Proteostasis and ageing: insights from long-lived mutant mice

The global increase in life expectancy is creating significant medical, social and economic challenges to current and future generations. Consequently, there is a need to identify the fundamental mechanisms underlying the ageing process. This knowledge should help develop realistic interventions capable of combatting age-related disease, and thus improving late-life health and vitality. While several mechanisms have been proposed as conserved lifespan determinants, the loss of proteostasis- where proteostasis is defined here as the maintenance of the proteome- appears highly relevant to both ageing and disease. Several studies have shown that multiple proteostatic mechanisms, including the endoplasmic reticulum (ER)-induced unfolded protein response (UPR), the ubiquitin-proteasome system (UPS) and autophagy, all appear indispensable for longevity in many long-lived invertebrate mutants. Similarly, interspecific comparisons suggest that proteostasis may be an important lifespan determinant in vertebrates. Over the last 20 years a number of long-lived mouse mutants have been described, many of which carry single-gene mutations within the growth-hormone, insulin/IGF-1 or mTOR signalling pathways. However, we still do not know how these mutations act mechanistically to increase lifespan and healthspan, and accordingly whether mechanistic commonality occurs between different mutants. Recent evidence supports the premise that the successful maintenance of the proteome during ageing may be linked to the increased lifespan and healthspan of long-lived mouse mutants

Evaporation of a Kerr black hole by emission of scalar and higher spin particles

We study the evolution of an evaporating rotating black hole, described by the Kerr metric, which is emitting either solely massless scalar particles or a mixture of massless scalar and nonzero spin particles. Allowing the hole to radiate scalar particles increases the mass loss rate and decreases the angular momentum loss rate relative to a black hole which is radiating nonzero spin particles. The presence of scalar radiation can cause the evaporating hole to asymptotically approach a state which is described by a nonzero value of $a_* \equiv a / M$. This is contrary to the conventional view of black hole evaporation, wherein all black holes spin down more rapidly than they lose mass. A hole emitting solely scalar radiation will approach a final asymptotic state described by $a_* \simeq 0.555$. A black hole that is emitting scalar particles and a canonical set of nonzero spin particles (3 species of neutrinos, a single photon species, and a single graviton species) will asymptotically approach a nonzero value of $a_*$ only if there are at least 32 massless scalar fields. We also calculate the lifetime of a primordial black hole that formed with a value of the rotation parameter $a_{*}$, the minimum initial mass of a primordial black hole that is seen today with a rotation parameter $a_{*}$, and the entropy of a black hole that is emitting scalar or higher spin particles.Comment: 22 pages, 13 figures, RevTeX format; added clearer descriptions for variables, added journal referenc

Spinning Down a Black Hole With Scalar Fields

We study the evolution of a Kerr black hole emitting scalar radiation via the Hawking process. We show that the rate at which mass and angular momentum are lost by the black hole leads to a final evolutionary state with nonzero angular momentum, namely $a/M \approx 0.555$.Comment: 4 pages (including 3 postscript figures), Revtex, uses epsf.tex, twocolumn.sty and header.sty (included). Submitted to Physical Review Letter

Acanthamoeba

Purpose. To review characteristics of confocal microscopy, clinical presentation, and clinical outcome in 372 cases of Acanthamoeba keratitis (AK) from 1999 to 2011. Methods. A retrospective case review was performed on 372 cases of AK diagnosed by confocal microscopy (CFM) at a single institution in Portland, Oregon, from 1999 to 2011. A numbered grading system was devised for describing the relative microscopic severity of the AK infections detected. Results. “grade 1,” 94 as “grade 2,” 40 as “grade 3,” and 62 as “grade 4.” Peak incidences occurred during 2000–2002 and 2005–2007. Seasonal variation was noted, with a peak during summer months. For the 231 cases with complete records, 64% indicated a history of soft contact lens use. Nine progressed to multiple failed penetrating keratoplasties (PKPs) or enucleation. Conclusion. We report an average of 31 new cases of AK per year from 1999 to 2011. This figure equates to 10.3 new cases/1,000,000/year for the Portland metropolitan area. Patients diagnosed with AK exhibited a wide spectrum of clinical and microscopic characteristics. Soft contact lens use remained the single largest risk factor

Independent Domestication of Two Old World Cotton Species

Domesticated cotton species provide raw material for the majority of the world\u27s textile industry. Two independent domestication events have been identified in allopolyploid cotton, one in Upland cotton ( Gossypium hirsutum L.) and the other to Egyptian cotton ( Gossypium barbadense L.). However, two diploid cotton species, Gossypium arboreum L. and Gossypium herbaceum L., have been cultivated for several millennia, but their status as independent domesticates has long been in question. Using genome resequencing data, we estimated the global abundance of various repetitive DNAs. We demonstrate that, despite negligible divergence in genome size, the two domesticated diploid cotton species contain different, but compensatory, repeat content and have thus experienced cryptic alterations in repeat abundance despite equivalence in genome size. Evidence of independent origin is bolstered by estimates of divergence times based on molecular evolutionary analysis of f7,000 orthologous genes, for which synonymous substitution rates suggest that G. arboreum and G. herbaceum last shared a common ancestor approximately 0.4–2.5 Ma. These data are incompatible with a shared domestication history during the emergence of agriculture and lead to the conclusion that G. arboreum and G. herbaceum were each domesticated independently

An examination of in-season external training load in semi-professional soccer players: considerations of one and two match weekly microcycles

The aim of the present study was to firstly, quantify the external training load (TL) of semi-professional soccer players during an annual season and secondly, to examine the influence of one (1MW) and two (2MW) match weekly microcycles. Data were collected from 24 semi-professional outfield soccer players during the 2018-2019 annual season using micro-electromechanical system (MEMS) devices for the following variables: Training duration (min), total distance (TD), Player Load (PL), high speed running (HSR) distance (5.5-7.0 m/s), and acceleration (ACC) efforts (>2 m/s2). Training sessions were defined as days before match day (i.e. MD minus), with match weeks broken down as either 1MW or 2MW. Data revealed higher TD, PL, and HSR distance on MD and MD-5 when compared to all other MD codes. MD-4 displayed significantly higher values compared to MD-1 (mean differences (Mdiff): TD: 785 ± 158 m; PL: 29 ± 9 au; HSR: 192 ± 63 m; ACC: 15 ± 3 #) and MD-2 (Mdiff: TD: 279 ± 137 m; HSR: 127 ± 54 m). During 2MW scenarios, both TD (Mdiff: 685 ± 328 m) and PL (Mdiff: 33 ± 14 au) were higher on MD-1 when compared to 1MW. However, lower values were observed for duration and HSR on MD-2 and MD-4 during 2MW compared to 1MW scenarios. These data suggest that there appears to be a progressive reduction in TD, PL, HSR and ACC leading into competitive matches based on MD- analysis. However, some variability exists in TL prescription as a result of different MW scenarios (i.e. 1MW vs. 2MW)