Localization of androgen-binding protein in proliferating Sertoli cells in culture.

The peroxidase and immunofluorescent localization patterns of androgen-binding protein (ABP), a biological marker of Sertoli cell function, have been examined in cultured Sertoli cells isolated from 20- to 22-day-old rats. ABP immunoreactivity in the form of cytoplasmic granules of variable diameter was observed in Sertoli cells with characteristic lipid droplets and a colony-forming, epithelial-like growth pattern. Incubation of cultures with [3H]thymidine demonstrated that Sertoli cells continue to produce ABP while retaining their capability for synthesizing DNA and undergoing mitosis. A variable number of cultured Sertoli cells became morphologically transformed after exposure to follitropin (follicle-stimulating hormone) and pharmacological agents acting on cyclic nucleotide metabolism. The induced change in Sertoli cell shape coincided with a disappearance of ABP-containing granules from the cytoplasm. These observations demonstrate that localization of ABP by immunological techniques is a valuable tool for the characterization of structural and functional properties of Sertoli cell in culture

Androgen-binding protein. Purification from rat epididymis, characterization, and immunocytochemical localization.

Androgen-binding protein (ABP) was purified from caput epididymis of the rat by sequential chromatography on DEAE-Sepharose, hydroxylapatite, dihydrotestosterone-17 beta-hemisuccinyl-1,6-diaminohexane-Sepharose, and Sephadex G-150. The final product migrated as a single band corresponding to a peak of protein-bound [3H]dihydrotestosterone on polyacrylamide gel electrophoresis. A molecular weight of 100,000 was estimated by sedimentation equilibrium. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, subunits of Mr = 47,000 and 41,000 were observed. Amino acid analysis indicated ABP to be rich in leucine while nonpolar aminoacids totaled only 51%. Its carbohydrate content is 25%. Antibodies to purified ABP were raised in a rabbit and evaluated by immunodiffusion, immunoelectrophoresis, binding inhibition, radioimmunoassay, and immunocytochemistry. Immunoperoxidase staining localized ABP in the basal and adluminal regions of seminiferous tubules of rat testis and in secretory granules of cultured Sertoli cells. In principal cells of caput epididymis, ABP is concentrated in the supranuclear region known to contain morphological specializations for absorption. These immunocytochemical results confirm that ABP synthesized and secreted by Sertoli cells in the testis is transported to the epididymal duct via testicular fluid and is taken up by epithelial cells of the proximal segments

Localization of androgen-binding protein in proliferating Sertoli cells in culture.

The peroxidase and immunofluorescent localization patterns of androgen-binding protein (ABP), a biological marker of Sertoli cell function, have been examined in cultured Sertoli cells isolated from 20- to 22-day-old rats. ABP immunoreactivity in the form of cytoplasmic granules of variable diameter was observed in Sertoli cells with characteristic lipid droplets and a colony-forming, epithelial-like growth pattern. Incubation of cultures with [3H]thymidine demonstrated that Sertoli cells continue to produce ABP while retaining their capability for synthesizing DNA and undergoing mitosis. A variable number of cultured Sertoli cells became morphologically transformed after exposure to follitropin (follicle-stimulating hormone) and pharmacological agents acting on cyclic nucleotide metabolism. The induced change in Sertoli cell shape coincided with a disappearance of ABP-containing granules from the cytoplasm. These observations demonstrate that localization of ABP by immunological techniques is a valuable tool for the characterization of structural and functional properties of Sertoli cell in culture

Short telomeres in ESCs lead to unstable differentiation

SummaryFunctional telomeres are critical for stem cell proliferation; however, whether they are equally important for the stability of stem cell differentiation is not known. We found that mouse embryonic stem cells (ESCs) with critically short telomeres (Tert−/− ESCs) initiated normal differentiation after leukemia inhibitory factor (LIF) withdrawal but, unlike control ESCs, failed to maintain stable differentiation when LIF was reintroduced to the growth medium. Tert−/− ESCs expressed higher levels of Nanog and, overall, had decreased genomic CpG methylation levels, which included the promoters of Oct4 and Nanog. This unstable differentiation phenotype could be rescued by telomere elongation via reintroduction of Tert, via suppression of Nanog by small hairpin RNA (shRNA) knockdown, or via enforced expression of the de novo DNA methyltransferase 3b. These results demonstrate an unexpected role of functional telomeres in the genome-wide epigenetic regulation of cell differentiation and suggest a potentially important role of telomere instability in cell fate during development or disease

Brief of Amici Curiae 56 Professors of Law and Economics in Support of Petition of Writ of Certiorari

28 U.S.C. § 1400(b) provides that a defendant in a patent case may be sued where the defendant is incorporated or has a regular and established place of business and has infringed the patent. This Court made clear in Fourco Glass Co. v. Transmirra Prods. Corp., 353 U.S. 222, 223 (1957), that those were the only permissible venues for a patent case. But the Federal Circuit has rejected Fourco and the plain meaning of § 1400(b), instead permitting a patent plaintiff to file suit against a defendant anywhere there is personal jurisdiction over that defendant. The result has been rampant forum shopping, particularly by patent trolls. 44% of 2015 patent lawsuits were filed in a single district: the Eastern District of Texas, a forum with plaintiff-friendly rules and practices, and where few of the defendants are incorporated or have established places of business. And an estimated 86% of 2015 patent cases were filed somewhere other than the jurisdictions specified in the statute. Colleen V. Chien & Michael Risch, Recalibrating Patent Venue, Santa Clara Univ. Legal Studies Research Paper No. 10-1 (Sept. 1, 2016), Table 3. This Court should grant certiorari to review the meaning of 28 U.S.C. § 1400(b) because the Federal Circuit’s dubious interpretation of the statute plays an outsized and detrimental role, both legally and economically, in the patent system

Brief of Amici Curiae 56 Professors of Law and Economics in Support of Petition of Writ of Certiorari

28 U.S.C. § 1400(b) provides that a defendant in a patent case may be sued where the defendant is incorporated or has a regular and established place of business and has infringed the patent. This Court made clear in Fourco Glass Co. v. Transmirra Prods. Corp., 353 U.S. 222, 223 (1957), that those were the only permissible venues for a patent case. But the Federal Circuit has rejected Fourco and the plain meaning of § 1400(b), instead permitting a patent plaintiff to file suit against a defendant anywhere there is personal jurisdiction over that defendant. The result has been rampant forum shopping, particularly by patent trolls. 44% of 2015 patent lawsuits were filed in a single district: the Eastern District of Texas, a forum with plaintiff-friendly rules and practices, and where few of the defendants are incorporated or have established places of business. And an estimated 86% of 2015 patent cases were filed somewhere other than the jurisdictions specified in the statute. Colleen V. Chien & Michael Risch, Recalibrating Patent Venue, Santa Clara Univ. Legal Studies Research Paper No. 10-1 (Sept. 1, 2016), Table 3. This Court should grant certiorari to review the meaning of 28 U.S.C. § 1400(b) because the Federal Circuit’s dubious interpretation of the statute plays an outsized and detrimental role, both legally and economically, in the patent system

Observations of metals in the intra-cluster medium

Because of their deep gravitational potential wells, clusters of galaxies retain all the metals produced by the stellar populations of the member galaxies. Most of these metals reside in the hot plasma which dominates the baryon content of clusters. This makes them excellent laboratories for the study of the nucleosynthesis and chemical enrichment history of the Universe. Here we review the history, current possibilities and limitations of the abundance studies, and the present observational status of X-ray measurements of the chemical composition of the intra-cluster medium. We summarise the latest progress in using the abundance patterns in clusters to put constraints on theoretical models of supernovae and we show how cluster abundances provide new insights into the star-formation history of the Universe.Comment: 28 pages, 12 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 16; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke

Early chronic kidney disease: diagnosis, management and models of care

Chronic kidney disease (CKD) is prevalent in many countries, and the costs associated with the care of patients with end-stage renal disease (ESRD) are estimated to exceed US$1 trillion globally. The clinical and economic rationale for the design of timely and appropriate health system responses to limit the progression of CKD to ESRD is clear. Clinical care might improve if early-stage CKD with risk of progression to ESRD is differentiated from early-stage CKD that is unlikely to advance. The diagnostic tests that are currently used for CKD exhibit key limitations; therefore, additional research is required to increase awareness of the risk factors for CKD progression. Systems modelling can be used to evaluate the impact of different care models on CKD outcomes and costs. The US Indian Health Service has demonstrated that an integrated, system-wide approach can produce notable benefits on cardiovascular and renal health outcomes. Economic and clinical improvements might, therefore, be possible if CKD is reconceptualized as a part of primary care. This Review discusses which early CKD interventions are appropriate, the optimum time to provide clinical care, and the most suitable model of care to adopt

Environmentally sustainable food consumption : a review and research agenda from a goal-directed perspective

The challenge of convincing people to change their eating habits toward more environmentally sustainable food consumption (ESFC) patterns is becoming increasingly pressing. Food preferences, choices and eating habits are notoriously hard to change as they are a central aspect of people's lifestyles and their socio-cultural environment. Many people already hold positive attitudes toward sustainable food, but the notable gap between favorable attitudes and actual purchase and consumption of more sustainable food products remains to be bridged. The current work aims to (1) present a comprehensive theoretical framework for future research on ESFC, and (2) highlight behavioral solutions for environmental challenges in the food domain from an interdisciplinary perspective. First, starting from the premise that food consumption is deliberately or unintentionally directed at attaining goals, a goal-directed framework for understanding and influencing ESFC is built. To engage in goal-directed behavior, people typically go through a series of sequential steps. The proposed theoretical framework makes explicit the sequential steps or hurdles that need to be taken for consumers to engage in ESFC. Consumers need to positively value the environment, discern a discrepancy between the desired versus the actual state of the environment, opt for action to reduce the experienced discrepancy, intend to engage in behavior that is expected to bring them closer to the desired end state, and act in accordance with their intention. Second, a critical review of the literature on mechanisms that underlie and explain ESFC (or the lack thereof) in high-income countries is presented and integrated into the goal-directed framework. This contribution thus combines a top-down conceptualization with a bottom-up literature review; it identifies and discusses factors that might hold people back from ESFC and interventions that might promote ESFC; and it reveals knowledge gaps as well as insights on how to encourage both short- and long-term ESFC by confronting extant literature with the theoretical framework. Altogether, the analysis yields a set of 33 future research questions in the interdisciplinary food domain that deserve to be addressed with the aim of fostering ESFC in the short and long term

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population