72 research outputs found
A study of amylolytic streptococci from the rumen of the sheep
Ruminants comprise a large class of mammals
distributed over the greater part of the earth's
surface. The digestive system of these animals has
been adapted for the digestion of grass and other
cellulosic materials which form the natural diet of
the group as a whole. Since this diet is both bulky
and indigestible it is to be expected that the ratio
of the capacity of the digestive system to body
weight is higher in ruminants than it is for example
in carnivorous animals. For this purpose the lower
part of the oesophagus in the ruminant forms a large
sac or rumen. The ingested food passes into the
rumen and is mixed with the dense rumen microbial
population. It is in the rumen that the digestion
of cellulose by rumen bacteria takes place. The
relationship between the rumen microflora and the
host is thought to be symbiotic and since a large
percentage of the world's human population is
dependent directly or indirectly upon ruminants for
food the economic importance of this symbiotic
relationship cannot be over emphasised. Especially
asp but for these animals much of the yearly crop of grass and other cellulosic material would not be
converted into protein but broken down by soil
bacteria and so be lost to man.In most parts of the world the continuous
growth of plants is not possible, due to the
sequence of the seasons or to the alternation of wet
and dry periods. Thus, at intervals, herbivores
must live on vegetation which has completed its
growth cycle and has become dry, woody and resistant
to digestion. The digestive system of the ruminant
can utilise such material and as a result these
animals are not seriously affected by drought and
other inclement weather conditions. This may account
for the success of the group in the modern world.
In addition it is this ability to utilise cellulose
efficiently that has led to the domestication and
breeding of the ruminant
Gendered endings: Narratives of male and female suicides in the South African Lowveld
This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11013-012-9258-y. Copyright @ Springer Science+Business Media, LLC 2012.Durkheim’s classical theory of suicide rates being a negative index of social solidarity downplays the salience of gendered concerns in suicide. But gendered inequalities have had a negative impact: worldwide significantly more men than women perpetrate fatal suicides. Drawing on narratives of 52 fatal suicides in Bushbuckridge, South Africa, this article suggests that Bourdieu’s concepts of ‘symbolic violence’ and ‘masculine domination’ provide a more appropriate framework for understanding this paradox. I show that the thwarting of investments in dominant masculine positions have been the major precursor to suicides by men. Men tended to take their own lives as a means of escape. By contrast, women perpetrated suicide to protest against the miserable consequences of being dominated by men. However, contra the assumption of Bourdieu’s concept of ‘habitus’, the narrators of suicide stories did reflect critically upon gender constructs
FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells
Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours
Recommended from our members
Restricting Microbial Exposure in Early Life Negates the Immune Benefits Associated with Gut Colonization in Environments of High Microbial Diversity
Background: Acquisition of the intestinal microbiota in early life corresponds with the development of the mucosal immune system. Recent work on caesarean-delivered infants revealed that early microbial composition is influenced by birthing method and environment. Furthermore, we have confirmed that early-life environment strongly influences both the adult gut microbiota and development of the gut immune system. Here, we address the impact of limiting microbial exposure after initial colonization on the development of adult gut immunity.
Methodology/Principal Findings: Piglets were born in indoor or outdoor rearing units, allowing natural colonization in the
immediate period after birth, prior to transfer to high-health status isolators. Strikingly, gut closure and morphological
development were strongly affected by isolator-rearing, independent of indoor or outdoor origins of piglets. Isolator-reared
animals showed extensive vacuolation and disorganization of the gut epithelium, inferring that normal gut closure requires
maturation factors present in maternal milk. Although morphological maturation and gut closure were delayed in isolatorreared
animals, these hard-wired events occurred later in development. Type I IFN, IL-22, IL-23 and Th17 pathways were
increased in indoor-isolator compared to outdoor-isolator animals during early life, indicating greater immune activation in
pigs originating from indoor environments reflecting differences in the early microbiota. This difference was less apparent
later in development due to enhanced immune activation and convergence of the microbiota in all isolator-reared animals.
This correlated with elevation of Type I IFN pathways in both groups, although T cell pathways were still more affected in
indoor-reared animals.
Conclusions/Significance: Environmental factors, in particular microbial exposure, influence expression of a large number
of immune-related genes. However, the homeostatic effects of microbial colonization in outdoor environments require
sustained microbial exposure throughout development. Gut development in high-hygiene environments negatively
impacts on normal succession of the gut microbiota and promotes innate immune activation which may impair immune
homeostasis
Epithelial endoplasmic reticulum stress orchestrates a protective IgA response.
Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell-dependent and -independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased lamina propria and luminal IgA. Increased numbers of IgA-producing plasma cells were observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that induce a barrier-protective TI IgA response.Wellcome Trust Senior Investigator Award 106260/Z/14/Z
HORIZON2020/European Research Council Consolidator Grant 64888
IQuaD dental trial; improving the quality of dentistry : a multicentre randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care
Peer reviewedPublisher PD
An individually-tailored smoking cessation intervention for rural Veterans: a pilot randomized trial
Triplet therapy with palbociclib, taselisib and fulvestrant in PIK3CA mutant breast cancer and doublet palbociclib and taselisib in pathway mutant solid cancers
Cyclin-dependent kinase-4/6 (CDK4/6) and phosphatidylinositol 3-kinase (PI3K) inhibitors synergise in PIK3CA mutant ER-positive HER2-negative breast cancer models. We conducted a phase Ib trial investigating safety and efficacy of doublet CDK4/6 inhibitor palbociclib plus selective PI3K inhibitor taselisib in advanced solid tumors, and triplet palbociclib plus taselisib plus fulvestrant in 25 patients with PIK3CA mutant, ER-positive HER2-negative advanced breast cancer. The triplet therapy response rate in PIK3CA mutant, ER-positive HER2-negative was 37.5% (95% CI 18.8-59.4). Durable disease control was observed in PIK3CA mutant ER-negative breast cancer and other solid tumors, with doublet therapy. Both combinations were well tolerated at pharmacodynamically active doses. In the triplet group, high baseline cyclin E1 expression associated with shorter progression-free survival (PFS) (HR 4.2, 95% CI 1.3-13.1, p=0.02). Early ctDNA dynamics demonstrated high on-treatment ctDNA association with shorter PFS (HR 5.2, 95% CI 1.4-19.4, p=0.04). Longitudinal plasma ctDNA sequencing provided genomic evolution evidence during triplet therapy
Impaired Carbohydrate Digestion and Transport and Mucosal Dysbiosis in the Intestines of Children with Autism and Gastrointestinal Disturbances
Gastrointestinal disturbances are commonly reported in children with autism, complicate clinical management, and may contribute to behavioral impairment. Reports of deficiencies in disaccharidase enzymatic activity and of beneficial responses to probiotic and dietary therapies led us to survey gene expression and the mucoepithelial microbiota in intestinal biopsies from children with autism and gastrointestinal disease and children with gastrointestinal disease alone. Ileal transcripts encoding disaccharidases and hexose transporters were deficient in children with autism, indicating impairment of the primary pathway for carbohydrate digestion and transport in enterocytes. Deficient expression of these enzymes and transporters was associated with expression of the intestinal transcription factor, CDX2. Metagenomic analysis of intestinal bacteria revealed compositional dysbiosis manifest as decreases in Bacteroidetes, increases in the ratio of Firmicutes to Bacteroidetes, and increases in Betaproteobacteria. Expression levels of disaccharidases and transporters were associated with the abundance of affected bacterial phylotypes. These results indicate a relationship between human intestinal gene expression and bacterial community structure and may provide insights into the pathophysiology of gastrointestinal disturbances in children with autism
Act now against new NHS competition regulations: an open letter to the BMA and the Academy of Medical Royal Colleges calls on them to make a joint public statement of opposition to the amended section 75 regulations.
- …