Reverse Signaling by MHC-I Molecules in Immune and Non-Immune Cell Types

Major histocompatibility complex (MHC) molecules are well-known for their role in antigen (cross-) presentation, thereby functioning as key players in the communication between immune cells, for example dendritic cells (DCs) and T cells, or immune cells and their targets, such as T cells and virus-infected or tumor cells. However, much less appreciated is the fact that MHC molecules can also act as signaling receptors. In this process, here referred to as reverse MHC class I (MHC-I) signaling, ligation of MHC molecules can lead to signal-transduction and cell regulatory effects in the antigen presenting cell. In the case of MHC-I, reverse signaling can have several outcomes, including apoptosis, migration, induced or reduced proliferation and cytotoxicity towards target cells. Here, we provide an overview of studies showing the signaling pathways and cell outcomes upon MHC-I stimulation in various immune and non-immune cells. Signaling molecules like RAC-alpha serine/threonine-protein kinase (Akt1), extracellular signal-regulated kinases 1/2 (ERK1/2), and nuclear factor-kappaB (NF-kappaB) were common signaling molecules activated upon MHC-I ligation in multiple cell types. For endothelial and smooth muscle cells, the in vivo relevance of reverse MHC-I signaling has been established, namely in the context of adverse effects after tissue transplantation. For other cell types, the role of reverse MHC-I signaling is less clear, since aspects like the in vivo relevance, natural MHC-I ligands and the extended downstream pathways are not fully known.The existing evidence, however, suggests that reverse MHC-I signaling is involved in the regulation of the defense against bacterial and viral infections and against malignancies. Thereby, reverse MHC-I signaling is a potential target for therapies against viral and bacterial infections, cancer immunotherapies and management of organ transplantation outcomes

Bioprospecting and characterization of poly-bhydroxyalkanoate (PHAs) producing bacteria isolated from Colombian sugarcane producing areas

Bioprospecting for poly-b-hydroxyalkanoate (PHA)-accumulating micro-organisms was carried out in sugarcane growing areas of Colombia. They were isolated in unbalanced culture medium (highcarbon/nitrogen ratio) with sucrose, fructose and glucose used as carbon source. PHAs producing bacteria were identified by staining with Sudan black and solubilising cellular components in sodiumhypochlorite. A arbitrary scale was established (ranging from 1 to 4) for selecting the best strains, acording to growth, staining with Sudan black and solubilising cellular material. 108 isolates rated higher than 2 were obtained by using this scale; 44 of these were selected for evaluating them in a balloon flask for their ability to grow in sucrose. Scheffe’s test grouped the isolates evaluated in the balloon flask for polymer production and productivity. The 6 best isolates were evaluated in a fermenter to determine their kinetic growth profiles, substrate consumption and polymer accumulation. Differential scanning calorimeter (DSC) was used on the recovered polymer for determining fusion temperature and the conclusion was reached that 2 strains accumulated poly--hydroxybutyrate (PHB) and another 4 accumulated hydroxy-butyrate copolymers and other monomer units. These 6 strains were molecularly characterised by partially sequencing the 16s rRNA ribosomal gene, localizing them in 4 clusters on the taxonomic tree

The XIIIth Banff Conference on Allograft Pathology: The Banff 2015 Heart Meeting Report: Improving Antibody-Mediated Rejection Diagnostics: Strengths, Unmet Needs, and Future Directions.

The 13th Banff Conference on Allograft Pathology was held in Vancouver, British Columbia, Canada from October 5 to 10, 2015. The cardiac session was devoted to current diagnostic issues in heart transplantation with a focus on antibody-mediated rejection (AMR) and small vessel arteriopathy. Specific topics included the strengths and limitations of the current rejection grading system, the central role of microvascular injury in AMR and approaches to semiquantitative assessment of histopathologic and immunophenotypic indicators, the role of AMR in the development of cardiac allograft vasculopathy, the important role of serologic antibody detection in the management of transplant recipients, and the potential application of new molecular approaches to the elucidation of the pathophysiology of AMR and potential for improving the current diagnostic system. Herein we summarize the key points from the presentations, the comprehensive, open and wide-ranging multidisciplinary discussion that was generated, and considerations for future endeavors

Low-Dose Naltrexone for Pruritus in Systemic Sclerosis

Pruritus is a common symptom in systemic sclerosis (SSc), an autoimmune disease which causes fibrosis and vasculopathy in skin, lung, and gastrointestinal tract (GIT). Unfortunately, pruritus has limited treatment options in this disease. Pilot trials of low-dose naltrexone hydrochloride (LDN) for pruritus, pain, and quality of life (QOL) in other GIT diseases have been successful. In this case series we report three patients that had significant improvement in pruritus and total GIT symptoms as measured by the 10-point faces scale and the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) questionnaire. This small case series suggests LDN may be an effective, highly tolerable, and inexpensive treatment for pruritus and GIT symptoms in SSc

2030 agenda and its considerations in the framework of artisanal fishing cooperatives in Mexico

Objective: Analyze the objectives proposed by the UN, linking them in a theoretical and practical way with the real situation of artisanal fishing cooperativism in Mexico, opposing the theoretical scope of the 2030 Agenda vs. the real praxis of artisanal fishing communities. Design/methodology/approach: Through the application of a Participatory Rapid Assessment Workshop, the points of the 2030 Agenda were discussed with three artisanal fishing communities in Mexico. The participants got to know in a theoretical way the objectives presented by the UN, they selected those that, in their opinion, are an important and punctual part of their fishing activity, to later analyze these objectives and compare them with their practical reality.   Results: Conclusions, proposals and points were obtained by the social subjects recognizing as a general argument that for the Mexican artisanal fishing cooperativism the objectives of the 2030 Agenda are possible as long as the action strategy promotes a cooperative culture with community values ??and social bond, respect for their environment and way of life, as well as the sustainability of the sea as an object of work. Limitations of the study/implications: The main implication was the enormous importance that exists in bringing the theoretical considerations of international organizations and decision makers to the social base where these proposals operate. , since these spaces create discussions that allow the necessary theoretical-practical analysis in the social sciences. Finding/conclusions: The neoliberal global economic system is the main disagreement of the 2030 Agenda. The Agenda encourages developed countries to support underdeveloped countries with knowledge, technology and investments to achieve sustainability, but it does not recognize local knowledge, uses and customs of developing countries as an effective alternative.Objective: To analyze the objectives proposed by the UN, linking them in a theoretical and practical way with the real condition of artisanal fishing cooperatives in Mexico, contrasting the theoretical scope of the 2030 Agenda vs. the real praxis of the communities of artisanal fishermen. Design / Methodology / Approach: Through the application of a Participatory Rapid Appraisal Workshop (PRAW) points of the Agenda 2030 were discussed with three artisanal fishing communities in Mexico. The participants learned in a theoretical way the objectives presented by the UN; selected those that in their opinion are important and punctual parts of their fishing activity; and then analyzed these objectives comparing them with their practical daily reality. Results: Conclusions and clarifications were obtained from the social subjects in which it was recognized as a general argument that for the Mexican artisanal fishing cooperatives framework the objectives of the 2030 Agenda are possible as long as the action strategy promotes a cooperative culture with community values and social bonds; respect for their environment and way of life; as well as the sustainability of the ocean as their means of work. Limitations / Implications of the study: the main implication noticed was the enormous importance that exists towards delivering theoretical considerations from international organizations and decision makers, to the social base who operates these proposals. These spaces create discussions that allow the theoretical analysis of practical needs which is mandatory in the social sciences. Findings / Conclusions: The neoliberal globalized economic system is the main disagreement for the 2030 Agenda. The 2030 Agenda encourages developed countries to support under-developed countries with knowledge, technology and investments to achieve sustainability. However, the Agenda does not recognize local knowledge, use forms and customs in those developing countries, as effective operational alternatives

Androgen Regulated Genes in Human Prostate Xenografts in Mice: Relation to BPH and Prostate Cancer

Benign prostatic hyperplasia (BPH) and prostate carcinoma (CaP) are linked to aging and the presence of androgens, suggesting that androgen regulated genes play a major role in these common diseases. Androgen regulation of prostate growth and development depends on the presence of intact epithelial-stromal interactions. Further, the prostatic stroma is implicated in BPH. This suggests that epithelial cell lines are inadequate to identify androgen regulated genes that could contribute to BPH and CaP and which could serve as potential clinical biomarkers. In this study, we used a human prostate xenograft model to define a profile of genes regulated in vivo by androgens, with an emphasis on identifying candidate biomarkers. Benign transition zone (TZ) human prostate tissue from radical prostatectomies was grafted to the sub-renal capsule site of intact or castrated male immunodeficient mice, followed by the removal or addition of androgens, respectively. Microarray analysis of RNA from these tissues was used to identify genes that were; 1) highly expressed in prostate, 2) had significant expression changes in response to androgens, and, 3) encode extracellular proteins. A total of 95 genes meeting these criteria were selected for analysis and validation of expression in patient prostate tissues using quantitative real-time PCR. Expression levels of these genes were measured in pooled RNAs from human prostate tissues with varying severity of BPH pathologic changes and CaP of varying Gleason score. A number of androgen regulated genes were identified. Additionally, a subset of these genes were over-expressed in RNA from clinical BPH tissues, and the levels of many were found to correlate with disease status. Our results demonstrate the feasibility, and some of the problems, of using a mouse xenograft model to characterize the androgen regulated expression profiles of intact human prostate tissues

Applied interpolation methodology with GIS used for artisanal fishing zoning in Bahía Magdalena, Mexico

Objective: To limit the artisanal fishing zones in the water mirror of Magdalena Bay, by means of interpolation. Design/methodology/approach: Through surveys, social, economic and biological production data, wich are collected from a sample of 56 artisanal fishing cooperatives. The data is integrated into a relational database with geospatial reference and geostatistically processed with interpolation methods using a geographic information system. Results: Four zoning maps based on the interpolation of the variables target species, fishing effort, extraction volume and sale value. Limitations on study/implications: The remoteness and difficult access to the study area. Findings/conclusions: The methodology can be used at the national level and generate a limitation of the priority zones for artisanal fishing in Mexico, contributing to decision making and management plans that can consider the variables of the fishermen's social life

Conservation threats and future prospects for the freshwater fishes of Ecuador: A hotspot of Neotropical fish diversity

Freshwater fish communities in Ecuador exhibit some of the highest levels of diversity and endemism in the Neotropics. Unfortunately, aquatic ecosystems in the country are under serious threat and conditions are deteriorating. In 2018–19, the government of Ecuador sponsored a series of workshops to examine the conservation status of Ecuador''s freshwater fishes. Concerns were identified for 35 species, most of which are native to the Amazon region, and overfishing of Amazonian pimelodid catfishes emerged as a major issue. However, much of the information needed to make decisions across fish groups and regions was not available, hindering the process and highlighting the need for a review of the conservation threats to Ecuador''s freshwater fishes. Here, we review how the physical alteration of rivers, deforestation, wetland and floodplain degradation, agricultural and urban water pollution, mining, oil extraction, dams, overfishing, introduced species and climate change are affecting freshwater fishes in Ecuador. Although many of these factors affect fishes throughout the Neotropics, the lack of data on Ecuadorian fish communities is staggering and highlights the urgent need for more research. We also make recommendations, including the need for proper enforcement of existing environmental laws, restoration of degraded aquatic ecosystems, establishment of a national monitoring system for freshwater ecosystems, investment in research to fill gaps in knowledge, and encouragement of public engagement in citizen science and conservation efforts. Freshwater fishes are an important component of the cultural and biological legacy of the Ecuadorian people. Conserving them for future generations is critical. © 2021 The Authors. Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of Fisheries Society of the British Isles

European and Asian contribution to the genetic diversity of mainland South American chickens

Chickens (Gallus gallus domesticus) from the Americas have long been recognized as descendants of European chickens, transported by early Europeans since the fifteenth century. However, in recent years, a possible pre-Columbian introduction of chickens to South America by Polynesian seafarers has also been suggested. Here, we characterize the mitochondrial control region genetic diversity of modern chicken populations from South America and compare this to a worldwide dataset in order to investigate the potential maternal genetic origin of modern-day chicken populations in South America. The genetic analysis of newly generated chicken mitochondrial control region sequences from South America showed that the majority of chickens from the continent belong to mitochondrial haplogroup E. The rest belongs to haplogroups A, B and C, albeit at very low levels. Haplogroup D, a ubiquitous mitochondrial lineage in Island Southeast Asia and on Pacific Islands is not observed in continental South America. Modern-day mainland South American chickens are, therefore, closely allied with European and Asian chickens. Furthermore, we find high levels of genetic contributions from South Asian chickens to those in Europe and South America. Our findings demonstrate that modern-day genetic diversity of mainland South American chickens appear to have clear European and Asian contributions, and less so from Island Southeast Asia and the Pacific Islands. Furthermore, there is also some indication that South Asia has more genetic contribution to European chickens than any other Asian chicken populations.Michael B. Herrera, Spiridoula Kraitsek, Jose A. Alcalde, Daniel Quiroz .... Vicki Thomson ... Jeremy J. Austin ... et al

Cardiac metabolomics and autopsy in a patient with early diffuse systemic sclerosis presenting with dyspnea: A case report

Introduction: Diffuse systemic sclerosis is associated with high mortality; however, the pathogenesis of cardiac death in these patients is not clear. Case presentation: A 56-year-old Caucasian female patient presented with dyspnea and requested to donate her body to science in order to improve understanding of diffuse systemic sclerosis pathogenesis. She had extensive testing for dyspnea including pulmonary function tests, an echocardiogram, cardiac magnetic resonance imaging, and right heart catheterization to characterize her condition. Her case highlights the morbidity seen in this disease, including the presence of extensive skin thickening, digital ulcerations, and scleroderma renal crisis. Conclusion: In this case report, we present the finding of cardiac tissue metabolomics, which may indicate a problem with vasodilation as a contributor to cardiac death in diffuse systemic sclerosis. The use of autopsy and tissue metabolomics in rare disease may help clarify disease pathogenesis