Conjoint analysis of researchers' hidden preferences for bibliometrics, altmetrics, and usage metrics

The amount of annually published scholarly articles is growing steadily, as is the number of indicators through which impact of publications is measured. Little is known about how the increasing variety of available metrics affects researchers' processes of selecting literature to read. We conducted ranking experiments embedded into an online survey with 247 participating researchers, most from social sciences. Participants completed series of tasks in which they were asked to rank fictitious publications regarding their expected relevance, based on their scores regarding six prototypical metrics. Through applying logistic regression, cluster analysis, and manual coding of survey answers, we obtained detailed data on how prominent metrics for research impact influence our participants in decisions about which scientific articles to read. Survey answers revealed a combination of qualitative and quantitative characteristics that researchers consult when selecting literature, while regression analysis showed that among quantitative metrics, citation counts tend to be of highest concern, followed by Journal Impact Factors. Our results suggest a comparatively favorable view of many researchers on bibliometrics and widespread skepticism toward altmetrics. The findings underline the importance of equipping researchers with solid knowledge about specific metrics' limitations, as they seem to play significant roles in researchers' everyday relevance assessments

Evidence of CD4+ T cell-mediated immune pressure on the Hepatitis C virus genome

Hepatitis C virus (HCV)-specific T cell responses are critical for immune control of infection. Viral adaptation to these responses, via mutations within regions of the virus targeted by CD8+ T cells, is associated with viral persistence. However, identifying viral adaptation to HCV-specific CD4+ T cell responses has been difficult although key to understanding anti-HCV immunity. In this context, HCV sequence and host genotype from a single source HCV genotype 1B cohort (n = 63) were analyzed to identify viral changes associated with specific human leucocyte antigen (HLA) class II alleles, as these variable host molecules determine the set of viral peptides presented to CD4+ T cells. Eight sites across the HCV genome were associated with HLA class II alleles implicated in infection outcome in this cohort (p ≤ 0.01; Fisher’s exact test). We extended this analysis to chronic HCV infection (n = 351) for the common genotypes 1A and 3A. Variation at 38 sites across the HCV genome were associated with specific HLA class II alleles with no overlap between genotypes, suggestive of genotype-specific T cell targets, which has important implications for vaccine design. Here we show evidence of HCV adaptation to HLA class II-restricted CD4+ T cell pressure across the HCV genome in chronic HCV infection without a priori knowledge of CD4+ T cell epitopes

Synthesis of small silver nanocubes in a hydrophobic solvent by introducing oxidative etching with Fe(III) species

The role of oxidative etching in the synthesis of noble-metal nanocrystals with a hydrophilic solvent (in particular, ethylene glycol) has been explored in our previous work. In this paper, we demonstrate that the mechanism of oxidative etching could be extended to the synthesis of single-crystal Ag nanocrystals in a hydrophobic solvent such as isoamyl ether. In this case, Fe(III) species in the form of FeCl3 or Fe(acac)(3) had to be introduced into the hydrophobic system as an effective etching agent. The final product contained single-crystal Ag nanocubes (slightly truncated) with an edge length as small as similar to 13.5 nm, a size that has been difficult to achieve using a hydrophilic system. The role of oxidative etching in the synthesis of noble-metal nanocrystals with a hydrophilic solvent (in particular, ethylene glycol) has been explored in our previous work. In this paper, we demonstrate that the mechanism of oxidative etching could be extended to the synthesis of single-crystal Ag nanocrystals in a hydrophobic solvent such as isoamyl ether. In this case, Fe(III) species in the form of FeCl3 or Fe(acac)(3) had to be introduced into the hydrophobic system as an effective etching agent. The final product contained single-crystal Ag nanocubes (slightly truncated) with an edge length as small as similar to 13.5 nm, a size that has been difficult to achieve using a hydrophilic system.NSF [DMR-0804088, ECS-0335765]; NIH [DP1 OD000798]; China Scholarship Counci

“Thinking about Not-Thinking”: Neural Correlates of Conceptual Processing during Zen Meditation

Recent neuroimaging studies have identified a set of brain regions that are metabolically active during wakeful rest and consistently deactivate in a variety the performance of demanding tasks. This “default network” has been functionally linked to the stream of thoughts occurring automatically in the absence of goal-directed activity and which constitutes an aspect of mental behavior specifically addressed by many meditative practices. Zen meditation, in particular, is traditionally associated with a mental state of full awareness but reduced conceptual content, to be attained via a disciplined regulation of attention and bodily posture. Using fMRI and a simplified meditative condition interspersed with a lexical decision task, we investigated the neural correlates of conceptual processing during meditation in regular Zen practitioners and matched control subjects. While behavioral performance did not differ between groups, Zen practitioners displayed a reduced duration of the neural response linked to conceptual processing in regions of the default network, suggesting that meditative training may foster the ability to control the automatic cascade of semantic associations triggered by a stimulus and, by extension, to voluntarily regulate the flow of spontaneous mentation

Effects of thymic selection of the T cell repertoire on HLA-class I associated control of HIV infection

Without therapy, most people infected with human immunodeficiency virus (HIV) ultimately progress to AIDS. Rare individuals (‘elite controllers’) maintain very low levels of HIV RNA without therapy, thereby making disease progression and transmission unlikely. Certain HLA class I alleles are markedly enriched in elite controllers, with the highest association observed for HLA-B57 (ref. 1). Because HLA molecules present viral peptides that activate CD8+ T cells, an immune-mediated mechanism is probably responsible for superior control of HIV. Here we describe how the peptide-binding characteristics of HLA-B57 molecules affect thymic development such that, compared to other HLA-restricted T cells, a larger fraction of the naive repertoire of B57-restricted clones recognizes a viral epitope, and these T cells are more cross-reactive to mutants of targeted epitopes. Our calculations predict that such a T-cell repertoire imposes strong immune pressure on immunodominant HIV epitopes and emergent mutants, thereby promoting efficient control of the virus. Supporting these predictions, in a large cohort of HLA-typed individuals, our experiments show that the relative ability of HLA-B alleles to control HIV correlates with their peptide-binding characteristics that affect thymic development. Our results provide a conceptual framework that unifies diverse empirical observations, and have implications for vaccination strategies.Mark and Lisa Schwartz FoundationNational Institutes of Health (U.S.) (Director’s Pioneer award)Philip T. and Susan M. Ragon FoundationJane Coffin Childs Memorial Fund for Medical ResearchBill & Melinda Gates FoundationNational Institute of Allergy and Infectious Diseases (U.S.)National Institutes of Health (U.S.) (contract no. HHSN261200800001E)National Institutes of Health (U.S.). Intramural Research ProgramNational Cancer Institute (U.S.)Center for Cancer Research (National Cancer Institute (U.S.)

Risk of chronic kidney disease after cancer nephrectomy.

The incidence of early stage renal cell carcinoma (RCC) is increasing and observational studies have shown equivalent oncological outcomes of partial versus radical nephrectomy for stage I tumours. Population studies suggest that compared with radical nephrectomy, partial nephrectomy is associated with decreased mortality and a lower rate of postoperative decline in kidney function. However, rates of chronic kidney disease (CKD) in patients who have undergone nephrectomy might be higher than in the general population. The risks of new-onset or accelerated CKD and worsened survival after nephrectomy might be linked, as kidney insufficiency is a risk factor for cardiovascular disease and mortality. Nephron-sparing approaches have, therefore, been proposed as the standard of care for patients with type 1a tumours and as a viable option for those with type 1b tumours. However, prospective data on the incidence of de novo and accelerated CKD after cancer nephrectomy is lacking, and the only randomized trial to date was closed prematurely. Intrinsic abnormalities in non-neoplastic kidney parenchyma and comorbid conditions (including diabetes mellitus and hypertension) might increase the risks of CKD and RCC. More research is needed to better understand the risk of CKD post-nephrectomy, to develop and validate predictive scores for risk-stratification, and to optimize patient management

Age and the Neural Network of Personal Familiarity

BACKGROUND: Accessing information that defines personally familiar context in real-world situations is essential for the social interactions and the independent functioning of an individual. Personal familiarity is associated with the availability of semantic and episodic information as well as the emotional meaningfulness surrounding a stimulus. These features are known to be associated with neural activity in distinct brain regions across different stimulus conditions (e.g., when perceiving faces, voices, places, objects), which may reflect a shared neural basis. Although perceiving context-rich personal familiarity may appear unchanged in aging on the behavioral level, it has not yet been studied whether this can be supported by neuroimaging data. METHODOLOGY/PRINCIPAL FINDINGS: We used functional magnetic resonance imaging to investigate the neural network associated with personal familiarity during the perception of personally familiar faces and places. Twelve young and twelve elderly cognitively healthy subjects participated in the study. Both age groups showed a similar activation pattern underlying personal familiarity, predominantly in anterior cingulate and posterior cingulate cortices, irrespective of the stimulus type. The young subjects, but not the elderly subjects demonstrated an additional anterior cingulate deactivation when perceiving unfamiliar stimuli. CONCLUSIONS/SIGNIFICANCE: Although we found evidence for an age-dependent reduction in frontal cortical deactivation, our data show that there is a stimulus-independent neural network associated with personal familiarity of faces and places, which is less susceptible to aging-related changes

Joining S100 proteins and migration:for better or for worse, in sickness and in health

The vast diversity of S100 proteins has demonstrated a multitude of biological correlations with cell growth, cell differentiation and cell survival in numerous physiological and pathological conditions in all cells of the body. This review summarises some of the reported regulatory functions of S100 proteins (namely S100A1, S100A2, S100A4, S100A6, S100A7, S100A8/S100A9, S100A10, S100A11, S100A12, S100B and S100P) on cellular migration and invasion, established in both culture and animal model systems and the possible mechanisms that have been proposed to be responsible. These mechanisms involve intracellular events and components of the cytoskeletal organisation (actin/myosin filaments, intermediate filaments and microtubules) as well as extracellular signalling at different cell surface receptors (RAGE and integrins). Finally, we shall attempt to demonstrate how aberrant expression of the S100 proteins may lead to pathological events and human disorders and furthermore provide a rationale to possibly explain why the expression of some of the S100 proteins (mainly S100A4 and S100P) has led to conflicting results on motility, depending on the cells used. © 2013 Springer Basel

RNA delivery by extracellular vesicles in mammalian cells and its applications.

The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications