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Li-Fraumeni syndrome (LFS) is a highly penetrant cancer predisposition syndrome that may present with a first cancer before or during adolescence/young adulthood. Families offered LFS genetic testing for their children can inform our understanding of how the unique developmental context of adolescence influences parental perspectives about genetic testing and discussions of cancer risk. In this study, semi-structured interviews were conducted with 46 parents of children at risk for LFS to capture those perspectives...

All dynamic species interaction models contain an assumption that describes how contact rates scale with population density. Choosing an appropriate contact-density function is important, because different functions have different implications for population dynamics and stability. However, this choice can be challenging, because there are many possible functions, and most are phenomenological and thus difficult to relate to underlying ecological processes. Using one such phenomenological function, we described a nonlinear relationship between field transmission rates and host density in a common snail-oligochaete symbiosis...

It is very important to control methane emissions to mitigate global warming. An intermittent micro-aeration control system was used to control methane emissions from an integrated vertical-flow constructed wetland (IVCW) to treat agricultural domestic wastewater pollution in this study. The optimized intermittent micro-aeration conditions were a 20-min aeration time and 340-min non-aeration time, 3.9 m3  h-1 aeration intensity, evenly distributed micro-aeration diffusers at the tank bottom, and an aeration period of every 6 h...

Bacterial resistance occurs by spontaneous mutations or horizontal gene transfer mediated by mobile genetic elements, which represents a great concern. Resistance to β-lactam antibiotics is mainly due to the production of β-lactamases, and an important mechanism of fluoroquinolone resistance is the acquisition plasmid determinants. The aim of this study was to verify the presence of β-lactamase-encoding genes and plasmid-mediated quinolone resistance genes in different water samples obtained from São Paulo state, Brazil...

PURPOSE: Symptom progression in Huntington disease (HD) is associated with cognitive decline which may interfere with the self-report of symptoms. Unfortunately, data to support or refute the psychometric reliability of patient-reported outcomes (PROs) as HD progresses are limited. This is problematic given that PROs are increasingly recognized as important measures of efficacy for new treatments. METHODS: We examined PRO data from the HDQLIFE Measurement System (Speech Difficulties; Swallowing Difficulties; Chorea) in 509 individuals with premanifest, early-stage, or late-stage HD...

RNA modifications are involved in many aspects of biological functions. N6-methyladenosine (m6 A) is one of the most important forms of RNA methylation and plays a vital role in regulating gene expression, protein translation, cell behaviors, and physiological conditions in many species, including humans. The dynamic and reversible modification of m6 A is conducted by three elements: methyltransferases ("writers"), such as methyltransferase-like protein 3 (METTL3) and METTL14; m6 A-binding proteins ("readers"), such as the YTH domain family proteins (YTHDFs) and YTH domain-containing protein 1 (YTHDC1); and demethylases ("erasers"), such as fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5)...

Bisecting GlcNAc, a branch structure in N-glycan, has unique functions and is involved in several diseases including Alzheimer's disease (AD). In this review, we provide an overview of the biosynthesis of bisecting GlcNAc and its physiological and pathological functions, particularly in the nervous system where bisecting GlcNAc is most highly expressed. The biosynthetic enzyme of bisecting GlcNAc is N-acetylglucosaminyltransferase-III (GnT-III). Overexpression, knockdown, and knockout of GnT-III have so far revealed various functions of bisecting GlcNAc, which are mediated by regulating the functions of key carrier proteins...

Glycosylation is considered one of the most complex and structurally diverse post-translational modifications of proteins. Glycans play important roles in many biological processes such as protein folding, regulation of protein stability, solubility and serum half-life. One of the ways to study glycosylation is systematic structural characterizations of protein glycosylation utilizing glycomics methodology based around mass spectrometry (MS). The most prevalent bottleneck stages for glycomic analyses is laborious sample preparation steps...

Infections by carbapenem-resistant Enterobacteriaceae (CRE) are difficult to manage owing to broad antibiotic resistance profiles and because of the inability of clinically-used β-lactamase inhibitors to counter the activity of metallo-β-lactamases often harbored by these pathogens. Of particular importance is New Delhi metallo-β-lactamase (NDM), which requires a dinuclear zinc ion cluster for catalytic activity. Here, we compare the structures and functions of clinical NDM variants 1-17. The impact of NDM variants on structure is probed by comparing comparing melting temperature and refolding efficiency and also by spectroscopy (UV-Vis, 1 H-NMR, and EPR) of di-cobalt metalloforms...

Wildlife-vehicle collisions (WVC) represent a major threat for wildlife and understanding how WVC spatial patterns relate to surrounding land cover can provide valuable information for deciding where to implement mitigation measures. However, these relations may be heavily biased as many casualties are undetected in roadkill surveys, e.g. due to scavenger activity, which may ultimately jeopardize conservation actions. We suggest using occupancy models to overcome imperfect detection issues, assuming that 'occupancy' represents the preference for crossing the road in a given site, i...

Climate change can impair ecosystem functions and services in extensive dry forests worldwide. However, attribution of climate change impacts on tree growth and forest productivity is challenging due to multiple inter-annual patterns of climatic variability associated with atmospheric and oceanic circulations. Moreover, growth responses to rising atmospheric CO2 , namely carbon fertilization, as well as size ontogenetic changes can obscure the climate change signature as well. Here we apply Structural Equation Models (SEM) to investigate the relative role of climate change on tree growth in an extreme Mediterranean environment (i...

Climate change places considerable stress on riverine ecosystems by altering flow regimes and increasing water temperature. This study evaluated how water temperature increases under climate change scenarios will affect stream invertebrates in pristine headwater streams. The studied headwater-stream sites were distributed within a temperate catchment of Japan and had similar hydraulic-geographical conditions, but were subject to varying temperature conditions due to altitudinal differences (100 to 850 m)...

Tetracycline hydrochloride (TH), indomethacin (IM), and bezafibrate (BF) belong to the three different important classes of pharmaceuticals, which are well known for their toxicity and environmental concerns. However, studies are still elusive to highlight the mechanistic toxicity of these pharmaceuticals and rank them using both, the toxicity prediction and confirmation approaches. Therefore, we employed the next generation toxicity testing in 21st century (TOX21) tools and estimated the in vitro/vivo toxic endpoints of mentioned pharmaceuticals, and then confirmed them using in vitro/vivo assays...

The quinazoline based drug prazosin (PRZ) is a potent inducer of apoptosis in human cancer cells. We recently reported that PRZ enters cells via endocytosis and induces tubulation of the endolysosomal system. In a proteomics approach aimed at identifying potential membrane proteins with binding affinity to quinazolines, we detected the oncoprotein CD98hc. We confirmed shuttling of CD98hc towards lysosomes and upregulation of CD98hc expression in PRZ treated cells. Gene knockout (KO) experiments revealed that endocytosis of PRZ still occurs in the absence of CD98hc - suggesting that PRZ does not enter the cell via CD98hc but misroutes the protein towards tubular lysosomes...

Paradoxically, the vast majority of research models intended to understand the relationship between exogenous exposures and lung disease are reduced to a single inhalant. This is understandable given the practical challenges of investigation, but is problematic in terms of translation to the real-world human condition. Furthermore, use of data from such models can lead to under-estimation of effect, which may adversely impact regulatory imperatives to protect public health based on the most robust information...

BACKGROUND: Viral bronchiolitis is one of the most common causes of hospitalisation in young infants. It has previously been shown that many United Kingdom (UK) hospital Trusts were not compliant with many aspects of the National Institute for Health and Care Excellence (NICE) bronchiolitis guideline prior to its publication. OBJECTIVES: This study aimed to investigate changes in the management of bronchiolitis by hospital Trusts between 2015 (before NICE guideline publication) and 2017, after publication...

OBJECTIVE: The aim of this study is to identify the prognostic role of MRI and EEG in posterior cortex epilepsies (PCES) and to characterize their clinical features. PATIENT AND METHODS: We retrospectively studied 54 consecutive patients (18 females, 36 males) from April 2011 to November 2015, who had undergone PCES surgery. Electro-clinical, pathological and surgical data were evaluated. Of the patients, 18 (33.3%) patients underwent a cortical resection (corticectomy), 10 (18...

Multiple endocrine neoplasia type 1 is a rare genetic syndrome, characterized by the co-occurrence, in the same individual or in related individuals of the same family, of hyperparathyroidism, duodenopancraetic neuroendocrine tumors, pituitary adenomas, adrenocortical tumors, and neuroendocrine tumors (carcinoids) in the thymus, the bronchi, or the stomach. Multiple endocrine neoplastic type 2 is a rare genetic syndrome, characterized by the familial occurrence of medullary thyroid carcinoma either isolated or associated with pheochromocytoma, primary hyperparathyroidism, or typical features (Marfanoid habitus, mucosal neuromas)...

The over discharge of mine tailing cause consequent heavy metal pollution. Phytoremediation as one of the most viable and efficient method for this problem has aroused much attention. In this research, the growth and physiological responses of Suaeda glauca and Arabidopsis thaliana plants were investigated, and the soil conditions (pH and enzyme activity) were evaluated further under varied levels of cadmium (Cd), lead (Pb) and manganese (Mn). The results showed that heavy metals could inhibit the growth of plants...

PURPOSE: Irinotecan (CPT-11) in combination with 5-fluorouracil (5FU) is widely used in the treatment of colorectal cancer. We assessed potential clinical variables that may predict toxicity and more specifically the role of UGT1A1 polymorphisms associated with irinotecan toxicity. We used data from the PETACC3 trial, which randomised patients in adjuvant setting to 6 months of leucovorin (LV) and 5FU (LV5/FU2) or LV5/FU2 + irinotecan. PATIENTS AND METHODS: Clinical and toxicity data were available for 2982 patients, DNA was available for 1200 (40%) of these patients...