Loss of function of male-specific lethal 3 (Msl3) does not affect spermatogenesis in rodents.

BACKGROUND: Male-specific lethal 3 (Msl3) is a member of the chromatin-associated male-specific lethal MSL complex, which is responsible for the transcriptional upregulation of genes on the X chromosome in males of Drosophila. Although the dosage complex operates differently in mammals, the Msl3 gene is conserved from flies to humans. Msl3 is required for meiotic entry during Drosophila oogenesis. Recent reports indicate that also in primates, Msl3 is expressed in undifferentiated germline cells before meiotic entry. However, if Msl3 plays a role in the meiotic entry of mammals has yet to be explored. RESULTS: To understand, if Msl3a plays a role in the meiotic entry of mammals, we used mouse spermatogenesis as a study model. Analyses of single-cell RNA-seq data revealed that, in mice, Msl3 is mostly expressed in meiotic cells. To test the role of Msl3 in meiosis, we used a male germline-specific Stra8-iCre driver and a newly generated Msl3flox conditional knock-out mouse line. Msl3 conditional loss-of-function in spermatogonia did not cause spermatogenesis defects or changes in the expression of genes related to meiosis. CONCLUSIONS: Our data suggest that, in mice, Msl3 exhibits delayed expression compared to Drosophila and primates, and loss-of-function mutations disrupting the chromodomain of Msl3 alone do not impede meiotic entry in rodents.

Correlation between Skp2 expression and nodal metastasis in stage I and II oral squamous cell carcinomas.

PURPOSE: The aim of this study was to investigate the role of S-phase kinase associated protein (Skp2) in the development of nodal metastasis and to assess its influence on prognosis in stage I and II oral squamous cell carcinomas (OSCCs). EXPERIMENTAL DESIGN: Seventy-one patients affected by OSCC (stage I-II) were observed in the period ranging from March 2003 to December 2006. The research was performed using immunohistochemical and histopathological analysis. RESULTS: The overall survival rate was 89.6% at 3 years, 87% at 5 years and 80.7% at 10 years. Patients with vascular or perineural invasion showed no statistically significant survival difference when compared with the ones with no invasion. The tumour depth of invasion did not prove to be related to the metastatic potential. Nine of the seventeen patients with Skp2 positive nuclei (≥20%) developed nodal metastasis. Conversely, only 6 of the 54 patients with a nuclear positivity lower than 20% developed a laterocervical metastasis (P=0.001). When comparing survival curves of Skp≥20% and Skp2<20% OSCCs, no significant P value emerged from the statistical analysis. CONCLUSIONS: This study is the first to report an important correlation between an Skp2 expression lower than 20% and the capability of the tumour not to develop nodal laterocervical metastases (P=0.001).

BDNF, NT-3 and NGF induce distinct new Ca2+ channel synthesis in developing hippocampal neurons.

Neurotrophins exert short- and long-term effects on synaptic transmission. The mechanism underlying these forms of synaptic plasticity is unknown although it is likely that intracellular Ca2+ and presynaptic Ca2+ channels play a critical role. Here we show that BDNF, NGF and NT-3 (10-100 ng/mL) exhibit a selective long-term up-regulation of voltage-gated Ca2+ current densities in developing hippocampal neurons of 6-20 days in culture. NGF and NT-3 appear more effective in up-regulating L-currents, while BDNF predominantly acts on non-L-currents (N, P/Q and R). The effects of the three neurotrophins were time- and dose-dependent. The EC50 was comparable for BDNF, NGF and NT-3 (10-16 ng/mL) while the time of half-maximal activation was significantly longer for NGF compared to BDNF (58 vs. 25 h). Despite the increased Ca2+ current density, the neurotrophins did not alter the voltage-dependence of channel activation, the kinetics parameters or the elementary properties of Ca2+ channels (single-channel conductance, probability of opening and mean open time). Neurotrophin effects were completely abolished by coincubation with the nonspecific Trk-receptor inhibitor K252a, the protein synthesis blocker anisomycin and the MAP-kinase inhibitor PD98059, while cotreatment with the PLC-gamma blocker, U73122, was without effect. Immunocytochemistry and Western blotting revealed that neurotrophins induced an increased MAP-kinase phosphorylation and its translocation to the nucleus. The present findings suggest that on a long time scale different neurotrophins can selectively up-regulate different Ca2+ channels. The action is mediated by Trk-receptors/MAP-kinase pathways and induces an increased density of newly available Ca2+ channels with unaltered gating activity.

Master's degree nursing education: state of the art.

This study examines the state of the art in master's nursing education in the United States in light of projected national trends in the health care delivery system. The specific questions addressed are: What are the general characteristics of master's programs, including admission requirements and prerequisites, program requirements, major and minor areas of clinical concentration, functional role preparation, and career mobility options? What is the curricular organization, particularly with respect to required core courses? Is there a difference between master's programs in schools with a doctoral program in nursing and those with master's programs only? Is there a difference between master's programs with public support and master's programs with private support? Data were collected from 175 accredited master's programs in 1990. Study results and the projected trends derived from Nursing's Agenda for Health Care Reform, Healthy People 2000: National Health Promotion and Disease Prevention Objectives, and Healthy America: Practitioners for 2005 provide the foundation for recommendations. Recommendations are organized around communication and curricular issues that master's nursing education needs to address as the profession approaches the 21st century.

Models for doctoral programs. First professional degree or terminal degree?

Forni summarizes the history and the present status of the doctoral degree in nursing. She surveys the critical issues, such as terminal versus first professional degree, academic versus professional focus, and the relationship of the doctoral degree to a master's degree.

Management of insulin allergy and resistance.

The pathophysiologic basis and therapy of insulin insensitivity and insulin allergy are discussed. Topics covered include primary and secondary causes of insulin insensitivity, management of insulin resistance (elimination of diabetogenic factors; use of less antigenic insulin, oral hypoglycemic agents, immunosuppression, or nonmammalian insulin), and insulin allergy and its treatment. A pharmacist's knowledge of insulin products and the pharmacologic activity of the oral hypoglycemic and immunosuppressive agents may aid in the care of patients who are allergic or resistant to insulin.

Phencyclidine poisoning.

Phencyclidine hydrochloride abuse has become increasingly common and should be considered in patients with unexplained acute psychosis, dystonic reactions, status epilepticus, or coma. Two phencyclidine-intoxicated patients had bizarre combinations or disorientation, hallucination, agitation, and dyskinetic motor activity. Supportive care and reduction of sensory stimulation are the basis for management of the symptoms.