SPAD array camera for localization based super resolution microscopy

Super resolution microscopy by localization is a stochastic based approach, where the resolution is determined by the localization accuracy [1] [2] [3]. The accuracy of localization heavily depends on the statistics of the data obtained with a camera during imaging. Current state of the art EMCCD (electron multiplying charge coupled device) cameras have frame rates up to 200 fps and hence a limited temporal resolution between frames. This can lead to ambiguities in localization. For example, a single fluorescent spot appearing at the same location in two successive frames is not considered for localization, because it is not clear, whether the spot arises from a single fluorophore in ON state for a long time or from two adjacent fluorophores, which switches ON and OFF. In this work, we explore for the first time the use of a single-photon counting SPAD (single photon avalanche diodes) array camera for super resolution microscopy. These cameras can provide high frame rates (up to 375000 fps), with improved temporal resolution between the frames, enabling a more accurate view of events that can be precisely tracked over time. The rich information obtained from such large number of frames leads to more accurate statistical estimations for overcoming the current ambiguities in localization. Also, SPAD array cameras are capable of reading frames having pixels depth of 1-bit. [4]. Such, a fine granularity enables the user to add any number of frames for identifying and localizing individual events with a very high accuracy. SPADs have been success fully used in performing time-resolved imaging measurements like FLIM (fluorescence life time imaging measurements). This allows us to extend the possibility of performing FLIM and super resolution imaging simultaneously. As a result, two different fluorophores can be separated based on their unique life times, enabling multi-channel operations using a single camera. An example of a preliminary image captured using a SPAD array camera is depicted in Figure

Dipeptidyl peptidase IV inhibitors in diabetes: more than inhibition of glucagon-like peptide-1 metabolism?

Inhibitors of the protease dipeptidyl peptidase IV (DPP-IV) are promising new drugs for the treatment of type 2 diabetes. They are thought to act by inhibiting the breakdown of glucagon-like peptide-1 and, thereby, selectively enhancing insulin release under conditions when it is physiologically required. These drugs are selective for DPP-IV, but the enzyme itself has a broad range of substrates other than glucagon-like peptide-1. Other high affinity substrates of DPP-IV including peptide YY may also play a role in the regulation of energy homeostasis. Moreover, DPP-IV is also known as CD26 and considered to be a moonlighting protein because it has a wide range of other functions unrelated to energy homeostasis, e.g. in immunity. The potential role of DPP-IV inhibition on substrates other than glucagon-like peptide-1 in diabetes patients remains to be elucidated

COVID-19 publications: Database coverage, citations, readers, tweets, news, Facebook walls, Reddit posts

© 2020 The Authors. Published by MIT Press. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1162/qss_a_00066The COVID-19 pandemic requires a fast response from researchers to help address biological, medical and public health issues to minimize its impact. In this rapidly evolving context, scholars, professionals and the public may need to quickly identify important new studies. In response, this paper assesses the coverage of scholarly databases and impact indicators during 21 March to 18 April 2020. The rapidly increasing volume of research, is particularly accessible through Dimensions, and less through Scopus, the Web of Science, and PubMed. Google Scholar’s results included many false matches. A few COVID-19 papers from the 21,395 in Dimensions were already highly cited, with substantial news and social media attention. For this topic, in contrast to previous studies, there seems to be a high degree of convergence between articles shared in the social web and citation counts, at least in the short term. In particular, articles that are extensively tweeted on the day first indexed are likely to be highly read and relatively highly cited three weeks later. Researchers needing wide scope literature searches (rather than health focused PubMed or medRxiv searches) should start with Dimensions (or Google Scholar) and can use tweet and Mendeley reader counts as indicators of likely importance

Scientific imperatives, clinical implications, and theoretical underpinnings for the investigation of the relationship between genetic variables and patient-reported quality-of-life outcomes

Objectives There is emerging evidence for a genetic basis of patient-reported quality-of-life (QOL) outcomes that can ultimately be incorporated into clinical research and practice. Objectives are (1) to provide arguments for the timeliness of investigating the genetic basis of QOL given the scientific advances in genetics and patient-reported QOL research; (2) to describe the clinical implications of such investigations; (3) to present a theoretical foundation for investigating the genetic underpinnings of QOL; and (4) to describe a series of papers resulting from the GENEQOL Consortium that was established to move this work forward. Methods Discussion of scientific advances based on relevant literature. Results In genetics, technological advances allow for increases in speed and efficiency and decreases in costs in exploring the genetic underpinnings of disease processes, drug metabolism, treatment response, and survival. In patient-based research, advances yield empirically based and stringent approaches to measurement that are scientifically robust. Insights into the genetic basis of QOL will ultimately allow early identification of patients susceptible to QOL deficits and to target care. The Wilson and Cleary model for patient-reported outcomes was refined by incorporating the genetic underpinnings of QOL. Conclusions This series of papers provides a path for QOL and genetics researchers to work together to move this field forward and to unravel the intricate interplay of the genetic underpinnings of patient-reported QOL outcomes. The ultimate result will be a greater understanding of the process relating disease, patient, and doctor that will have the potential to lead to improved survival, QOL, and health services deliver

The establishment of the GENEQOL consortium to investigate the genetic disposition of patient-reported quality-of-life outcomes

To our knowledge, no comprehensive, interdisciplinary initiatives have been taken to examine the role of genetic variants on patient-reported quality-of-life outcomes. The overall objective of this paper is to describe the establishment of an international and interdisciplinary consortium, the GENEQOL Consortium, which intends to investigate the genetic disposition of patient-reported quality-of-life outcomes. We have identified five primary patient-reported quality-of-life outcomes as initial targets: negative psychological affect, positive psychological affect, self-rated physical health, pain, and fatigue. The first tangible objective of the GENEQOL Consortium is to develop a list of potential biological pathways, genes and genetic variants involved in these quality-of-life outcomes, by reviewing current genetic knowledge. The second objective is to design a research agenda to investigate and validate those genes and genetic variants of patient-reported quality-of-life outcomes, by creating large datasets. During its first meeting, the Consortium has discussed draft summary documents addressing these questions for each patient-reported quality-of-life outcome. A summary of the primary pathways and robust findings of the genetic variants involved is presented here. The research agenda outlines possible research objectives and approaches to examine these and new quality-of-life domains. Intriguing questions arising from this endeavor are discussed. Insight into the genetic versus environmental components of patient-reported quality-of-life outcomes will ultimately allow us to explore new pathways for improving patient care. If we can identify patients who are susceptible to poor quality of life, we will be able to better target specific clinical interventions to enhance their quality of life and treatment outcome

River research and applications across borders

Rivers flow across national borders, unfettered by political distinctions, and the ecological health of rivers is closely linked to their degree of connectivity. River research today is more global than it has ever been, but we show that river research, engineering, and management still operate within homegrown local paradigms. As a basis for this discussion, we studied the citation networks surrounding the most widely cited papers in our field, assessing the degree to which researchers have collaborated across geographical boundaries and fully drawn from the international literature. Despite gains over time, our field remains surprisingly and pervasively provincial. The likely explanation for provincial bias is that researchers are generally more familiar and comfortable with their own research methods, sites, and agendas. However, local focus has tangible consequences. For example, contrasting paradigms and differing approaches to river restoration and to flood-risk management show that opportunities are lost when we fail to learn from the successes and failures of other regions. As Sharp and Leshner (2014; p. 579) have argued, "the search for solutions needs to draw upon the talents and innovative ideas of scientists, engineers, and societal leaders worldwide to overcome traditional and nationalistic paradigms that have so far been inadequate to meeting these challenges.

CD34 marks angiogenic tip cells in human vascular endothelial cell cultures

The functional shift of quiescent endothelial cells into tip cells that migrate and stalk cells that proliferate is a key event during sprouting angiogenesis. We previously showed that the sialomucin CD34 is expressed in a small subset of cultured endothelial cells and that these cells extend filopodia: a hallmark of tip cells in vivo. In the present study, we characterized endothelial cells expressing CD34 in endothelial monolayers in vitro. We found that CD34-positive human umbilical vein endothelial cells show low proliferation activity and increased mRNA expression of all known tip cell markers, as compared to CD34-negative cells. Genome-wide mRNA profiling analysis of CD34-positive endothelial cells demonstrated enrichment for biological functions related to angiogenesis and migration, whereas CD34-negative cells were enriched for functions related to proliferation. In addition, we found an increase or decrease of CD34-positive cells in vitro upon exposure to stimuli that enhance or limit the number of tip cells in vivo, respectively. Our findings suggest cells with virtually all known properties of tip cells are present in vascular endothelial cell cultures and that they can be isolated based on expression of CD34. This novel strategy may open alternative avenues for future studies of molecular processes and functions in tip cells in angiogenesis