Sertoli cells synthesize and secrete transferrin-like protein

One of the major proteins secreted by Sertoli cells (Band 3) has a molecular weight on sodium dodecyl sulfate-polyacrylamide gels which corresponds to rat serum transferrin. The preparation of Sertoli cell-secreted proteins contains an iron-binding protein with electrophoretic properties on native polyacrylamide gels similar to serum transferrin. Antibodies against Sertoli cell-secreted proteins contain a component which will immunoprecipitate serum transferrin. Antibodies to serum transferrin cross-react with and immunoprecipitate a major component (Band 3) of [35S]-methionine-labeled Sertoli cell-secreted proteins. We propose that testicular transferrin is a major secretory product of Sertoli cells in culture. In addition to transferrin, antiserum to rat serum proteins will immunoprecipitate one other polypeptide from preparations of Sertoli cell-secreted proteins

A sulfated glycoprotein synthesized by Sertoli cells and by epididymal cells is a component of the sperm membrane

We report here the purification, partial characterization and immunofluorescent localization of a dimeric acidic glycoprotein (DAG-protein) secreted by cultures of Sertoli cells of rat testes. Partially purified protein was obtained after chromatography over Sepharose 4B under conditions which favored a soluble, nonaggregated form of the protein. Rechromatography over the same column under reducing conditions yielded very pure monomers of 41,000 daltons and 29,000 daltons. Antibodies were prepared against the mixed monomers and used to immunoprecipitate proteins in spent medium from cultures incubated with [35S] methionine, 35SO4 = or tunicamycin. DAG-protein and another protein (Band 4, 70,000 daltons) were coprecipitated by the antiserum and all contained 35SO4 = in their structures. It was shown by Western blotting that the antiserum cross-reacted very weakly with Band 4 protein. The DAG-protein polypeptides secreted in the presence of tunicamycin were assumed to lack N-glycosylation and exhibited apparent molecular weights of 27,000 and 21,000 daltons. Immunoprecipitations of media from organ cultures of testis and epididymis yielded DAG-protein of slightly lower molecular weight than the protein secreted in Sertoli cell cultures. Indirect immunofluorescence of DAG-protein in paraffin sections of testis and epididymis revealed that the protein was concentrated in the cytoplasm of Sertoli cells, on the stereocilia of epididymal principal cells, in the cytoplasm of epididymal halo cells, and was associated with late spermatids and mature sperm. Sperm were specifically labeled on the acrosome, at the neck, and on the endpiece of the tail. No enzymatic or structural function has been ascribed to DAG-protein as yet, but the protein must play a pivotal role in spermatogenesis because it is secreted by both the testis and epididymis and becomes an integral component of sperm

Adam Smith and Colonialism

In the context of debates about liberalism and colonialism, the arguments of Adam Smith have been taken as illustrative of an important line of anti-colonial liberal thought. The reading of Smith presented here challenges this interpretation. It argues that Smith’s opposition to colonial rule derived largely from its impact on the metropole, rather than on its impact on the conquered and colonised; that Smith recognised colonialism had brought ‘improvement’ in conquered territories and that Smith struggled to balance recognition of moral diversity with a universal moral framework and a commitment to a particular interpretation of progress through history. These arguments have a wider significance as they point towards some of the issues at stake in liberal anti-colonial arguments more generally

mitoTALEN Eliminates Mutant mtDNA Genomes in Neurons

Mutations in the mitochondrial DNA (mtDNA) commonly cause severe encephalopathies. Because most of these mtDNA alterations are heteroplasmic, we used a mitochondrial-targeted TALEN (mitoTALEN) to specifically eliminate the mutant mtDNA in the CNS of a mouse model harboring a heteroplasmic mutation in the mitochondrial tRNA alanine gene (m.5024C>T). Delivery to neurons was achieved by using AAV-PHP.eB and neuronal expression was obtained by using a neuronal-specific synapsin promoter. We found that most CNS regions were effectively transduced and showed a significant reduction in mutant mtDNA. This reduction was accompanied by an increase in mitochondrial tRNA alanine level, which is drastically reduced by the mutation. These results showed, for the first time, that mitochondrial-targeted gene editing can be effective in reducing CNS mutant mtDNA in vivo, paving the way for clinical trials in patients with mitochondrial encephalopathies

Gender-Sensitive Violence Risk Assessment:Predictive Validity of Six Tools in Female Forensic Psychiatric Patients

Most violence risk assessment tools have been validated predominantly in males. In this multicenter study, the Historical, Clinical, Risk Management-20 (HCR-20), Historical, Clinical, Risk Management-20 Version 3 (HCR-20(V3)), Female Additional Manual (FAM), Short-Term Assessment of Risk and Treatability (START), Structured Assessment of Protective Factors for violence risk (SAPROF), and Psychopathy Checklist-Revised (PCL-R) were coded on file information of 78 female forensic psychiatric patients discharged between 1993 and 2012 with a mean follow-up period of 11.8 years from one of four Dutch forensic psychiatric hospitals. Notable was the high rate of mortality (17.9%) and readmission to psychiatric settings (11.5%) after discharge. Official reconviction data could be retrieved from the Ministry of Justice and Security for 71 women. Twenty-four women (33.8%) were reconvicted after discharge, including 13 for violent offenses (18.3%). Overall, predictive validity was moderate for all types of recidivism, but low for violence. The START Vulnerability scores, HCR-20(V3), and FAM showed the highest predictive accuracy for all recidivism. With respect to violent recidivism, only the START Vulnerability scores and the Clinical scale of the HCR-20(V3) demonstrated significant predictive accuracy

A direct path to dependable software

What would it take to make software more dependable? Until now, most approaches have been indirect: some practices – processes, tools or techniques – are used that are believed to yield dependable software, and the argument for dependability rests on the extent to which the developers have adhered to them. This article argues instead that developers should produce direct evidence that the software satisfies its dependability claims. The potential advantages of this approach are greater credibility (since the argument is not contingent on the effectiveness of the practices) and reduced cost (since development resources can be focused where they have the most impact)

Covert Neurological Symptoms Associated With Silent Infarcts From Midlife to Older Age: The Atherosclerosis Risk in Communities Study

Unrecognized or unreported stroke-like symptoms, called covert symptoms, occur in persons free of clinical stroke. Whether covert symptoms are associated with subclinical brain infarcts (SBI) is unknown. This study examined the association between covert stroke-like symptoms and SBI/stroke in persons with no history of stroke or TIA