Effect of Metabolic Acidosis on Immunoregulation in Prevalent Hemodialysis Patients

Objective to evaluate the relationship between IL-10 and serum bicarbonate and metabolic acidosis in prevalent hemodialysis patients. Methods Type of Study: prospective case control study. Study Setting: The study was conducted at Ain Shams University hospital hemodialysis unit. Sample Size: 40 patients with ESRD on regular HD and 20 healthy control. Study Population: Maintenance hemodialysis patients Results The results suggested that serum IL-10 level was significantly higher in chronic HD patients than healthy subjects and this is compatible with the idea that higher levels of IL‑10 are needed in HD patients to limit their strong inflammatory activation associated with uremia and the dialysis technique. There was no significant differences in IL-10 levels noticed between patients with different causes of ESRD. This study also showed negative correlation between IL-10 and serum bicarbonate levels. We also found that there was significant positive correlation between baseline levels of IL-10 and CRP which may be because of dialysis inadequacy that is associated with chronic inflammatory state resulting in high CRP levels. Conclusion The incidence and prevalence of ESRD have risen dramatically which may be due to the increasing prevalence of diabetes and hypertension. Although regular hemodialysis decreases levels of mortality in these patients, it is still considered a condition associated with inflammation. The current study revealed high IL-10 levels among HD patients who had metabolic acidosis. Further research needs to be done to reveal beneficial effects of these finding.

The WRAD complex represents a therapeutically exploitable target for cancer stem cells in glioblastoma

SummaryGlioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We employed spatially resolved loss-of-function screening in GBM patient-derived organoids to identify essential epigenetic regulators and identified WDR5 as indispensable for CSCs. WDR5 is a component of the WRAD complex, which promotes SET1-family-mediated Lys4 methylation of histone H3, associated with positive regulation of transcription. Genetic and pharmacologic inhibition of WDR5 reduced growth and self-renewal of CSCs as well as CSC-mediated tumor growth. Further, WDR5 inhibitors partially blocked WRAD complex assembly, reduced H3K4 trimethylation, and inhibited tumor growth. These findings highlight the role of WDR5 and the WRAD complex in CSCs for maintaining the CSC state and provide a rationale for therapeutic development of WRAD complex inhibitors for GBM and other advanced cancers.

Within- and Trans-Generational Environmental Adaptation to Climate Change: Perspectives and New Challenges

The current and projected impacts of climate change are shaped by unprecedented rates of change in environmental conditions. These changes likely mismatch the existing coping capacities of organisms within-generations and impose challenges for population resilience across generations. To better understand the impacts of projected scenarios of climate change on organismal fitness and population maintenance, it is crucial to consider and integrate the proximate sources of variability of plastic and adaptive responses to environmental change in future empirical approaches. Here we explore the implications of considering: (a) the variability in different time-scale events of climate change; (b) the variability in plastic responses from embryonic to adult developmental stages; (c) the importance of considering the species life-history traits; and (d) the influence of trans-generational effects for individual survival and population maintenance. Finally, we posit a list of future challenges with questions and approaches that will help to elucidate knowledge gaps, to better inform conservation and management actions in preserving ecosystems and biodiversity.

Comprehensive DNA methylation-transcriptome profiles association analysis During the Treatment of Acute Myelocytic Leukemia

Background: Epigenetic modifications have recently attracted much attention in the study of the biological mechanisms of acute myelocytic leukemia (AML) for therapy and prognosis. However, studies on DNA methylation changes during AML treatment are limited. Objective: The comprehensive DNA methylation-transcriptome profiles association analysis in this study aimed to establish whole-genome DNA methylation profiles and explore DNA methylation-related genes and their potential functions before and after treatment. And more appropriate biomarkers are expected to be identified for therapy strategies in AML. Method: Illumina 450K and RNA-Seq data were obtained from The Cancer Genome Atlas. We performed comprehensive DNA methylation-transcriptome profiles association analysis, pathway analysis, correlation analysis, and survival analyses. The StarBase database was utilized to predict interactions between lncRNAs, miRNAs and target mRNAs. Results: In total, 1592 distinct CpG sites and 2419 different expression transcripts were identified between pre-treatment and post-treatment AML. The significantly enriched functions of methylated genes were stem cell differentiation, cell population maintenance, and cell development. The expression of UGT3A2, MOG, and VSTM1 was correlated with DNA methylation levels (r2>0.5). Lastly, we identified 4 lncRNAs, 9 miRNAs and 142 mRNAs to construct a lncRNA-miRNA-mRNA ceRNA network. Conclusion: Our results revealed that DNA methylation was altered before and after treatment. Alterations in DNA methylation affected target gene expression and participated in the key biological processes of AML. Therefore, ceRNA networks may provide further insight into the study of favorable therapeutic markers in AML.

Plasticity and Multiplicity of Trophic Modes in the Dinoflagellate Karlodinium and Their Pertinence to Population Maintenance and Bloom Dynamics

As the number of mixotrophic protists has been increasingly documented, “mixoplankton”, a third category separated from the traditional categorization of plankton into “phytoplankton” and “zooplankton”, has become a new paradigm and research hotspot in aquatic plankton ecology. While species of dinoflagellates are a dominant group among all recorded members of mixoplankton, the trophic modes of Karlodinium, a genus constituted of cosmopolitan toxic species, were reviewed due to their representative features as mixoplankton and harmful algal blooms (HABs)-causing dinoflagellates. Among at least 15 reported species in the genus, three have been intensively studied for their trophic modes, and all found to be phagotrophic. Their phagotrophy exhibits multiple characteristics: (1) omnivority, i.e., they can ingest a variety of preys in many forms; (2) flexibility in phagotrophic mechanisms, i.e., they can ingest small preys by direct engulfment and much bigger preys by myzocytosis using a peduncle; (3) cannibalism, i.e., species including at least K. veneficum can ingest the dead cells of their own species. However, for some recently described and barely studied species, their tropical modes still need to be investigated further regarding all of the above-mentioned aspects. Mixotrophy of Karlodinium plays a significant role in the population dynamics and the formation of HABs in many ways, which thus deserves further investigation in the aspects of physiological ecology, environmental triggers (e.g., levels of inorganic nutrients and/or presence of preys), energetics, molecular (genes and gene expression regulations) and biochemical (e.g., relevant enzymes and signal molecules) bases, origins, and evaluation of the advantages of being a phagotroph.

Этноэкономика как фактор развития регионов (на примере республик Калмыкии и Бурятии)

Ethnic trade is one of the high-potential areas of the regional economy as it contributes to the growth of self-employment and the income of the population, maintenance of the rural settlements, traditional ways of natural resource use, unique manufacturing techniques. According to several researchers, nowadays ethno-economics successfully develops in service industry. The new areas of the ethno-economic development include ethno-tourism, folk crafts and handicrafts, and also raw material processing. The goal of the article is to study ethno-economic aspects of contemporary businesses in Mongol-origin regions of Russia: Kalmykia and Buryatia. There was an opinion poll among the representatives of ethnic businesses in both regions. The experts in Kalmykia as well as Buryatia point out the popularity and high demand for ethnic products, handmade goods in the areas such as ethnic fashion, ethnic design, and also ethnic tourism, ethnic restaurants that indicate the prospects of ethnic businesses and ethnic trade in the given regions. The active restoration of Buddhism, reinstatement and development of national culture and also rich natural resources make the regions in question attractive for tourists. Cultural events held in these regions are among top-destinations of eventful and eco-tourism in the country. Thus, the ethno-economics of these regions that transferred from commercial specifics to specification in service industry is one of the sources of development of the given regions.

Protecting nursery areas without fisheries management is not enough to conserve the most endangered parrotfish of the Atlantic Ocean

Marine protected areas (MPAs) are a primary strategy for marine conservation worldwide, having as a common goal the protection of essential habitats to enhance fish population recovery. However, MPAs alone may not be effective because species are not isolated from critical impacts occurring outside their boundaries. We evaluated how protecting critical nursery habitats affect the population of an important fishing target, using a 6-year database to predict juvenile hotspots and estimate population trends of the endemic and endangered parrotfish Scarus trispinosus within a mosaic of MPAs at the Abrolhos Bank, NE Brazil. We found that important nursery habitats are within no-take areas, but both juvenile and adult populations still show a declining trend over time. MPAs failed to ensure population maintenance and recovery likely due to overfishing in adjacent areas and the lack of compliance to management rules within multiple-use and within no-take MPAs. MPAs alone are not enough to protect ecologically important endangered species, but is still one of the only conservation strategies, particularly in developing countries. Our results shed light on the need for a wider adoption of more effective conservation policies in addition to MPAs, both in Brazil and in countries with similar governance contexts.

4531 Setting the Stage for Research Success: Creation of Standardized Physician-Scientist Training Program Guidelines to Facilitate Research During Clinical Training

OBJECTIVES/GOALS: To ameliorate the leaky pipeline of physician-scientists, we must address the factors that cause medical trainees to disengage from research. Here we describe the development of standardized Physician-Scientist Training Program guidelines that may be implemented across disciplines to address these challenges. METHODS/STUDY POPULATION: Maintenance of a robust pool of physician-scientists is critical to meet the rapidly growing need for novel therapeutics. A variety of factors contribute to the decline of this pool. Key among these are a lengthy training period that segregates research from clinical training, thus impeding research progress and milestones that allow for a successful research career. Through engagement of residency program directors and Vice Chairs of Research, we have created a series of guidelines that promote residency research tracks and enable better integration of research and clinical training time. Guidelines have been piloted in the Departments of Pediatrics, Medicine and Surgery in the context of 2 new R38-supported programs. RESULTS/ANTICIPATED RESULTS: Our physician-Scientist Training Program (PSTP) guidelines were developed by our central Office of Physician-Scientist Development (OPSD) after a successful pilot of an integrated research residency program in the Department of Pediatrics [Duke Pediatric Research Scholars (DPRS); Hurst, et al, 2019], which has included 36 resident and fellow scholars over 3 years. To date, eight clinical departments have adopted our PSTP guidelines as part of their R38-supported or pending programs. The OPSD has recently created a tracking database for scholar metrics, which will further promote PSTP development by enabling centralized reporting on scholar success to individual programs. DISCUSSION/SIGNIFICANCE OF IMPACT: PSTP guidelines enable effective implementation of new programs by sharing best practices and lessons learned, standardizing expectations, and defining metrics of success. By promoting proven strategies for integrated clinical and research training, PSTP guidelines may aid in retaining trainees pursuing research careers.