Loneliness, Depression, and Inflammation: Evidence from the Multi-Ethnic Study of Atherosclerosis

Objective Both objective and subjective aspects of social isolation have been associated with alterations in immune markers relevant to multiple chronic diseases among older adults. However, these associations may be confounded by health status, and it is unclear whether these social factors are associated with immune functioning among relatively healthy adults. The goal of this study was to examine the associations between perceived loneliness and circulating levels of inflammatory markers among a diverse sample of adults. Methods Data come from a subset of the Multi-Ethnic Study of Atherosclerosis (n = 441). Loneliness was measured by three items derived from the UCLA Loneliness Scale. The association between loneliness and C-reactive protein (CRP) and fibrinogen was assessed using multivariable linear regression analyses. Models were adjusted for demographic and health characteristics. Results Approximately 50% of participants reported that they hardly ever felt lonely and 17.2% felt highly lonely. Individuals who were unmarried/unpartnered or with higher depressive symptoms were more likely to report being highly lonely. There was no relationship between perceived loneliness and ln(CRP) (β = -0.051, p = 0.239) adjusting for demographic and health characteristics. Loneliness was inversely associated with ln(fibrinogen) (β = -0.091, p = 0.040), although the absolute magnitude of this relationship was small. Conclusion These results indicate that loneliness is not positively associated with fibrinogen or CRP among relatively healthy middle-aged adults

PyNAST: a flexible tool for aligning sequences to a template alignment

Motivation: The Nearest Alignment Space Termination (NAST) tool is commonly used in sequence-based microbial ecology community analysis, but due to the limited portability of the original implementation, it has not been as widely adopted as possible. Python Nearest Alignment Space Termination (PyNAST) is a complete reimplementation of NAST, which includes three convenient interfaces: a Mac OS X GUI, a command-line interface and a simple application programming interface (API)

The Jefferson Scale of Empathy: a nationwide study of measurement properties, underlying components, latent variable structure, and national norms in medical students.

The Jefferson Scale of Empathy (JSE) is a broadly used instrument developed to measure empathy in the context of health professions education and patient care. Evidence in support of psychometrics of the JSE has been reported in health professions students and practitioners with the exception of osteopathic medical students. This study was designed to examine measurement properties, underlying components, and latent variable structure of the JSE in a nationwide sample of first-year matriculants at U.S. colleges of osteopathic medicine, and to develop a national norm table for the assessment of JSE scores. A web-based survey was administered at the beginning of the 2017-2018 academic year which included the JSE, a scale to detect good impression responses, and demographic/background information. Usable surveys were received from 6009 students enrolled in 41 college campuses (median response rate = 92%). The JSE mean score and standard deviation for the sample were 116.54 and 10.85, respectively. Item-total score correlations were positive and statistically significant (p \u3c 0.01), and Cronbach α = 0.82. Significant gender differences were observed on the JSE scores in favor of women. Also, significant differences were found on item scores between top and bottom third scorers on the JSE. Three factors of Perspective Taking, Compassionate Care, and Walking in Patient\u27s Shoes emerged in an exploratory factor analysis by using half of the sample. Results of confirmatory factor analysis with another half of the sample confirmed the 3-factor model. We also developed a national norm table which is the first to assess students\u27 JSE scores against national data

Implications of Diet for the Extinction of Saber-Toothed Cats and American Lions

The saber-toothed cat, Smilodon fatalis, and American lion, Panthera atrox, were among the largest terrestrial carnivores that lived during the Pleistocene, going extinct along with other megafauna ~12,000 years ago. Previous work suggests that times were difficult at La Brea (California) during the late Pleistocene, as nearly all carnivores have greater incidences of tooth breakage (used to infer greater carcass utilization) compared to today. As Dental Microwear Texture Analysis (DMTA) can differentiate between levels of bone consumption in extant carnivores, we use DMTA to clarify the dietary niches of extinct carnivorans from La Brea. Specifically, we test the hypothesis that times were tough at La Brea with carnivorous taxa utilizing more of the carcasses. Our results show no evidence of bone crushing by P. atrox, with DMTA attributes most similar to the extant cheetah, Acinonyx jubatus, which actively avoids bone. In contrast, S. fatalis has DMTA attributes most similar to the African lion Panthera leo, implying that S. fatalis did not avoid bone to the extent previously suggested by SEM microwear data. DMTA characters most indicative of bone consumption (i.e., complexity and textural fill volume) suggest that carcass utilization by the extinct carnivorans was not necessarily more complete during the Pleistocene at La Brea; thus, times may not have been tougher than the present. Additionally, minor to no significant differences in DMTA attributes from older (~30-35 Ka) to younger (~11.5 Ka) deposits offer little evidence that declining prey resources were a primary cause of extinction for these large cats

Redox-dependent dimerization of p38 alpha mitogen-activated protein kinase with mitogen-activated protein kinase kinase 3

The kinase p38α MAPK (p38α) plays a pivotal role in many biological processes. p38α is activated by canonical upstream kinases that phosphorylate the activation region. The purpose of our study was to determine whether such activation may depend on redox-sensing cysteines within p38α. p38α was activated and formed a disulfide-bound heterodimer with MAP2K3 (MKK3) in rat cardiomyocytes and isolated hearts exposed to H2O2 This disulfide heterodimer was sensitive to reduction by mercaptoethanol and was enhanced by the thioredoxin-reductase inhibitor auranofin. We predicted that Cys-119 or Cys-162 of p38α, close to the known MKK3 docking domain, were relevant for these redox characteristics. The C119S mutation decreased whereas the C162S mutation increased the dimer formation, suggesting that these two Cys residues act as vicinal thiols, consistent with C119S/C162S being incapable of sensing H2O2 Similarly, disulfide heterodimer formation was abolished in H9C2 cells expressing both MKK3 and p38α C119S/C162S and subjected to simulated ischemia and reperfusion. However, the p38α C119S/C162S mutants did not exhibit appreciable alteration in activating dual phosphorylation. In contrast, the anti-inflammatory agent 10-nitro-oleic acid (NO2-OA), a component of the Mediterranean diet, reduced p38α activation and covalently modified Cys-119/Cys-162, probably obstructing MKK3 access. Moreover, NO2-OA reduced the dephosphorylation of p38α by hematopoietic tyrosine phosphatase (HePTP). Furthermore, steric obstruction of Cys-119/Cys-162 by NO2-OA pretreatment in Langendorff-perfused murine hearts prevented the p38-MKK3 disulfide dimer formation and attenuated H2O2-induced contractile dysfunction. Our findings suggest that cysteine residues within p38α act as redox sensors that can dynamically regulate the association between p38 and MKK3.</p

Design and synthesis of wm5 analogues as HIV-1 TAR RNA binders

The 6-aminoquinolone WM5, previously identified by us, is among the most selective small molecules known as TAR RNA binders to show anti-HIV activity. Methods: Starting from WM5, a series of analogues modified at N-1, C-6 or C-7 position was prepared by inserting guanidine or amidine groups as well as other protonable moieties intended to electrostatically bind the phosphate backbone of TAR. All the compounds were tested for their ability to inhibit HIV-1 replication in MT-4 cells and in parallel for their cytotoxicity. The active compounds were also evaluated for their ability to interfere with the formation of the Tat-TAR complex using a Fluorescence Quenching Assay (FQA). Results: Some of the synthesized compounds showed an anti-HIV-1 activity in the sub-micromolar range with the naphthyridone derivatives being the most potent. Three of the synthesized derivatives were able to interact with the Tat-TAR complex formation presenting Ki values improved as compared to the values obtained with WM5. Conclusion: The addition of a pyridine-based protonable side chain at the N-1 position of the quinolone/naphthyridone core imparted to the compounds the ability to interfere with Tat-TAR complex formation and HIV-1 replicatio

Ultrastructural study of cultured ovine bone marrow-derived mesenchymal stromal cells.

Ovine bone marrow-derived mesenchymal stromal cells (oBM-MSCs) represent a good animal model for cell-based therapy and tissue engineering. Despite their use as a new therapeutic tool for several clinical applications, the morphological features of oBM-MSCs are yet unknown. Therefore, in this study the ultrastructural phenotype of these cells was analysed by transmission electron microscopy (TEM). The oBM-MSCs were isolated from the iliac crest and cultured until they reached near-confluence. After trypsinization, they were processed to investigate their ultrastructural features as well as specific surface marker proteins by flow cytometry and immunogold electron microscopy. Flow cytometry displayed that all oBM-MSCs lacked expression of CD31, CD34, CD45, HLA-DR whereas they expressed CD44, CD58, HLAI and a minor subset of the cell population (12%) exhibited CD90. TEM revealed the presence of two morphologically distinct cell types: cuboidal electron-lucent cells and spindle-shaped electron-dense cells, both expressing the CD90 antigen. Most of the electron-lucent cells showed glycogen aggregates, dilated cisternae of RER, moderately developed Golgi complex, and secretory activity. The electron-dense cell type was constituted by two different cell-populations: type A cells with numerous endosomes, dense bodies, rod-shaped mitochondria and filopodia; type B cells with elongated mitochondria, thin pseudopodia and cytoplasmic connectivity with electron-lucent cells. These morphological findings could provide a useful support to identify “in situ” the cellular components involved in the cell-therapy when cultured oBM-MSCs are injected

Riflettanza di superfici vulcaniche:la campagna 2003 sul Monte Etna

The results obtained in Mt. Etna spectroradiometric field survey of June 2003 are presented and discussed. The goal of the survey was the analysis of the reflectance properties of the young pyroclastic deposits produced after the effusive activity of 2002-2003 and of the older lava flows. To achieve this goal, a template was created in order to organize the field data collected in a number of selected sites characterised by different surface materials. The results show that reflectance of pyroclastic flows is always very low and constant, besides grain size and composition of the flow. Pahoehoe units show higher reflectance values, even though the spectral characterisation of the older lava flows must take into account weathering products and vegetation coverage

NAST: a multiple sequence alignment server for comparative analysis of 16S rRNA genes

Microbiologists conducting surveys of bacterial and archaeal diversity often require comparative alignments of thousands of 16S rRNA genes collected from a sample. The computational resources and bioinformatics expertise required to construct such an alignment has inhibited high-throughput analysis. It was hypothesized that an online tool could be developed to efficiently align thousands of 16S rRNA genes via the NAST (Nearest Alignment Space Termination) algorithm for creating multiple sequence alignments (MSA). The tool was implemented with a web-interface at . Each user-submitted sequence is compared with Greengenes' ‘Core Set’, comprising ∼10 000 aligned non-chimeric sequences representative of the currently recognized diversity among bacteria and archaea. User sequences are oriented and paired with their closest match in the Core Set to serve as a template for inserting gap characters. Non-16S data (sequence from vector or surrounding genomic regions) are conveniently removed in the returned alignment. From the resulting MSA, distance matrices can be calculated for diversity estimates and organisms can be classified by taxonomy. The ability to align and categorize large sequence sets using a simple interface has enabled researchers with various experience levels to obtain bacterial and archaeal community profiles

Dietary responses of Sahul (Pleistocene Australia-New Guinea) megafauna to climate and environmental change

Throughout the late Quaternary, the Sahul (Pleistocene Australia-New Guinea) vertebrate fauna was dominated by a diversity of large mammals, birds, and reptiles, commonly referred to as megafauna. Since ca. 450-400 Ka, approximately 88 species disappeared in Sahul, including kangaroos exceeding 200 kg in size, wombat-like animals the size of hippopotamuses, flightless birds, and giant monitor lizards that were likely venomous. Ongoing debates over the primary cause of these extinctions have typically favored climate change or human activities. Improving our understanding of the population biology of extinct megafauna as more refined paleoenvironmental data sets become available will assist in identifying their potential vulnerabilities. Here, we apply a multiproxy approach to analyze fossil teeth from deposits dated to the middle and late Pleistocene at Cuddie Springs in southeastern Australia, assessing relative aridity via oxygen isotopes as well as vegetation and megafaunal diets using both carbon isotopes and dental microwear texture analyses. We report that the Cuddie Springs middle Pleistocene fauna was largely dominated by browsers, including consumers of C4 shrubs, but that by late Pleistocene times the C4 dietary component was markedly reduced. Our results suggest dietary restriction in more arid conditions. These dietary shifts are consistent with other independently derived isotopic data from eggshells and wombat teeth that also suggest a reduction in C4 vegetation after ∼ 45 Ka in southeastern Australia, coincident with increasing aridification through the middle to late Pleistocene. Understanding the ecology of extinct species is important in clarifying the primary drivers of faunal extinction in Sahul. The results presented here highlight the potential impacts of aridification on marsupial megafauna. The trend to increasingly arid conditions through the middle to late Pleistocene (as identified in other paleoenvironmental records and now also observed, in part, in the Cuddie Springs sequence) may have stressed the most vulnerable animals, perhaps accelerating the decline of late Pleistocene megafauna in Australia