Direct analysis of organic priority pollutants by IMS

Many routine methods for monitoring of trace amounts of atmospheric organic pollutants consist of several steps. Typical steps are: (1) collection of the air sample; (2) trapping of organics from the sample; (3) extraction of the trapped organics; and (4) identification of the organics in the extract by GC (gas chromatography), HPLC (High Performance Liquid Chromatography), or MS (Mass Spectrometry). These methods are often cumbersome and time consuming. A simple and fast method for monitoring atmospheric organics using an IMS (Ion Mobility Spectrometer) is proposed. This method has a short sampling time and does not require extraction of the organics since the sample is placed directly in the IMS. The purpose of this study was to determine the responses in the IMS to organic 'priority pollutants'. Priority pollutants including representative polycyclic aromatic hydrocarbons (PAHs), phthalates, phenols, chlorinated pesticides, and polychlorinated biphenyls (PCB's) were analyzed in both the positive and negative detection mode at ambient atmospheric pressure. Detection mode and amount detected are presented

The World's Rediscovered Species: Back from the Brink?

Each year, numerous species thought to have disappeared are rediscovered. Yet, do these rediscoveries represent the return of viable populations or the delayed extinction of doomed species? We document the number, distribution and conservation status of rediscovered amphibian, bird, and mammal species globally. Over the past 122 years, at least 351 species have been rediscovered, most occurring in the tropics. These species, on average, were missing for 61 years before being rediscovered (range of 3–331 years). The number of rediscoveries per year increased over time and the majority of these rediscoveries represent first documentations since their original description. Most rediscovered species have restricted ranges and small populations, and 92% of amphibians, 86% of birds, and 86% of mammals are highly threatened, independent of how long they were missing or when they were rediscovered. Under the current trends of widespread habitat loss, particularly in the tropics, most rediscovered species remain on the brink of extinction

Caspase-2-mediated cell death is required for deleting aneuploid cells

Caspase-2, one of the most evolutionarily conserved of the caspase family, has been implicated in maintenance of chromosomal stability and tumour suppression. Caspase-2 deficient (Casp2-/-) mice develop normally but show premature ageing-related traits and when challenged by certain stressors, succumb to enhanced tumour development and aneuploidy. To test how caspase-2 protects against chromosomal instability, we utilized an ex vivo system for aneuploidy where primary splenocytes from Casp2-/- mice were exposed to anti-mitotic drugs and followed up by live cell imaging. Our data show that caspase-2 is required for deleting mitotically aberrant cells. Acute silencing of caspase-2 in cultured human cells recapitulated these results. We further generated Casp2C320S mutant mice to demonstrate that caspase-2 catalytic activity is essential for its function in limiting aneuploidy. Our results provide direct evidence that the apoptotic activity of caspase-2 is necessary for deleting cells with mitotic aberrations to limit aneuploidy.S Dawar, Y Lim, J Puccini, M White, P Thomas, L Bouchier-Hayes, D R Green, L Dorstyn and S Kuma

Landscape homogenization due to agricultural intensification disrupts the relationship between reproductive success and main prey abundance in an avian predator

Selecting high-quality habitat and the optimal time to reproduce can increase individual fitness and is a strong evolutionary factor shaping animal populations. However, few studies have investigated the interplay between land cover heterogeneity, limitation in food resources, individual quality and spatial variation in fitness parameters. Here, we explore how individuals of different quality respond to possible mismatches between a cue for prey availability (land cover heterogeneity) and the actual fluctuating prey abundance.Peer reviewe

Aneuploidy and chromosomal instability in cancer: a jackpot to chaos

Genomic instability (GIN) is a hallmark of cancer cells that facilitates the acquisition of mutations conferring aggressive or drug-resistant phenotypes during cancer evolution. Chromosomal instability (CIN) is a form of GIN that involves frequent cytogenetic changes leading to changes in chromosome copy number (aneuploidy). While both CIN and aneuploidy are common characteristics of cancer cells, their roles in tumor initiation and progression are unclear. On the one hand, CIN and aneuploidy are known to provide genetic variation to allow cells to adapt in changing environments such as nutrient fluctuations and hypoxia. Patients with constitutive aneuploidies are more susceptible to certain types of cancers, suggesting that changes in chromosome copy number could positively contribute to cancer evolution. On the other hand, chromosomal imbalances have been observed to have detrimental effects on cellular fitness and might trigger cell cycle arrest or apoptosis. Furthermore, mouse models for CIN have led to conflicting results. Taken together these findings suggest that the relationship between CIN, aneuploidy and cancer is more complex than what was previously anticipated. Here we review what is known about this complex ménage à trois, discuss recent evidence suggesting that aneuploidy, CIN and GIN together promote a vicious cycle of genome chaos. Lastly, we propose a working hypothesis to reconcile the conflicting observations regarding the role of aneuploidy and CIN in tumorigenesis

Removal of the endocrine disrupter butyl benzyl phthalate from the environment

Butyl benzyl phthalate (BBP), an aryl alkyl ester of 1,2-benzene dicarboxylic acid, is extensively used in vinyl tiles and as a plasticizer in PVC in many commonly used products. BBP, which readily leaches from these products, is one of the most important environmental contaminants, and the increased awareness of its adverse effects on human health has led to a dramatic increase in research aimed at removing BBP from the environment via bioremediation. This review highlights recent progress in the degradation of BBP by pure and mixed bacterial cultures, fungi, and in sludge, sediment, and wastewater. Sonochemical degradation, a unique abiotic remediation technique, and photocatalytic degradation are also discussed. The degradation pathways for BBP are described, and future research directions are considered

Distinct functions of HTLV-1 Tax1 from HTLV-2 Tax2 contribute key roles to viral pathogenesis

While the human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), to date, its close relative HTLV-2 is not associated with ATL or other types of malignancies. Accumulating evidence shows that HTLV-1 Tax1 and HTLV-2 Tax2 have many shared activities, but the two proteins have a limited number of significantly distinct activities, and these distinctions appear to play key roles in HTLV-1 specific pathogenesis. In this review, we summarize the functions of Tax1 associated with cell survival, cell proliferation, persistent infection as well as pathogenesis. We emphasize special attention to distinctions between Tax1 and Tax2

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19. Funding Sponsored by the University of Dundee and supported through an Investigator Initiated Research award from Insmed, Bridgewater, NJ; STOP-COVID19 trial