Cholesterol-induced mammary tumorigenesis is enhanced by adiponectin deficiency: role of LDL receptor upregulation

published_or_final_versio

A common framework for approaches to extreme event attribution

The extent to which a given extreme weather or climate event is attributable to anthropogenic climate change is a question of considerable public interest. From a scientific perspective, the question can be framed in various ways, and the answer depends very much on the framing. One such framing is a risk-based approach, which answers the question probabilistically, in terms of a change in likelihood of a class of event similar to the one in question, and natural variability is treated as noise. A rather different framing is a storyline approach, which examines the role of the various factors contributing to the event as it unfolded, including the anomalous aspects of natural variability, and answers the question deterministically. It is argued that these two apparently irreconcilable approaches can be viewed within a common framework, where the most useful level of conditioning will depend on the question being asked and the uncertainties involved

Projections of the current and future disease burden of hepatitis C virus infection in Malaysia

The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods.An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed.In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039.The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia

Loss of Arc renders the visual cortex impervious to the effects of sensory experience or deprivation

A myriad of mechanisms have been suggested to account for the full richness of visual cortical plasticity. We found that visual cortex lacking Arc is impervious to the effects of deprivation or experience. Using intrinsic signal imaging and chronic visually evoked potential recordings, we found that Arc−/− mice did not exhibit depression of deprived-eye responses or a shift in ocular dominance after brief monocular deprivation. Extended deprivation also failed to elicit a shift in ocular dominance or open-eye potentiation. Moreover, Arc−/− mice lacked stimulus-selective response potentiation. Although Arc−/− mice exhibited normal visual acuity, baseline ocular dominance was abnormal and resembled that observed after dark-rearing. These data suggest that Arc is required for the experience-dependent processes that normally establish and modify synaptic connections in visual cortex.Howard Hughes Medical InstituteNational Science Foundation (U.S.

Vigorous lateral export of the meltwater outflow from beneath an Antarctic ice shelf

The instability and accelerated melting of the Antarctic Ice Sheet are among the foremost elements of contemporary global climate change1, 2. The increased freshwater output from Antarctica is important in determining sea level rise1, the fate of Antarctic sea ice and its effect on the Earth’s albedo4, 5, ongoing changes in global deep-ocean ventilation6, and the evolution of Southern Ocean ecosystems and carbon cycling7, 8. A key uncertainty in assessing and predicting the impacts of Antarctic Ice Sheet melting concerns the vertical distribution of the exported meltwater. This is usually represented by climate-scale models3–5, 9 as a near-surface freshwater input to the ocean, yet measurements around Antarctica reveal the meltwater to be concentrated at deeper levels10, 11, 12, 13, 14. Here we use observations of the turbulent properties of the meltwater outflows from beneath a rapidly melting Antarctic ice shelf to identify the mechanism responsible for the depth of the meltwater. We show that the initial ascent of the meltwater outflow from the ice shelf cavity triggers a centrifugal overturning instability that grows by extracting kinetic energy from the lateral shear of the background oceanic flow. The instability promotes vigorous lateral export, rapid dilution by turbulent mixing, and finally settling of meltwater at depth. We use an idealized ocean circulation model to show that this mechanism is relevant to a broad spectrum of Antarctic ice shelves. Our findings demonstrate that the mechanism producing meltwater at depth is a dynamically robust feature of Antarctic melting that should be incorporated into climate-scale models

Becoming a new neuron in the adult olfactory bulb

New neurons are continually recruited throughout adulthood in certain regions of the adult mammalian brain. How these cells mature and integrate into preexisting functional circuits remains unknown. Here we describe the physiological properties of newborn olfactory bulb interneurons at five different stages of their maturation in adult mice. Patch-clamp recordings were obtained from tangentially and radially migrating young neurons and from neurons in three subsequent maturation stages. Tangentially migrating neurons expressed extrasynaptic GABAA receptors and then AMPA receptors, before NMDA receptors appeared in radially migrating neurons. Spontaneous synaptic activity emerged soon after migration was complete, and spiking activity was the last characteristic to be acquired. This delayed excitability is unique to cells born in the adult and may protect circuits from uncontrolled neurotransmitter release and neural network disruption. Our results show that newly born cells recruited into the olfactory bulb become neurons, and a unique sequence of events leads to their functional integration

A review of the distribution of particulate trace elements in urban terrestrial environments and its application to considerations of risk

We review the evolution, state of the art and future lines of research on the sources, transport pathways, and sinks of particulate trace elements in urban terrestrial environments to include the atmosphere, soils, and street and indoor dusts. Such studies reveal reductions in the emissions of some elements of historical concern such as Pb, with interest consequently focusing on other toxic trace elements such as As, Cd, Hg, Zn, and Cu. While establishment of levels of these elements is important in assessing the potential impacts of human society on the urban environment, it is also necessary to apply this knowledge in conjunction with information on the toxicity of those trace elements and the degree of exposure of human receptors to an assessment of whether such contamination represents a real risk to the city’s inhabitants and therefore how this risk can be addressed

Nonlinear landscape and cultural response to sea-level rise

Rising sea levels have been associated with human migration and behavioral shifts throughout prehistory, often with an emphasis on landscape submergence and consequent societal collapse. However, the assumption that future sea-level rise will drive similar adaptive responses is overly simplistic. While the change from land to sea represents a dramatic and permanent shift for preexisting human populations, the process of change is driven by a complex set of physical and cultural processes with long transitional phases of landscape and socioeconomic change. Here, we use reconstructions of prehistoric sea-level rise, paleogeographies, terrestrial landscape change, and human population dynamics to show how the gradual inundation of an island archipelago resulted in decidedly nonlinear landscape and cultural responses to rising sea levels. Interpretation of past and future responses to sea-level change requires a better understanding of local physical and societal contexts to assess plausible human response patterns in the future

Homeostatic Plasticity Studied Using In Vivo Hippocampal Activity-Blockade: Synaptic Scaling, Intrinsic Plasticity and Age-Dependence

Homeostatic plasticity is thought to be important in preventing neuronal circuits from becoming hyper- or hypoactive. However, there is little information concerning homeostatic mechanisms following in vivo manipulations of activity levels. We investigated synaptic scaling and intrinsic plasticity in CA1 pyramidal cells following 2 days of activity-blockade in vivo in adult (postnatal day 30; P30) and juvenile (P15) rats. Chronic activity-blockade in vivo was achieved using the sustained release of the sodium channel blocker tetrodotoxin (TTX) from the plastic polymer Elvax 40W implanted directly above the hippocampus, followed by electrophysiological assessment in slices in vitro. Three sets of results were in general agreement with previous studies on homeostatic responses to in vitro manipulations of activity. First, Schaffer collateral stimulation-evoked field responses were enhanced after 2 days of in vivo TTX application. Second, miniature excitatory postsynaptic current (mEPSC) amplitudes were potentiated. However, the increase in mEPSC amplitudes occurred only in juveniles, and not in adults, indicating age-dependent effects. Third, intrinsic neuronal excitability increased. In contrast, three sets of results sharply differed from previous reports on homeostatic responses to in vitro manipulations of activity. First, miniature inhibitory postsynaptic current (mIPSC) amplitudes were invariably enhanced. Second, multiplicative scaling of mEPSC and mIPSC amplitudes was absent. Third, the frequencies of adult and juvenile mEPSCs and adult mIPSCs were increased, indicating presynaptic alterations. These results provide new insights into in vivo homeostatic plasticity mechanisms with relevance to memory storage, activity-dependent development and neurological diseases