Objective The objective of this study was to determine the effects of changes in farm management on daily milk yield (DMY), milk composition and microbiological quality of CM. Methods Yearly changes in milk fat (MFC), protein (MPC), ash (MAC), totals solid (TSC) contents, total bacteria (TBC), coliform (CC), yeast and mould (YMC), somatic cell (SCC) counts and fatty acid profile of CM were determined by monthly taken milk samples and analyses. Results The means of DMY, MFC, MPC, MAC, TSC, TBC, CC, YMC and SCC of milk were 3.53 ± 0.290 kg, 3.80% ± 0.285%, 4.36% ± 0.212%, 0.81% ± 0.013%, 11.95% ± 0.380%, 7.24 × 10 5 cfu/mL, 1.31 × 10 5 cfu/mL, 912 cfu/mL and 2.45 × 10 5 cells/mL, respectively. The effect of the changes (Year 2 vs. Year 1) was statistically significant for MFC, MPC, TSC and Log 10 TBC ( p < 0.05), and significant effects of lactation stage were determined for DMY, MFC, MAC, TSC, Log 10 TBC and Log 10 YMC ( p < 0.05). The highest fatty acid (FA) amount in CM was found for palmitic (C16:0), oleic (C18:1 n 9c), stearic (C18:0), myristic (C14:0) and palmitoleic (C16:1) acids with the concentrations of 31.59% ± 0.45%, 21.88% ± 0.81%, 13.43% ± 0.67%, 12.22% ± 0.26% and 12.18% ± 0.34% of fat, respectively. The correlation coefficients of MFC, MPC and TSC with SCFA and MCFA were moderate and negative but with long chain Fas (LCFA) were positive and moderate. Log 10 SCC was also negatively correlated with total polyunsaturated FAs (PUFA) (−0.414; p < 0.05), SCFA (−0.475; p < 0.01), MCFA (−0.573; p < 0.01) and positively correlated with LCFA (0.588; p < 0.01). Conclusion Although management causes significant changes in composition, TBC and FA profile, CM has high UFA, low SCFA, high LCFA and better atherogenic index (AI). The high microbiological level at the beginning and middle of lactation and the negative correlation of these traits with milk components reveal that various measures should be taken to improve hygienic conditions to process CM into quality products.

Phages play key roles in the pathogenicity and adaptation of the human pathogen Staphylococcus aureus. However, little is known about the molecular recognition events that mediate phage adsorption to the surface of S. aureus. The lysogenic siphophage ϕ11 infects S. aureus SA113. It was shown previously that ϕ11 requires α- or β-N-acetylglucosamine (GlcNAc) moieties on cell wall teichoic acid (WTA) for adsorption. Gp45 was identified as the receptor binding protein (RBP) involved in this process and GlcNAc residues on WTA were found to be the key component of the ϕ11 receptor. Here we report the crystal structure of the RBP of ϕ11, which assembles into a large, multidomain homotrimer. Each monomer contains a five-bladed propeller domain with a cavity that could accommodate a GlcNAc moiety. An electron microscopy reconstruction of the ϕ11 host adhesion component, the baseplate, reveals that six RBP trimers are assembled around the baseplate core. The Gp45 and baseplate structures provide insights into the overall organization and molecular recognition process of the phage ϕ11 tail. This assembly is conserved among most glycan-recognizing Siphoviridae, and the RBP orientation would allow host adhesion and infection without an activation step.

The present study was designed to investigate and compare the effects of dietary selenium (Se) and vitamin E on some physiological parameters and histological changes in liver, heart, and skin tissues, as well as the blood parameters and the related enzymes. Both sex young rabbits were fed with deficient (9.8 micrograms/kg diet), adequate (225 micrograms/kg diet), and rich (4.2 mg/kg diet) Se and vitamin E diets for 12-15 wk for this purpose. As the plasma Se levels and the erythrocyte glutathione (GSH) peroxidase activity decreased (79.8 +/- 9.4 ng/mL and 2.0 +/- 0.3 U/g Hb, respectively) in the deficient group, these values increased (100.4 +/- 2.7 ng/mL and 14.5 +/- 4.3 U/g Hb) in the rich group significantly with respect to the control group. The other antioxidant enzyme activities and the related element levels did not change significantly in either one of the experimental groups. Although the platelet counts of the two experimental groups were not different from the control values, the collagen and the adenosine diphosphate (ADP) stimulated platelet aggregation rate and intensity increased in the deficient group (p < 0.05) and decreased very significantly (p < 0.001) in the rich group. In both of the experimental groups, as the percentage values of the neutrophils decreased, the lymphocytes and the eosinophils increased significantly. According to the light microscopic investigations, the observed lesions of considerable intensity within the tissues that elicit cell degenerations were more pronounced in the animals fed with the rich diet than in those fed with the deficient diet. The deficiency as well as toxicity of Se and the deficiency of vitamin E caused several alterations in the physiological functions of the tissues, and these alterations were supported by the histological lesions within these tissues.