Assessing the Sensitivity of Different Life Stages for Sexual Disruption in Roach (Rutilus rutilus) Exposed to Effluents from Wastewater Treatment Works

Surveys of U.K. rivers have shown a high incidence of sexual disruption in populations of wild roach (Rutilus rutilus) living downstream from wastewater treatment works (WwTW), and the degree of intersex (gonads containing both male and female structural characteristics) has been correlated with the concentration of effluent in those rivers. In this study, we investigated feminized responses to two estrogenic WwTWs in roach exposed for periods during life stages of germ cell division (early life and the postspawning period). Roach were exposed as embryos from fertilization up to 300 days posthatch (dph; to include the period of gonadal sex differentiation) or as postspawning adult males, and including fish that had received previous estrogen exposure, for either 60 or 120 days when the annual event of germ cell proliferation occurs. Both effluents induced vitellogenin synthesis in both life stages studied, and the magnitude of the vitellogenic responses paralleled the effluent content of steroid estrogens. Feminization of the reproductive ducts occurred in male fish in a concentration-dependent manner when the exposure occurred during early life, but we found no effects on the reproductive ducts in adult males. Depuration studies (maintenance of fish in clean water after exposure to WwTW effluent) confirmed that the feminization of the reproductive duct was permanent. We found no evidence of ovotestis development in fish that had no previous estrogen exposure for any of the treatments. In wild adult roach that had previously received exposure to estrogen and were intersex, the degree of intersex increased during the study period, but this was not related to the immediate effluent exposure, suggesting a previously determined programming of ovotestis formation

Discovery of a Second Nova Eruption of V2487 Ophiuchi

A directed search for previously-undiscovered nova eruptions was conducted in the astronomical plate archives at Harvard College Observatory and Sonneberg Observatory. We found that an eruption of V2487 Oph (Nova Oph 1998) occurred on 1900 June 20. V2487 Oph was previously classified as a classical nova, which we identified as a probable recurrent nova based on its large expansion velocities and the presence of high excitation lines in the outburst spectrum. The event was recorded on Harvard plate AM 505, at a B magnitude of 10.27 +/- 0.11, which is near peak. The outburst can only be seen on one plate, but the image has a characteristic dumbbell shape (caused by a double exposure) that is identical to the other star images on the plate, and thus is not a plate defect. We conclude that this is in fact a previously-undiscovered nova outburst of V2487 Oph, confirming our prediction that it is a recurrent nova. We also examine the discovery efficiency for eruptions of the system and conclude that a randomly-timed outburst has, on average, a 30% chance of being discovered in the past century. Using this, we deduce a recurrence time for V2487 Oph of approximately 18 years, which implies that the next eruption is expected around 2016.Comment: 18 pages, 2 figures, to be published in the Astronomical Journa

Apical localization of ITPK1 enhances its ability to be a modifier gene product in a murine tracheal cell model of cystic fibrosis

A new aspect of research into the pathogenesis of cystic fibrosis (CF) is a genetics-based search for ;modifier genes' that may affect the severity of CF lung disease. Using an alternative, cell biological approach, we show that ITPK1 should be considered a modifier gene. ITPK1 synthesizes an intracellular signal, inositol (3,4,5,6)-tetrakisphosphate [Ins(3,4,5,6)P4]. A bio-activatable, cell-permeable analogue of Ins(3,4,5,6)P4 inhibited Ca2+-dependent secretion of Cl- from polarized monolayers of immortalized mouse tracheal epithelial cells (MTEs). Analysis by high-pressure liquid chromatography showed endogenous Ins(3,4,5,6)P4 levels in CF MTEs were approximately 60% below those in wild-type MTEs (P<0.03). This adaptation, which improves purinergic activation of Ca2+-dependent Cl- secretion in CF MTEs, was exceptionally specific; there was no effect upon the cellular levels of all the other inositol phosphate signals. Real-time PCR provided the explanation: the level of ITPK1 expression in wild-type MTEs was twice as high as that in CF MTEs (P<0.002). The biological impact of this differential gene expression is amplified by ITPK1 being concentrated at the apical membrane of MTEs, which we discovered following confocal immunofluorescence microscopy. Compartmentalization of Ins(3,4,5,6)P4 synthesis adjacent to its site of action will enhance its regulatory capacity

Transcriptomics and proteomics reveal two waves of translational repression during the maturation of malaria parasite sporozoites.

Plasmodium sporozoites are transmitted from infected mosquitoes to mammals, and must navigate the host skin and vasculature to infect the liver. This journey requires distinct proteomes. Here, we report the dynamic transcriptomes and proteomes of both oocyst sporozoites and salivary gland sporozoites in both rodent-infectious Plasmodium yoelii parasites and human-infectious Plasmodium falciparum parasites. The data robustly define mRNAs and proteins that are upregulated in oocyst sporozoites (UOS) or upregulated in infectious sporozoites (UIS) within the salivary glands, including many that are essential for sporozoite functions in the vector and host. Moreover, we find that malaria parasites use two overlapping, extensive, and independent programs of translational repression across sporozoite maturation to temporally regulate protein expression. Together with gene-specific validation experiments, these data indicate that two waves of translational repression are implemented and relieved at different times during sporozoite maturation, migration and infection, thus promoting their successful development and vector-to-host transition

Lower density and shorter duration of nasopharyngeal carriage by pneumococcal serotype 1 (St217) may explain its increased invasiveness over other serotypes

ABSTRACT Streptococcus pneumoniae is a frequent colonizer of the human nasopharynx and a major cause of life-threating invasive infections such as pneumonia, meningitis and sepsis. Over 1 million people die every year due to invasive pneumococcal disease (IPD), mainly in developing countries. Serotype 1 is a common cause of IPD; however, unlike other serotypes, it is rarely found in the carrier state in the nasopharynx, which is often considered a prerequisite for disease. The aim of this study was to understand this dichotomy. We used murine models of carriage and IPD to characterize the pathogenesis of African serotype 1 (sequence type 217) pneumococcal strains obtained from the Queen Elizabeth Central Hospital in Blantyre, Malawi. We found that ST217 pneumococcal strains were highly virulent in a mouse model of invasive pneumonia, but in contrast to the generally accepted assumption, can also successfully establish nasopharyngeal carriage. Interestingly, we found that cocolonizing serotypes may proliferate in the presence of serotype 1, suggesting that acquisition of serotype 1 carriage could increase the risk of developing IPD by other serotypes. RNA sequencing analysis confirmed that key virulence genes associated with inflammation and tissue invasiveness were upregulated in serotype 1. These data reveal important new insights into serotype 1 pathogenesis, with implications for carriage potential and risk of invasive disease through interactions with other cocolonizing serotypes, an often-overlooked factor in transmission and disease progression. IMPORTANCE The pneumococcus causes serious diseases such as pneumonia, sepsis, and meningitis and is a major cause of morbidity and mortality worldwide. Serotype 1 accounts for the majority of invasive pneumococcal disease cases in sub-Saharan Africa but is rarely found during nasopharyngeal carriage. Understanding the mechanisms leading to nasopharyngeal carriage and invasive disease by this serotype can help reduce its burden on health care systems worldwide. In this study, we also uncovered the potential impact of serotype 1 on disease progression of other coinfecting serotypes, which can have important implications for vaccine efficacy. Understanding the interactions between different serotypes during nasopharyngeal carriage may lead to improved intervention methods and therapies to reduce pneumococcal invasive disease levels

Analysis of inositol phosphate metabolism by capillary electrophoresis electrospray ionization mass spectrometry

The analysis of myo-inositol phosphates (InsPs) and myo-inositol pyrophosphates (PP-InsPs) is a daunting challenge due to the large number of possible isomers, the absence of a chromophore, the high charge density, the low abundance, and the instability of the esters and anhydrides. Given their importance in biology, an analytical approach to follow and understand this complex signaling hub is desirable. Here, capillary electrophoresis (CE) coupled to electrospray ionization mass spectrometry (ESI-MS) is implemented to analyze complex mixtures of InsPs and PP-InsPs with high sensitivity. Stable isotope labeled (SIL) internal standards allow for matrix-independent quantitative assignment. The method is validated in wild-type and knockout mammalian cell lines and in model organisms. SIL-CE-ESI-MS enables the accurate monitoring of InsPs and PP-InsPs arising from compartmentalized cellular synthesis pathways, by feeding cells with either [13C6]-myo-inositol or [13C6]-D-glucose. In doing so, we provide evidence for the existence of unknown inositol synthesis pathways in mammals, highlighting the potential of this method to dissect inositol phosphate metabolism and signalling

Global regime shift dynamics of catastrophic sea urchin overgrazing

A pronounced, widespread and persistent regime shift among marine ecosystems is observable on temperate rocky reefs as a result of sea urchin overgrazing. Here, we empirically define regime-shift dynamics for this grazing system which transitions between productive macroalgal beds and impoverished urchin barrens. Catastrophic in nature, urchin overgrazing in a well-studied Australian system demonstrates a discontinuous regime shift, which is of particular management concern as recovery of desirable macroalgal beds requires reducing grazers to well below the initial threshold of overgrazing. Generality of this regime-shift dynamic is explored across 13 rocky reef systems (spanning 11 different regions from both hemispheres) by compiling available survey data (totalling 10 901 quadrats surveyed in situ) plus experimental regime-shift responses (observed during a total of 57 in situ manipulations). The emergent and globally coherent pattern shows urchin grazing to cause a discontinuous ‘catastrophic’ regime shift, with hysteresis effect of approximately one order of magnitude in urchin biomass between critical thresholds of overgrazing and recovery. Different life-history traits appear to create asymmetry in the pace of overgrazing versus recovery. Once shifted, strong feedback mechanisms provide resilience for each alternative state thus defining the catastrophic nature of this regime shift. Importantly, human-derived stressors can act to erode resilience of desirable macroalgal beds while strengthening resilience of urchin barrens, thus exacerbating the risk, spatial extent and irreversibility of an unwanted regime shift for marine ecosystems.Peer reviewe

Fracture–dislocation of the shoulder and brachial plexus palsy: a terrible association

Primary post-traumatic anterior dislocation of the shoulder with associated fracture of the greater tuberosity and brachial plexus injury is rare and, to our knowledge, has never previously been reported in the literature. We present a case of this unhappy triad in which a brachial plexus injury was diagnosed and treated 3 weeks later. The characteristics of this rare condition are discussed on the basis of our case and the published literature in order to improve early diagnosis and treatment of this lesion