Cell lineage specification during development of the anterior lateral plate mesoderm and forelimb field

The lateral plate mesoderm (LPM) is a transient embryonic tissue that gives rise to a diverse range of mature cell types, including the cardiovascular system, the urogenital system, endoskeleton of the limbs, and mesenchyme of the gut. While the genetic processes that drive development of these tissues are well defined, the early cell fate choices underlying LPM development and specification are poorly understood. In this study, we utilize single-cell transcriptomics to define cell lineage specification during development of the anterior LPM and the forelimb field in the chicken embryo. We identify the molecular pathways directing differentiation of the aLPM towards a somatic or splanchnic cell fate, and subsequent emergence of the forelimb mesenchyme. We establish the first transcriptional atlas of progenitor, transitional and mature cell types throughout the early forelimb field and uncover the global signalling pathways which are active during LPM differentiation and forelimb initiation. Specification of the somatic and splanchnic LPM from undifferentiated mesoderm utilizes distinct signalling pathways and involves shared repression of early mesodermal markers, followed by activation of lineage-specific gene modules. We identify rapid activation of the transcription factor TWIST1 in the somatic LPM preceding activation of known limb initiation genes, such as TBX5, which plays a likely role in epithelial-to-mesenchyme transition of the limb bud mesenchyme. Furthermore, development of the somatic LPM and limb is dependent on ectodermal BMP signalling, where BMP antagonism reduces expression of key somatic LPM and limb genes to inhibit formation of the limb bud mesenchyme. Together, these findings provide new insights into molecular mechanisms that drive fate cell choices during specification of the aLPM and forelimb initiation.

On the clinical significance of biovars ureaplasma urealyticum

Developing of chronic salpingoophoritis, non-specific bacterial vaginitis and specific candidamytotic vaginitis ought to be associated with complicated obstetric anamnesis and presence of biovar Parvo ureaplasmas predominantly found in womens genital tracts. The correlation may be seen between identifying biovar Parvo ureaplasmas in men and arising of torpid and chronic infectious urethritis, that may testify to its more intensive pathogenic effect comparing with biovar T- 9GO. Detection of biovar T-960 in urogenital system in men and women doesnt exclude the possibility of inflammation, that implies adequate complex therapy identical to that in case of biovar Parvo.

The Role of LIM Kinase in the Male Urogenital System

The LIM kinases (LIMK1 and LIMK2), known as downstream effectors, and the Rho-associated protein kinase (ROCK), a regulator of actin dynamics, have effects on a diverse set of cellular functions. The LIM kinases are involved in the function of the male urogenital system by smooth muscle contraction via phosphorylation of cofilin and subsequent actin cytoskeleton reorganization. Although LIMK1 and LIMK2 share sequence similarities as serine protein kinases, different tissue distribution patterns and distinct localization during cell cycle progression suggest other biological functions for each kinase. During meiosis and mitosis, the LIMK1/2–cofilin signaling facilitates the orchestrated chromatin remodeling between gametogenesis and the actin cytoskeleton. A splicing variant of the LIMK2 transcript was expressed only in the testis. Moreover, positive signals with LIMK2-specific antibodies were detected mainly in the nucleus of the differentiated stages of germ cells, such as spermatocytes and early round spermatids. LIMK2 plays a vital role in proper spermatogenesis, such as meiotic processes of spermatogenesis after puberty. On the other hand, the literature evidence revealed that a reduction in LIMK1 expression enhanced the inhibitory effects of a ROCK inhibitor on the smooth muscle contraction of the human prostate. LIMK1 may have a role in urethral obstruction and bladder outlet obstruction in men with benign prostatic hyperplasia. Moreover, LIMK1 expression was reduced in urethral stricture. The reduced LIMK1 expression caused the impaired proliferation and migration of urethral fibroblasts. In addition, the activated LIMK2–cofilin pathway contributes to cavernosal fibrosis after cavernosal nerve injury. Recent evidence demonstrated that short-term inhibition of LIMK2 from the immediate post-injury period prevented cavernosal fibrosis and improved erectile function in a rat model of cavernosal nerve injury. Furthermore, chronic inhibition of the LIMK2–cofilin pathway significantly restrained the cavernosal veno-occlusive dysfunction, the primary pathophysiologic mechanism of post-prostatectomy erectile dysfunction through suppressing fibrosis in the corpus cavernosum. In conclusion, the LIM kinases–cofilin pathway appears to play a role in the function of the male urogenital system through actin cytoskeleton reorganization and contributes to the pathogenesis of several urogenital diseases. Therefore, LIM kinases may be a potential treatment target in urogenital disorder.

A case report of an uncommon presentation of Nephroblastoma (Wilms tumor): in an older child with polycythemia and elevated erythropoietin

Introduction/Objective Wilms tumor (nephroblastoma), is a neoplasm that has a prevalence of 1 per 10,000 before the age of fifteen, with 50% occurring before age 3. WT1 (11p13) gene, a zinc finger transcription factor, is expressed in early urogenital system development and mutations here represent one of the primary pathways to the development of Wilms tumor. Although mouse model studies have shown that WT1 may be a transcriptional activator of erythropoietin (EPO) gene, increases in serum erythropoietin are rarely seen in patients with Wilms tumor. Concurrent polycythemia is a further rarity with only 11 such reports in literature. This is intriguing since WT1 mutations represent the most common mutation pathway in Wilms Tumor. Interestingly, other tumor types associated with elevated serum EPO and polycythemia (e.g. renal cell carcinoma and metanephric adenoma) are thought to do so through the generation of hypoxia inducible factor, and induction of VEGF. Methods/Case Report Here we present a case of Wilms tumor in a 7-year-old female who was establishing care after moving to Vermont. Physical examination showed possible splenomegaly ultimately discovered to be a large LUQ abdominal mass with a concurrent discovery of polycythemia. Subsequent serum EPO was 308 (Ref: 2.6-18.5 mIU/mL).). The mass was surgically removed with resolution of polycythemia. Histological evaluation showed a triphasic, blastema predominant Wilms tumor with favorable histology. Heterologous, vascular differentiation was seen in the stroma, positive for CD34 and CD31, and negative for D2-40. Results (if a Case Study enter NA) NA Conclusion Based on these findings, this phenomenon may be related to increased VEGF expression resulting in this patient’s increased serum EPO and polycythemia, and heterologous vascular differentiation within the tumor stroma. This is the first report of histology in a case of Wilms tumor associated with high serum EPO and polycythemia and may indicate an alternative pathway for the generation of EPO in Wilms tumor.

Association of a GATA Binding Protein 4 Polymorphism with the Risk of Hypospadias in the Chinese Children

<b><i>Purpose:</i></b> GATA binding protein 4 (GATA4) has been implicated in the etiology of congenital malformation of the urogenital system. The present study investigated the influence of <i>GATA4</i> polymorphisms on susceptibility to hypospadias. <b><i>Methods:</i></b> We genotyped 4 potentially functional polymorphisms (rs12458, rs12825, rs884662, and rs904018) in <i>GATA4</i> in the hospital-based case-control study including 410 child patients and 520 nonmalformed individuals by the TaqMan MGB method. Risk associations were assessed using unconditional logistic regression, adjusted for potential confounding factors. <b><i>Results:</i></b> A significant association was found between rs12458 (3′-UTR of <i>GATA4</i>) and susceptibility to hypospadias (<i>p</i> = 0.008). Compared with rs12458 AA genotype individuals, those harboring the variant allele (rs12458 AT/TT) were correlated with significantly higher risk of hypospadias (AT/TT vs. AA: OR = 1.42, 95% CI = 1.17–2.35, <i>p</i> = 0.036). Furthermore, the rs12458T allele showed significantly decreased activity in a luciferase reporter assay, indicating a possible role of rs12458 variant in regulating the combination of microRNAs with the <i>GATA4</i> mRNA. <b><i>Conclusions:</i></b> The present results indicate that the functional <i>GATA4</i> rs12458 variant confers individuals’ susceptibility to hypospadias, possibly through regulating the <i>GATA4</i> expression level.

Towards reliable diagnostics of prostate cancer via breath

Early detection of cancer is a key ingredient for saving many lives. Unfortunately, cancers of the urogenital system are difficult to detect at early stage. The existing noninvasive diagnostics of prostate cancer (PCa) suffer from low accuracy (< 70%) even at advanced stages. In an attempt to improve the accuracy, a small breath study of 63 volunteers representing three groups: (1) of 19 healthy, (2) 28 with PCa, (3) with 8 kidney cancer (KC) and 8 bladder cancer (BC) was performed. Ultrabroadband mid-infrared Fourier absorption spectroscopy revealed eight spectral ranges (SRs) that differentiate the groups. The resulting accuracies of supervised analyses exceeded 95% for four SRs in distinguishing (1) vs (2), three for (1) vs (3) and four SRs for (1) vs (2) + (3). The SRs were then attributed to volatile metabolites. Their origin and involvement in urogenital carcinogenesis are discussed.

Transgenic fluorescent zebrafish lines that have revolutionized biomedical research

Since its debut in the biomedical research fields in 1981, zebrafish have been used as a vertebrate model organism in more than 40,000 biomedical research studies. Especially useful are zebrafish lines expressing fluorescent proteins in a molecule, intracellular organelle, cell or tissue specific manner because they allow the visualization and tracking of molecules, intracellular organelles, cells or tissues of interest in real time and in vivo. In this review, we summarize representative transgenic fluorescent zebrafish lines that have revolutionized biomedical research on signal transduction, the craniofacial skeletal system, the hematopoietic system, the nervous system, the urogenital system, the digestive system and intracellular organelles.

A Triad of Unilateral Renal Dysgenesis with Ipsilateral Seminal Vesical and Ejaculatory Duct Obstruction: An Uncommon Urogenital Congenital Anomaly, Zinner Syndrome—A Case Report

Zinner syndrome is a rare congenital anomaly of the urogenital system resulting from an in utero insult during the first trimester. This entity comprises a triad of unilateral renal agenesis/dysgenesis with ipsilateral seminal vesical and ejaculatory duct obstruction. This combination of urinary and genital abnormalities occurs because of the closely related embryological origin of these structures from the distal mesonephric (Wolffian) duct. Nearly 200 cases of seminal vesical cysts with ipsilateral renal agenesis have been reported in the literature. The affected person generally presents in early adulthood when the reproductive activity commences. In this report, we present a case of a 22-year-old male with complaints of painful ejaculation.

Epidemiological and Clinical Profile of Patients in the Medical Emergency Department at Amissa Bongo Regional Hospital in Franceville (ABRH), Gabon; Retrospective Cross-sectional Study

Objective: To evaluate the different non-surgical predominant pathologies in the emergency department of the Amissa Bongo regional hospital in Franceville, Haut-Ogooué. Materials and Methods: Using consultation registers and some medical records, we retrospectively studied the epidemiological and clinical profile of patients who consulted for a medical and non-surgical or gynaeco-obstetrical emergency, from 1 January 2018 to 31 December 2018. Results: During this period, 19597 patients consulted for a medical emergency at the Amissa Bongo regional hospital in Franceville in Haut-Ogooué (Gabon). This high score indicated that the majority of patients came from the different districts of the commune of Franceville and other departments of the province. Three periods of high attendance were distinguished: the long dry season (37.3%), the short rainy season (28.4%) and the long rainy season (24%), compared to the short dry season (10.3%). Infectious diseases were recurrent with 63.16%, and with 67% of cases, malaria (severe and simple) was more frequent. Non-infectious emergencies were also noted, such as diseases of the respiratory system (1791 cases = 24.81%), diseases of the digestive system (1028 cases = 14.24%), skin diseases (809 cases = 24.81%), cardiovascular diseases (800 cases = 11.21%), blood diseases (686 cases = 9. 5%), diseases of the urogenital system (588 cases = 8.14%), diseases of the locomotor system (510 cases = 7.06%), ENT diseases (451 cases = 6.24%), diseases of the glands and metabolism (296 cases = 4.10%), diseases of the nervous system and the senses (260 cases = 3.60%) Conclusion: Compared to non-infectious diseases, infectious and parasitic diseases are recurrent at CHRAB. They therefore require special attention from the health authorities of this hospital, and even of Gabon.