Dand5 is involved in zebrafish tailbud cell movement

Funding Information: This work was supported by the Fundação para a Ciência e a Tecnologia (FCT-ANR/BEX-BID/0153/2012 research grant and by the Project LysoCil funded by the European Union Horizon 2020 research and innovation under grant agreement No. 811087. SSL was funded by an FCT CEEC contract for Principal Investigator reference 2018CEECIND/02170/2018 and CB was funded by a FCT SFRH/BD/141034/2018 PhD fellowship. NMS and IGC Fish Facilities were supported from the research infrastructure Congento, co-financed by Lisboa Regional Operational Programme (Lisboa 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and FCT under the project LISBOA-01-0145-FEDER-022170. Publisher Copyright: Copyright © 2023 Bota, Martins and Lopes.During vertebrate development, symmetry breaking occurs in the left-right organizer (LRO). The transfer of asymmetric molecular information to the lateral plate mesoderm is essential for the precise patterning of asymmetric internal organs, such as the heart. However, at the same developmental time, it is crucial to maintain symmetry at the somite level for correct musculature and vertebrae specification. We demonstrate how left-right signals affect the behavior of zebrafish somite cell precursors by using live imaging and fate mapping studies in dand5 homozygous mutants compared to wildtype embryos. We describe a population of cells in the vicinity of the LRO, named Non-KV Sox17:GFP+ Tailbud Cells (NKSTCs), which migrate anteriorly and contribute to future somites. We show that NKSTCs originate in a cluster of cells aligned with the midline, posterior to the LRO, and leave that cluster in a left-right alternating manner, primarily from the left side. Fate mapping revealed that more NKSTCs integrated somites on the left side of the embryo. We then abolished the asymmetric cues from the LRO using dand5−/− mutant embryos and verified that NKSTCs no longer displayed asymmetric patterns. Cell exit from the posterior cluster became bilaterally synchronous in dand5−/− mutants. Our study revealed a new link between somite specification and Dand5 function. The gene dand5 is well known as the first asymmetric gene involved in vertebrate LR development. This study revealed a new link for Dand5 as a player in cell exit from the maturation zone into the presomitic mesoderm, affecting the expression patterns of myogenic factors and tail size.publishersversionpublishe

Municipal solid waste management in Kazakhstan : astana and almaty case studies

The present paper provides an overview of the Municipal Solid Waste (MSW) management in Kazakhstan and focuses in more detail on two major cities, Astana, the new capital and Almaty, the former capital of the country. Legislation, current management policy, facilities and infrastructure, as well as typical solid waste quantity and composition are presented and analysed in detail in the light of the recently approved long-Term waste management plan. The analysis is supported by the implementation of a Decision Support Tool (DSS), which provides insights in waste management needs and supports comparison and ranking of Integrated Waste Management (IWMP) alternatives. Finally, a certain IWMP plan is proposed, which could be used as a basis for further detailed feasibility studies

Endogenous and exogenous testosterone and the risk of prostate cancer and increased prostate-specific antigen (PSA) level: a meta-analysis

Objective: To review and quantify the association between endogenous and exogenoustestosterone and prostate-specific antigen (PSA) and prostate cancer. Methods: Literature searches were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Prospectivecohort studies that reported data on the associations between endogenous testosterone and prostate cancer, and placebo-controlled randomized trials of testosterone replacement therapy (TRT) that reported data on PSA and/or prostate cancer cases were retained. Meta-analyses were performed using random-effects models, with tests for publication bias and heterogeneity. Results: Twenty estimates were included in a meta-analysis, which produced a summary relative risk (SRR) of prostate cancer for an increase of 5 nmol/L of testosterone of 0.99 (95% confidence interval [CI] 0.96, 1.02) without heterogeneity (I2 = 0%).Based on 26 trials, the overall difference in PSA levels after onset of use of TRT was 0.10 ng/mL (-0.28, 0.48). Results were similar when conducting heterogeneity analyses by mode of administration, region, age at baseline, baseline testosterone, trial duration, type of patients and type of TRT. The SRR of prostate cancer as an adverse effect from 11 TRT trials was 0.87 (95% CI0.30; 2.50). Results were consistent across studies. Conclusions: Prostate cancer appears to be unrelated to endogenous testosterone levels. TRT for symptomatic hypogonadism does not appear to increase PSA levels nor the risk of prostate cancer development. The current data are reassuring, although some caution is essential until multiple studies with longer follow-up are available

Clostridium Difficile in a Tertiary Pediatric Hospital

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Transcranial magnetic stimulation–associated mania with psychosis: A case report

Transcranial magnetic stimulation (TMS) is a noninvasive procedure used in the treatment of depression. We observed TMS-associated mania with psychotic symptoms in a 55-year-old male diagnosed with MDD and generalized anxiety disorder without history of psychosis or mania. Owing to poor pharmacotherapeutic response and worsening symptomatology, TMS was introduced while continuing phenelzine; this was initially successful in demonstrating positive effects on mood. However, the patient began to develop symptoms consistent with mania with psychosis and was hospitalized. Both TMS and phenelzine were discontinued, leading to significant improvement of the symptoms of mania and psychosis. Phenelzine was later reintroduced for maintenance treatment of depression and anxiety, with no recurrence of mania or psychosis. This case report implicates TMS as a possible cause of mania and psychosis symptoms

Phosphorylation at Ser-181 of oncogenic KRAS is required for tumor growth

KRAS phosphorylation has been reported recently to modulate the activity of mutant KRAS protein in vitro. In this study, we defined S181 as a specific phosphorylation site required to license the oncogenic function of mutant KRAS in vivo. The phosphomutant S181A failed to induce tumors in mice, whereas the phosphomimetic mutant S181D exhibited an enhanced tumor formation capacity, compared with the wild-type KRAS protein. Reduced growth of tumors composed of cells expressing the nonphosphorylatable KRAS S181A mutant was correlated with increased apoptosis. Conversely, increased growth of tumors composed of cells expressing the phosphomimetic KRAS S181D mutant was correlated with increased activation of AKT and ERK, two major downstream effectors of KRAS. Pharmacologic treatment with PKC inhibitors impaired tumor growth associated with reduced levels of phosphorylated KRAS and reduced effector activation. In a panel of human tumor cell lines expressing various KRAS isoforms, we showed that KRAS phosphorylation was essential for survival and tumorigenic activity. Furthermore, we identified phosphorylated KRAS in a panel of primary human pancreatic tumors. Taken together, our findings establish that KRAS requires S181 phosphorylation to manifest its oncogenic properties, implying that its inhibition represents a relevant target to attack KRAS-driven tumors

Nephrolithiasis in a Portuguese Pediatric Population

Introduction and Aims: Nephrolithiasis incidence in children has increased considerably. It is associated with substantial morbidity, recurrence and increased adulthood cardiovascular risk and chronic kidney disease. A thorough investigation is essential, as rare forms of urolithiasis have increased risk of renal failure. We aim to determine the epidemiology and outcomes of a pediatric population with nephrolithiasis presented in a nephrology unit of a tertiary centre. Methods: Retrospective study of the records of all children (<18 years) with nephrolithiasis diagnosis between 2008‑17. Clinical features, etiology, recurrence, treatment, and outcomes were evaluated and compared throughout the study period through two equal periods (2008‑12 versus 2013‑17). Results: We identified 80 cases: isolated nephrolithiasis (86%) and associated with nephrocalcinosis (14%). Mean follow‑up was 36 months (14–120). Median age at presentation was 8.6 years [3 months – 17 years]: 21% < 2 years‑old and 46% ≥ 10 years. The annual ratio of referrals for nephrolithiasis increased on average 1.2% per year [0.3‑11.8%]. Multiple etiological factors were present in 34%. A metabolic abnormality was identified in 54%: hypocitraturia (34%), hypercalcuria (24%), hyperoxaluria (15%), hyperuricosuria (15%) and cystinuria (1%), without age predominance (p=0.2). Urinary tract infection (24%) was the next most significant etiology and was more frequent below 2 years of age (p=0.001) and associated with struvite calculi (p=0.033). Median age at diagnosis was significantly lower in the study’s first half (5 vs 10 years; p=0.019) and an infectious etiology was more frequent (p=0.043). In a logistic‑regression analysis, a family history of nephrolithiasis was associated with a metabolic cause (p<0.01). Sixty‑three percent became stone free and 24% had recurrence. Discussion: Nephrolithiasis new referrals gradually increased throughout the study period. The most common etiology was metabolic, which is usually responsible for nephrolithiasis appearance and its recurrence, emphasizing the need for a complete evaluation.info:eu-repo/semantics/publishedVersio