Genomic regulation of natural variation in cortical and noncortical brain volume

BACKGROUND: The relative growth of the neocortex parallels the emergence of complex cognitive functions across species. To determine the regions of the mammalian genome responsible for natural variations in cortical volume, we conducted a complex trait analysis using 34 strains of recombinant inbred (Rl) strains of mice (BXD), as well as their two parental strains (C57BL/6J and DBA/2J). We measured both neocortical volume and total brain volume in 155 coronally sectioned mouse brains that were Nissl stained and embedded in celloidin. After correction for shrinkage, the measured cortical and noncortical brain volumes were entered into a multiple regression analysis, which removed the effects of body size and age from the measurements. Marker regression and interval mapping were computed using WebQTL. RESULTS: An ANOVA revealed that more than half of the variance of these regressed phenotypes is genetically determined. We then identified the regions of the genome regulating this heritability. We located genomic regions in which a linkage disequilibrium was present using WebQTL as both a mapping engine and genomic database. For neocortex, we found a genome-wide significant quantitative trait locus (QTL) on chromosome 11 (marker D11Mit19), as well as a suggestive QTL on chromosome 16 (marker D16Mit100). In contrast, for noncortex the effect of chromosome 11 was markedly reduced, and a significant QTL appeared on chromosome 19 (D19Mit22). CONCLUSION: This classic pattern of double dissociation argues strongly for different genetic factors regulating relative cortical size, as opposed to brain volume more generally. It is likely, however, that the effects of proximal chromosome 11 extend beyond the neocortex strictly defined. An analysis of single nucleotide polymorphisms in these regions indicated that ciliary neurotrophic factor (Cntf) is quite possibly the gene underlying the noncortical QTL. Evidence for a candidate gene modulating neocortical volume was much weaker, but Otx1 deserves further consideration

Orientation and velocity dependence of the nonequilibrium partition coefficient

Monte Carlo simulations based on a Spin-1 Ising Model for binary alloys have been used to investigate the non-equilibrium partition coefficient (k(sub neq)) as a function of solid-liquid interface velocity and orientation. In simulations of Si with a second component k(sub neq) is greater in the [111] direction than the [100] direction in agreement with experimental results reported by Azlz et al. The simulated partition coefficient scales with the square of the step velocity divided by the diffusion coefficient of the secondary component in the liquid

Too Little, Too Late: How the Tidal Evolution of Hot Jupiters affects Transit Surveys of Clusters

The tidal evolution of hot Jupiters may change the efficiency of transit surveys of stellar clusters. The orbital decay that hot Jupiters suffer may result in their destruction, leaving fewer transiting planets in older clusters. We calculate the impact tidal evolution has for different assumed stellar populations, including that of 47~Tuc, a globular cluster that was the focus of an intense HST search for transits. We find that in older clusters one expects to detect fewer transiting planets by a factor of two for surveys sensitive to Jupiter-like planets in orbits out to 0.5~AU, and up to a factor of 25 for surveys sensitive to Jupiter-like planets in orbits out to 0.08~AU. Additionally, tidal evolution affects the distribution of transiting planets as a function of semi-major axis, producing larger orbital period gaps for transiting planets as the age of the cluster increases. Tidal evolution can explain the lack of detected exoplanets in 47~Tuc without invoking other mechanisms. Four open clusters residing within the {\em Kepler} fields of view have ages that span 0.4-8~Gyr--if {\em Kepler} can observe a significant number of planets in these clusters, it will provide key tests for our tidal evolution hypothesis. Finally, our results suggest that observers wishing to discover transiting planets in clusters must have sufficient accuracy to detect lower mass planets, search larger numbers of cluster members, or have longer observation windows to be confident that a significant number of transits will occur for a population of stars.Comment: 23 pages including 6 figures, accepted to Ap

Web-Based Psychological Interventions for People Living With and Beyond Cancer:Meta-Review of What Works and What Does Not for Maximizing Recruitment, Engagement, and Efficacy

BACKGROUND: Despite high levels of psychological distress experienced by many patients with cancer, previous research has identified several barriers to accessing traditional face-to-face psychological support. Web-based psychosocial interventions have emerged as a promising alternative. OBJECTIVE: This meta-review aimed to synthesize evidence on recruitment challenges and enablers, factors that promote engagement and adherence to web-based intervention content, and factors that promote the efficacy of web-based psychosocial interventions for patients with cancer and cancer survivors. METHODS: We conducted a systematic search of previous reviews that investigated the recruitment, engagement, and efficacy of web-based and app-based psychosocial interventions in adult patients with cancer and cancer survivors. We searched PubMed, CINAHL, PsycINFO, and the Cochrane Library database for relevant literature. The search terms focused on a combination of topics pertaining to neoplasms and telemedicine. Two independent authors conducted abstract screening, full text screening, and data extraction for each identified article. RESULTS: A total of 20 articles met eligibility criteria. There was inconsistency in the reporting of uptake and engagement data; however, anxiety about technology and perceived time burden were identified as 2 key barriers. Web-based psychosocial oncology interventions demonstrated efficacy in reducing depression and stress but reported weak to mixed findings for distress, anxiety, quality of life, and well-being. Although no factors consistently moderated intervention efficacy, preliminary evidence indicated that multicomponent interventions and greater communication with a health care professional were preferred by participants and were associated with superior effects. CONCLUSIONS: Several consistently cited barriers to intervention uptake and recruitment have emerged, which we recommend future intervention studies address. Preliminary evidence also supports the superior efficacy of multicomponent interventions and interventions that facilitate communication with a health care professional. However, a greater number of appropriately powered clinical trials, including randomized trials with head-to-head comparisons, are needed to enable more confident conclusions regarding which web-based psychosocial oncology interventions work best and for whom. TRIAL REGISTRATION: PROSPERO CRD42020202633; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=20263

Improving energy efficiency in private rented housing : what makes landlords act?

The private rented sector in England contains some of the least energy efficient properties in the country and houses more vulnerable households than any other sector. Occupants endure dangerously cold homes and fuel poverty but have no direct influence over the energy performance of their homes. The choices that occupants make regarding energy are constrained by the material characteristics of a property: something only the landlord can alter. Enduringly poor conditions in the sector indicate that an initiative that convinces landlords of the benefits of improving energy efficiency remains elusive. Based on a review of existing research and 30 interviews with landlords, this paper identifies factors which deter landlords from acting to improve energy efficiency. Factors include lack of knowledge regarding the consequences of energy inefficiency and possible solutions, the absence of direct financial incentives (the principal–agent problem), local housing market and cultural factors. It also identifies a number of motivating factors that may encourage landlords to invest in energy efficiency. It is argued that policies to tackle energy inefficiency in the sector should take account of these factors in order to improve effectiveness. Keywords Private rented sector, Domestic energy efficiency, Principal–agent, The Green Deal, Private landlords, Split incentiv

Clinical Aspects of Feline Retroviruses: A Review

Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia), and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less commonly diagnosed than in the previous 20 years; prevalence has been decreasing in most countries. However, FeLV importance may be underestimated as it has been shown that regressively infected cats (that are negative in routinely used FeLV tests) also can develop clinical signs. FIV can cause an acquired immunodeficiency syndrome that increases the risk of opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. This article provides a review of clinical syndromes in progressively and regressively FeLV-infected cats as well as in FIV-infected cats

An analysis of the CoRoT-2 system: A young spotted star and its inflated giant planet

Context: CoRoT-2b is one of the most anomalously large exoplanet known. Given its large mass, its large radius cannot be explained by standard evolution models. Interestingly, the planet's parent star is an active, rapidly rotating solar-like star with a large fraction (7 to 20%) of spots. Aims: We want to provide constraints on the properties of the star-planet system and understand whether the planet's inferred large size may be due to a systematic error on the inferred parameters, and if not, how it may be explained. Methods: We combine stellar and planetary evolution codes based on all available spectroscopic and photometric data to obtain self-consistent constraints on the system parameters. Results: We find no systematic error in the stellar modeling (including spots and stellar activity) that would yield the required ~10% reduction in size for the star and thus the planet. Two classes of solutions are found: the usual main sequence solution for the star yields for the planet a mass of 3.67+/-0.13 Mjup, a radius of 1.55+/-0.03 Rjup for an age that is at least 130Ma, and should be less than 500Ma given the star's fast rotation and significant activity. We identify another class of solutions on the pre-main sequence, in which case the planet's mass is 3.45\pm 0.27 Mjup, its radius is 1.50+/-0.06 Rjup for an age between 30 and 40 Ma. These extremely young solutions provide the simplest explanation for the planet's size which can then be matched by a simple contraction from an initially hot, expanded state, provided the atmospheric opacities are increased by a factor ~3 compared to usual assumptions for solar compositions atmospheres. Other solutions imply in any case that the present inflated radius of CoRoT-2b is transient and the result of an event that occurred less than 20 Ma ago: a giant impact with another Jupiter-mass planet, or interactions with another object in the system which caused a significant rise of the eccentricity followed by the rapid circularization of its orbit. Conclusions: Additional observations of CoRoT-2 that could help understanding this system include searches for infrared excess and the presence of a debris disk and searches for additional companions. The determination of a complete infrared lightcurve including both the primary and secondary transits would also be extremely valuable to constrain the planet's atmospheric properties and to determine the planet-to-star radius ratio in a manner less vulnerable to systematic errors due to stellar activity.Comment: 16 pages, 15 figures, accepted for A&

Hepadnavirus DNA Is Detected in Canine Blood Samples in Hong Kong but Not in Liver Biopsies of Chronic Hepatitis or Hepatocellular Carcinoma

Chronic hepatitis and hepatocellular carcinoma (HCC) caused by the hepadnavirus hepatitis B virus (HBV) are significant causes of human mortality. A hepatitis-B-like virus infecting cats, domestic cat hepadnavirus (DCH), was reported in 2018. DCH DNA is hepatotropic and detectable in feline blood or serum (3.2 to 12.3%). Detection of HBV DNA has been reported in sera from 10% of free-roaming dogs in Brazil, whereas 6.3% of sera from dogs in Italy tested positive for DCH DNA by real-time quantitative PCR (qPCR). If DCH, HBV, or another hepadnavirus is hepatotropic in dogs, a role for such a virus in the etiology of canine idiopathic chronic hepatitis (CH) or HCC warrants investigation. This study investigated whether DCH DNA could be detected via qPCR in blood from dogs in Hong Kong and also whether liver biopsies from dogs with confirmed idiopathic CH or HCC contained hepadnaviral DNA using two panhepadnavirus conventional PCRs (cPCR) and a DCH-specific cPCR. DCH DNA was amplified from 2 of 501 (0.4%) canine whole-blood DNA samples. A second sample taken 6 or 7 months later from each dog tested negative in DCH qPCR. DNA extracted from 101 liver biopsies from dogs in Hong Kong or the USA, diagnosed by board-certified pathologists as idiopathic CH (n = 47) or HCC (n = 54), tested negative for DCH DNA and also tested negative using panhepadnavirus cPCRs. This study confirms that DCH DNA can be detected in canine blood by qPCR, although at a much lower prevalence than that reported previously. We identified no evidence to support a pathogenic role for a hepadnavirus in canine idiopathic CH or HCC

Cobomarsen, an oligonucleotide inhibitor of miR-155, slows DLBCL tumor cell growth in vitro and in vivo

MicroRNA-155, is an oncogenic miRNA, highly expressed in B-cell malignancies, particularly in the non-Germinal Center B-cell or activated B-cell subtype of Diffuse Large B-cell Lymphoma (non-GCB/ABC-DLBCL), where it is considered a potential diagnostic and prognostic biomarker. Thus, miR-155 inhibition represents an important therapeutic strategy for B-cell lymphomas. In this study, we tested the efficacy and pharmacodynamic activity of an oligonucleotide inhibitor of miR-155, cobomarsen, in ABC-DLBCL cell lines and in corresponding xenograft mouse models. In addition, we assessed the therapeutic efficacy and safety of cobomarsen in a patient diagnosed with aggressive ABC-DLBCL

How to Build Reputation in Financial Markets

A company's reputation for accountability and trustworthiness is a critical factor in its ability to attract the financial resources required to support its strategies. However, there has been little research done on how companies build and preserve the trust of financial markets. This research highlights a number of practices and features that seem to positively influence the formation of corporate reputation in financial markets. Collectively, the findings indicate that companies are guided by knowledgeable, respected and committed leaders, that are transparent and comprehensive in their communication of corporate plans, and that display credible and independent control systems are more likely to gather the consensus of the financial community around bold strategic plans