Grape-associated fungal community patterns persist from berry to wine on a fine geographical scale.

Wine grape fungal community composition is influenced by abiotic factors including geography and vintage. Compositional differences may correlate with different wine metabolite composition and sensory profiles, suggesting a microbial role in the shaping of a wine's terroir, or regional character. While grape and wine-associated fungal community composition has been studied extensively at a regional and sub-regional scale, it has not been explored in detail on fine geographical scales over multiple harvests. Over two years, we examined the fungal communities on Vitis Vinifera cv. Pinot noir grape berry surfaces, in crushed grapes, and in lab spontaneous fermentations from three vineyards within a < 1 km radius in Canada's Okanagan Valley wine region. We also evaluated the effect of winery environment exposure on fungal community composition by sampling grapes crushed and fermented in the winery at commercial scale. Spatiotemporal community structure was evident among grape berry surface, crushed grape and fermentation samples, with each vineyard exhibiting a distinct fungal community signature. Crushed grape fungal populations were richer in fermentative yeast species compared to grape berry surface fungal populations. Our study suggests that, as on a regional level, fungal populations may contribute to fine-scale -terroir,' with significant implications for single-vineyard wines.

Skeletal muscle metabolism and contraction performance regulation by teneurin C-terminal-associated peptide-1.

Skeletal muscle regulation is responsible for voluntary muscular movement in vertebrates. The genes of two essential proteins, teneurins and latrophilins (LPHN), evolving in ancestors of multicellular animals form a ligand-receptor pair, and are now shown to be required for skeletal muscle function. Teneurins possess a bioactive peptide, termed the teneurin C-terminal associated peptide (TCAP) that interacts with the LPHNs to regulate skeletal muscle contractility strength and fatigue by an insulin-independent glucose importation mechanism in rats. CRISPR-based knockouts and siRNA-associated knockdowns of LPHN-1 and-3 in the C2C12 mouse skeletal cell line shows that TCAP stimulates an LPHN-dependent cytosolic Ca2+ signal transduction cascade to increase energy metabolism and enhance skeletal muscle function via increases in type-1 oxidative fiber formation and reduce the fatigue response. Thus, the teneurin/TCAP-LPHN system is presented as a novel mechanism that regulates the energy requirements and performance of skeletal muscle.

Antimicrobial resistance in dairy slurry tanks: A critical point for measurement and control.

Waste from dairy production is one of the largest sources of contamination from antimicrobial resistant bacteria (ARB) and genes (ARGs) in many parts of the world. However, studies to date do not provide necessary evidence to inform antimicrobial resistance (AMR) countermeasures. We undertook a detailed, interdisciplinary, longitudinal analysis of dairy slurry waste. The slurry contained a population of ARB and ARGs, with resistances to current, historical and never-used on-farm antibiotics; resistances were associated with Gram-negative and Gram-positive bacteria and mobile elements (ISEcp1, Tn916, Tn21-family transposons). Modelling and experimental work suggested that these populations are in dynamic equilibrium, with microbial death balanced by fresh input. Consequently, storing slurry without further waste input for at least 60 days was predicted to reduce ARB spread onto land, with > 99 % reduction in cephalosporin resistant Escherichia coli. The model also indicated that for farms with low antibiotic use, further reductions are unlikely to reduce AMR further. We conclude that the slurry tank is a critical point for measurement and control of AMR, and that actions to limit the spread of AMR from dairy waste should combine responsible antibiotic use, including low total quantity, avoidance of human critical antibiotics, and choosing antibiotics with shorter half-lives, coupled with appropriate slurry storage.

Role of Teneurin C-Terminal Associated Peptides (TCAP) on Intercellular Adhesion and Communication.

The teneurin C-terminal associated peptides (TCAP) are encoded by the terminal exon of all metazoan teneurin genes. Evidence supports the liberation of a soluble TCAP peptide either by proteolytic cleavage from the mature transmembrane teneurin protein or by a separately transcribed mRNA. Synthetic versions of TCAP, based on its genomic structure, are efficacious at regulating intercellular communication by promoting neurite outgrowth and increasing dendritic spine density in vitro and in vivo in rodent models. This is achieved through cytoskeletal re-arrangement and metabolic upregulation. The putative receptors for TCAPs are the latrophilin (LPHN) family of adhesion G-protein coupled receptors, which facilitate TCAP's actions through G-proteins associated with cAMP and calcium-regulating signalling pathways. The teneurin/TCAP and latrophilin genes are phylogenetically ancient, likely serving primitive functions in cell adhesion and energy regulation which have been since adapted for a more complex role in synaptogenesis in vertebrate nervous systems.

Synthetic Peptides as Therapeutic Agents: Lessons Learned From Evolutionary Ancient Peptides and Their Transit Across Blood-Brain Barriers.

Peptides play a major role in the transmission of information to and from the central nervous system. However, because of their structural complexity, the development of pharmacological peptide-based therapeutics has been challenged by the lack of understanding of endogenous peptide evolution. The teneurin C-terminal associated peptides (TCAP) possess many of the required attributes of a practical peptide therapeutic. TCAPs, associated with the teneurin transmembrane proteins that bind to the latrophilins, members of the Adhesion family of G-protein-coupled receptors (GPCR). Together, this ligand-receptor unit plays an integral role in synaptogenesis, neurological development, and maintenance, and is present in most metazoans. TCAP has structural similarity to corticotropin-releasing factor (CRF), and related peptides, such as calcitonin and the secretin-based peptides and inhibits the (CRF)-associated stress response. Latrophilins are structurally related to the secretin family of GPCRs. TCAP is a soluble peptide that crosses the blood-brain barrier and regulates glucose transport into the brain. We posit that TCAP represents a phylogenetically older peptide system that evolved before the origin of the CRF-calcitonin-secretin clade of peptides and plays a fundamental role in the regulation of cell-to-cell energy homeostasis. Moreover, it may act as a phylogenetically older peptide system that evolved as a natural antagonist to the CRF-mediated stress response. Thus, TCAP's actions on the CNS may provide new insights into the development of peptide therapeutics for the treatment of CNS disorders.

Activity of the Carboxy-Terminal Peptide Region of the Teneurins and Its Role in Neuronal Function and Behavior in Mammals.

Teneurin C-terminal associated peptides (TCAPs) are an evolutionarily ancient family of 40- to 41-residue bioactive peptides located on the extracellular end of each of the four teneurin transmembrane proteins. TCAP-1 may exist as a tethered peptide at the teneurin-1 carboxy end or as an independent peptide that is either released via post-transcriptional cleavage from its teneurin-1 pro-protein or independently expressed as its own mRNA. In neurons, soluble TCAP-1 acts as a paracrine factor to regulate cellular activity and neuroplastic interactions. In vitro studies indicate that, by itself, synthetic TCAP-1 promotes neuron growth and protects cells from chemical insult. In vivo, TCAP-1 increases hippocampal neuron spine density, reduces stress-induced behavior and ablates cocaine-seeking behaviors. Together, these studies suggest that the physiological effects of TCAP-1 are a result of an inhibition of corticotropin-releasing factor (CRF) activity leading to increased energy production. This hypothesis is supported by in vivo functional positron emissions tomography studies, which demonstrate that TCAP-1 significantly increases glucose uptake in rat brain. Complimentary in vitro studies show that enhanced glucose uptake is the result of TCAP-1-induced insertion of the glucose transporter into the neuronal plasma membrane, leading to increased glucose uptake and ATP production. Interestingly, TCAP-1-mediated glucose uptake occurs through a novel insulin-independent pathway. This review will focus on examining the role of TCAP on neuronal energy metabolism in the central nervous system.

A systematic review of the effects of CYP2D6 phenotypes on risperidone treatment in children and adolescents.

The second generation antipsychotic drug risperidone is widely used in the field of child and adolescent psychiatry to treat conditions associated with disruptive behavior, aggression and irritability, such as autism spectrum disorders. While risperidone can provide symptomatic relief for many patients, there is considerable individual variability in the therapeutic response and side-effect profile of the medication. One well established biological factor that contributes to these individual differences is genetic variation in the cytochrome P450 enzyme 2D6. The 2D6 enzyme metabolizes risperidone and therefore affects drug levels and dosing. In the present review, we summarize the current literature on 2D6 variants and their effects on risperidone responses, specifically in children and adolescents. Relevant articles were identified through systematic review, and after irrelevant articles were discarded, ten studies were included in the review. Most prospective studies were well controlled, but often did not have a large enough sample size to make robust statements about rarer variants, including those categorized as ultra-rapid and poor metabolizers. Individual studies demonstrated a role for different genetic variants in risperidone drug efficacy, pharmacokinetics, hyperprolactinemia, weight gain, extrapyramidal symptoms and drug-drug interactions. Where studies overlapped in measurements, there was typically a consensus between results. These findings indicate that the value of 2D6 genotyping in the youth population treated with risperidone requires further study, in particular with the less common variants.