Myelin messenger ribonucleic acids : their association with the cytoskeleton and their subcellular distribution

This work presents an examination of the subcellular localization of the major myelin proteins of oligodendrocytes, and the messages that encode these proteins. The association of these messages with the cytoskeleton is also examined. All messages investigated show some degree of association with the cytoskeleton; Indeed messages encoding actin and tubulin are found exclusively bound to the cytoskeleton. In general a specific myelin message and its protein counterpart are found in the same area of the cell. This suggests that these messages are translated close to their targetted site. In most Instances the messages being probed by in situ hybridization are being sought for the first time in cells grown in tissue culture, and in some instances messages are being probed for the first time ever. In addition, the messages encoding DM-20 and PLP are found in different areas of the cell. As these are the products of a single gene, this suggests that there is a significant role to be played by differential splicing in individual cells. The role of cytoske1eton-mRNA association in the targetting and assembly of myelin proteins is discussed

Microbial diversity in the digestive tract of two different breeds of sheep

Aims: This work aims to determine the factors which play a role in establishing the microbial population throughout the digestive tract in ruminants and is necessary to enhance our understanding of microbial establishment and activity. Methods and Results: This study used Terminal Restriction Fragment Length Polymorphism (TRFLP) to investigate the microbial profiles of 11 regions of the digestive tract of two breeds of sheep (Beulah and Suffolk). TRFLP data revealed that the regions of the digestive tract were highly significantly different in terms of the composition of the bacterial communities within three distinct clusters of bacterial colonisation (foregut, midgut and hindgut). The data also show that breed was a significant factor in the establishment of the bacterial component of the microbial community, but that no difference was detected between ciliated protozoal populations. Conclusions: We infer that not only are the different regions of the tract important in determining the composition of the microbial communities in the sheep, but so too is the breed of the animal. Significance and Impact of Study: This is the first time that a difference has been detected in the digestive microbial population of two different breeds of sheep

Metataxonomic and histopathological study of rabbit epizootic enteropathy in Mexico.

Epizootic rabbit enteropathy (ERE) affects young rabbits and represents 32% of the enteropathies in rabbit production farms in Mexico. The etiology of this syndrome has not been clarified yet. A metataxonomic and histopathology study of ERE was carried out to compare the gastrointestinal microbiota and histopathological lesions of healthy and positive-ERE rabbits. The metataxonomic study was done using an Illumina MiSeq (MiSeq® system, Illumina, San Diego California, USA) massive segmentation platform, and a Divisive Amplicon Denoising Algorithm 2 (DADA2 algorithm) was used to obtain Shannon and Simpson diversity indices as well as the relative abundance of the identified communities. For the histopathological study, paraffin sections of the cecum, ileo-cecal valve, and colon were stained with eosin and hematoxylin. AxioVision 4.9 software (Carl Zeiss MicroImaging GmbH, Jena, Germany) was used to measure the crypt depths. Statistical analysis was done using PERMANOVA analysis for the metataxonomic study and ANOVA for the histopathology study. Histopathologic analysis showed smaller sizes of crypts in the colon of ERE rabbits. Differences were observed in the diversity and abundance of the gastrointestinal microbiota between the analyzed groups. The genus Clostridium and the species Cloacibacillus porcorum and Akkermansia muciniphila were associated with ERE. The results obtained from this study can provide information for future clarification of the etiology and proposals of effective treatments

Effect of feeding insoluble fiber on the microbiota and metabolites of the caecum and feces of rabbits recovering from epizootic rabbit enteropathy relative to non-infected rabbits.

This study aimed to investigate the effect of feeding insoluble fiber on the microbiota and metabolites of the caecum and feces of rabbits recovering from epizootic rabbit enteropathy relative to non-infected rabbits. Rabbits that had either recovered from epizootic rabbit enteropathy or ones that had never had epizootic rabbit enteropathy were fed on a diet of 32% or 36% neutral detergent fiber until they were 70 days of age. At this point, the short-chain fatty acid and ammonia levels were measured in caecotroph and fecal samples and compared using 2 × 2 ANOVA. The microbial composition of the samples was also analyzed using next-generation sequencing and compared by PERMANOVA. Caecotrophic samples from previously affected rabbits on lower fiber diets had higher short-chain fatty acid contents and higher species diversity index values for some indices (p [less than] 0.05), although the fecal samples showed lower species diversity levels (p [less than] 0.05). In addition, the PERMANOVA analyses demonstrated that differences were detected in the microbial composition of both fecal and caecotrophic samples, depending on the disease status at the outset of the experiment (p [less than] 0.05). The results of this work show that, although there is some potential in the use of high-fiber diets for the treatment of rabbits that have had epizootic rabbit enteropathy, they are not able to produce the same digestive tract properties as those seen in rabbits that have never had the condition. This is true even after the rabbits have recovered from epizootic rabbit enteropathy

Genetic diversity and phylogenetic analysis of the native mountain ponies of Britain and Ireland reveal a novel rare population

The conservation of unique populations of animals is critical in order to preserve valuable genetic diversity and, where populations are free-living, maintain their irreplaceable influence upon habitat ecology. An accurate assessment of genetic diversity and structure within and between populations is crucial in order to design and implement conservation strategies in natural and domesticated species. Moreover, where it is possible to identify relic populations that are related to a structured breed an ideal opportunity presents itself to model processes that reveal historical factors that have shaped genetic diversity. The origins of native UK mountain and moorland ponies are uncertain, but they may have directly descended from prehistoric populations and potentially harbour specific adaptations to the uplands of Britain and Ireland. To date, there have been no studies of population structure and genetic diversity present within a free-living group of ponies in the Carneddau mountain range of North Wales. Herein, we describe the use of microsatellites and SNPs together with analysis of the mitochondrial control region to quantify the extent and magnitude of genetic diversity present in the feral Carneddau pony and relate this to several recognised British and Irish pony breeds. Our results establish that the feral Carneddau ponies represent a unique and distinctive population that merits recognition as a defined population and conservation priority. We discuss the implications for conservation of this population as a unique pool of genetic diversity adapted to the British uplands and potentially of particular value in maintaining the biodiversity of these habitats

Human cellular restriction factors that target HIV-1 replication

Recent findings have highlighted roles played by innate cellular factors in restricting intracellular viral replication. In this review, we discuss in brief the activities of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G), bone marrow stromal cell antigen 2 (BST-2), cyclophilin A, tripartite motif protein 5 alpha (Trim5α), and cellular microRNAs as examples of host restriction factors that target HIV-1. We point to countermeasures encoded by HIV-1 for moderating the potency of these cellular restriction functions

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials