Adiponectin is associated with cardiovascular disease in male renal transplant recipients: baseline results from the LANDMARK 2 study

BACKGROUND: Adiponectin is a major adipocyte-derived protein with insulin-sensitizing, anti-inflammatory and anti-atherogenic properties. Adiponectin levels correlate inversely with renal function and higher levels are predictive of lower cardiovascular disease (CVD) in patients with normal renal function and chronic kidney disease. No data exists on the association between adiponectin and CVD in renal transplant recipients (RTR). METHODS: Standard biochemistry, clinical data and adiponectin were collected from 137 RTR recruited to the LANDMARK 2 study at baseline. The LANDMARK 2 study is an ongoing randomized controlled study that compares the outcome of aggressive risk factor modification for cardiovascular disease versus standard post-transplant care in renal transplant recipients with impaired glucose tolerance or diabetes mellitus. RESULTS: Mean patient age was 53.4 +/- 12 years and the median post-transplantation period was 5 (0.5-31.9) years. Mean serum adiponectin level was 12.3 +/- 7.1 microg/mL. On univariate analysis, adiponectin was positively associated with female gender (P = 0.01) and serum high-density lipoprotein (HDL) concentration (P < 0.001), and inversely with body mass index (P = 0.009), metabolic syndrome (P = 0.047), abnormal glucose tolerance (P = 0.01), C-reactive protein (P = 0.001) and serum triglyceride (P < 0.001). On stepwise multivariate analysis, adiponectin in males was negatively correlated with combined baseline CVD (P = 0.03), waist-hip ratio (P = 0.003) and glomerular filtration rate (P = 0.046), and positively with HDL (P < 0.001). In contrast, in females adiponectin was inversely associated with C-reactive protein (P = 0.001) and serum triglyceride. CONCLUSION: In conclusion, adiponectin is positively correlated with inflammation, dyslipidemia and abnormal glucose tolerance in RTR. Furthermore, hypoadiponectinemia correlated with increased baseline CVD in male RTR

Estrogen Receptor-α Mediates Diethylstilbestrol-Induced Feminization of the Seminal Vesicle in Male Mice

Background: Studies have shown that perinatal exposure to the synthetic estrogen diethylstilbestrol (DES) leads to feminization of the seminal vesicle (SV) in male mice, as illustrated by tissue hyperplasia, ectopic expression of the major estrogen-inducible uterine secretory protein lactoferrin (LF), and reduced expression of SV secretory protein IV (SVS IV)

The beginning of time? Evidence for catastrophic drought in Baringo in the early nineteenth century

New developments in the collection of palaeo-data over the past two decades have transformed our understanding of climate and environmental history in eastern Africa. This article utilises instrumental and proxy evidence of historical lake-level fluctuations from Baringo and Bogoria, along with other Rift Valley lakes, to document the timing and magnitude of hydroclimate variability at decadal to century time scales since 1750. These data allow us to construct a record of past climate variation not only for the Baringo basin proper, but also across a sizable portion of central and northern Kenya. This record is then set alongside historical evidence, from oral histories gathered amongst the peoples of northern Kenya and the Rift Valley and from contemporary observations recorded by travellers through the region, to offer a reinterpretation of human activity and its relationship to environmental history in the nineteenth century. The results reveal strong evidence of a catastrophic drought in the early nineteenth century, the effects of which radically alters our historical understanding of the character of settlement, mobility and identity within the Baringo–Bogoria basin

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor

There's no place like OM:Vesicular sorting and secretion of the peptidylarginine deiminase of Porphyromonas gingivalis

The oral pathogen Porphyromonas gingivalis is one of the major periodontal agents and it has been recently hailed as a potential cause of the autoimmune disease rheumatoid arthritis. In particular, the peptidylarginine deiminase enzyme of P. gingivalis (PPAD) has been implicated in the citrullination of certain host proteins and the subsequent appearance of antibodies against citrullinated proteins, which might play a role in the etiology of rheumatoid arthritis. The aim of this study was to investigate the extracellular localization of PPAD in a large panel of clinical P. gingivalis isolates. Here we show that all isolates produced PPAD. In most cases PPAD was abundantly present in secreted outer membrane vesicles (OMVs) that are massively produced by P. gingivalis, and to minor extent in a soluble secreted state. Interestingly, a small subset of clinical isolates showed drastically reduced levels of the OMV-bound PPAD and secreted most of this enzyme in the soluble state. The latter phenotype is strictly associated with a lysine residue at position 373 in PPAD, implicating the more common glutamine residue at this position in PPAD association with OMVs. Further, one isolate displayed severely restricted vesiculation. Together, our findings show for the first time that neither the major association of PPAD with vesicles, nor P. gingivalis vesiculation per se, are needed for P. gingivalis interactions with the human host

Mass Spectrometric Analyses of Organophosphate Insecticide Oxon Protein Adducts

OBJECTIVE: Organophosphate (OP) insecticides continue to be used to control insect pests. Acute and chronic exposures to OP insecticides have been documented-to cause adverse health effects, but few OP-adducted proteins have been correlated with these illnesses at the molecular level. Our aim was to review the literature covering the current state of the art in mass spectrometry (MS) used to identify OP protein biomarkers. DATA SOURCES AND EXTRACTION: We identified general and specific research reports related to OP insecticides, OP toxicity, OP structure, and protein MS by searching PubMed and Chemical Abstracts for articles published before December 2008. DATA SYNTHESIS: A number of OP-based insecticides share common structural elements that result in predictable OP-protein adducts. The resultant OP-protein adducts show an increase in molecular mass that can be identified by MS and correlated with the OP agent. Customized OP-containing probes have also been used to tag and identify protein targets that can be identified by MS. CONCLUSIONS: MS is a useful and emerging tool for the identification of proteins that are modified by activated organophosphate insecticides. MS can characterize the structure of the OP adduct and also the specific amino acid residue that forms the key bond with the OP. Each protein that is modified in a unique way by an OP represents a unique molecular biomarker that with further research can lead to new correlations with exposure

The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

Objectives: Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). Method: MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. Results: We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Conclusions: Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. Key Points: • PCC functioning during episodic memory relates to hippocampal functioning in MCI. • PCC functioning during episodic memory does not relate to hippocampal structure in MCI. • Functional network changes are an important predictor of PCC functioning in MCI

Digital futures challenge-based learning in Higher Education in Europe: The DIFUCH Erasmus+ Project

Within DIFUCH, we are developing innovative challenge-based pedagogies, tools and platforms for the virtual delivery of a joint programme within a groundbreaking-breaking and flexible academic structure in Europe. This Erasmus+ project is focused on delivering new multi-disciplinary, transnational, cross-sectional future skills-orientated modules and learning pathways that address societal challenges. In this paper, we present the current work of DIFUCH to develop an innovative programme underpinned by Challenge Based Learning (CBL) that addresses local and global societal challenges and strengthens interactions between education, research, and external stakeholders for a positive effect on our communities. This project facilitates the improvement of learning outcomes vis-à-vis university learners' perception of social responsibility, their ability to deal with complex societal challenges from social and economic stability to global warming, their ability to put knowledge into practice, team building and communications skills.This work has been supported by Erasmus Plus KA2 within the project 2021-1-PT01-KA220-HED-000023536.info:eu-repo/semantics/publishedVersio

EFFECTS OF FIRE AND HERBIVORY ON THE STABILITY OF SAVANNA ECOSYSTEMS

Savanna ecosystems are characterized by the co-occurrence of trees and grass-es. In this paper, we argue that the balance between trees and grasses is, to a large extent, determined by the indirect interactive effects of herbivory and fire. These effects are based on the positive feedback between fuel load (grass biomass) and fire intensity. An increase in the level of grazing leads to reduced fuel load, which makes fire less intense and, thus, less damaging to trees and, consequently, results in an increase in woody vegetation. The system then switches from a state with trees and grasses to a state with solely trees. Similarly, browsers may enhance the effect of fire on trees because they reduce woody biomass, thus indirectly stimulating grass growth. This consequent increase in fuel load results in more intense fire and increased decline of biomass. The system then switches from a state with solely trees to a state with trees and grasses. We maintain that the interaction between fire and herbivory provides a mechanistic explanation for observed discontinuous changes in woody and grass biomass. This is an alternative for the soil degradation mechanism, in which there is a positive feedback between the amount of grass biomass and the amount of water that infiltrates into the soil. The soil degradation mechanism predicts no discontinuous chang-es, such as bush encroachment, on sandy soils. Such changes, however, are frequently ob-served. Therefore, the interactive effects of fire and herbivory provide a more plausible explanation for the occurrence of discontinuous changes in savanna ecosystems