Diabetic gut microbiota dysbiosis as an inflammaging and immunosenescence condition that fosters progression of retinopathy and nephropathy

The increased prevalence of type 2 diabetes mellitus (T2DM) and life expectancy of diabetic patients fosters the worldwide prevalence of retinopathy and nephropathy, two major microvascular complications that have been difficult to treat with contemporary glucose-lowering medications. The gut microbiota (GM) has become a lively field research in the last years; there is a growing recognition that altered intestinal microbiota composition and function can directly impact the phenomenon of ageing and age-related disorders. In fact, human GM, envisaged as a potential source of novel therapeutics, strongly modulates host immunity and metabolism. It is now clear that gut dysbiosis and their products (e.g. p-cresyl sulfate, trimethylamine?N?oxide) dictate a secretory associated senescence phenotype and chronic low-grade inflammation, features shared in the physiological process of ageing (“inflammaging”) as well as in T2DM (“metaflammation”) and in its microvascular complications. This review provides an in-depth look on the crosstalk between GM, host immunity and metabolism. Further, it characterizes human GM signatures of elderly and T2DM patients. Finally, a comprehensive scrutiny of recent molecular findings (e.g. epigenetic changes) underlying causal relationships between GM dysbiosis and diabetic retinopathy/nephropathy complications is pinpointed, with the ultimate goal to unravel potential pathophysiological mechanisms that may be explored, in a near future, as personalized disease-modifying therapeutic approaches.     

Non-Specific Factors that may influence Significance of Urinary Steroid Excretion in Breast Cancer

The urinary excretion of corticosteroids (17-oxogenic steroids) and adrenal androgens (11-deoxy-17-oxosteroids) was studied in women below the age of 50 in a variety of clinical situations for comparison with a normal group. The conditions studied were: chronic debility from non-malignant disease, weight reduction, admission to hospital and surgery for varicose veins, hepatic non-malignant disease, and non-mammary cancer.The objective of the study was to determine whether the changes found in early and advanced breast cancer and used to judge the prognosis of the disease are specific to the disease or are merely incidental to the degree of illness caused by the disease.Similar changes to those found in breast cancer—principally a reduction in the excretion of the androgens—were found in the women with severe hepatic disease and in advanced non-mammary cancer. These were also found to follow the effects of severe surgical stress.It is concluded that the changes found in breast cancer are a measure of the general systemic disturbance caused by the disease and are not due specifically to it. Nevertheless, the value of their prognostic significance remains unchallenged.     

Bone loss: Factors that regulate osteoclast differentiation - an update

Osteoclast activation is a critical cellular process for pathological bone resorption, such as erosions in rheumatoid arthritis (RA) or generalized bone loss. Among many factors triggering excessive osteoclast activity, cytokines such as IL-1 or tumour necrosis factor (TNF)-α play a central role. New members of the TNF receptor ligand family (namely receptor activator of nuclear factor-κB [RANK] and RANK ligand [RANKL]) have been discovered whose cross-interaction is mandatory for the differentiation of osteoclasts from hemopoietic precursors, in both physiological and pathological situations. Osteoprotegerin, a decoy receptor which blocks this interaction, decreases osteoclast activity and could have a fascinating therapeutic potential in conditions associated with upregulated bone resorption.     

Bone loss. Factors that regulate osteoclast differentiation: an update

Osteoclast activation is a critical cellular process for pathological bone resorption, such as erosions in rheumatoid arthritis (RA) or generalized bone loss. Among many factors triggering excessive osteoclast activity, cytokines such as IL-1 or tumour necrosis factor (TNF)-alpha play a central role. New members of the TNF receptor ligand family (namely receptor activator of nuclear factor-kappa B [RANK] and RANK ligand [RANKL]) have been discovered whose cross-interaction is mandatory for the differentiation of osteoclasts from hemopoietic precursors, in both physiological and pathological situations. Osteoprotegerin, a decoy receptor which blocks this interaction, decreases osteoclast activity and could have a fascinating therapeutic potential in conditions associated with upregulated bone resorption.     

Parasitism may enhance rather than reduce the predatory impact of an invader

Invasive species can have profound impacts on communities and it is increasingly recognized that such effects may be mediated by parasitism. The ‘enemy release’ hypothesis posits that invaders may be successful and have high impacts owing to escape from parasitism. Alternatively, we hypothesize that parasites may increase host feeding rates and hence parasitized invaders may have increased community impacts. Here, we investigate the influence of parasitism on the predatory impact of the invasive freshwater amphipod Gammarus pulex. Up to 70 per cent of individuals are infected with the acanthocephalan parasite Echinorhynchus truttae, but parasitized individuals were no different in body condition to those unparasitized. Parasitized individuals consumed significantly more prey (Asellus aquaticus; Isopoda) than did unparasitized individuals. Both parasitized and unparasitized individuals displayed Type-II functional responses (FRs), with the FR for parasitized individuals rising more steeply, with a higher asymptote, compared with unparasitized individuals. While the parasite reduced the fitness of individual females, we predict a minor effect on population recruitment because of low parasite prevalence in the peak reproductive period. The parasite thus has a large per capita effect on predatory rate but a low population fitness effect, and thus may enhance rather than reduce the impact of this invader.     

Plant tannins and insect herbivores: an appraisal

Abstract. 1. The bioassays with tannins and insects, and the ecological studies on insects implicating tannins, are summarized and discussed.
2. Because of the great variation now shown in all aspects of the insect-tannin relationship, the difficulty of making generalizations is stressed.
3. The significance of plant tannins for insect herbivores is reconsidered in the light of recent work and little-known older work, which illustrate the very varied nature of its effects.     

Salutogenic factors that may enhance lifelong oral health in an elderly Japanese population

Objectives: The objective of this study was to assess which factors affected the maintenance of more than 20 teeth in Japanese patients aged 80 years and older, using a life‐course perspective. Subjects and methods: The oral examination was carried out by dentists. The questionnaire asked about family background, background during various stages of growing up, tooth brushing, snacking, job history, health examination, war experience, number of children, oral health condition and dietary preferences. Some of the questions asked about conditions when they were a primary school student, 20 years old, 40 years old and 60 years old. Multivariable logistic‐regression analysis was used to adjust for sex at significant life stages. Results: The group with mothers who did not prefer sweet food had an approximately four times greater chance of having ≥20 teeth compared with the group with mothers who preferred sweet food. Those participants who did not prefer sweet food themselves were approximately three to five times more likely to be in the ≥20 tooth group compared with those who preferred sweet food at all stages of their life course. Non‐smokers and those who quit smoking were three times more likely to be in the ≥20 tooth group than those who smoked throughout the years from 20 to 60 years of age. Conclusions: Factors associated with the maintenance of a sufficient number of functioning teeth were: not having a mother with a preference for sweet food, not having a preference for sweet food themselves and not smoking over a long period.     

Glutamate may be an efferent transmitter that elicits inhibition in mouse taste buds

Recent studies suggest that l-glutamate may be an efferent transmitter released from axons innervating taste buds. In this report, we determined the types of ionotropic synaptic glutamate receptors present on taste cells and that underlie this postulated efferent transmission. We also studied what effect glutamate exerts on taste bud function. We isolated mouse taste buds and taste cells, conducted functional imaging using Fura 2, and used cellular biosensors to monitor taste-evoked transmitter release. The findings show that a large fraction of Presynaptic (Type III) taste bud cells (～50%) respond to 100 μM glutamate, NMDA, or kainic acid (KA) with an increase in intracellular Ca(2+). In contrast, Receptor (Type II) taste cells rarely (4%) responded to 100 μM glutamate. At this concentration and with these compounds, these agonists activate glutamatergic synaptic receptors, not glutamate taste (umami) receptors. Moreover, applying glutamate, NMDA, or KA caused taste buds to secrete 5-HT, a Presynaptic taste cell transmitter, but not ATP, a Receptor cell transmitter. Indeed, glutamate-evoked 5-HT release inhibited taste-evoked ATP secretion. The findings are consistent with a role for glutamate in taste buds as an inhibitory efferent transmitter that acts via ionotropic synaptic glutamate receptors.     

Factors that may mediate the relationship between physical activity and the risk for developing knee osteoarthritis

Studies investigating the effect of physical activity on risk for developing osteoarthritis at weight-bearing joints have reported conflicting results. We examine evidence to suggest that this may be due to the existence of subgroups of individuals who differ in their response to physical activity, as well as methodological issues associated with the assessment of knee joint structure and physical activity. Recommendations for future studies of physical activity and the development of knee osteoarthritis are discussed.     

Assembly in vivo of mouse muscle acetylcholine receptor: identification of an alpha subunit species that may be an assembly intermediate

We have studied assembly of acetylcholine receptor in vivo using subunit-specific monoclonal antibodies and immunoprecipitation with alpha-bungarotoxin and antitoxin. We have identified three distinct forms of the alpha subunit. The newly synthesized alpha subunit species has a sedimentation coefficient of 5S and is recognized only by antibody specific for SDS-denatured alpha subunit. We have called this species alpha 61. The 5S alpha Tx species is not associated with beta subunits and is probably monomeric. alpha Tx is formed from alpha 61 with a half-time of 15 min and an efficiency of approximately equal to 30%. Formation of alpha Tx involves a conformational change, and we suggest that this conformation is dependent upon or stabilized by disulfide bond formation. The assembly of alpha Tx with beta subunits (and probably gamma and delta) into a 9S complex appears to be an efficient but slow process requiring more than 90 min. Unassembled alpha 61 subunits are degraded rapidly. However, subunit degradation is a result of failure to assemble, rather than its cause.     

Entomogenous fungi in tropical forest ecosystems: an appraisal

Abstract. 1. Species of the genus Cordyceps (Ascomycotina; Clavicipitales) are the commonest fungi encountered on arthropods in tropical forests.
2. The asexual states of Cordyceps may occur in conjunction with or separately from the perfect state and are classified in the genera Hirsutella, Hymenostilbe, Nomuraea, Paecilomyces and Verticillium of the imperfect fungi (Deuteromycotina; Moniliales).
3. Most Cordyceps species have a restricted host range and this rigid host specificity, at the generic or tribal level, is especially evident in ant-fungal associations.
4. Pathogenicity was not tested but circumstantial evidence is presented which supports the view that Cordyceps species are primary pathogens of arthropods.
5. Observations of living, infected ants suggest that behavioural patterns are radically altered, possibly altruistically orientated.
6. It is thought that entomogenous fungi are involved in the regulation of arthropod populations and may help to maintain stability in tropical forest ecosystems.
7. The value of these organisms to man may be in the metabolites they produce rather than in their direct usage as biological control agents of insect pests.     

DNABIND: an interactive microcomputer program searching for nucleotide sequences that may code for conserved DNA-binding protein motifs

This paper presents a simple program for interactive searchingfor nucleotide sequences that may code for the helix—turn—helix,zinc finger or leucine zipper motifs in proteins. The helix—turn—helixmotifs are predicted using the recently published method ofDodd and Egan, while zinc fingers and leucine zippers are searchedfor by our original methods. DNABIND is shown to detect allfour known helix—turn—helix motifs in bacteriophagelambda genes and both zinc fingers of the adrl gene of yeast.