Requirement for DNA Ligase IV during Embryonic Neuronal Development

The embryonic ventricular and subventricular zones (VZ/SVZ) contain the neuronal stem and progenitor cells and undergo rapid proliferation. The intermediate zone (IZ) contains nonreplicating, differentiated cells. The VZ/SVZ is hypersensitive to radiation-induced apoptosis. Ablation of DNA non-homologous end-joining (NHEJ) proteins, XRCC4 or DNA ligase IV (LigIV), confers ataxia telangiectasia mutated (ATM)-dependent apoptosis predominantly in the IZ. We examine the mechanistic basis underlying these distinct sensitivities using a viable LigIV (Lig4(Y288C)) mouse, which permits an examination of the DNA damage responses in the embryonic and adult brain. Via combined analysis of DNA breakage, apoptosis, and cell-cycle checkpoint control in tissues, we show that apoptosis in the VZ/SVZ and IZ is activated by low numbers of DNA double-strand breaks (DSBs). Unexpectedly, high sensitivity in the VZ/SVZ arises from sensitive activation of ATM-dependent apoptosis plus an ATM-independent process. In contrast, the IZ appears to be hypersensitive to persistent DSBs. NHEJ functions efficiently in both compartments. The VZ/SVZ and IZ regions incur high endogenous DNA breakage, which correlates with VZ proliferation. We demonstrate a functional G(2)/M checkpoint in VZ/SVZ cells and show that it is not activated by low numbers of DSBs, allowing damaged VZ/SVZ cells to transit into the IZ. We propose a novel model in which microcephaly in LIG4 syndrome arises from sensitive apoptotic induction from persisting DSBs in the IZ, which arise from high endogenous breakage in the VZ/SVZ and transit of damaged cells to the IZ. The VZ/SVZ, in contrast, is highly sensitive to acute radiation-induced DSB formation

Young and Early Career Investigators: Report from a Global HIV Vaccine Enterprise Working Group

The scientific challenges facing HIV-1 vaccine development are unprecedented in the history of vaccinology. As a result, investigators, funders, and other stakeholders generally agree that “game-changing” ideas are required. While innovation can certainly arise from investigators at all career stages, young and early-career investigators, defined as those under 40 years of age or within 10 years of their final degree or clinical training, are especially key contributors of novel and transformative ideas. Young and early-career investigators bring energy, enthusiasm, and fresh perspectives that are unbiased by prevailing dogma and that are essential to scientific progress

Starch gelatinization under shearless and shear conditions

This article reviews the development of studying starch gelatinization under shear and shearless conditions, in particular the technologies used to detect the degree of gelatinization. Advantages and disadvantages of each technology were discussed and then some examples were presented to demonstrate their application. A new technology RheoScope, an instrument that can measure viscosity under shear stress and simultaneously observes variation of starch particles using a microscope, was also introduced. It was found the definition of "gelatinization" could be different for different detection technologies. Under shearless condition full gelatinization of starch needs about ratio of water 3/starch 1, while the gelatinization under shear condition requires less water content since shear stress enhances the processing. The number of endotherm and enthalpy of gelatinization depends on amylose/amylopectin, moisture and lipid content

Effectiveness of common household cleaning agents in reducing the viability of human influenza A/H1N1

In the event of an influenza pandemic, the majority of people infected will be nursed at home. It is therefore important to determine simple methods for limiting the spread of the virus within the home. The purpose of this work was to test a representative range of common household cleaning agents for their effectiveness at killing or reducing the viability of influenza A virus

The stellar content of the halo of NGC 5907 from deep Hubble Space Telescope NICMOS imaging

We present H-band images obtained with NICMOS of a field 75'' (5kpc) above the plane of the disk of the edge-on spiral galaxy NGC 5907. Ground-based observations have shown that NGC 5907 has a luminous halo with a shallow radial profile between 4 and 8 kpc that roughly traces the dark matter distribution of the galaxy deduced from its rotation curve. Our NICMOS observations were designed to resolve bright giants in the halo of NGC 5907 to constrain its stellar composition with the goal of understanding its nature and origin. More than 100 stars are expected in the NICMOS images if the dwarf-to-giant ratio in the halo of NGC 5907 is consistent with that expected from standard stellar initial mass functions, and if ground-based estimates of the distance to NGC 5907 and the integrated colors of its halo are correct. Instead we observe only one candidate giant star. This apparent discrepancy can be resolved by assuming either a significantly larger distance than suggested by several studies, or a halo metallicity much lower than suggested by ground-based colors and as low as metal-poor Galactic globular clusters. If previous distance and halo color estimates for NGC 5907 are correct, our NICMOS results suggest that its extended light is composed of stars that formed with an initial mass function different than that observed locally, leading to a much higher ratio of dwarfs to giants. We describe how these three possible explanations for the absence of bright giants in our NICMOS images of the halo of NGC 5907 might be constrained by future observations.Comment: Accepted for publication in the Astronomical Journal, 23 pages, 6 figure

Detecting Spam Game Reviews on Steam with a Semi-Supervised Approach

The potential value of online reviews has led to more and more spam reviews appearing on the web. These spam reviews are widely distributed, harmful, and difficult to identify manually. In this paper, we explore and implement generalised approaches for identifying online deceptive spam game reviews from Steam. We analyse spam game reviews and present and validate some techniques to detect them. In addition, we aim to identify the unique features of game reviews and to create a labelled game review dataset based on different features. We were able to create a labelled dataset that can be used to identify spam game reviews in future research. Our method resulted in 5,021 of the 33,450 unlabelled Steam reviews being labelled as spam reviews, or approximately 15%. This falls within the expected range of 10-20% and maps to the Yelp figures of 14-20% of reviews are spam

Five More Massive Binaries in the Cygnus OB2 Association

We present the orbital solutions for four OB spectroscopic binaries, MT145, GSC 03161-00815, 2MASS J20294666+4105083, and Schulte 73, and the partial orbital solution to the B spectroscopic binary, MT372, as part of an ongoing study to determine the distribution of orbital parameters for massive binaries in the Cygnus OB2 Association. MT145 is a new, single-lined, moderately eccentric (e=0.291+/-0.009) spectroscopic binary with period of 25.140+/-0.008 days. GSC 03161-00815 is a slightly eccentric (e=0.10+/-0.01), eclipsing, interacting and double-lined spectroscopic binary with a period of 4.674+/-0.004 days. 2MASS J20294666+4105083 is a moderately eccentric (e=0.273+/-0.002) double-lined spectroscopic binary with a period of 2.884+/-0.001 days. Schulte 73 is a slightly eccentric (e=0.169+/-0.009), double-lined spectroscopic binary with a period of 17.28+/-0.03 days and the first "twin" in our survey with a mass ratio of q=0.99+/-0.02. MT372 is a single-lined, eclipsing system with a period of 2.228 days and low eccentricity (e~0). Of the now 18 known OB binaries in Cyg OB2, 14 have periods and mass ratios. Emerging evidence also shows that the distribution of log(P) is flat and consistent with Oepik's Law.Comment: Accepted to Astronomical Journa

Precision and neuronal dynamics in the human posterior parietal cortex during evidence accumulation

Primate studies show slow ramping activity in posterior parietal cortex (PPC) neurons during perceptual decision-making. These findings have inspired a rich theoretical literature to account for this activity. These accounts are largely unrelated to Bayesian theories of perception and predictive coding, a related formulation of perceptual inference in the cortical hierarchy. Here, we tested a key prediction of such hierarchical inference, namely that the estimated precision (reliability) of information ascending the cortical hierarchy plays a key role in determining both the speed of decision-making and the rate of increase of PPC activity. Using dynamic causal modelling of magnetoencephalographic (MEG) evoked responses, recorded during a simple perceptual decision-making task, we recover ramping-activity from an anatomically and functionally plausible network of regions, including early visual cortex, the middle temporal area (MT) and PPC. Precision, as reflected by the gain on pyramidal cell activity, was strongly correlated with both the speed of decision making and the slope of PPC ramping activity. Our findings indicate that the dynamics of neuronal activity in the human PPC during perceptual decision-making recapitulate those observed in the macaque, and in so doing we link observations from primate electrophysiology and human choice behaviour. Moreover, the synaptic gain control modulating these dynamics is consistent with predictive coding formulations of evidence accumulation

From Plasmodium vivax outbreak to elimination: lessons learnt from a retrospective analysis of data from Guantang

BACKGROUND: Malaria was once a serious public health problem in China, with Plasmodium vivax the major species responsible for more than 90% of local transmission. Following significant integrated malaria control and elimination programmes, malaria burden declined, and since 2017 China has not recorded any indigenous case. To understand the historical malaria transmission patterns and epidemic characteristics in China and insights useful to guide P. vivax malaria control and elimination elsewhere, a retrospective study was carried out. METHODS: Historical data from a pilot study conducted in Guantang, Luyi in central China from 1971-1995, were digitized. The data included monthly numbers of reported cases, febrile cases, parasite carriage rates, the neonatal infection rate, and entomological data regarding Anopheles sinensis. RESULTS: Following 25 years of continuous integrated malaria control activities, malaria incidence in Guantang decreased from 4,333 cases per 10,000 in 1970 before integrated implementation to 0.23 cases per 10,000 in 1991, and no cases in 1992-1995. Some fluctuations in incidence were observed between 1977 and 1981. During the period parasite rates, antibody levels and the neonatal infection rate also decreased. The pattern of seasonality confirmed that P. vivax in Henan Province was primarily of the long incubation type (temperate) during non-transmission period. The findings retrospectively provide a scientific basis for the implementation of mass campaigns of liver stage hypnozoite clearance. Entomological studies indicated that An. sinensis was the only vector, and it preferred bovine to human hosts, predominantly biting and resting outdoors. Mosquito densities declined between 1971 and 1984. CONCLUSION: The integrated malaria control approach in Guantang effectively controlled malaria and achieved elimination. Analysis of the effectiveness of the programme can provide guidance to other regions or countries with similar ecological settings aiming to move from malaria control to elimination. There is a potential challenge in the maintenance of non-transmission status owing to imported cases and the long dormancy of liver stage hypnozoites

Contribution of DNA repair and cell cycle checkpoint arrest to the maintenance of genomic stability

DNA damage response mechanisms encompass pathways of DNA repair, cell cycle checkpoint arrest and apoptosis. Together, these mechanisms function to maintain genomic stability in the face of exogenous and endogenous DNA damage. ATM is activated in response to double strand breaks and initiates cell cycle checkpoint arrest. Recent studies in human fibroblasts have shown that ATM also regulates a mechanism of end-processing that is required for a component of double strand break repair. Human fibroblasts rarely undergo apoptosis after ionising radiation and, therefore, apoptosis is not considered in our review. The dual function of ATM raises the question as to how the two processes, DNA repair and checkpoint arrest, interplay to maintain genomic stability. In this review, we consider the impact of ATM's repair and checkpoint functions to the maintenance of genomic stability following irradiation in G2. We discuss evidence that ATM's repair function plays little role in the maintenance of genomic stability following exposure to ionising radiation. ATM's checkpoint function has a bigger impact on genomic stability but strikingly the two damage response pathways co-operate in a more than additive manner. In contrast, ATM's repair function is important for survival post irradiation