Systematic Phenomics Analysis Deconvolutes Genes Mutated in Intellectual Disability into Biologically Coherent Modules

Intellectual disability (ID) disorders are genetically and phenotypically extremely heterogeneous. Can this complexity be depicted in a comprehensive way as a means of facilitating the understanding of ID disorders and their underlying biology? We provide a curated database of 746 currently known genes, mutations in which cause ID (ID-associated genes [ID-AGs]), classified according to ID manifestation and associated clinical features. Using this integrated resource, we show that ID-AGs are substantially enriched with co-expression, protein-protein interactions, and specific biological functions. Systematic identification of highly enriched functional themes and phenotypes revealed typical phenotype combinations characterizing process-defined groups of ID disorders, such as chromatin-related disorders and deficiencies in DNA repair. Strikingly, phenotype classification efficiently breaks down ID-AGs into subsets with significantly elevated biological coherence and predictive power. Custom-made functional Drosophila datasets revealed further characteristic phenotypes among ID-AGs and specific clinical classes. Our study and resource provide systematic insights into the molecular and clinical landscape of ID disorders, represent a significant step toward overcoming current limitations in ID research, and prove the utility of systematic human and cross-species phenomics analyses in highly heterogeneous genetic disorders.     

Environmental impacts of food consumption and nutrition: where are we and what is next?

Purpose

This article introduces the special issue “LCA of nutrition and food consumption” and 14 papers selected from the Ninth LCA Food Conference in San Francisco in October 2014.

Literature overview

The scientific literature in the field of food LCA has increased more than ten times during the last 15 years. Nutrition has a high contribution to the total environmental impacts of consumption. Agricultural production often dominates the impacts, but its importance depends on the type of product, its production mode, transport, and processing. Local or domestic products reduce transports, but this advantage can be lost if the impacts of the raw material production are substantially increased. Diets containing less meat tend to be more environmentally friendly. Several studies concluded that respecting the dietary recommendations for a healthy diet would reduce the overall environmental impacts in the developed countries, although this is not a universal conclusion.

Contribution of this special issue

Eight papers analyze the environmental impacts of catering and in-house food consumption and impacts on sectoral and national levels; four papers presents tools and methods to better assess the impacts of nutrition and to implement the results in practical decision-making. Finally, two contributions analyze the impacts of food waste and reduction options.

Challenges for the environmental assessment of nutrition

(i) Comprehensive assessment. Most studies only analyze climate impacts, although data, methods, and tools are readily available for a more comprehensive analysis. (ii) Assessment of sustainability. The social dimension remains the weakest pillar. (iii) Data availability is still an obstacle, but significant progress has been made in recent years. (iv) Lack of harmonization of methodologies makes comparisons among studies difficult. (v) Land use. Enhanced consideration of land use impacts on biodiversity and ecosystem services is required in LCA. (vi) Defining the functional unit including nutritional aspects, food security, and health needs further work. (vii) Consumer behavior. Its impacts are still little assessed. (viii) Communication of the environmental impact assessment results to stakeholders including policy-makers and consumers needs additional efforts.

Research needs and outlook

(i) Development of holistic approaches for the assessment of sustainable food systems, (ii) assessment of land use related impacts and inclusion of ecosystem services, (iii) exploration of LCA results for policy support and decision-making, (iv) investigation of food consumption patterns in developing and emerging countries, and (v) harmonization of databases.

     

Effect of LY53857, a selective 5HT2 receptor antagonist, on 5HT-induced increases in cutaneous vascular permeability in rats

Both serotonin and histamine increased cutaneous vascular permeability in rats; however, serotonin was approximately 100-fold more potent than histamine. LY53857 (0.1 and 1.0 mg/kg, i.p.), a selective 5HT2 receptor antagonist, blocked serotonin- but not histamine-induced increases in cutaneous vascular permeability. the alpha 1 receptor antagonist, prazosin, did not significantly affect increases in vascular permeability produced by serotonin. These data extend previous studies with LY53857 by further documenting its selectivity as a 5HT2 receptor antagonist. In addition, these results with a selective 5HT2 receptor antagonist provide evidence that 5HT2 receptor activation may be the predominant mechanism associated with vascular permeability changes induced by serotonin.     

Cocaine: its use in otolaryngology

A review of 120 patients who had a discharge diagnosis of intermediate coronary syndrome showed 12 patients with documented transient ST elevation during spontaneous rest pain consistent with Prinzmetal''s angina. Coronary arteriography showed severe proximal occlusive coronary atherosclerosis in nine of the patients, and normal or minimal disease in the other three patients. In two of these three, there was documented coronary arterial spasm with reproduction of symptoms during arteriography. Although a shorter history of chest pain, presence of an old myocardial infarction and a positive finding on electrocardiogram treadmill test tended to predict the patients with severe occlusive coronary artery disease, these methods were inadequate to select candidates for arteriography. All patients responded well to nitroglycerine while in the hospital. Five of the nine patients with coronary artery disease had coronary bypass operations, with two excellent, two fair and one poor result. One of the three patients with normal findings on coronary arteriograms died with refractory ventricular arrhythmia six months after study. The other two have had good-to-moderate relief of symptoms on long-acting vasodilators and propranolol. Current concepts of the syndrome of Prinzmetal''s angina and ST elevation are reviewed. It appears that this syndrome has a wide spectrum of clinical presentations and coronary arteriographic anatomies.     

Spectrum of rapid eye movement sleep behavior disorder (overlap between rapid eye movement sleep behavior disorder and other parasomnias)

Parasomnia Overlap Disorder (POD) was described and named in 1997 with a series of 33 cases of rapid eye movement (REM) sleep behavior disorder (RBD) combined with a disorder of arousal from non-rapid eye movement (NREM) sleep (sleepwalking, sleep terrors) that emerged idiopathically or symptomatically with neurological and other disorders. POD is a subtype of RBD in the International Classification of Sleep Disorders Diagnostic and Coding Manual, second edition (ICSD-2). An updated classification of POD also includes subclinical RBD-NREM parasomnia, RBD-sleep-related eating disorder, RBD-sexsomnia, RBD-rhythmic movement disorder, and status dissociatus (SD), which is another subtype of RBD in the ICSD-2. Similar to POD, a core feature of SD is sleep motor-behavioral dyscontrol, with release of dream-related behaviors suggestive of RBD, but with nearly continuous ambiguous polygraphic sleep precluding the identification of NREM/REM sleep states. SD exemplifies extreme state dissociation. SD is always a symptomatic disorder, and is causally associated with a broad range of neurologic disorders, often with thalamic, limbic, striatal, and pontine involvement. The parasomnia behaviors associated with POD and SD — typical RBD behaviors — can often be controlled with bedtime clonazepam therapy, including the abnormal dreaming.

     

In reply to hertwich & pease, Int. J. LCA 3 (4) 180 — 181, “ISO 14042 restricts use and development of impact assessment”

Life Cycle Impact Assessment describes indicators and does not predict actual impacts. The value of an LCA is its comprehensive review of all stages of a product’s life cycle and its synoptic view of all relevant environmental issues. The current version of the 14042 draft describes the uniqueness of Life Cycle Impact Assessment approach which is distinct from other assessment techniques. The wording was designed to help users of the standard understand how and why LCIA is distinct from other assessment methods. In closing, we would like to highlight our opinion that the present document on the level of a DIS is sound, stable and practical within the ISO 14040 series of standards. We do not agree withHertwich & Pease that the present document prevents the use of LCIA. It makes a choice regarding the exclusion of weighting across categories in order to prevent misuse in deriving inappropriate claims. And for characterisation it has achieved a well founded synthesis. In addition, we strongly believe that this standard will stimulate the international scientific discussion of LCA and will substantially contribute to enhanced and more valuable applications of LCA in the future.     

Contrasting dynamics of water and mineral nutrients in stems shown by stable isotope tracers and cryo‐SIMS

Lateral exchange of water and nutrients between xylem and surrounding tissues helps to de‐couple uptake from utilization in all parts of a plant. We studied the dynamics of these exchanges, using stable isotope tracers for water (H₂¹⁸O), magnesium (²⁶Mg), potassium (⁴¹K) and calcium (⁴⁴Ca) delivered via a cut stem for various periods to the transpiration stream of bean shoots (Phaseolus vulgaris cv. Fardenlosa Shiny). Tracers were subsequently mapped in stem cross‐sections with cryo‐secondary ion mass spectrometry. The water tracer equilibrated within minutes across the entire cross‐section. In contrast, the nutrient tracers showed a very heterogeneous exchange between xylem vessels and the different stem tissues, even after 4 h. Dynamics of nutrients in the tissues revealed a fast and extensive exchange of nutrients in the xylem parenchyma, with, for example, calcium being completely replaced by tracer in less than 5 min. Dilution of potassium tracer during its 30 s transit in xylem sap through the stem showed that potassium concentration was up‐regulated over many hours, to the extent that some of it was probably supplied by phloem recirculation from the shoot.