Fossilized skin reveals coevolution with feathers and metabolism in feathered dinosaurs and early birds

Feathers are remarkable evolutionary innovations that are associated with complex adaptations of the skin in modern birds. Fossilised feathers in non-avian dinosaurs and basal birds provide insights into feather evolution, but how associated integumentary adaptations evolved is unclear. Here we report the discovery of fossil skin, preserved with remarkable nanoscale fidelity, in three non-avian maniraptoran dinosaurs and a basal bird from the Cretaceous Jehol biota (China). The skin comprises patches of desquamating epidermal corneocytes that preserve a cytoskeletal array of helically coiled α-keratin tonofibrils. This structure confirms that basal birds and non-avian dinosaurs shed small epidermal flakes as in modern mammals and birds, but structural differences imply that these Cretaceous taxa had lower body heat production than modern birds. Feathered epidermis acquired many, but not all, anatomically modern attributes close to the base of the Maniraptora by the Middle Jurassic

Renal Medullary and Cortical Correlates in Fibrosis, Epithelial Mass, Microvascularity, and Microanatomy Using Whole Slide Image Analysis Morphometry

Renal tubulointerstitial injury often leads to interstitial fibrosis and tubular atrophy (IF/TA). IF/TA is typically assessed in the renal cortex and can be objectively quantitated with computerized image analysis (IA). However, the human medulla accounts for a substantial proportion of the nephron; therefore, medullary scarring will have important cortical consequences and may parallel overall chronic renal injury. Trichrome, periodic acid–Schiff (PAS), and collagen III immunohistochemistry (IHC) were visually examined and quantitated on scanned whole slide images (WSIs) (N = 67 cases). When tuned to measure fibrosis, IA of trichrome and Trichrome-PAS (T-P) WSIs correlated for all anatomic compartments (among cortex, medulla, and entire tissue, r = 0.84 to 0.89, P all <0.0001); and collagen III deposition correlated between compartments (r = 0.69 to 0.89, P <0.0001 to 0.0002); however, trichrome and T-P measures did not correlate with collagen deposition, suggesting heterogeneous contributions to extracellular matrix deposition. Epithelial cell mass (EPCM) correlated between cortex and medulla when measured with cytokeratin IHC and with the trichrome red portion (r = 0.85 and 0.66, respectively, all P < 0.0001). Visual assessment also correlated between compartments for fibrosis and EPCM. Correlations were found between increasing medullary inner stripe (IS) width and fibrosis in all of the tissue and the medulla by trichrome morphometry (r = 0.56, P < 0.0001, and r = 0.48, P = 0.00008, respectively). Weak correlations were found between increasing IS width and decreasing visual assessment of all tissue EPCM. Microvessel density (MVD) and microvessel area (MVA) measured using a MVD algorithm applied to CD34 IHC correlated significantly between all compartments (r = 0.76 to 0.87 for MVD and 0.71 to 0.87 for MVA, P all < 0.0001). Overall, these findings demonstrate the interrelatedness of the cortex and medulla and the importance of considering the renal parenchyma as a whole

The evolution of azole resistance in Candida albicans sterol 14α-demethylase (CYP51) through incremental amino acid substitutions

Recombinant Candida albicans CYP51 (CaCYP51) proteins containing 23 single and 5 double amino acid substitutions found in clinical strains and the wild-type enzyme were expressed in Escherichia coli and purified by Ni2+-nitrilotriacetic acid agarose chromatography. Catalytic tolerance to azole antifungals was assessed by determination of the concentration causing 50% enzyme inhibition (IC50) using CYP51 reconstitution assays. The greatest increase in the IC50 compared to that of the wild-type enzyme was observed with the five double substitutions Y132F+K143R (15.3-fold), Y132H+K143R (22.1-fold), Y132F+F145L (10.1-fold), G307S+G450E (13-fold), and D278N+G464S (3.3-fold). The single substitutions K143R, D278N, S279F, S405F, G448E, and G450E conferred at least 2-fold increases in the fluconazole IC50, and the Y132F, F145L, Y257H, Y447H, V456I, G464S, R467K, and I471T substitutions conferred increased residual CYP51 activity at high fluconazole concentrations. In vitro testing of select CaCYP51 mutations in C. albicans showed that the Y132F, Y132H, K143R, F145L, S405F, G448E, G450E, G464S, Y132F+K143R, Y132F+F145L, and D278N+G464S substitutions conferred at least a 2-fold increase in the fluconazole MIC. The catalytic tolerance of the purified proteins to voriconazole, itraconazole, and posaconazole was far lower and limited to increased residual activities at high triazole concentrations for certain mutations rather than large increases in IC50 values. Itraconazole was the most effective at inhibiting CaCYP51. However, when tested against CaCYP51 mutant strains, posaconazole seemed to be the most resistant to changes in MIC as a result of CYP51 mutation compared to itraconazole, voriconazole, or fluconazole

Family coordination in families who have a child with autism spectrum disorder

Little is known about the interactions of families where there is a child with autism spectrum disorder (ASD). The present study applies the Lausanne Trilogue Play (LTP) to explore both its applicability to this population as well as to assess resources and areas of deficit in these families. The sample consisted of 68 families with a child with ASD, and 43 families with a typically developing (TD) child. With respect to the global score for family coordination there were several negative correlations: the more severe the symptoms (based on the child’s ADOS score), the more family coordination was dysfunctional. This correlation was particularly high when parents had to play together with the child. In the parts in which only one of the parents played actively with the child, while the other was simply present, some families did achieve scores in the functional range, despite the child’s symptom severity. The outcomes are discussed in terms of their clinical implications both for assessment and for interventio

Sorl1 as an Alzheimer's disease predisposition gene?

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressively disabling impairments in memory, cognition, and non-cognitive behavioural symptoms. Sporadic AD is multifactorial and genetically complex. While several monogenic mutations cause early-onset AD and gene alleles have been suggested as AD susceptibility factors, the only extensively validated susceptibility gene for late-onset AD is the apolipoprotein E (APOE) epsilon4 allele. Alleles of the APOE gene do not account for all of the genetic load calculated to be responsible for AD predisposition. Recently, polymorphisms across the neuronal sortilin-related receptor (SORL1) gene were shown to be significantly associated with AD in several cohorts. Here we present the results of our large case-control whole-genome scan at over 500,000 polymorphisms which presents weak evidence for association and potentially narrows the association interval

Bio-informatics assessment schema (BIAS) to improve myocardial perfusion image diagnostic and prognostic value: the NHLBI-sponsored women's ischemia syndrome evaluation (WISE) study

Introduction: When assessing myocardial perfusion image (MPI) data for diagnosis or prediction of prognosis it is common to evaluate the technology using a Receiver-Operator Characteristic (ROC) curve. The diagonal response represents the knowledge prior to conducting the test (i.e. the diagonal represents random chance). We present an approach termed Bio-Informatics Assessment Schema (BIAS) that provides an elevated baseline from which to evaluate the MPI reading, i.e. indicating that at baseline, more data is available than random chance. Here we describe how the BIAS formulae are generated for cardiovascular magnetic resonance image (CMRI) data applied to the Women's Ischemia Syndrome Evaluation (WISE) Study

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Development of a nurse home visitation intervention for intimate partner violence

<p>Abstract</p> <p>Background</p> <p>Despite an increase in knowledge about the epidemiology of intimate partner violence (IPV), much less is known about interventions to reduce IPV and its associated impairment. One program that holds promise in preventing IPV and improving outcomes for women exposed to violence is the Nurse-Family Partnership (NFP), an evidence-based nurse home visitation program for socially disadvantaged first-time mothers. The present study developed an intervention model and modification process to address IPV within the context of the NFP. This included determining the extent to which the NFP curriculum addressed the needs of women at risk for IPV or its recurrence, along with client, nurse and broader stakeholder perspectives on how best to help NFP clients cope with abusive relationships.</p> <p>Methods</p> <p>Following a preliminary needs assessment, an exploratory multiple case study was conducted to identify the core components of the proposed IPV intervention. This included qualitative interviews with purposeful samples of NFP clients and community stakeholders, and focus groups with nurse home visitors recruited from four NFP sites. Conventional content analysis and constant comparison guided data coding and synthesis. A process for developing complex interventions was then implemented.</p> <p>Results</p> <p>Based on data from 69 respondents, an IPV intervention was developed that focused on identifying and responding to IPV; assessing a client's level of safety risk associated with IPV; understanding the process of leaving and resolving an abusive relationship and system navigation. A need was identified for the intervention to include both universal elements of healthy relationships and those tailored to a woman's specific level of readiness to promote change within her life. A clinical pathway guides nurses through the intervention, with a set of facilitators and corresponding instructions for each component.</p> <p>Conclusions</p> <p>NFP clients, nurses and stakeholders identified the need for modifications to the existing NFP program; this led to the development of an intervention that includes universal and targeted components to assist NFP nurses in addressing IPV with their clients. Plans for feasibility testing and evaluation of the effectiveness of the IPV intervention embedded within the NFP, and compared to NFP-only, are discussed.</p