Patients with mental disorders show many biological abnormalities which distinguish them from normal volunteers; however, few of these have led to tests with clinical utility. Several reasons ...contribute to this delay: lack of a biological 'gold standard' definition of psychiatric illnesses; a profusion of statistically significant, but minimally differentiating, biological findings; 'approximate replications' of these findings in a way that neither confirms nor refutes them; and a focus on comparing prototypical patients to healthy controls which generates differentiations with limited clinical applicability. Overcoming these hurdles will require a new approach. Rather than seek biomedical tests that can 'diagnose' DSM-defined disorders, the field should focus on identifying biologically homogenous subtypes that cut across phenotypic diagnosis--thereby sidestepping the issue of a gold standard. To ensure clinical relevance and applicability, the field needs to focus on clinically meaningful differences between relevant clinical populations, rather than hypothesis-rejection versus normal controls. Validating these new biomarker-defined subtypes will require longitudinal studies with standardized measures which can be shared and compared across studies--thereby overcoming the problem of significance chasing and approximate replications. Such biological tests, and the subtypes they define, will provide a natural basis for a 'stratified psychiatry' that will improve clinical outcomes across conventional diagnostic boundaries.
Specialized plant terpenoids have found fortuitous uses in medicine due to their evolutionary and biochemical selection for biological activity in animals. However, these highly functionalized ...natural products are produced through complex biosynthetic pathways for which we have a complete understanding in only a few cases. Here we review some of the most effective and promising plant terpenoids that are currently used in medicine and medical research and provide updates on their biosynthesis, natural occurrence, and mechanism of action in the body. This includes pharmacologically useful plastidic terpenoids such as
-menthane monoterpenoids, cannabinoids, paclitaxel (taxol
), and ingenol mebutate which are derived from the 2-
-methyl-d-erythritol-4-phosphate (MEP) pathway, as well as cytosolic terpenoids such as thapsigargin and artemisinin produced through the mevalonate (MVA) pathway. We further provide a review of the MEP and MVA precursor pathways which supply the carbon skeletons for the downstream transformations yielding these medically significant natural products.
The Botryosphaeriales (Dothideomycetes) includes numerous endophytic, saprobic, and plant pathogenic species associated with a wide range of symptoms, most commonly on woody plants. In a recent ...phylogenetic treatment of 499 isolates in the culture collection (CBS) of the Westerdijk Institute, we evaluated the families and genera accommodated in this order of important fungi. The present study presents multigene phylogenetic analyses for an additional 230 isolates, using ITS, tef1, tub2, LSU and rpb2 loci, in combination with morphological data. Based on these data, 58 species are reduced to synonymy, and eight novel species are described. They include Diplodia afrocarpi (Afrocarpus, South Africa), Dothiorella diospyricola (Diospyros, South Africa), Lasiodiplodia acaciae ( Acacia, Indonesia), Neofusicoccum podocarpi (Podocarpus, South Africa), N. rapaneae (Rapanea, South Africa), Phaeobotryon ulmi (Ulmus, Germany), Saccharata grevilleae (Grevillea, Australia) and S . hakeiphila (Hakea, Australia). The results have clarified the identity of numerous isolates that lacked Latin binomials or had been deposited under incorrect names in the CBS collection in the past. They also provide a solid foundation for more in-depth future studies on taxa in the order. Sequences of the tef1, tub2 and rpb2 genes proved to be the most reliable markers. At the species level, results showed that the most informative genes were inconsistent, but that a combination of four candidate barcodes (ITS, tef1, tub2 and rpb2) provided reliable resolution. Furthermore, given the large number of additional isolates included in this study, and newly generated multigene DNA datasets, several species could also be reduced to synonymy. The study illustrates the value of reassessing the identity of older collections in culture collections utilising modern taxonomic frameworks and methods.
•It provides recommendations for risk reduction and screening in hereditary breast and ovarian cancer syndrome.•It focuses on risk reduction and screening mainly in unaffected carriers and ...high-resource settings.•The panel encompasses an international multidisciplinary group of experts.•Recommendations are based on available scientific data and the authors’ collective expert opinion.
In this paper we give an account of the genera and species in the Botryosphaeriaceae. We consider morphological characters alone as inadequate to define genera or identify species, given the ...confusion it has repeatedly introduced in the past, their variation during development, and inevitable overlap as representation grows. Thus it seems likely that all of the older taxa linked to the Botryosphaeriaceae, and for which cultures or DNA sequence data are not available, cannot be linked to the species in this family that are known from culture. Such older taxa will have to be disregarded for future use unless they are epitypified. We therefore focus this paper on the 17 genera that can now be recognised phylogenetically, which concentrates on the species that are presently known from culture. Included is a historical overview of the family, the morphological features that define the genera and species and detailed descriptions of the 17 genera and 110 species. Keys to the genera and species are also provided. Phylogenetic relationships of the genera are given in a multi-locus tree based on combined SSU, ITS, LSU, EF1-α and β-tubulin sequences. The morphological descriptions are supplemented by phylogenetic trees (ITS alone or ITS + EF1-α) for the species in each genus.
Taxonomic novelties: New species – Neofusicoccum batangarum Begoude, Jol. Roux & Slippers. New combinations – Botryosphaeria fabicerciana (S.F. Chen, D. Pavlic, M.J. Wingf. & X.D. Zhou) A.J.L. Phillips & A. Alves, Botryosphaeria ramosa (Pavlic, T.I. Burgess, M.J. Wingf.) A.J.L. Phillips & A. Alves, Cophinforma atrovirens (Mehl & Slippers) A. Alves & A.J.L. Phillips, Cophinforma mamane (D.E. Gardner) A.J.L. Phillips & A. Alves, Dothiorella pretoriensis (Jami, Gryzenh., Slippers & M.J. Wingf.) Abdollahz. & A.J.L. Phillips, Dothiorella thailandica (D.Q. Dai., J.K. Liu & K.D. Hyde) Abdollahz., A.J.L. Phillips & A. Alves, Dothiorella uruguayensis (C.A. Pérez, Blanchette, Slippers & M.J. Wingf.) Abdollahz. & A.J.L. Phillips, Lasiodiplodia lignicola (Ariyawansa, J.K. Liu & K.D. Hyde) A.J.L. Phillips, A. Alves & Abdollahz., Neoscytalidium hyalinum (C.K. Campb. & J.L. Mulder) A.J.L. Phillips, Groenewald & Crous, Sphaeropsis citrigena (A.J.L. Phillips, P.R. Johnst. & Pennycook) A.J.L. Phillips & A. Alves, Sphaeropsis eucalypticola (Doilom, J.K. Liu, & K.D. Hyde) A.J.L. Phillips, Sphaeropsis porosa (Van Niekerk & Crous) A.J.L. Phillips & A. Alves. Epitypification (basionym) – Sphaeria sapinea Fries. Neotypifications (basionyms) – Botryodiplodia theobromae Pat., Physalospora agaves Henn, Sphaeria atrovirens var. visci Alb. & Schwein.
Phthalates and bisphenol A (BPA) are widely used industrial chemicals that may adversely impact human health. Human exposure is ubiquitous and can occur through diet, including consumption of ...processed or packaged food.
To examine associations between recent fast food intake and BPA and urinary metabolites of di(2-ethylhexyl) phthalate (ΣDEHPm) and diisononyl phthalate (DiNPm) among the U.S.
We combined data on 8,877 participants from the National Health and Nutrition Examination Survey (NHANES 2003-2010). Using 24-hr dietary recall data, we quantified: a) fast food intake percent of total energy intake (TEI) from fast food; b) fast food-derived fat intake (percent of TEI from fat in fast food); and c) fast food intake by food group (dairy, eggs, grains, meat, and other). We examined associations between dietary exposures and urinary chemical concentrations using multivariate linear regression.
We observed evidence of a positive, dose-response relationship between fast food intake and exposure to phthalates (p-trend < 0.0001) but not BPA; participants with high consumption (≥ 34.9% TEI from fast food) had 23.8% (95% CI: 11.9%, 36.9%) and 39.0% (95% CI: 21.9%, 58.5%) higher levels of ΣDEHPm and DiNPm, respectively, than nonconsumers. Fast food-derived fat intake was also positively associated with ΣDEHPm and DiNPm (p-trend < 0.0001). After adjusting for other food groups, ΣDEHPm was associated with grain and other intake, and DiNPm was associated with meat and grain intake.
Fast food may be a source of exposure to DEHP and DiNP. These results, if confirmed, could inform individual and regulatory exposure reduction strategies.
Zota AR, Phillips CA, Mitro SD. 2016. Recent fast food consumption and bisphenol A and phthalates exposures among the U.S. population in NHANES, 2003-2010. Environ Health Perspect 124:1521-1528; http://dx.doi.org/10.1289/ehp.1510803.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The adequate simulation of internal climate variability is key for our understanding of climate as it underpins efforts to attribute historical events, predict on seasonal and decadal time scales, ...and isolate the effects of climate change. Here the skill of models in reproducing observed modes of climate variability is assessed, both across and within the CMIP3, CMIP5, and CMIP6 archives, in order to document model capabilities, progress across ensembles, and persisting biases. A focus is given to the well-observed tropical and extratropical modes that exhibit small intrinsic variability relative to model structural uncertainty. These include El Niño–Southern Oscillation (ENSO), the Pacific decadal oscillation (PDO), the North Atlantic Oscillation (NAO), and the northern and southern annular modes (NAM and SAM). Significant improvements are identified in models’ representation of many modes. Canonical biases, which involve both amplitudes and patterns, are generally reduced across model generations. For example, biases in ENSO-related equatorial Pacific sea surface temperature, which extend too far westward, and associated atmospheric teleconnections, which are too weak, are reduced. Stronger tropical expression of the PDO in successive CMIP generations has characterized their improvement, with some CMIP6 models generating patterns that lie within the range of observed estimates. For the NAO, NAM, and SAM, pattern correlations with observations are generally higher than for other modes and slight improvements are identified across successive model generations. For ENSO and PDO spectra and extratropical modes, changes are small compared to internal variability, precluding definitive statements regarding improvement.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Idiopathic interstitial pneumonias (IIPs) have a progressive and often fatal course, and their enigmatic etiology has complicated approaches to effective therapies. Idiopathic pulmonary fibrosis ...(IPF) is the most common of IIPs and shares with IIPs an increased incidence with age and unexplained scarring in the lung. Short telomeres limit tissue renewal capacity in the lung and germ-line mutations in telomerase components, hTERT and hTR, underlie inheritance in a subset of families with IPF. To examine the hypothesis that short telomeres contribute to disease risk in sporadic IIPs, we recruited patients who have no family history and examined telomere length in leukocytes and in alveolar cells. To screen for mutations, we sequenced hTERT and hTR. We also reviewed the cases for features of a telomere syndrome. IIP patients had shorter leukocyte telomeres than age-matched controls (P < 0.0001). In a subset (10%), IIP patients had telomere lengths below the first percentile for their age. Similar to familial cases with mutations, IPF patients had short telomeres in alveolar epithelial cells (P < 0.0001). Although telomerase mutations were rare, detected in 1 of 100 patients, we identified a cluster of individuals (3%) with IPF and cryptogenic liver cirrhosis, another feature of a telomere syndrome. Short telomeres are thus a signature in IIPs and likely play a role in their age-related onset. The clustering of cryptogenic liver cirrhosis with IPF suggests that the telomere shortening we identify has consequences and can contribute to what appears clinically as idiopathic progressive organ failure in the lung and the liver.
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