POS-1 Regulation of Endo-mesoderm Identity in C. elegans: A Dissertation

How do embryos develop with such poise from a single zygote to multiple cells with different identities, and yet survive? At the four-cell stage of the C. elegans embryo, only the blastomere EMS adopts the endo-mesoderm identity. This fate requires SKN-1, the master regulator of endoderm and mesoderm differentiation. However, in the absence of the RNA binding protein POS-1, EMS fails to fulfill its fate despite the presence of SKN-1. pos-1(-) embryos die gutless. Conversely, the RNA binding protein MEX-5 prevents ectoderm blastomeres from adopting the endo-mesoderm identity by repressing SKN-1. mex-5(-) embryos die with excess muscle at the expense of skin and neurons. Through forward and reverse genetics, I found that genes gld-3/Bicaudal C, cytoplasmic adenylase gld-2, cye-1/Cyclin E, glp-1/Notch and the novel gene neg-1 are suppressors that restore gut development despite the absence of pos-1. Both POS-1 and MEX-5 bind the 3’UTR of neg-1 mRNA and its poly(A) tail requires GLD-3/2 for elongation. Moreover, neg-1 requires MEX-5 for its expression in anterior ectoderm blastomeres and is repressed in EMS by POS-1. Most neg-1(-) embryos die with defects in anterior ectoderm development where the mesoderm transcription factor pha-4 becomes ectopically expressed. This lethality is reduced by the concomitant loss of med- 1, a key mesoderm-promoting transcription factor. Thus the endo-mesoderm identity of EMS is determined by the presence of SKN- 1 and the POS-1 repression of neg-1, whose expression is promoted by MEX-5. Together they promote the anterior ectoderm identity by repressing mesoderm differentiation. Such checks and balances ensure the vital plurality of cellular identity without the lethal tyranny of a single fate

Cost-effectiveness Evaluations Among the Direct Oral Anticoagulants for the Prevention and Treatment of Venous Thromboembolism: Systematic Review

Venous thromboembolism (VTE) is associated with high recurrence, mortality, and cost burden. Direct oral anticoagulants (DOACs) are currently used for VTE treatment, and they offer more benefits over warfarin, despite being more expensive. There is no consensus on the most cost-effective DOAC agent, especially in VTE. This systematic review aims to summarize the comparative cost-effectiveness studies and their impact among DOACs in the treatment of VTE. Literature systematic review of PubMed, Embase, and EconLit was conducted in February 2018 to identify all cost-effectiveness studies of DOAC for the treatment and prevention of VTE. Two independent investigators systematically collected search results and assessed the quality of the studies. The search identified 7 articles, all of which had dabigatran and rivaroxaban as comparators, 6 of which also included apixaban, and 2 of which also had edoxaban. Results of 3 articles concluded that apixaban is a dominant strategy compared to other DOACs in terms of Incremental Cost-Effectiveness Ratio (ICER) in the treatment and prevention of recurrent VTE. One article compared rivaroxaban and dabigatran, with the latter dominating rivaroxaban in terms of ICER. Compared to other DOACs, 2 articles reported apixaban being associated with highest annual total medical cost avoidance of US$4244 and US$4440 per patient-year (ppy), respectively. One article reported that apixaban had the highest annual total medical cost differences of US$918 ppy compared to other DOACs. This systematic review demonstrates that apixaban is considered a cost-effective strategy for VTE treatment and prevention of recurrent VTE.This report was made possible by Qatar University grant # (QUST-1-CPH-2019-3). The statements made herein are solely the responsibility of the authors.Scopu

Sinai and Norfa chicken diversity revealed by microsatellite markers

The present study aimed to outline the population differentiation of Sinai and Norfa chicken, native to Egypt, with microsatellite markers. Twenty microsatellite loci recommended by the Food and Agriculture Organization (FAO) were used. Fifty eight birds were sampled (29 for each strain: 12 males + 17 females). Data were collected and genetic diversity indicators were assessed utilizing the approaches implemented in FSTAT, Cervus 3.0.7 and GenAlEx 6.5 software programmes. A total number of 182 alleles were detected with an average value of 9.1 allele per locus. The expected heterozygosity was 6.625 and 6.343 in Norfa and Sinai chickens, respectively. Norfa chickens produced 15 private alleles, while there were 9 unique alleles detected in Sinai chickens (13.18% private alleles as a percentage of the total observed number of alleles). Fixation indices’ (FST, FIS, and FIT) values were 0.060, 0.410 and 0.438, respectively, across all 20 loci investigated. Results indicated that the studied populations were genetically differentiated. Consequently, they have high breeding potential. Efforts should be made to incorporate the other local chicken strains as unique genetic resources into conservation programmes. This should begin with proper management of these flocks to ensure the maintenance of their genetic diversity over time by avoiding inbreeding. Such information is likely to have a profound effect on the success of genetic improvement and completes information from phenotypes and biometric measurements of the domestic chickens in Egypt.Keywords: Egyptian, genetic diversity, local chicken, microsatellit

An Optimum Performance of A Flat-Type Solar Air Heater With A Porous Absorber

This investigation is concerned with the design and performance of a flat solar air heater in which air flows perpendicular from a vented transparent cover through a porous absorber plate. The design phase involves a stability analysis to determine the critical distance (maximum allowable distance) between the absorber and transparent plates, for suppressing convection currents, under a variety of environmental and operating conditions. These results are expected to be useful to designers of solar collectors. In addition, the thermal performance of this solar heater at its optimum design conditions was computed for a wide range of system parameters illustrating the contributions of conduction and radiative modes of heat transfer. The results indicate that best operating efficiency can be obtained when running the collector with mass flow rate, m > 40 Kg/m2 hr

Arthropods on Mars?

As presented in this report numerous fossils like forms resembling a variety of marine arthropods including crustaceans, sea spiders, scorpions, arachnids, nematodes, annelids, tube worms, sea snakes, Kimberlla, Namacalathus, Lophotrochozoa, armored trilobites and millipedes have been found in Gale Crater (on Sols 302, 553, 753, 781, 809, 869, 880, 905, 1032), and Meridiani Planum both of which have hosted rivers, lakes, and inland seas. Similar specimens are mixed within a variety of divergent fossillike forms and are also found on distant sediment and mud stone. All specimens are distinct from underlying substrate and there are no obvious patterns or repetitions typically produced by erosion or weathering. Although without extraction and direct examination it is impossible to precisely determine the identity of all these specimens, the same problems bedevil identification of Burgess Shale fossils some of which are presented in this report for comparative analysis. The discoveries presented here and in other reports supports the theory that metazoans and other marine organisms evolved in the lakes, oceans and inland seas of Mars

The Taman Siswa in Postwar Indonesia

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Diosgenin alleviates D-galactose-induced oxidative stress in rats’ brain and liver targeting aging and apoptotic marker genes

The theory of aging is primarily concerned with oxidative stress caused by an imbalance in reactive oxygen species generation and cellular antioxidants. To alleviate the oxidative stress, we investigated the protective effect of diosgenin (DSG) for D-galactose (D-gal) using 20 and 40 mg of DSG/kg/day/orally for 42 days. The findings showed that D-gal caused brain and liver oxidative injuries by upregulating aging and oxidative markers. To counteract the oxidative stress caused by D-gal, DSG upregulated glutathione peroxidase-1, superoxide dismutase-1, and glutathione S-transferase-α. DSG also diminished the expression of p53, p21, Bcl-2-associated X protein, caspase-3, and mammalian target of rapamycin in brain and liver, as well as the build-up of β-galactosidase. DSG, in a dose-dependent manner, decreased the oxidative aging effects of D-gal in brain and liver tissues through targeting of aging and apoptotic marker genes. Finally, it should be noted that consuming DSG supplements is a suggesting natural preventative agent that may counteract aging and preserve health through improvement of body antioxidant status and control aging associated inflammation and cellular apoptosis

The Flip of the Coin of Personalized Cancer Immunotherapy: A Focused Review on Rare Immune Checkpoint Related Adverse Effects

Immune checkpoint inhibitors (ICIs) are a type of cancer immunotherapy that has provided a tremendous breakthrough in the field of oncology. Currently approved checkpoint inhibitors target the cytotoxic T-lymphocyte-associated protein 4 (CTLA4), programmed death receptor-1 (PD-1), and programmed death-ligand 1(PD-L1). One of the most known complications of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs). In this chapter, we will focus on selected rare or very rare irAEs, shedding the light on the other side of the coin of personalized cancer immunotherapy. We will also discuss general management approach of irAEs with an in-depth look on each one of these rare irAEs. The chapter will also cover principles of immunotherapy rechallenge post-occurrence of irAEs, and the impact of irAEs incidence on the efficacy of ICI. We will discuss some of the rare or very rare irAEs including cutaneous irAEs, immune-mediated Hypophysitis, hematological irAEs, ophthalmic irAEs, checkpoint inhibitor pneumonitis (CIP), neurologic irAEs, infectious irAEs, and cardiac irAEs. This chapter tried to highlight the significance of identifying emerging rare and very rare irAEs while considering initial assessments and management approaches identified in various clinical practice guideline and primary literature data