Relationship of phosphorus content in carp otoliths with that in ambient water in Xiaoxi Port of the Taihu Lake, East China

It has been of high concern that the phosphorus pollution is getting serious after lake eutrophication in the Taihu Lake, the third largest freshwater lake in China. As a sensitive  recorder of the ambient water and fish exposures, fish otolith has been studied as a potential dynamic monitor of water quality by many biologists and mineralogists. In order to work out the correlation of phosphorus enrichment in carp otoliths to the ambient water of the carps, the phosphorus concentration in carp otoliths was measured in situ using laser ablation plasma mass spectrometry (LA-ICP-MS) and comparison with the relevant data of the water was conducted. Significant positive correlation was found for phosphorus concentration in carp otoliths to the ambient water in the corresponding time. Therefore, the wild carp otoliths have the potential to act as an environmental indicator of water phosphorus pollution and lake eutrophication.Key words: Carp otoliths, environmental pollution, lake eutrophication, phosphorus enrichment, mineral monitoring, Taihu Lake

Na+-leak channel, non-selective (NALCN) regulates myometrial excitability and facilitates successful parturition

Background/Aims: Uterine contractility is controlled by electrical signals generated by myometrial smooth muscle cells. Because aberrant electrical signaling may cause inefficient uterine contractions and poor reproductive outcomes, there is great interest in defining the ion channels that regulate uterine excitability. In human myometrium, the Na+ leak channel, non-selective (NALCN) contributes to a gadolinium-sensitive, Na+-dependent leak current. The aim of this study was to determine the role of NALCN in regulating uterine excitability and examine its involvement in parturition. Methods: Wildtype C57BL/6J mice underwent timed-mating and NALCN uterine expression was measured at several time points across pregnancy including pregnancy days 7, 10, 14, 18 and 19. Sharp electrode current clamp was used to measure uterine excitability at these same time points. To determine NALCN’s contribution to myometrial excitability and pregnancy outcomes, we created smooth-muscle-specific NALCN knockout mice by crossing NALCNfx/fx mice with myosin heavy chain Cre (MHCCreeGFP) mice. Parturition outcomes were assessed by observation via surveillance video recording cre control, flox control, smNALCN+/-, and smNALCN-/- mice. Myometrial excitability was compared between pregnancy day 19 flox controls and smNALCN-/- mice. Results: We found that in the mouse uterus, NALCN protein levels were high early in pregnancy, decreased in mid and late pregnancy, and then increased in labor and postpartum. Sharp electrode current clamp recordings of mouse longitudinal myometrial samples from pregnancy days 7, 10, 14, 18, and 19 revealed day-dependent increases in burst duration and interval and decreases in spike density. NALCN smooth muscle knockout mice had reduced myometrial excitability exemplified by shortened action potential bursts, and an increased rate of abnormal labor, including prolonged and dysfunctional labor. Conclusions: Together, our findings demonstrate that the Na+ conducting channel NALCN contributes to the myometrial action potential waveform and is important for successful labor outcomes

Identifying effects of multiple treatments in the presence of unmeasured confounding

Identification of treatment effects in the presence of unmeasured confounding is a persistent problem in the social, biological, and medical sciences. The problem of unmeasured confounding in settings with multiple treatments is most common in statistical genetics and bioinformatics settings, where researchers have developed many successful statistical strategies without engaging deeply with the causal aspects of the problem. Recently there have been a number of attempts to bridge the gap between these statistical approaches and causal inference, but these attempts have either been shown to be flawed or have relied on fully parametric assumptions. In this paper, we propose two strategies for identifying and estimating causal effects of multiple treatments in the presence of unmeasured confounding. The auxiliary variables approach leverages auxiliary variables that are not causally associated with the outcome; in the case of a univariate confounder, our method only requires one auxiliary variable, unlike existing instrumental variable methods that would require as many instruments as there are treatments. An alternative null treatments approach relies on the assumption that at least half of the confounded treatments have no causal effect on the outcome, but does not require a priori knowledge of which treatments are null. Our identification strategies do not impose parametric assumptions on the outcome model and do not rest on estimation of the confounder. This work extends and generalizes existing work on unmeasured confounding with a single treatment, and provides a nonparametric extension of models commonly used in bioinformatics

Mineralogical and geochemical study of carp otoliths from Baiyangdian Lake and Miyun Water Reservoir in China

Carp otoliths from two different freshwaters (Baiyangdian Lake and Miyun Water Reservoir) were mineralogically and chemically analyzed. The water quality standard of Miyun Water Reservoir is Grade 2 which is much better than the Grade 5 of Baiyangdian Lake. The aim of this study was to examine the differences in otoliths in mineralogy and chemistry from the two sites with quite different qualities. All the analyzed carps showed lapillus and sagitta otoliths made of aragonite, except for B-22 (from Baiyangdian Lake) whose lapillus consisted of vaterite and sagitta consisted of aragonite and vaterite; all asteriscus are composed of vaterite. It is inferred that the occurrence of vaterictic otoliths is linked to poor water quality. Chemical analysis showed that significant difference of Pb concentration between sites was tested by t-test of the compare means (t-test comparison: t = 2.043, P<0.05). While the sitespecific differences of the other metals were not significant. In addition, a significant difference of Sn concentration was tested as well (t-test comparison: t = 2.652, P<0.05). Average content of lapilli Pb is consistent with the water dissolved Pb measurement, with higher dissolved Pb concentration in Baiyangdian Lake relative to the Miyun Water Reservoir.Key words: Carp otoliths, water quality, mineralogy, chemistry, Pb

Early neuronal accumulation of DNA double strand breaks in Alzheimer's disease.

The maintenance of genomic integrity is essential for normal cellular functions. However, it is difficult to maintain over a lifetime in postmitotic cells such as neurons, in which DNA damage increases with age and is exacerbated by multiple neurological disorders, including Alzheimer's disease (AD). Here we used immunohistochemical staining to detect DNA double strand breaks (DSBs), the most severe form of DNA damage, in postmortem brain tissues from patients with mild cognitive impairment (MCI) or AD and from cognitively unimpaired controls. Immunostaining for γH2AX-a post-translational histone modification that is widely used as a marker of DSBs-revealed increased proportions of γH2AX-labeled neurons and astrocytes in the hippocampus and frontal cortex of MCI and AD patients, as compared to age-matched controls. In contrast to the focal pattern associated with DSBs, some neurons and glia in humans and mice showed diffuse pan-nuclear patterns of γH2AX immunoreactivity. In mouse brains and primary neuronal cultures, such pan-nuclear γH2AX labeling could be elicited by increasing neuronal activity. To assess whether pan-nuclear γH2AX represents DSBs, we used a recently developed technology, DNA damage in situ ligation followed by proximity ligation assay, to detect close associations between γH2AX sites and free DSB ends. This assay revealed no evidence of DSBs in neurons or astrocytes with prominent pan-nuclear γH2AX labeling. These findings suggest that focal, but not pan-nuclear, increases in γH2AX immunoreactivity are associated with DSBs in brain tissue and that these distinct patterns of γH2AX formation may have different causes and consequences. We conclude that AD is associated with an accumulation of DSBs in vulnerable neuronal and glial cell populations from early stages onward. Because of the severe adverse effects this type of DNA damage can have on gene expression, chromatin stability and cellular functions, DSBs could be an important causal driver of neurodegeneration and cognitive decline in this disease

Review of ongoing initiatives to improve prescribing efficiency in China; angiotensin receptor blockers as a case history

Pharmaceutical expenditure is rising by 16% per annum in China and is now 46% of total expenditure. Initiatives to moderate growth include drug pricing regulations and encouraging international non-proprietary name prescribing. However, there is no monitoring of physician prescribing quality and perverse incentives. Assess changes in angiotensin receptor blocker (ARB) utilization and expenditure as more generics become available; compare findings to Europe. Observational retrospective study of ARB utilization and expenditure between 2006 and 2012 in the largest hospital in Chongqing district. Variable and low use of generics versus originators with a maximum of 31% among single ARBs. Similar for fixed dose combinations. Prices typically reduced over time, greatest for generic telmisartan (-54%), mirroring price reductions in some European countries. However, no preferential increase in prescribing of lower cost generics. Accumulated savings of 33 million CNY for this large provider if they adopted European practices. Considerable opportunities to improve prescribing efficiency in China