Effects of linseed oil supplementation in Holstein dairy calves received starters based on either corn or barley grain on growth performance and immune response.

This study evaluated the effects of linseed oil (LO) and two-grain sources on growth performance, microbial protein yield (MPY), blood metabolites, and inflammatory markers in Holstein dairy calves. Forty-eight 3-day-old dairy calves (24 males and 24 females) with starting BW of 40.3 ± 1.6 kg were allocated in a completely randomised block design with a 2 × 2 factorial arrangement as follows; (1) Corn grain (CG) with no LO supplementation (CG-NLO), (2) CG with 2.5% LO supplementation (CG-LO), (3) Barley grain (BG) with no LO supplementation (BG-NLO), and (4) BG with 2.5% LO supplementation (BG-LO). The calves were weaned on d 59 but the study lasted for 14 days after weaning (Day 73 of experiment). The results showed that starter feed intake was influenced neither by grain source nor linseed oil. However, average daily gain, BW, hip height, and MPY were improved in calves received BG compared to CG diets. Linseed oil supplementation had no significant effects on growth performance and MPY. During preweaning period, calves fed BG-LO had the greatest feed efficiency and the highest wither height. However, the greatest tumour necrosis factor and serum amyloid A were observed in BG-NLO. Despite, LO supplementation did not influence growth performance of animals per se; however, it reduced circulating inflammatory markers in calves during preweaning period. Based on this study condition, BG is more favourable than CG in dairy calves from the daily gain and microbial protein synthesis perspectives, and supplementing the starters with n-3 FA can be strategy to improve immune performance of calves fed barley-based starter diets.

Fingolimod effects on the brain are mediated through biochemical modulation of bioenergetics, autophagy, and neuroinflammatory networks.

Fingolimod (FTY720) is an oral drug approved by the Food and Drug Administration (FDA) for management of multiple sclerosis (MS) symptoms, which has also shown beneficial effects against Alzheimer's (AD) and Parkinson's (PD) diseases pathologies. Although an extensive effort has been made to identify mechanisms underpinning its therapeutic effects, much remains unknown. Here, we investigated Fingolimod induced proteome changes in the cerebellum (CB) and frontal cortex (FC) regions of the brain which are known to be severely affected in MS, using a tandem mass tag (TMT) isobaric labeling-based quantitative mass-spectrometric approach to investigate the mechanism of action of Fingolimod. This study identified 6749 and 6319 proteins in CB and FC, respectively, and returned 2609 and 3086 differentially expressed proteins in mouse CB and FC, respectively, between Fingolimod treated and control groups. Subsequent bioinformatics analyses indicated a metabolic reprogramming in both brain regions of the Fingolimod treated group, where oxidative phosphorylation was upregulated while glycolysis and pentose phosphate pathway were downregulated. In addition, modulation of neuroinflammation in the Fingolimod treated group was indicated by upregulation of retrograde endocannabinoid signaling and autophagy pathways, and downregulation of neuroinflammation related pathways including neutrophil degranulation and the IL-12 mediated signaling pathway. Our findings suggest that Fingolimod may exert its protective effects on the brain by inducing metabolic reprogramming and neuroinflammation pathway modulation.

Supplementation of n-3 fatty acid and ruminal undegradable to degradable protein ratio in young lambs raised under heat condition: effects on growth performance and urinary purine derivatives.

The present study evaluated the effect of supplementation alpha-linolenic fatty acid source (ALA) with different rumen undegradable to degradable protein ratios [low ratio (LR) = 26:74; high ratio (HR) = 36:64 based on CP%] on growth performance, nutrient digestibility, fecal score, animal feeding behavior, and urinary purine derivatives (PD) in young lambs during hot season. Forty 10-day-old lambs (averaging body weight of 7.9 ± 0.8 kg) were used in a completely randomized block design with a 2 × 2 factorial arrangement as following treatments (10 lambs/treatment): (1) no n-3 FA supplementation with LR diet (NALA-LR), (2) no ALA supplementation with HR diet (NALA-HR), (3) supplementation of ALA with LR diet (ALA-LR), and (4) supplementation of ALA with HR diet (ALA-HR). Results showed that ALA supplementation slightly increased feed efficiency (FE; tendency, P = 0.076), improved fecal score (P = 0.045), and reduced rectal temperature (tendency, P = 0.064) during pre-weaning period. The HR diets improved average daily gain (ADG; P < 0.01), wither height (post-weaning; P = 0.015), and final BW (P = 0.048) compared with LR diets. The greatest ADG (pre-weaning; P = 0.012), structural growth, and the lowest urinary nitrogen exertion (P = 0.043) were found in the ALA-HR treatment. No change was found for ruminal fermentation, nutrient digestibility, and animal behavior in lambs fed different experimental treatments. In summary, results indicated that concurrent feeding of ALA and high dietary RUP:RDP ratio can be recommendable that is likely due to more efficient nitrogen utilization when young lambs are raised during hot season. HIGHLIGHTS: • The interaction of n-3 FA and nitrogen was evaluated in pre-weaning lambs raised under heat condition. • Supplementation of n-3 FA increased FE and improved fecal score in heat-exposed lambs during pre-weaning period. • The high RUP:RDP ratio improved skeletal growth during post-weaning period. • Concurrent feeding of n-3 FA and high dietary RUP:RDP ratio is recommendable in young lambs raised during hot season.

A Proteomic View of Cellular and Molecular Effects of Cannabis.

Cannabis (Cannabis sativa), popularly known as marijuana, is the most commonly used psychoactive substance and is considered illicit in most countries worldwide. However, a growing body of research has provided evidence of the therapeutic properties of chemical components of cannabis known as cannabinoids against several diseases including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease, schizophrenia and glaucoma; these have prompted changes in medicinal cannabis legislation. The relaxation of legal restrictions and increased socio-cultural acceptance has led to its increase in both medicinal and recreational usage. Several biochemically active components of cannabis have a range of effects on the biological system. There is an urgent need for more research to better understand the molecular and biochemical effects of cannabis at a cellular level, to understand fully its implications as a pharmaceutical drug. Proteomics technology is an efficient tool to rigorously elucidate the mechanistic effects of cannabis on the human body in a cell and tissue-specific manner, drawing conclusions associated with its toxicity as well as therapeutic benefits, safety and efficacy profiles. This review provides a comprehensive overview of both in vitro and in vivo proteomic studies involving the cellular and molecular effects of cannabis and cannabis-derived compounds.

Pollen development in cotton (Gossypium hirsutum) is highly sensitive to heat exposure during the tetrad stage.

The development of gametes in plants is acutely susceptible to heatwaves as brief as a few days, adversely affecting pollen maturation and reproductive success. Pollen in cotton (Gossypium hirsutum) was differentially affected when tetrad and binucleate stages were exposed to heat, revealing new insights into the interaction between heat and pollen development. Squares were tagged and exposed to 36/25°C (day/night, moderate heat) or 40/30°C (day/night, extreme heat) for 5 days. Mature pollen grains and leaves were collected for physiological and proteomic responses. While photosynthetic competence was not compromised even at 40°C, leaf tissues became leakier. In contrast, pollen grains were markedly smaller after the tetrad stage was exposed to 40°C and boll production was reduced by 65%. Sugar levels in pollen grains were elevated after exposure to heat, eliminating carbohydrate deficits as a likely cause of poor reproductive capacity. Proteomic analysis of pure pollen samples revealed a particularly high abundance of 70-kDa heat shock (Hsp70s) and cytoskeletal proteins. While short-term bursts of heat had a minor impact on leaves, male gametophyte development was profoundly damaged. Cotton acclimates to maxima of 36°C at both the vegetative and reproductive stages but 5-days exposure to 40°C significantly impairs reproductive development.

Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CLpro targeting repurposed drug candidates.

BACKGROUND: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection rate continues to grow exponentially. SARS coronavirus 2 (SARS-CoV-2) is a single stranded RNA pathogen which is characterised by a high mutation rate. It is vital to explore the mutagenic capability of the viral genome that enables SARS-CoV-2 to rapidly jump from one host immunity to another and adapt to the genetic pool of local populations. METHODS: For this study, we analysed 2301 complete viral sequences reported from SARS-CoV-2 infected patients. SARS-CoV-2 host genomes were collected from The Global Initiative on Sharing All Influenza Data (GISAID) database containing 9 genomes from pangolin-CoV origin and 3 genomes from bat-CoV origin, Wuhan SARS-CoV2 reference genome was collected from GeneBank database. The Multiple sequence alignment tool, Clustal Omega was used for genomic sequence alignment. The viral replicating enzyme, 3-chymotrypsin-like cysteine protease (3CLpro) that plays a key role in its pathogenicity was used to assess its affinity with pharmacological inhibitors and repurposed drugs such as anti-viral flavones, biflavanoids, anti-malarial drugs and vitamin supplements. RESULTS: Our results demonstrate that bat-CoV shares > 96% similar identity, while pangolin-CoV shares 85.98% identity with Wuhan SARS-CoV-2 genome. This in-depth analysis has identified 12 novel recurrent mutations in South American and African viral genomes out of which 3 were unique in South America, 4 unique in Africa and 5 were present in-patient isolates from both populations. Using state of the art in silico approaches, this study further investigates the interaction of repurposed drugs with the SARS-CoV-2 3CLpro enzyme, which regulates viral replication machinery. CONCLUSIONS: Overall, this study provides insights into the evolving mutations, with implications to understand viral pathogenicity and possible new strategies for repurposing compounds to combat the nCovid-19 pandemic.

Distribution and development of molecularly distinct perineuronal nets in visual thalamus.

Visual information is detected by the retina and transmitted into the brain by retinal ganglion cells. In rodents, the visual thalamus is a major recipient of retinal ganglion cells axons and is divided into three functionally distinct nuclei: the dorsal lateral geniculate nucleus (dLGN), ventral LGN (vLGN), and intergeniculate leaflet. Despite being densely innervated by retinal input, each nucleus in rodent visual thalamus possesses diverse molecular profiles which underpin their unique circuitry and cytoarchitecture. Here, we combined large-scale unbiased proteomic and transcriptomic analyses to elucidate the molecular expression profiles of the developing mouse dLGN and vLGN. We identified several extracellular matrix proteins as differentially expressed in these regions, particularly constituent molecules of perineuronal nets (PNNs). Remarkably, we discovered at least two types of molecularly distinct Aggrecan-rich PNN populations in vLGN, exhibiting non-overlapping spatial, temporal, and cell-type specific expression patterns. The mechanisms responsible for the formation of these two populations of PNNs also differ as the formation of Cat315+ PNNs (but not WFA+ PNNs) required input from the retina. This study is first to suggest that cell type- and molecularly specific supramolecular assemblies of extracellular matrix may play important roles in the circuitry associated with the subcortical visual system and in the processing of visual information. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. Cover Image for this issue: doi: 10.1111/jnc.14203.

A Proteomics Approach to Discover Drought Tolerance Proteins in Wheat Pollen Grain at Meiosis Stage.

Plants reproductive phase, when grain yield and consequently farmers' investment is most in jeopardy, is considered as the most sensitive stage to drought stress. In this study, we aimed to explore the proteomic response of wheat anther at meiosis stage in a drought tolerant, Darab, and susceptible, Shiraz, wheat genotypes. Wheat plants were exposed to drought stress at meiosis stage for four days under controlled environmental conditions. Then, anthers from both genotypes were sampled, and their proteomes were examined via quantitative proteomics analysis. Our results demonstrated that short-term stress at meiosis stage reduced plant seed-setting compared to well-watered plants. This reduction was more pronounced in the susceptible genotype, Shiraz, by 51%, compared to the drought tolerant Darab by 14.3%. Proteome analysis revealed that 60 protein spots were drought responsive, out of which 44 were identified using a mass spectrometer. We observed a dramatic up-regulation of several heat shock proteins, as well as induction of Bet v I allergen family proteins, peroxiredoxin-5, and glutathione transferase with similar abundance in both genotypes. However, the abundance of proteins such as several stress response related proteins, including glutaredoxin, proteasome subunit alpha type 5, and ribosomal proteins showed a different response to drought stress in two genotypes. The differential abundance of proteins in two genotypes may suggest mechanisms by which tolerant genotype cope with drought stress. To the best of our knowledge, this is the first proteome analysis of plant reproductive tissue response to drought stress in wheat and could broaden our insight into plant adaptation to drought stress.