Mullerian inhibiting substance: a gonadal hormone with multiple functions

Mullerian inhibiting substance (MIS) is the gonadal hormone that causes regression of the Mullerian ducts, the anlagen of the female internal reproductive structures, during male embryogenesis. MIS is a member of the large transforming growth factor-beta (TGF beta) multigene family of glycoproteins that are involved in the regulation of growth and differentiation. The proteins in this gene family are all produced as dimeric precursors and undergo posttranslational processing for activation, requiring cleavage and dissociation to release bioactive C-terminal fragments. Similarly, the 140 kilodalton (kDa) disulfide-linked homodimer of MIS is proteolytically cleaved to generate its active C-terminal fragments. The sexually dimorphic expression of MIS in Sertoli cells of the testis and granulosa cells of the ovary is critical for normal differentiation of the internal reproductive tract structures. A number of extra-Mullerian functions such as control of germ cell maturation and gonadal morphogenesis, induction of the abdominal phase of testicular descent, suppression of lung maturation, and growth inhibition of transformed cells have also been proposed for this growth-inhibitory hormone and will be discussed. This article will summarize the current understanding of the biology and multiple functions of MIS including its activation, regulation, and mechanism of action and discuss areas of interest in ongoing research

Report of the SNOMS Project 2006 to 2012, SNOMS SWIRE NOCS Ocean Monitoring System. Part 1: Narrative description

The ocean plays a major role in controlling the concentration of carbon dioxide (CO2) in the atmosphere. Increasing concentrations of CO2 in the atmosphere are a threat to the stability of the earth’s climate. A better understanding of the controlling role of the ocean will improve predictions of likely future changes in climate and the impact of the uptake of CO2 itself on marine eco-systems caused by the associated acidification of the ocean waters. The SNOMS Project (SWIRE NOCS Ocean Monitoring System) is a ground breaking joint research project supported by the Swire Group Trust, the Swire Educational Trust, the China Navigation Company (CNCo) and the Natural Environment Research Council. It collects high quality data on concentrations of CO2 in the surface layer of the ocean. It contributes to the international effort to better quantify (and understand the driving processes controlling) the exchanges of CO2 between the ocean and the atmosphere. In 2006 and 2007 a system that could be used on a commercial ship to provide data over periods of several months with only limited maintenance by the ships crew was designed and assembled by NOCS. The system was fitted to the CNCo ship the MV Pacific Celebes in May 2007. The onboard system was supported by web pages that monitored the progress of the ship and the functioning of the data collection system. To support the flow of data from the ship to the archiving of the data at the Carbon Dioxide Information Analysis Center (CDIAC in the USA) data processing procedures were developed for the quality control and systematic handling of the data. Data from samples of seawater collected by the ships crew and analysed in NOC (730 samples) have been used to confirm the consistency of the data from the automated measurement system on the ship. To examine the data collected between 2007 and 2012 the movements of the ship are divided into 16 voyages. Initially The Celebes traded on a route circum-navigating the globe via the Panama and Suez Canals. In 2009 the route shifted to one between Australia and New Zealand to USA and Canada. Analysis of the data is an on going process. It has demonstrated that the system produces reliable data. Data are capable of improving existing estimates of seasonal variability. The work has improved knowledge of gas exchange processes. Data from the crew-collected-samples are helping improve our ability to estimate alkalinity in different areas. This helps with the study of ocean acidification. Data from the 9 round trips in the Pacific are currently being examined along with data made available by the NOAA-PMEL laboratory forming time series from 2004 to 2012. The data from the Pacific route are of considerable interest. One reason is that the data monitors variations in the fluxes of CO2 associated with the current that flows westwards along the equator. This is one of the major natural sources of CO2 from the ocean into the atmosphere

International Docking Standardization NASA

This slide presentation reviews the different types of docking types. The objective is the pressurized vehicle connection and crew transfer. Androgynous Docking is defined as the joining or coming together of two free flying space vehicles with alike interfaces. Androgynous mating allows for collaboration between any two vehicles. The subsytems of an androgynous mating system are reviewed, including: Hard docking subsystems: latch system, tunnel housing, alignment system and seal

Measurements of serum mullerian inhibiting substance in the evaluation of children with nonpalpable gonads

BACKGROUND: Mullerian inhibiting substance, produced constitutively by the prepubertal testes, promotes involution of the mullerian ducts during normal male sexual differentiation. In children with virilization and nonpalpable gonads, only those with testicular tissue should have detectable serum concentrations of mullerian inhibiting substance. METHODS: We measured serum mullerian inhibiting substance in 65 children with virilization at birth and nonpalpable gonads (age at diagnosis, 2 days to 11 years) and serum testosterone in 54 of them either after the administration of human chorionic gonadotropin or during the physiologic rise in testosterone that occurs in normal infants. RESULTS: The mean (+/-SD) serum mullerian inhibiting substance concentration in the 17 children with no testicular tissue was 0.7+/-0.5 ng per milliliter, as compared with 37.5+/-39.6 ng per milliliter in the 48 children with testes (P CONCLUSIONS: Measurements of serum mullerian inhibiting substance can be used to determine testicular status in prepubertal children with nonpalpable gonads, thus differentiating anorchia from undescended testes in boys with bilateral cryptorchidism and serving as a measure of testicular integrity in children with intersexual anomalies

Neural tube defects in four Shetland sheepdog puppies: clinical characterisation and computed tomography investigation

Case report Here we report on the occurrence of neural tube defects in four related Shetland sheepdog puppies. Neural tube defects present as a range of congenital malformations affecting the spine, skull and associated structures. Despite the severity of these malformations and their relatively high prevalence in humans, the aetiology is not well understood. It is even less well characterised in veterinary medicine. Affected puppies were investigated using computed tomography and then post-mortem examination. Computed tomography identified a range of brain and spine abnormalities in the affected animals, including caudal anencephaly, encephalocele, spina bifida and malformed vertebrae. Other observed abnormalities in these puppies, including cranioschisis, atresia ani and hydrocephalus, may be secondary to, or associated with, the primary neural tube defects identified. Conclusion This case report describes multiple related cases of neural tube defects in an Australian cohort of dogs. This study also highlights the potential of advanced imaging techniques in identifying congenital anomalies in stillborn and neonatal puppies. Further research is required to investigate the aetiology of neural tube defects in this group of affected Shetland sheepdogs

Autoantibody-targeted treatments for acute exacerbations of idiopathic pulmonary fibrosis

Background: Severe acute exacerbations (AE) of idiopathic pulmonary fibrosis (IPF) are medically untreatable and often fatal within days. Recent evidence suggests autoantibodies may be involved in IPF progression. Autoantibody-mediated lung diseases are typically refractory to glucocorticoids and nonspecific medications, but frequently respond to focused autoantibody reduction treatments. We conducted a pilot trial to test the hypothesis that autoantibody-targeted therapies may also benefit AE-IPF patients. Methods: Eleven (11) critically-ill AE-IPF patients with no evidence of conventional autoimmune diseases were treated with therapeutic plasma exchanges (TPE) and rituximab, supplemented in later cases with intravenous immunoglobulin (IVIG). Plasma anti-epithelial (HEp-2) autoantibodies and matrix metalloproteinase-7 (MMP7) were evaluated by indirect immunofluorescence and ELISA, respectively. Outcomes among the trial subjects were compared to those of 20 historical control AE-IPF patients treated with conventional glucocorticoid therapy prior to this experimental trial. Results: Nine (9) trial subjects (82%) had improvements of pulmonary gas exchange after treatment, compared to one (5%) historical control. Two of the three trial subjects who relapsed after only five TPE responded again with additional TPE. The three latest subjects who responded to an augmented regimen of nine TPE plus rituximab plus IVIG have had sustained responses without relapses after 96-to-237 days. Anti-HEp-2 autoantibodies were present in trial subjects prior to therapy, and were reduced by TPE among those who responded to treatment. Conversely, plasma MMP7 levels were not systematically affected by therapy nor correlated with clinical responses. One-year survival of trial subjects was 46+15% vs. 0% among historical controls. No serious adverse events were attributable to the experimental medications. Conclusion: This pilot trial indicates specific treatments that reduce autoantibodies might benefit some severely-ill AE-IPF patients. These findings have potential implications regarding mechanisms of IPF progression, and justify considerations for incremental trials of autoantibody-targeted therapies in AE-IPF patients. Trial Registration: ClinicalTrials.gov NCT01266317

High Frequency of Cytomegalovirus-Specific Cytotoxic T-Effector Cells in HLA-A*0201-Positive Subjects during Multiple Viral Coinfections

How the cellular immune response copes with diverse antigenic competition is poorly understood. Responses of virus-specific cytotoxic T lymphocytes (CTL) were examined longitudinally in an individual coinfected with human immunodeficiency virus type 1 (HIV-1), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). CTL responses to all 3 viruses were quantified by limiting dilution analysis and staining with HLA-A*0201 tetrameric complexes folded with HIV-1, EBV, and CMV peptides. A predominance of CMV-pp65-speciflc CTL was found, with a much lower frequency of CTL to HIV-1 Gag and Pol and to EBV-BMLF1 and LMP2. The high frequency of CMV-speciflc CTL, compared with HIV-1- and EBV-specific CTL, was confirmed in an additional 16 HLA-A*0201-positive virus-coinfected subjects. Therefore, the human immune system can mount CTL responses to multiple viral antigens simultaneously, albeit with different strength