Slow motions in nondeuterated proteins: Concerted chemical shift modulations of backbone nuclei

A simple method designed to measure autorelaxation rates of double- and zero-quantum coherences DQC/ZQC{C′N} involving a carbonyl C′ and the neighboring amide N nucleus in protein backbones provides valuable insight into slow motions in spite of interference both from the attached amide proton HN and from remote protons such as Hα in nondeuterated proteins. The method has been applied to human ubiquiti

Community supported agriculture farmers' perceptions of management benefits and drawbacks

Community Supported Agriculture (CSA) is a direct partnership between producer(s) and a group of consumers/members to share the risks and responsibilities of farming activities. CSA aims at producing and providing environmentally, socially, economically, and nutritionally sustainable food. Past research has focused on CSA members\u2019 motivations. This research aims to gain a better understanding of CSA farmers\u2019 perceived benefits and drawbacks in managing a CSA farm, and whether CSA management perception varies in dierent countries. The research collected data from 35 farmers that were based in the United States (US) and Hungary (HU). Data elaboration includes a one-way Anova test, Chi-square test, principal component analysis, and multiple multivariate linear regressions. The results support that US and HU farmers have similar positive perceptions of CSA farming management, especially in food quality, nutritional value products, environmental, and community benefits. The main dierences concentrate on economic, financial, and management perceptions. CSA success as an alternative agro-food production and distribution system relies on the capability to involve CSA members. Therefore, CSA farmers\u2019 management skills may evolve to ensure the performance of communication and community engaging practices. The main CSA concern is ensuring a fair income and living wage for the farmers and labor force. There is a need for better balancing non-monetary and monetary benefits for the farmers

Digenic inheritance of human primary microcephaly delineates centrosomal and non-centrosomal pathways.

Primary microcephaly (PM) is characterized by a small head since birth and is vastly heterogeneous both genetically and phenotypically. While most cases are monogenic, genetic interactions between Aspm and Wdr62 have recently been described in a mouse model of PM. Here, we used two complementary, holistic in vivo approaches: high throughput DNA sequencing of multiple PM genes in human patients with PM, and genome-edited zebrafish modeling for the digenic inheritance of PM. Exomes of patients with PM showed a significant burden of variants in 75 PM genes, that persisted after removing monogenic causes of PM (e.g., biallelic pathogenic variants in CEP152). This observation was replicated in an independent cohort of patients with PM, where a PM gene panel showed in addition that the burden was carried by six centrosomal genes. Allelic frequencies were consistent with digenic inheritance. In zebrafish, non-centrosomal gene casc5 -/- produced a severe PM phenotype, that was not modified by centrosomal genes aspm or wdr62 invalidation. A digenic, quadriallelic PM phenotype was produced by aspm and wdr62. Our observations provide strong evidence for digenic inheritance of human PM, involving centrosomal genes. Absence of genetic interaction between casc5 and aspm or wdr62 further delineates centrosomal and non-centrosomal pathways in PM

Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria.

The original designation of "Arrhythmogenic right ventricular (dysplasia/) cardiomyopathy"(ARVC) was used by the scientists who first discovered the disease, in the pre-genetic and pre-cardiac magnetic resonance era, to describe a new heart muscle disease predominantly affecting the right ventricle, whose cardinal clinical manifestation was the occurrence of malignant ventricular arrhythmias. Subsequently, autopsy investigations, genotype-phenotype correlations studies and the increasing use of contrast-enhancement cardiac magnetic resonance showed that the fibro-fatty replacement of the myocardium represents the distinctive phenotypic feature of the disease that affects the myocardium of both ventricles, with left ventricular involvement which may parallel or exceed the severity of right ventricular involvement. This has led to the new designation of "Arrhythmogenic Cardiomyopathy" (ACM), that represents the evolution of the original term of ARVC. The present International Expert Consensus document proposes an upgrade of the criteria for diagnosis of the entire spectrum of the phenotypic variants of ACM. The proposed "Padua criteria" derive from the diagnostic approach to ACM, which has been developed over 30 years by the multidisciplinary team of basic researchers and clinical cardiologists of the Medical School of the University of Padua. The Padua criteria are a working framework to improve the diagnosis of ACM by introducing new diagnostic criteria regarding tissue characterization findings by contrast-enhanced cardiac magnetic resonance, depolarization/repolarization ECG abnormalities and ventricular arrhythmia features for diagnosis of the left ventricular phenotype. The proposed diagnostic criteria need to be further validated by future clinical studies in large cohorts of patients

Experimental aluminum pathology in rabbits: effects of hydrophilic and lipophilic compounds.

Aluminum lactate [Al(lact)3] (hydrophilic, hydrolytically unstable) and aluminum acetylacetonate [Al(acae)3] (lipophilic, hydrolytically stable) were tested as potential toxicants to rabbits upon IV administration both as aqueous solutions and as liposome suspensions. Both chemicals behaved as cardiotoxic agents when administered as aqueous solutions, but Al(acae)3 was at least two orders of magnitude more active than Al(lact)3. Al(acae)3, but not Al(lact)3, caused myocardial infarcts resembling those in humans (with contraction bands) at doses as low as 0.24 mg/kg body weight, as well as a prominent acanthocytosis. Al(lact)3, when administered as a liposome suspension, was about 300 times more toxic than in aqueous solution, although cardiac damage was not infarctual in character. Both chemical and physical speciation of aluminum(III) thus play an essential role in determining the toxicity of the metal

Application of prioritization approaches to optimize environmental monitoring and testing of pharmaceuticals

Pharmaceuticals are ubiquitous in the natural environment with concentrations expected to rise as human population increases. Environmental risk assessments are available for a small portion of pharmaceuticals in use, raising concerns over the potential risks posed by other drugs that have little or no data. With >1900 active pharmaceutical ingredients in use, it would be a major task to test all of the compounds with little or no data. Desk-based prioritization studies provide a potential solution by identifying those substances that are likely to pose the greatest risk to the environment and which, therefore, need to be considered a priority for further study. The aim of this review was to (1) provide an overview of different prioritization exercises performed for pharmaceuticals in the environment and the results obtained; and (2) propose a new holistic risk-based prioritization framework for drugs in the environment. The suggested models to underpin this framework are discussed in terms of validity and applicability. The availability of data required to run the models was assessed and data gaps identified. The implementation of this framework may harmonize pharmaceutical prioritization efforts and ensure that, in the future, experimental resources are focused on molecules, endpoints, and environmental compartments that are biologically relevant

Risk-based prioritization of pharmaceuticals in the natural environment in Iraq

Numerous studies have demonstrated the occurrence of pharmaceuticals in the natural environment, raising concerns about their impact on non-target organisms or human health. One region where little is known about the exposure and effects of pharmaceuticals in the environment is Iraq. Due to the high number of pharmaceuticals used by the public health sector in Iraq (hospitals and care centres) and distributed over the counter, there is a need for a systematic approach for identifying substances that should be monitored in the environment in Iraq and assessed in terms of environmental risk. In this study, a risk-based prioritization approach was applied to 99 of the most dispensed pharmaceuticals in three Iraqi cities, Baghdad, Mosul and Basrah. Initially, information on the amounts of pharmaceuticals used in Iraq was obtained. The top used medicines were found to be paracetamol, amoxicillin and metformin with total annual consumption exceeding 1000 tonnes per year. Predicted environmental concentrations (PECs) and predicted no-effect concentrations (PNECs), derived from ecotoxicological end-points and effects related to the therapeutic mode of action, were then used to rank the pharmaceuticals in terms of risks to different environmental compartments. Active pharmaceutical ingredients used as antibiotics, antidepressants and analgesics were identified as the highest priority in surface water, sediment and the terrestrial environment. Antibiotics were also prioritized according to their susceptibility to kill or inhibit the growth of bacteria or to accelerate the evolution and dissemination of antibiotic-resistant genes in water. Future work will focus on understanding the occurrence, fate and effects of some of highly prioritized substances in the environment

Background matching in the brown shrimp Crangon crangon : adaptive camouflage and behavioural-plasticity

A combination of burrowing behaviour and very efficient background matching makes the brown shrimp Crangon crangon almost invisible to potential predators and preys. This raises questions on how shrimp succeed in concealing themselves in the heterogeneous and dynamic estuarine habitats they inhabit and what type of environmental variables and behavioural factors affect their colour change abilities. Using a series of behavioural experiments, we show that the brown shrimp is capable of repeated fast colour adaptations (20% change in dark pigment cover within one hour) and that its background matching ability is mainly influenced by illumination and sediment colour. Novel insights are provided on the occurrence of non-adaptive (possibly stress) responses to background changes after long-time exposure to a constant background colour or during unfavourable conditions for burying. Shrimp showed high levels of intra- and inter-individual variation, demonstrating a complex balance between behavioural-plasticity and environmental adaptation. As such, the study of crustacean colour changes represents a valuable opportunity to investigate colour adaptations in dynamic habitats and can help us to identify the mayor environmental and behavioural factors influencing the evolution of animal background matching