Testosterone and follicle-stimulating hormone (FSH) are required to obtain full reproductive potential. In the testis, somatic Sertoli cells transduce signals from testosterone and FSH into the production of factors that are required by germ cells as they mature into spermatozoa. Recent advances in identifying new signaling pathways that are regulated by FSH and testosterone have allowed for refinement in the understanding of the independent, overlapping and synergistic actions of these hormones. In this review, we discuss the signaling pathways that are regulated by FSH and testosterone as well as the resulting metabolic and gene expression changes that occur as related to Sertoli cell proliferation, differentiation and the support of spermatogenesis.Reproduction (2005) 130 15-28

A new pathway of testosterone (T) action in Sertoli cells was recently identified that may be required to support spermatozoa production (spermatogenesis) and fertility. Specifically, T acts via the androgen receptor (AR) to rapidly activate the MAPK cascade and the cAMP response element-binding protein (CREB) transcription factor in Sertoli cells. In further characterizing the signaling pathway that transduces T actions, we now find that a population of AR is localized to the plasma membrane and that AR associates with Src kinase after T stimulation. In addition, we demonstrate that Src kinase is activated by T and that Src kinase activity is required for stimulation of the ERK MAPK and CREB. Furthermore, we determine that activation of the epidermal growth factor receptor downstream of Src contributes to the activation of the MAPK cascade and CREB. The elucidation of this nonclassical pathway of T action in the testis may provide new targets for the control of male fertility.

Background: Hospital staff are vulnerable and at high risk of novel coronavirus disease (COVID-19) infection. The aim of this study was to monitor the psychological distress in hospital staff and examine the relationship between the psychological distress and possible causes during the COVID-19 epidemic. Methods: An online survey was conducted from February 1 to February 14, 2020. Hospital staff from five national COVID-19 designated hospitals in Chongqing participated. Data collected included demographics and stress responses to COVID-19: 1) the impact of event scale to measure psychological stress reactions; 2) generalized anxiety disorder 7 to measure anxiety symptoms; 3) Patient Health Questionnaire 9 to measure depression symptoms; 4) Yale-Brown Obsessive-Compulsive Scale to measure obsessive-compulsive symptoms (OCS); and 5) Patient Health Questionnaire 15 to measure somatization symptoms. Multiple logistic regression analysis was used to identify factors that were correlated with psychological distress. Results: Hospital staff that participated in this study were identified as either doctors or nurses. A total of 456 respondents completed the questionnaires with a response rate of 91.2%. The mean age was 30.67 ± 7.48 years (range, 17 to 64 years). Of all respondents, 29.4% were men. Of the staff surveyed, 43.2% had stress reaction syndrome. The highest prevalence of psychological distress was OCS (37.5%), followed by somatization symptoms (33.3%), anxiety symptoms (31.6%), and depression symptoms (29.6%). Univariate analyses indicated that female subjects, middle aged subjects, subjects in the low income group, and subjects working in isolation wards were prone to experience psychological distress. Multiple logistic regression analysis showed “Reluctant to work or considered resignation” (odds ratio [OR], 5.192; 95%CI, 2.396–11.250; P < .001 ), “Afraid to go home because of fear of infecting family” (OR, 2.099; 95%CI, 1.299–3.391; P = .002 ) “Uncertainty about frequent modification of infection and control procedures” (OR, 1.583; 95%CI, 1.061–2.363; P = .025 ), and“Social support” (OR, 1.754; 95%CI, 1.041–2.956; P = .035 ) were correlated with psychological reactions. “Reluctant to work or considered resignation” and “Afraid to go home because of fear of infecting family” were associated with a higher risk of symptoms of Anxiety (OR, 3.622; 95% CI, 1.882–6.973; P < .001 ; OR, 1.803; 95% CI, 1.069–3.039; P = .027), OCS (OR, 5.241; 95% CI, 2.545–10.793; P < .001 ; OR, 1.999; 95% CI, 1.217–3.282; P = .006 ) and somatization (OR, 5.177; 95% CI, 2.595–10.329; P ...

Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a member of the long chain family of acyl-CoA synthetase proteins, which have recently been shown to serve an important role in ferroptosis. Previous studies have suggested that ferroptosis is involved in the occurrence of glioma; however, the role of ACSL4 in glioma remains unknown. In the present study, a reduction of ferroptosis in human glioma tissues and glioma cells was observed. Subsequently, it was demonstrated that the expression of ACSL4 was also downregulated in human glioma tissues and cells. A ferroptosis inhibitor and inducer were used to investigate the effects of ferroptosis on viability. The results showed that promoting ferroptosis inhibited the proliferation of glioma cells, and that the use of inducers had the reverse effect. Therefore, it was hypothesized that the reduction in ACSL4 expression may have been involved in ferroptosis and proliferation in glioma. Overexpression of ACSL4 decreased expression of glutathione peroxidase 4 and increased the levels of ferroptotic markers, including 5-hydroxyeicosatetraenoic (HETE), 12-HETE and 15-HETE. Additionally, ACSL4 overexpression resulted in an increase in lactate dehydrogenase release and a reduction in cell viability. The opposite results were observed when ACSL4 was silenced. These findings suggest that ACSL4 regulates ferroptosis and proliferation of glioma cells. To further investigate the mechanism underlying ACSL4-mediated regulation of proliferation in glioma cells, cells were treated with small interfering (si)-ACSL4 and sorafenib, a ferroptosis inducer. sorafenib attenuated the ability of siRNA-mediated silencing of ACSL4, thus improving cell viability. These results demonstrate that ACSL4 protects glioma cells and exerts anti-proliferative effects by activating a ferroptosis pathway and highlight the pivotal role of ferroptosis regulation by ACSL4 in its protective effects on glioma. Therefore, ACSL4 may serve as a novel therapeutic target for the treatment of glioma.

Genetic diversity of Xanthomonas campestris pv. campestris

Construction of a microarray based on the genome of Xanthomonas campestris pv.campestris (Xcc), and its use to analyse 18 other virulent Xcc strains, revealed insights into the genetic diversity and determinants of host specificity of Xcc strains.

Signaling to the mechanistic target of rapamycin (mTOR) regulates diverse cellular processes, including protein translation, cellular proliferation, metabolism, and autophagy. These effects are mediated in part by the mTOR targets S6 kinase (S6K) and eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). Most models place Akt upstream of the best-studied mTOR complex, mTORC1; however, studies have called into question whether Akt is necessary for this pathway, at least in T cells. We found that the adaptor protein Carma1 [caspase recruitment domain (CARD)-containing membrane-associated protein 1 (Carma1)] and at least one of its associated proteins, the paracaspase MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1), were required for optimal activation of mTOR in T cells in response to stimulation of the T cell receptor (TCR) and the coreceptor CD28. However, another common binding partner of Carma1 and MALT1, Bcl10, was not required for TCR-dependent activation of the mTOR pathway. Consistent with these findings, MALT1 activity was required for the proliferation of CD4 + T cells, but not early TCR-dependent activation events. Also consistent with an effect on mTOR, MALT1 activity was required for the increased metabolic flux in activated CD4 + T cells. Together, our data suggest that Carma1 and MALT1 play previously unappreciated roles in the activation of mTOR signaling in T cells after engagement of the TCR.

Hypoxic ischemic encephalopathy (HIE) is a type of neonatal brain injury, which occurs due to lack of supply and oxygen deprivation to the brain. It is associated with a high morbidity and mortality rate. There are several therapeutic strategies that can be used to improve outcomes in patients with HIE. These include cell therapies such as marrow mesenchymal stem cells (MSCs) and umbilical cord blood stem cells (UCBCs), which are being incorporated into the new protocols for the prevention of ischemic brain damage. The focus of this review is to discuss the mechanism of oxidative stress in HIE and summarize the current available treatments for HIE. We hope that a better understanding of the relationship between oxidative stress and HIE will provide new insights on the potential therapy of this devastating condition.

Background: The precise role of the Akt kinase in NF-B induction by the TCR and CD28 is still unclear. Results: We have found that Akt makes a quantitative contribution to NF-B induction in T cells, selectively impacting a subset of downstream genes. Conclusion: Although Akt is not a canonical member of the NF-B pathway, it can modulate NF-B signaling and transcription. Significance: These findings may open the way to more selective modulation of NF-B-dependent pathways.