When fragments link : a bibliometric perspective on the development of fragment-based drug discovery

Fragment-based drug discovery (FBDD) is a highly interdisciplinary field, rich in ideas integrated from pharmaceutical sciences, chemistry, biology, and physics, among others. To enrich our understanding of the development of the field, we used bibliometric techniques to analyze 3642 publications in FBDD, complementing accounts by key practitioners. Mapping its core papers, we found the transfer of knowledge from academia to industry. Co-authorship analysis showed that university–industry collaboration has grown over time. Moreover, we show how ideas from other scientific disciplines have been integrated into the FBDD paradigm. Keyword analysis showed that the field is organized into four interconnected practices: library design, fragment screening, computational methods, and optimization. This study highlights the importance of interactions among various individuals and institutions from diverse disciplines in newly emerging scientific fields. We study the organizational aspects of the development of fragment-based drug discovery (FBDD), using tools from bibliometrics

Drivers and sustainability of bird hunting in Madagascar

Bird conservation depends on robust data on the densities of and threats to each species, and an understanding of the choices and incentives of bird hunters. This first comprehensive study of bird hunting and its effects in Madagascar uses 8 years of data on 87 bird species to determine bird densities and hunting pressure, incentives, choices, methods, spatial variation, and sustainability on the Masoala Peninsula of Madagascar. We find that bird hunting is common, affecting human wellbeing and, for some species, long-term population viability. Hunters caught more abundant species of lower trophic levels and consumers preferred the flavor of abundant granivores and nectarivores, while they disliked carnivores, scavengers, and species with common cultural proscriptions. Wealth increased species selectivity among consumers, whereas food insecurity increased hunting pressure overall. Projected and documented declines in at least three species are concerning, qualifying at least two for increased IUCN threatened species categories. We provide novel, data-driven assessments of hunting's threat to Madagascar's birds, identify key species of concern, and suggest both species- and consumer-specific conservation actions

Insights into the mechanisms of phreatic eruptions from continuous high frequency volcanic gas monitoring: Rinc\uf3n de la Vieja Volcano, Costa Rica

Understanding the trigger mechanisms of phreatic eruptions is key to mitigating the effects of these hazardous but poorly forecastable volcanic events. It has recently been established that high-rate volcanic gas observations are potentially very suitable to identifying the source processes driving phreatic eruptions, and to eventually detecting precursory changes prior to individual phreatic blasts. In February-May 2017, we deployed a Multi-GAS instrument to continuously monitor gas concentrations in the crater lake plume of Rincon de la Vieja, a remote and poorly monitored active volcano in Costa Rica, site of frequent phreatic/phreatomagmatic eruptions. Forty-two phreatic/phreatomagmatic eruptions were seismically recorded during our investigated period, 9 of which were also recorded for gas by the Multi-GAS. To the best of our knowledge, these represent the first instrumentally measured gas compositions during individual phreatic/phreatomagmatic explosions at an active volcano. Our results show that during background quiescent degassing the Rincon de la Vieja crater lake plume was characterized by high CO2/SO2 ratios of 64 +/- 59 and H2S/SO2 ratios of 0.57 +/- 0.20. This composition is interpreted as reflecting hydrothermal (re) processing of magma-sourced gas in the sub-limnic environment. Phreatic blasts were recorded by the Multi-GAS as brief (1-2min long) pulses of elevated gas mixing ratios (up to similar to 52 ppmv SO2 and > 3,000 ppmv CO2), or more than an order of magnitude higher than during background degassing (similar to 1 ppmv SO2 and similar to 450 ppmv CO2). During the phreatic eruption(s), the H2S/SO2 ratio was systematically lower (< 0.18) than during background degassing, but the CO2/SO2 ratio remained high (and variable), ranging from 37 to 390. These S-poor compositions for the eruptive gas imply extensive processing of the source magmatic gas during pre-eruptive hydrothermal storage, likely by deposition of native S and/or sulfate. Our gas results are thus overall consistent with a mechanismof phreatic eruptions triggered by accumulation of magmatic-hydrothermal gases beneath a hydrothermal seal. We claim that real-time Multi-GAS monitoring is urgently needed at other crater lake-hosting volcanoes (e.g., Ruapehu, Aso), where phreatic eruptions may similarly be preceded by phases of reduced S degassing at the surface

Human Ageing Genomic Resources:updates on key databases in ageing research

Ageing is a complex and multifactorial process. For two decades, the Human Ageing Genomic Resources (HAGR) have aided researchers in the study of various aspects of ageing and its manipulation. Here, we present the key features and recent enhancements of these resources, focusing on its six main databases. One database, GenAge, focuses on genes related to ageing, featuring 307 genes linked to human ageing and 2205 genes associated with longevity and ageing in model organisms. AnAge focuses on ageing, longevity, and life-history across animal species, containing data on 4645 species. DrugAge includes information about 1097 longevity drugs and compounds in model organisms such as mice, rats, flies, worms and yeast. GenDR provides a list of 214 genes associated with the life-extending benefits of dietary restriction in model organisms. CellAge contains a catalogue of 866 genes associated with cellular senescence. The LongevityMap serves as a repository for genetic variants associated with human longevity, encompassing 3144 variants pertaining to 884 genes. Additionally, HAGR provides various tools as well as gene expression signatures of ageing, dietary restriction, and replicative senescence based on meta-analyses. Our databases are integrated, regularly updated, and manually curated by experts. HAGR is freely available online (https://genomics.senescence.info/).</p

Human Ageing Genomic Resources:updates on key databases in ageing research

Ageing is a complex and multifactorial process. For two decades, the Human Ageing Genomic Resources (HAGR) have aided researchers in the study of various aspects of ageing and its manipulation. Here, we present the key features and recent enhancements of these resources, focusing on its six main databases. One database, GenAge, focuses on genes related to ageing, featuring 307 genes linked to human ageing and 2205 genes associated with longevity and ageing in model organisms. AnAge focuses on ageing, longevity, and life-history across animal species, containing data on 4645 species. DrugAge includes information about 1097 longevity drugs and compounds in model organisms such as mice, rats, flies, worms and yeast. GenDR provides a list of 214 genes associated with the life-extending benefits of dietary restriction in model organisms. CellAge contains a catalogue of 866 genes associated with cellular senescence. The LongevityMap serves as a repository for genetic variants associated with human longevity, encompassing 3144 variants pertaining to 884 genes. Additionally, HAGR provides various tools as well as gene expression signatures of ageing, dietary restriction, and replicative senescence based on meta-analyses. Our databases are integrated, regularly updated, and manually curated by experts. HAGR is freely available online (https://genomics.senescence.info/).</p

A Consensus Set of Outcomes for Parkinson's Disease from the International Consortium for Health Outcomes Measurement

Background: Parkinson's disease (PD) is a progressive neurodegenerative condition that is expected to double in prevalence due to demographic shifts. Value-based healthcare is a proposed strategy to improve outcomes and decrease costs. To move towards an actual value-based health care system, condition-specific outcomes that are meaningful to patients are essential. Objective: Propose a global consensus standard set of outcome measures for PD. Methods: Established methods for outcome measure development were applied, as outlined and used previously by the International Consortium for Health Outcomes Measurement (ICHOM). An international group, representing both patients and experts from the fields of neurology, psychiatry, nursing, and existing outcome measurement efforts, was convened. The group participated in six teleconferences over a six-month period, reviewed existing data and practices, and ultimately proposed a standard set of measures by which patients should be tracked, and how often data should be collected. Results: The standard set applies to all cases of idiopathic PD, and includes assessments of motor and non-motor symptoms, ability to work, PD-related health status, and hospital admissions. Baseline demographic and clinical variables are included to enable case mix adjustment. Conclusions: The Standard Set is now ready for use and pilot testing in the clinical setting. Ultimately, we believe that using the set of outcomes proposed here will allow clinicians and scientists across the world to document, report, and compare PD-related outcomes in a standardized fashion. Such international benchmarks will improve our understanding of the disease course and allow for identification of 'best practices', ultimately leading to better informed treatment decisions.This project was funded by the International Consortium for Health Outcome Measurement.S

The On-Site Analysis of the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) observatory will be one of the largest ground-based very high-energy gamma-ray observatories. The On-Site Analysis will be the first CTA scientific analysis of data acquired from the array of telescopes, in both northern and southern sites. The On-Site Analysis will have two pipelines: the Level-A pipeline (also known as Real-Time Analysis, RTA) and the level-B one. The RTA performs data quality monitoring and must be able to issue automated alerts on variable and transient astrophysical sources within 30 seconds from the last acquired Cherenkov event that contributes to the alert, with a sensitivity not worse than the one achieved by the final pipeline by more than a factor of 3. The Level-B Analysis has a better sensitivity (not be worse than the final one by a factor of 2) and the results should be available within 10 hours from the acquisition of the data: for this reason this analysis could be performed at the end of an observation or next morning. The latency (in particular for the RTA) and the sensitivity requirements are challenging because of the large data rate, a few GByte/s. The remote connection to the CTA candidate site with a rather limited network bandwidth makes the issue of the exported data size extremely critical and prevents any kind of processing in real-time of the data outside the site of the telescopes. For these reasons the analysis will be performed on-site with infrastructures co-located with the telescopes, with limited electrical power availability and with a reduced possibility of human intervention. This means, for example, that the on-site hardware infrastructure should have low-power consumption. A substantial effort towards the optimization of high-throughput computing service is envisioned to provide hardware and software solutions with high-throughput, low-power consumption at a low-cost.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer

MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment