IL-17A Promotes Granulocyte Infiltration,Myelin Loss,Microglia Activation,and Behavioral Deficits During Cuprizone-Induced Demyelination

Recent evidence suggests a pivotal role of the proinflammatory cytokine interleukin - 17A (IL-17) in demyelinating autoimmune diseases of the central nervous system (CNS) such as multiple sclerosis (MS). Nevertheless, it remains unclear if this cytokine exerts direct effects on CNS resident cells during MS or modulates the function of infiltrating immune cells towards a more detrimental phenotype. Here, we investigated the effects of locally produced IL-17 during experimental demyelination of the CNS using the cuprizone (CPZ) model in mice with (GF/IL17) or without transgenic production of IL-17 by astrocytes in the CNS. During early demyelination, GF/IL17 mice demonstrated enhanced activity and decreased anxiety-related behavior in the elevated plus maze suggesting a more severe disease course. Furthermore, in GF/IL17 mice, toxic demyelination was accelerated and synthesis of myelin proteins was reduced. Early demyelination was accompanied by an increased ratio of infiltrating granulocytes in GF/ILl17 mice. The presence of IL-17 during CPZ treatment increased the accumulation of activated microglia and sustained microglial proliferation during myelin loss. Taken together, our results argue for a detrimental role of IL-17 during demyelinating diseases.     

Yes-associated Protein (YAP) Promotes Cell Survival by Inhibiting Proapoptotic Dendrin Signaling

Kidney podocytes are highly specialized terminally differentiated cells that form the final barrier to urinary protein loss. Podocytes are a target for injury by metabolic, autoimmune, hereditary, inflammatory, and other stressors. Persistence of podocyte injury leads to podocyte death and loss, which results in progressive kidney damage and ultimately kidney failure. Dendrin is a dual compartment protein with proapoptotic signaling properties. Nuclear relocation of dendrin in response to glomerular injury promotes podocyte apoptosis. Here we show that Yes-associated protein (YAP), a downstream target of Hippo kinases and an inhibitor of apoptosis, is expressed in the nucleus of podocytes. The WW domains of YAP mediate the interaction with the PPXY motifs of dendrin. This interaction is functionally relevant because YAP binding to dendrin reduces dendrin-dependent, staurosporine-induced apoptosis in co-transfected HEK293 cells. Moreover gene silencing of YAP in podocytes increases adriamycin-induced podocyte apoptosis. It also increases staurosporine-induced caspase-3/7 activity, which is rescued by dendrin depletion in YAP knockdown cells. Our findings elucidate YAP binding to dendrin as a prosurvival mechanism. The antiapoptotic signaling properties of YAP in podocytes could hold significance in the quest for targeted therapeutics aimed at preventing podocyte loss.     

IL-1RN +2018T>C polymorphism is correlated with colorectal cancer

Epidemiological and experimental evidence indicates chronic inflammation as a risk factor for colorectal cancer. We investigated whether IL-1B ?511C>T (rs16944), IL-1B +3954C>T (rs1143634) and IL1-RN +2018T>C (rs419598) cytokine polymorphisms are correlated with colorectal cancer. Blood samples were obtained from 377 Romanian subjects: 144 patients with sporadic colorectal cancer and 233 healthy controls. Polymorphisms were analyzed by allelic discrimination TaqMan PCR assays with specific probes. The results of our study showed that IL-1RN +2018T>C polymorphism is associated with colorectal cancer. We found that there was a significant difference in the frequency of CC genotype between patients with colorectal cancer and the control group (OR 2.42, 95 % CI: 1.06–5.53, p = 0,034) when TT genotype was used as reference. Furthermore, in a stratified analysis, a positive association was found only for IL-1RN +2018CC genotype, that was limited to early I and II stages (OR 2.72, 95 % CI: 1.05–7.03, p = 0,033). We did not find any association between any of the IL-1B polymorphisms and colorectal cancer. In conclusion this study found that IL-1RN +2018T>C polymorphism is associated with colorectal cancer, mainly for localized disease.     

Biogenic Forsterite and Opal as a Product of Biodeterioration and Lichen Stromatolite Formation in Table Mountain Systems (Tepuis) of Venezuela

Biogenic physical weathering and leaching of the quartzite dominated table mountain systems of South America is a slow but strongly biologically influenced process. Observations and analyses on the basis of sample materials collected during an expedition to the protected areas of the most conspicuous tepuis of Venezuela are reported. The rock material consists of more than 98% silica, and the waters collected reflect rainwater quality further deprived of some essential elements. Wear-down of these rocks is recognized as a biogeomorphogenetic process ruled by the microbiota surviving under harsh and nutrient-poor conditions. Poikilotrophic subaerial biofilms of cyanobacteria, fungi, and some lichens perforate quartz grains and idiomorphic quartz crystals, as well as the subcrystalline cement. The typical pattern of biopitting is regarded as proof of biogenic quartz destruction. Within the subaerial biofilms, which form a massive cover of the slowly biocorroded rock surface, lichens were found that mineralize to microstromatolitic structures in situ. The mineralization occurs exclusively in the lichen thalli and not in the associated massive biofilms of free-living cyanobacteria and fungi. The minerals deposited were identified as opal and considerable amounts of forsterite, the pure Mg end-member of the olivine mixing series (fayalite being the pure iron silicate). Forsterite, thus far, has been regarded as an igneous mineral phase typical for mantle-derived rocks, highly metamorphic dolomitic marbles, and as a planetary mineral found in meteorites. The biogenic dissolution/mineralization paragenesis is explained by the slow weathering and bioleaching processes dominant on these table mountains and by the exclusion of all other potential biomineralization products due to the peculiar geochemistry of the interstitial and run-off water on these plateaus, thus leading to the exceptional biogenesis of forsterite under surface conditions.     

Expression of genes involved in rhamnolipid synthesis in Pseudomonas aeruginosa PAO1 in a bioreactor cultivation

There is a growing demand for economic bioprocesses based on sustainable resources rather than petrochemical-derived substances. Particular attention has been paid to rhamnolipids—surface-active glycolipids—that are naturally produced by Pseudomonas aeruginosa. Rhamnolipids have gained increased attention over the past years due to their versatile chemical and biological properties as well as numerous biotechnological applications. However, rhamnolipid synthesis is tightly governed by a complex growth-dependent regulatory network. Quantitative comprehension of the molecular and metabolic mechanisms during bioprocesses is key to manipulating and improving rhamnolipid production capacities in P. aeruginosa. In this study, P. aeruginosa PAO1 was grown under nitrogen limitation with sunflower oil as carbon and nitrate as nitrogen source in a batch fermentation process. Gene expression was monitored using quantitative PCR over the entire time course. Until late deceleration phase, an increase in relative gene expression of the las, rhl, and pqs quorum-sensing regulons was observed. Thereafter, expression of the rhamnolipid synthesis genes, rhlA and rhlC, as well as the las regulon was downregulated. RhlR was shown to remain upregulated at the late phase of the fermentation process.     

Mild eccentric exercise increases Hsp72 content in skeletal muscles from adult and late middle-aged rats

The loss of muscle mass with age or sarcopenia contributes to increased morbidity and mortality. Thus, preventing muscle loss with age is important for maintaining health. Hsp72, the inducible member of the Hsp70 family, is known to provide protection to skeletal muscle and can be increased by exercise. However, ability to increase Hsp72 by exercise is intensity-dependent and appears to diminish with advanced age. Thus, other exercise modalities capable of increasing HSP content and potentially preventing the age related loss of muscle need to be explored. The purpose of this study was to determine if the stress from one bout of mild eccentric exercise was sufficient to elicit an increase in Hsp72 content in the vastus intermedius (VI) and white gastrocnemius (WG) muscles, and if the Hsp72 response differed between adult and late middle-aged rats. To do this, 30 adult (6 months) and late middle-aged (24 months) F344BN rats were randomly divided into three groups (n = 6/group): control (C), level exercise (16 m^.min⁻¹) and eccentric exercise (16 m^.min⁻¹, 16 degree decline). Exercised animals were sacrificed immediately post-exercise or after 48 hours. Hematoxylin and Eosin staining was used to assess muscle damage, while Western Blotting was used to measure muscle Hsp72 content. A nested ANOVA with Tukey post hoc analysis was performed to determine significant difference (p < 0.05) between groups. Hsp72 content was increased in the VI for both adult and late middle-aged rats 48 hours after eccentric exercise when compared to level and control groups but no differences between age groups was observed. Hsp72 was not detected in the WG following any type of exercise. In conclusion, mild eccentric exercise can increase Hsp72 content in the rat VI muscle and this response is maintained into late middle-age.     

MiRNAs roles in the diagnosis,prognosis and treatment of colorectal cancer

ABSTRACT

Introduction: The liver is the main location for metastasization in stage IV colorectal cancers.

Areas covered: This review intends to comprehensively present the most important studies conducted in the past few years concerning the role of miRNAs in colorectal cancer liver metastases, trying to clarify some aspects regarding tumor biology and favorite liver metastasization site.

Expert commentary: Recent advances in tissue and serum RNA extraction has considerably improved the field of microRNAs studies. These molecules known to play a crucial role in the metastatic stage indicate a starting point in the development of clinical biomarkers with a possible role in the stratification of high-risk patients for adequate treatment.     

Attention in natural scenes: contrast affects rapid visual processing and fixations alike

For natural scenes, attention is frequently quantified either by performance during rapid presentation or by gaze allocation during prolonged viewing. Both paradigms operate on different time scales, and tap into covert and overt attention, respectively. To compare these, we ask some observers to detect targets (animals/vehicles) in rapid sequences, and others to freely view the same target images for 3 s, while their gaze is tracked. In some stimuli, the target''s contrast is modified (increased/decreased) and its background modified either in the same or in the opposite way. We find that increasing target contrast relative to the background increases fixations and detection alike, whereas decreasing target contrast and simultaneously increasing background contrast has little effect. Contrast increase for the whole image (target + background) improves detection, decrease worsens detection, whereas fixation probability remains unaffected by whole-image modifications. Object-unrelated local increase or decrease of contrast attracts gaze, but less than actual objects, supporting a precedence of objects over low-level features. Detection and fixation probability are correlated: the more likely a target is detected in one paradigm, the more likely it is fixated in the other. Hence, the link between overt and covert attention, which has been established in simple stimuli, transfers to more naturalistic scenarios.     

Mapping Global Diversity Patterns for Migratory Birds

Nearly one in five bird species has separate breeding and overwintering distributions, and the regular migrations of these species cause a substantial seasonal redistribution of avian diversity across the world. However, despite its ecological importance, bird migration has been largely ignored in studies of global avian biodiversity, with few studies having addressed it from a macroecological perspective. Here, we analyse a dataset on the global distribution of the world’s birds in order to examine global spatial patterns in the diversity of migratory species, including: the seasonal variation in overall species diversity due to migration; the contribution of migratory birds to local bird diversity; and the distribution of narrow-range and threatened migratory birds. Our analyses reveal a striking asymmetry between the Northern and Southern hemispheres, evident in all of the patterns investigated. The highest migratory bird diversity was found in the Northern Hemisphere, with high inter-continental turnover in species composition between breeding and non-breeding seasons, and extensive regions (at high latitudes) where migratory birds constitute the majority of the local avifauna. Threatened migratory birds are concentrated mainly in Central and Southern Asia, whereas narrow-range migratory species are mainly found in Central America, the Himalayas and Patagonia. Overall, global patterns in the diversity of migratory birds indicate that bird migration is mainly a Northern Hemisphere phenomenon. The asymmetry between the Northern and Southern hemispheres could not have easily been predicted from the combined results of regional scale studies, highlighting the importance of a global perspective.