Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis.

Age-related loss of muscle mass and strength can be accelerated by impaired recovery of muscle mass following a transient atrophic stimulus. The aim of this study was to identify the mechanisms underlying the attenuated recovery of muscle mass and strength in old rats following disuse-induced atrophy. Adult (9 month) and old (29 month) male F344BN rats underwent hindlimb unloading (HU) followed by reloading. HU induced significant atrophy of the hindlimb muscles in both adult (17-38%) and old (8-29%) rats, but only the adult rats exhibited full recovery of muscle mass and strength upon reloading. Upon reloading, total RNA and protein synthesis increased to a similar extent in adult and old muscles. At baseline and upon reloading, however, proteasome-mediated degradation was suppressed leading to an accumulation of ubiquitin-tagged proteins and p62. Further, ER stress, as measured by CHOP expression, was elevated at baseline and upon reloading in old rats. Analysis of mRNA expression revealed increases in HDAC4, Runx1, myogenin, Gadd45a, and the AChRs in old rats, suggesting neuromuscular junction instability/denervation. Collectively, our data suggests that with aging, impaired neuromuscular transmission and deficits in the proteostasis network contribute to defects in muscle fiber remodeling and functional recovery of muscle mass and strength

Modelling biodiversity trends in the montado (wood pasture) landscapes of the Alentejo, Portugal

Abstract Context Montados are dynamic agroforestry systems of southern Portugal, with high economic and ecological values. Changes in land use and cover have important implications for landscape-level biodiversity and its conservation. Objectives Our objectives were to evaluate the biodiversity values and trends in a montado system in the Alentejo, Portugal so as to inform landscape level conservation approaches. In doing so, we aimed to develop a replicable and robust approach drawing together field observation, expert opinion, and remote sensing to produce predictions relevant to land management planning. Methods Field sampling and subsequent analysis of data on the birds, butterflies and plants in eight distinct land covers allowed the identification of two principal habitat groupings of importance: ‘montado mosaic’ and ‘shrubland’. Morphological spatial pattern analysis was performed on Landsat-derived GIS habitat layers for 1984 and 2009, generating maps and statistics for change in the different landscape functional classes. In addition, we demonstrated how the modelling of ecotones between open and closed biomes can identify the preferred hunting grounds of the threatened Iberian lynx and black vulture, flagship species whose conservation provides benefits to the area’s wider biodiversity values. Results Total and core area of montado mosaics and shrubland increased over the 25 year period, whilst the amount of habitat connectivity declined in the case of shrubland. Considerable local variation in these trends highlighted targetable areas for conservation action (e.g. through agri-environment spending). Conclusions A rapid and robust approach was demonstrated, with potentially wider utility for biodiversity assessment and planning

Higgs friends and counterfeits at hadron colliders

We consider the possibility of "Higgs counterfeits" - scalars that can be produced with cross sections comparable to the SM Higgs, and which decay with identical relative observable branching ratios, but which are nonetheless not responsible for electroweak symmetry breaking. We also consider a related scenario involving "Higgs friends," fields similarly produced through gg fusion processes, which would be discovered through diboson channels WW, ZZ, gamma gamma, or even gamma Z, potentially with larger cross sections times branching ratios than for the Higgs. The discovery of either a Higgs friend or a Higgs counterfeit, rather than directly pointing towards the origin of the weak scale, would indicate the presence of new colored fields necessary for the sizable production cross section (and possibly new colorless but electroweakly charged states as well, in the case of the diboson decays of a Higgs friend). These particles could easily be confused for an ordinary Higgs, perhaps with an additional generation to explain the different cross section, and we emphasize the importance of vector boson fusion as a channel to distinguish a Higgs counterfeit from a true Higgs. Such fields would naturally be expected in scenarios with "effective Z's," where heavy states charged under the SM produce effective charges for SM fields under a new gauge force. We discuss the prospects for discovery of Higgs counterfeits, Higgs friends, and associated charged fields at the LHC.Comment: 27 pages, 5 figures. References added and typos fixe

The Extremes of Thermonuclear Supernovae

The majority of thermonuclear explosions in the Universe seem to proceed in a rather standardised way, as explosions of carbon-oxygen (CO) white dwarfs in binary systems, leading to 'normal' Type Ia supernovae (SNe Ia). However, over the years a number of objects have been found which deviate from normal SNe Ia in their observational properties, and which require different and not seldom more extreme progenitor systems. While the 'traditional' classes of peculiar SNe Ia - luminous '91T-like' and faint '91bg-like' objects - have been known since the early 1990s, other classes of even more unusual transients have only been established 20 years later, fostered by the advent of new wide-field SN surveys such as the Palomar Transient Factory. These include the faint but slowly declining '02es-like' SNe, 'Ca-rich' transients residing in the luminosity gap between classical novae and supernovae, extremely short-lived, fast-declining transients, and the very luminous so-called 'super-Chandrasekhar' SNe Ia. Not all of them are necessarily thermonuclear explosions, but there are good arguments in favour of a thermonuclear origin for most of them. The aim of this chapter is to provide an overview of the zoo of potentially thermonuclear transients, reviewing their observational characteristics and discussing possible explosion scenarios.Comment: Author version of a chapter for the 'Handbook of Supernovae', edited by A. Alsabti and P. Murdin, Springer. 50 pages, 7 figure

The pathology of familial breast cancer: The pre-BRCA1/BRCA2 era - historical perspectives

A proportion of breast carcinomas develop as a result of a genetic predispostion to the disease. Prior to cloning of the BRCA1 and BRCA2 genes a limited number of studies were carried out to identify specific histopathological characteristics of hereditary breast cancer. These studies are the subject of this review. The main finding was the association of the (atypical) medullary type of breast cancer with a family history; the most important caveat being that medullary breast cancer is found more frequently in young patients. In view of the frequent bilateral occurrence of lobular cancer, this histologic type is also likely to be associated with a predisposing genetic defect. Future investigations will have to test this hypothesis. In addition to mutations in the BRCA1 and BRCA2 genes, there are as yet unidentified genetic defects predisposing to breast cancer development, and histopathology may well help in identifying these genes in the future

Semiquantitative Estimates of Rainfall Variability During the 8.2 kyr Event in California Using Speleothem Calcium Isotope Ratios

A multiproxy record from a fast-growing stalagmite reveals variable hydroclimate on the California coast across the 8.2 kyr event and a precursor event likely caused by initial drainage of proglacial Lake Agassiz. Using speleothem δ Ca, we develop the first semiquantitative estimates of paleorainfall variability for California through calibration with measurements of the modern climate and cave environment. We find that the magnitude of rainfall variability during the 8.2 kyr event approached the multiyear variability observable in the recent past (1950–2019) and the magnitude of variability during the precursor event likely exceeded this range. Additionally, we observe other instances of multidecadal variability comparable in magnitude to the precursor event during the record. Our work suggests that speleothem calcium isotope ratios are a powerful semiquantitative means to reconstruct paleorainfall, although numerous factors must be assessed in each cave system before applying this approach. 4

Effects and Action Mechanisms of Berberine and Rhizoma coptidis on Gut Microbes and Obesity in High-Fat Diet-Fed C57BL/6J Mice

Gut microbes play important roles in regulating fat storage and metabolism. Rhizoma coptidis (RC) and its main active compound, berberine, have either antimicrobial or anti-obesity activities. In the present study, we hypothesize that RC exerts anti-obesity effects that are likely mediated by mechanisms of regulating gut microbes and berberine may be a key compound of RC. Gut microbes and glucose and lipid metabolism in high-fat diet-fed C57BL/6J (HFD) mice in vivo are investigated after RC and berberine treatments. The results show that RC (200 mg/kg) and berberine (200 mg/kg) significantly lower both body and visceral adipose weights, and reduce blood glucose and lipid levels, and decrease degradation of dietary polysaccharides in HFD mice. Both RC and berberine significantly reduce the proportions of fecal Firmicutes and Bacteroidetes to total bacteria in HFD mice. In the trial ex vivo, both RC and berberine significantly inhibit the growth of gut bacteria under aerobic and anaerobic conditions. In in vitro trials, both RC and berberine significantly inhibit the growth of Lactobacillus (a classical type of Firmicutes) under anaerobic conditions. Furthermore, both RC and berberine significantly increase fasting-induced adipose factor (Fiaf, a key protein negatively regulated by intestinal microbes) expressions in either intestinal or visceral adipose tissues. Both RC and berberine significantly increase mRNA expressions of AMPK, PGC1α, UCP2, CPT1α, and Hadhb related to mitochondrial energy metabolism, which may be driven by increased Fiaf expression. These results firstly suggest that antimicrobial activities of RC and berberine may result in decreasing degradation of dietary polysaccharides, lowering potential calorie intake, and then systemically activating Fiaf protein and related gene expressions of mitochondrial energy metabolism in visceral adipose tissues. Taken together, these action mechanisms may contribute to significant anti-obesity effects. Findings in the present study also indicate that pharmacological regulation on gut microbes can develop an anti-obesity strategy

Madagascar's grasses and grasslands:anthropogenic or natural?

Grasses, by their high productivity even under very low pCO2, their ability to survive repeated burning and to tolerate long dry seasons, have transformed the terrestrial biomes in the Neogene and Quaternary. The expansion of grasslands at the cost of biodiverse forest biomes in Madagascar is often postulated as a consequence of the Holocene settlement of the island by humans. However, we show that the Malagasy grass flora has many indications of being ancient with a long local evolutionary history, much predating the Holocene arrival of humans. First, the level of endemism in the Madagascar grass flora is well above the global average for large islands. Second, a survey of many of the more diverse areas indicates that there is a very high spatial and ecological turnover in the grass flora, indicating a high degree of niche specialization. We also find some evidence that there are both recently disturbed and natural stable grasslands: phylogenetic community assembly indicates that recently severely disturbed grasslands are phylogenetically clustered, whereas more undisturbed grasslands tend to be phylogenetically more evenly distributed. From this evidence, it is likely that grass communities existed in Madagascar long before human arrival and so were determined by climate, natural grazing and other natural factors. Humans introduced zebu cattle farming and increased fire frequency, and may have triggered an expansion of the grasslands. Grasses probably played the same role in the modification of the Malagasy environments as elsewhere in the tropics

Distinguishing Various Models of the 125 GeV Boson in Vector Boson Fusion

The hint of a new particle around 125 GeV at the LHC through the decay modes of diphoton and a number of others may point to quite a number of possibilities. While at the LHC the dominant production mechanism for the Higgs boson of the standard model and some other extensions is via the gluon fusion process, the alternative vector boson fusion is more sensitive to electroweak symmetry breaking through the gauge-Higgs couplings and therefore can be used to probe for models beyond the standard model. In this work, using the well known dijet-tagging technique to single out the vector boson fusion mechanism, we investigate its capability to discriminate a number of models that have been suggested to give an enhanced inclusive diphoton production rate, including the standard model Higgs boson, fermiophobic Higgs boson, Randall-Sundrum radion, inert-Higgs-doublet model, two-Higgs-doublet model, and the MSSM. The rates in vector-boson fusion can give more information of the underlying models to help distinguishing among the models.Comment: 31 pages, 3 figures; in this version some wordings are change