Essential and recurrent roles for hairpin RNAs in silencing de novo sex chromosome conflict in Drosophila simulans.

Meiotic drive loci distort the normally equal segregation of alleles, which benefits their own transmission even in the face of severe fitness costs to their host organism. However, relatively little is known about the molecular identity of meiotic drivers, their strategies of action, and mechanisms that can suppress their activity. Here, we present data from the fruitfly Drosophila simulans that address these questions. We show that a family of de novo, protamine-derived X-linked selfish genes (the Dox gene family) is silenced by a pair of newly emerged hairpin RNA (hpRNA) small interfering RNA (siRNA)-class loci, Nmy and Tmy. In the w[XD1] genetic background, knockout of nmy derepresses Dox and MDox in testes and depletes male progeny, whereas knockout of tmy causes misexpression of PDox genes and renders males sterile. Importantly, genetic interactions between nmy and tmy mutant alleles reveal that Tmy also specifically maintains male progeny for normal sex ratio. We show the Dox loci are functionally polymorphic within D. simulans, such that both nmy-associated sex ratio bias and tmy-associated sterility can be rescued by wild-type X chromosomes bearing natural deletions in different Dox family genes. Finally, using tagged transgenes of Dox and PDox2, we provide the first experimental evidence Dox family genes encode proteins that are strongly derepressed in cognate hpRNA mutants. Altogether, these studies support a model in which protamine-derived drivers and hpRNA suppressors drive repeated cycles of sex chromosome conflict and resolution that shape genome evolution and the genetic control of male gametogenesis.

Molecular control of the female germline stem cell niche size in Drosophila.

Adult stem cells have a unique capacity to renew themselves and generate differentiated cells that are needed in the body. These cells are recruited and maintained by the surrounding microenvironment, known as the stem cell niche, during organ development. Thus, the stem cell niche is required for proper tissue homeostasis, and its dysregulation is associated with tumorigenesis and tissue degeneration. The identification of niche components and the mechanisms that regulate niche establishment and maintenance, however, are just beginning to be uncovered. Germline stem cells (GSCs) of the Drosophila ovary provide an excellent model for studying the stem cell niche in vivo because of their well-characterized cell biology and the availability of genetic tools. In this review, we introduce the ovarian GSC niche, and the key signaling pathways for niche precursor segregation, niche specification, and niche extracellular environment establishment and niche maintenance that are involved in regulating niche size during development and adulthood.

Tumor Suppressor Lzap Suppresses Wnt/ß-Catenin Signaling to Promote Zebrafish Embryonic Ventral Cell Fates via the Suppression of Inhibitory Phosphorylation of Glycogen Synthase Kinase 3.

Wnt/ß-catenin signaling controls various cell fates in metazoan development, and its dysregulation is often associated with cancer formation. However, regulations of this signaling pathway are not completely understood. Here, we report that Lzap, a tumor suppressor, controls nuclear translocation of ß-catenin. In zebrafish embryos disruption of lzap increases the expression of chordin (chd), which encodes a bone morphogenetic protein (BMP) antagonist that is localized in prospective dorsal cells and promotes dorsal fates. Consistently, lzap-deficient embryos with attenuated BMP signaling are dorsalized, which can be rescued by overexpression of zebrafish lzap or bmp2b or human LZAP. The expansion of chd expression in embryos lacking lzap is due to the accumulation of nuclear ß-catenin in ventral cells, in which ß-catenin is usually degraded. Furthermore, the activity of GSK3, a master regulator of ß-catenin degradation, is suppressed in lzap-deficient embryos via inhibitory phosphorylation. Finally, we also report that a similar regulatory axis is also likely to be present in a human tongue carcinoma cell line, SAS. Our results reveal that Lzap is a novel regulator of GSK3 for the maintenance of ventral cell properties and may prevent carcinogenesis via the regulation of ß-catenin degradation.

Increased intraoperative vein ligation in microsurgical varicocelectomy is associated with pain improvement.

Varicocele is a major cause of male infertility. However, few studies have discussed the potential associations between the pain caused by varicocele and preoperative and intraoperative factors. The aim of this study was to evaluate factors potentially associated with changes in pain score after microsurgical varicocelectomy. This retrospective study was conducted between August 2020 and August 2022 at China Medical University Hospital in Taichung, Taiwan. Patient characteristics including age, body mass index, semen analysis, testicular volume, and the number of veins ligated were collected. Preoperative and intraoperative factors were analyzed to determine if they were correlated with changes in numeric rating scale (NRS) after microsurgical varicocelectomy. A total of 44 patients with clinical varicocele underwent subinguinal microsurgical varicocelectomy and were analyzed. The overall pain resolution rate was 91%, and the average satisfaction score after surgery was 9.2 according to their subjective feelings. Multivariate analysis revealed that severe varicocele grade (odds ratio [OR] 16.5, 95% confidence interval [CI] 3.01-90.47; P = .018) and the number of veins ligated (OR 6, 95% CI 1.6-22.48; P = .013), were significantly associated with changes in NRS after surgery. In addition, the area under the receiver operating characteristic curve for changes in NRS and the total number of veins ligated was 0.869. Microsurgical varicocelectomy had a high success rate for scrotal pain and satisfaction. Severe varicocele grade and the number of veins ligated in microsurgical varicocelectomy were associated with postoperative pain improvement.

Do open data impact citizens' behavior? Assessing face mask panic buying behaviors during the Covid-19 pandemic.

Data are essential for digital solutions and supporting citizens' everyday behavior. Open data initiatives have expanded worldwide in the last decades, yet investigating the actual usage of open data and evaluating their impacts are insufficient. Thus, in this paper, we examine an exemplary use case of open data during the early stage of the Covid-19 pandemic and assess its impacts on citizens. Based on quasi-experimental methods, the study found that publishing local stores' real-time face mask stock levels as open data may have influenced people's purchase behaviors. Results indicate a reduced panic buying behavior as a consequence of the openly accessible information in the form of an online mask map. Furthermore, the results also suggested that such open-data-based countermeasures did not equally impact every citizen and rather varied among socioeconomic conditions, in particular the education level.

A Positive Fluid Balance in the First Week Was Associated With Increased Long-Term Mortality in Critically Ill Patients: A Retrospective Cohort Study.

Introduction: Early fluid balance has been found to affect short-term mortality in critically ill patients; however, there is little knowledge regarding the association between early cumulative fluid balance (CFB) and long-term mortality. This study aims to determine the distinct association between CFB day 1-3 (CFB 1-3) and day 4-7 (CFB 4-7) and long-term mortality in critically ill patients. Patients and Methods: This study was conducted at Taichung Veterans General Hospital, a tertiary care referral center in central Taiwan, by linking the hospital critical care data warehouse 2015-2019 and death registry data of the Taiwanese National Health Research Database. The patients followed up until deceased or the end of the study on 31 December 2019. We use the log-rank test to examine the association between CFB 1-3 and CFB 4-7 with long-term mortality and multivariable Cox regression to identify independent predictors during index admission for long-term mortality in critically ill patients. Results: A total of 4,610 patients were evaluated. The mean age was 66.4 ± 16.4 years, where 63.8% were men. In patients without shock, a positive CFB 4-7, but not CFB 1-3, was associated with 1-year mortality, while a positive CFB 1-3 and CFB 4-7 had a consistent and excess hazard of 1-year mortality among critically ill patients with shock. The multivariate Cox proportional hazard regression model identified that CFB 1-3 and CFB 4-7 (with per 1-liter increment, HR: 1.047 and 1.094; 95% CI 1.037-1.058 and 1.080-1.108, respectively) were independently associated with high long-term mortality in critically ill patients after adjustment of relevant covariates, including disease severity and the presence of shock. Conclusions: We found that the fluid balance in the first week, especially on days 4-7, appears to be an early predictor for long-term mortality in critically ill patients. More studies are needed to validate our findings and elucidate underlying mechanisms.

QSOFA and SOFA scores are valuable tools for predicting postoperative sepsis resulting from ureteroscopic lithotripsy (URSL).

The sequential organ failure assessment (SOFA) and quick sequential organ failure assessment (qSOFA) scores are new tools which are used to assess sepsis based on the Third International Consensus Definitions for Sepsis and Septic Shock Task Force. This study aimed to evaluate the feasibility of using the SOFA and qSOFA to predict post-ureteroscopic lithotripsy (URSL) sepsis. Patients who underwent URSL due to ureteral stone obstruction were retrospectively reviewed using SOFA and qSOFA scores. Patient characteristics including age, gender, comorbidities, American Society of Anesthesiologists Classification, stone burden, stone location, hydronephrosis status, infectious status, preoperative SOFA and qSOFA score were collected. Preoperative factors were analyzed to determine if they were correlated with postoperative sepsis. A total of 830 patients were included in this study, of whom 32 (3.9%) had postoperative sepsis. Multivariate analysis revealed that older age, proximal ureteral stones, severe hydronephrosis, and high preoperative qSOFA or SOFA score were significantly associated with postoperative sepsis. The areas under the curves of a qSOFA score ≥ 1 and SOFA score ≥ 2 for predicting postoperative sepsis were 0.754 and 0.823, respectively. Preoperative qSOFA and SOFA scores are convenient and effective for predicting post-URSL sepsis. Further preventive strategies should be performed in these high-risk patients.

A retroperitoneal cavernous hemangioma arising from the gonadal vein: A case report.

RATIONALE: Cavernous hemangioma (CH) is not commonly found within the abdomen or the retroperitoneum. We report the first case of CH originating from the gonadal vein. DIAGNOSIS: A retroperitoneal tumor was found incidentally in a 57-year-old female patient. The differential diagnoses from the initial imaging studies included gastrointestinal stromal tumor, carcinoid tumor, neurogenic tumor, metastasis, lymphadenopathy, or another rare tumor. INTERVENTIONS: A surgical en-bloc excision was performed via a subcostal incision and intravenous CH arising from a gonadal vein was diagnosis by the urological pathologist. OUTCOMES: After the surgery, no complications were noted. A computed tomography scan was performed after 3 months follow-up and no tumor recurrence was found. LESSONS: This case reminds us that CH should be listed as one of the differential diagnoses for a retroperitoneal tumor. A definite diagnosis of CH relies on surgical resection. The prognosis is well if adequate resection is performed.

A Targeted RNAi Screen Reveals Drosophila Female-Sterile Genes That Control the Size of Germline Stem Cell Niche During Development.

Adult stem cells maintain tissue homeostasis. This unique capability largely depends on the stem cell niche, a specialized microenvironment, which preserves stem cell identity through physical contacts and secreted factors. In many cancers, latent tumor cell niches are thought to house stem cells and aid tumor initiation. However, in developing tissue and cancer it is unclear how the niche is established. The well-characterized germline stem cells (GSCs) and niches in the Drosophila melanogaster ovary provide an excellent model to address this fundamental issue. As such, we conducted a small-scale RNAi screen of 560 individually expressed UAS-RNAi lines with targets implicated in female fertility. RNAi was expressed in the soma of larval gonads, and screening for reduced egg production and abnormal ovarian morphology was performed in adults. Twenty candidates that affect ovarian development were identified and subsequently knocked down in the soma only during niche formation. Feminization factors (Transformer, Sex lethal, and Virilizer), a histone methyltransferase (Enhancer of Zeste), a transcriptional machinery component (Enhancer of yellow 1), a chromatin remodeling complex member (Enhancer of yellow 3) and a chromosome passenger complex constituent (Incenp) were identified as potentially functioning in the control of niche size. The identification of these molecules highlights specific molecular events that are critical for niche formation and will provide a basis for future studies to fully understand the mechanisms of GSC recruitment and maintenance.

Smad-Independent BMP Signaling in Somatic Cells Limits the Size of the Germline Stem Cell Pool.

In developing organisms, proper tuning of the number of stem cells within a niche is critical for the maintenance of adult tissues; however, the involved mechanisms remain largely unclear. Here, we demonstrate that Thickveins (Tkv), a type I bone morphogenetic protein (BMP) receptor, acts in the Drosophila developing ovarian soma through a Smad-independent pathway to shape the distribution of BMP signal within the niche, impacting germline stem cell (GSC) recruitment and maintenance. Somatic Tkv promotes Egfr signaling to silence transcription of Dally, which localizes BMP signals on the cell surface. In parallel, Tkv promotes Hh signaling, which promotes escort cell cellular protrusions and upregulates expression of the Drosophila BMP homolog, Dpp, forming a positive feedback loop that enhances Tkv signaling and strengthens the niche boundary. Our results reveal a role for non-canonical BMP signaling in the soma during GSC establishment and generally illustrate how complex, cell-specific BMP signaling mediates niche-stem cell interactions.

Hedgehog signaling establishes precursors for germline stem cell niches by regulating cell adhesion.

Stem cells require different types of supporting cells, or niches, to control stem cell maintenance and differentiation. However, little is known about how those niches are formed. We report that in the development of the Drosophila melanogaster ovary, the Hedgehog (Hh) gradient sets differential cell affinity for somatic gonadal precursors to specify stromal intermingled cells, which contributes to both germline stem cell maintenance and differentiation niches in the adult. We also report that Traffic Jam (an orthologue of a large Maf transcription factor in mammals) is a novel transcriptional target of Hh signaling to control cell-cell adhesion by negative regulation of E-cadherin expression. Our results demonstrate the role of Hh signaling in niche establishment by segregating somatic cell lineages for differentiation.