70-Kilodalton Heat Shock Protein Induction in Cerebellar Astrocytes and Cerebellar Granule Cells In Vitro: Comparison with Immunocytochemical Localization After Hyperthermia In Vivo

Induction of the 70-kDa heat shock protein, hsp70, was evaluated in cultured cerebellar astrocytes and granule cell neurons subjected to a hyperthermic stress, using a monoclonal antibody and an oligonucleotide probe that selectively recognize stress-inducible species of hsp70-related proteins and RNAs, respectively. Immunoblots of cultures enriched in either granule cells or astrocytes, and immunocytochemical localization studies in cocultures of these cell types, demonstrated that hsp70 induction was restricted to the astrocyte population. Amino acid incorporation experiments showed little difference in the loss and recovery of overall protein synthesis activity in these two cell types following transient hyperthermic stress. RNA blot hybridizations confirmed the preferential glial induction of hsp70. In vivo immunocytochemical studies in brains of adult rats following hyperthermia were consistent with earlier observations that suggested a primarily glial and vascular localization of the heat shock response in most brain regions, although the intense immunoreactivity in the cerebellar granule cell layer suggests that there is induction of hsp70 in these neurons under in vivo conditions. These results suggest the potential value of such defined cell cultures in identifying mechanisms responsible for differences in the heat shock response of various cell types in vitro, and in revealing factors that may account for the apparent absence of the stress response in cultured cerebellar granule cell neurons.     

Artificial selection of stable rhizosphere microbiota leads to heritable plant phenotype changes

Artificial selection of microbiota opens new avenues for improving plants. However, reported results lack consistency. We hypothesised that the success in artificial selection of microbiota depends on the stabilisation of community structure. In a ten-generation experiment involving 1,800 plants, we selected rhizosphere microbiota of Brachypodium distachyon associated with high or low leaf greenness, a proxy of plant performance. The microbiota structure showed strong fluctuations during an initial transitory phase, with no detectable leaf greenness heritability. After five generations, the microbiota structure stabilised, concomitantly with heritability in leaf greenness. Selection, initially ineffective, did successfully alter the selected property as intended, especially for high selection. We show a remarkable correlation between the variability in plant traits and selected microbiota structures, revealing two distinct sub-communities associated with high or low leaf greenness, whose abundance was significantly steered by directional selection. Understanding microbiota structure stabilisation will improve the reliability of artificial microbiota selection.     

Dynamic changes to the endocannabinoid system in models of chronic pain

The analgesic effects of cannabinoid ligands, mediated by CB1 receptors are well established. However, the side-effect profile of CB1 receptor ligands has necessitated the search for alternative cannabinoid-based approaches to analgesia. Herein, we review the current literature describing the impact of chronic pain states on the key components of the endocannabinoid receptor system, in terms of regionally restricted changes in receptor expression and levels of key metabolic enzymes that influence the local levels of the endocannabinoids. The evidence that spinal CB2 receptors have a novel role in the modulation of nociceptive processing in models of neuropathic pain, as well as in models of cancer pain and arthritis is discussed. Recent advances in our understanding of the spinal location of the key enzymes that regulate the levels of the endocannabinoid 2-AG are discussed alongside the outcomes of recent studies of the effects of inhibiting the catabolism of 2-AG in models of pain. The complexities of the enzymes capable of metabolizing both anandamide (AEA) and 2-AG have become increasingly apparent. More recently, it has come to light that some of the metabolites of AEA and 2-AG generated by cyclooxygenase-2, lipoxygenases and cytochrome P450 are biologically active and can either exacerbate or inhibit nociceptive signalling.     

Parenteral nutrition during neoadjuvant chemotherapy for patients with non-metastatic gastric or esophago-gastric cancer to reduce postoperative morbidity (PERCOG): study protocol for a randomized controlled trial

Background

The majority of patients with gastric or esophago-gastric cancer are at risk for malnutrition. Preoperative malnutrition was shown to increase the incidence of postoperative complications following abdominal surgery. However, it remains unclear if preoperative parenteral nutritional support during neoadjuvant chemotherapy (NACT) may be effective to reduce the rate of postoperative complications in these patients.

Methods/Design

The PERCOG trial is a randomized controlled multicenter observer-blinded trial, investigating if the improvement of the general condition of patients with non-metastasized gastric cancer or cancer of the esophago-gastric junction during NACT by supplemental parenteral nutrition can decrease the postoperative Comprehensive Complication Index (CCI). Statistical analysis of the primary endpoint measure (CCI on postoperative day 30) will be based on the intention-to-treat population. The global level of significance is set at 5% and the sample size (n?=?150) is determined to assure a power of 80%.

Discussion

The results of the PERCOG trial will provide high-level evidence for clinical recommendations regarding the administration of preoperative supportive parenteral nutrition and provide all participating patients the opportunity of an improved treatment.

Trial registration

German Clinical Trials Register, DRKS00009451. Registered on 3 July 2017.

     

Dermatoglyphic asymmetry and diversity in some pathologies

The evaluation of dermatoglyphic asymmetry represents a specific estimate of the stability of intrauterine development. In the present study, we analyzed the level of asymmetry and diversity in the radial and ulnar counts of each finger in 400 health Sardinian individuals and in 469 Sardinian subjects with four common diseases in Sardinia: type 1 diabetes, type 2 diabetes, arterial hypertension and multiple sclerosis. To measure the asymmetry, we used three indices: fluctuating asymmetry, the index of asymmetry and the index of diversity. The differences from the control group are only rarely significant. The values of fluctuating asymmetry do not present a particular distribution in relation to the pathologies, while the values of {ie139-1} and diversity are usually higher in the pathological groups. The differentiation is especially evident in the subjects with multiple sclerosis, intermediate in the diabetics and practically nil in the hypertense individuals.     

Assortative mating and offspring well-being: theory and empirical findings from a native Amazonian society in Bolivia

Mate choice matters for inclusive fitness, household economic efficiency, assimilation, stratification, and economic inequalities in society. In positive assortative mating, people pair with someone who resembles them along a trait, whereas in negative assortative mating, people pair with someone who differs from them along a trait. In industrial nations, people tend to follow positive assortative mating for fundamental demographic dimensions (e.g., age, schooling) and might practice negative assortative mating for economic outcomes (e.g., earnings). Research on assortative mating has focused on industrial nations, generally compared only one trait between couples, and paid scant attention to the effects of assortative mating for offspring well-being. If assortative mating enhances inclusive fitness, it might also enhance offspring well-being. Drawing on data from a farming–foraging society in the Bolivian Amazon (Tsimane') that practices preferential cross-cousin marriage, we (a) identify six parental traits (age, knowledge, wealth, schooling, height, and smiles) for which Tsimane' might practice assortative mating and (b) test the hypothesis that assortative mating enhances offspring well-being. Proxies for offspring well-being include height and school attainment. Tsimane' resemble people of industrial nations in practicing mostly positive assortative mating. Pairwise, mother–father and Pearson correlations of age, schooling, and earnings among Tsimane' resemble correlations of industrial nations. Correlation coefficients for the six parental traits were far higher than correlations that might happened just by chance. We found weak support for the hypothesis that assortative mating improves offspring well-being.     

Intravenous Shiga toxin 2 promotes enteritis and renal injury characterized by polymorphonuclear leukocyte infiltration and thrombosis in Dutch Belted rabbits

Enterohemorrhagic Escherichia coli (EHEC) infection causes hemolytic uremic syndrome, a leading cause of acute renal failure in children. Dutch Belted (DB) rabbits are susceptible to EHEC-induced disease. Using real-time quantitative RT-PCR we measured the renal mRNA expression of cytokines and fibrinolytic factors in DB rabbits challenged with intravenous Shiga toxin 2 (Stx2) (1200 ng/kg). Group 1 rabbits received an incremental dose during an 8-day period whereas Group 2 rabbits received a single dose. Group 1 rabbits developed mild disease. In contrast, Group 2 rabbits developed severe diarrhea, higher levels of circulating polymorphonuclear leukocytes, increased mean platelet volume, and increased fibrinogen levels. Group 2 rabbits developed polymorphonuclear leukocyte infiltration in the intestine and kidney as well as glomerular congestion, luminal constriction, and mesangial glomerulonephropathy. These renal lesions were associated with up-regulation of interleukin-8 (P<0.006), plasminogen activator inhibitor-1 (P<0.04), and tissue plasminogen activator (P<0.05). Circulating Stx2 promoted dose-dependent enteritis and renal injury characterized by inflammation and impaired fibrinolysis leading to thrombosis.     

Plant species traits are the predominant control on litter decomposition rates within biomes worldwide

Worldwide decomposition rates depend both on climate and the legacy of plant functional traits as litter quality. To quantify the degree to which functional differentiation among species affects their litter decomposition rates, we brought together leaf trait and litter mass loss data for 818 species from 66 decomposition experiments on six continents. We show that: (i) the magnitude of species-driven differences is much larger than previously thought and greater than climate-driven variation; (ii) the decomposability of a species' litter is consistently correlated with that species' ecological strategy within different ecosystems globally, representing a new connection between whole plant carbon strategy and biogeochemical cycling. This connection between plant strategies and decomposability is crucial for both understanding vegetation-soil feedbacks, and for improving forecasts of the global carbon cycle.