Bioerosion and sediment ingestion by the Caribbean parrotfish Scarus vetula and Sparisoma viride:Implications of fish size, feeding mode and habitat use

Erosion rates and sources of sediment ingested were quantified for the 2 most abundant parrotfish species on a leeward fringing reef of Bonaire, Netherlands Antilles: Scarus vetula and Sparisoma viride. Direct estimates of erosion by different size classes were obtained from daily feeding rates and grazing scar frequency, scar volume and substrate density. Foraging preference and distribution of fish on the reef were used to examine patterns of bioerosion at 2 spatial scales: reef zones and individual substrates used for grazing. Sediment mass ingested by fish provided an independent check on erosion rates, and was partitioned according to source. S. vetula, employing a scraping feeding mode, removed less material from grazed substrates than similar sized S. viride, which forages by excavating the substrate. Erosion rates increased strongly with fish size in both species. The (indigestible) carbonate derived from epilithic algae accounted for all sediment ingested by juvenile fish. In adult fish, the proportion of freshly eroded carbonate substrate ingested increased with fish size. The distribution of adults of these large scarids over different reef zones determines the rate of bioerosion on a large spatial scale. The highest bioerosional rates occur on the shallow reef (ca 7 kg m(-2) yr(-1)), and they decrease with depth. Parrotfish foraging preferences, and the effects of food type and skeletal density of substrates on the size of the grazing scars, cause large differences in bioerosional rates on a small spatial scale. The highest rates of bioerosion occur on substrates infested with boring algae and of low skeletal density, while high-density substrates and substrates covered with crustose corallines undergo lower rates. Living coral is rarely eaten by scarids, and largely escapes erosion by grazing

Increased mitochondrial activity in a novel IDH1-R132H mutant human oligodendroglioma xenograft model: in situ detection of 2-HG and α-KG

Background: Point mutations in genes encoding NADP+-dependent isocitrate dehydrogenases (especially IDH1) are common in lower grade diffuse gliomas and secondary glioblastomas and occur early during tumor development. The contribution of these mutations to gliomagenesis is not completely understood and research is hampered by the lack of relevant tumor models. We previously described the development of the patient-derived high-grade oligodendroglioma xenograft model E478 that carries the commonly occurring IDH1-R132H mutation. We here report on the analyses of E478 xenografts at the genetic, histologic and metabolic level. Results: LC-MS and in situ mass spectrometric imaging by LESA-nano ESI-FTICR revealed high levels of the proposed oncometabolite D-2-hydroxyglutarate (D-2HG), the product of enzymatic conversion of α-ketoglutarate (α-KG) by IDH1-R132H, in the tumor but not in surrounding brain parenchyma. α-KG levels and total NADP+-dependent IDH activity were similar in IDH1-mutant and -wildtype xenografts, demonstrating that IDH1-mutated cancer cells maintain α-KG levels. Interestingly, IDH1-mutant tumor cells in vivo present with high densities of mitochondria and increased levels of mitochondrial activity as compared to IDH1-wildtype xenografts. It is not yet clear whether this altered mitochondrial activity is a driver or a consequence of tumorigenesis. Conclusions: The oligodendroglioma model presented here is a valuable model for further functional elucidation of the effects of IDH1 mutations on tumor metabolism and may aid in the rational development of novel therapeutic strategies for the large subgroup of gliomas carrying IDH1 mutations

Maternal risk associated with the VACTERL association:A case-control study

Background The VACTERL association (VACTERL) includes at least three of these congenital anomalies: vertebral, anal, cardiac, trachea-esophageal, renal, and limb anomalies. Assisted reproductive techniques (ART), pregestational diabetes mellitus, and chronic lower obstructive pulmonary disorders (CLOPD) have been associated with VACTERL. We aimed to replicate these findings and were interested in additional maternal risk factors. Methods A case-control study using self-administered questionnaires was performed including 142 VACTERL cases and 2,135 population-based healthy controls. Multivariable logistic regression analyses were performed to estimate confounder adjusted odds ratios (aOR) and 95% confidence intervals (95%CI). Results Parents who used invasive ART had an increased risk of VACTERL in offspring (aOR 4.4 [95%CI 2.1-8.8]), whereas the increased risk for mothers with CLOPD could not be replicated. None of the case mothers had pregestational diabetes mellitus. Primiparity (1.5 [1.1-2.1]) and maternal pregestational overweight and obesity (1.8 [1.2-2.8] and 1.8 [1.0-3.4]) were associated with VACTERL. Consistent folic acid supplement use during the advised periconceptional period may reduce the risk of VACTERL (0.5 [0.3-1.0]). Maternal smoking resulted in an almost twofold increased risk of VACTERL. Conclusion We identified invasive ART, primiparity, pregestational overweight and obesity, lack of folic acid supplement use, and smoking as risk factors for VACTERL

Uncontrolled maternal chronic respiratory diseases in pregnancy: A new potential risk factor suggested to be associated with anorectal malformations in offspring

Background: Chronic respiratory diseases and use of antiasthmatic medication during pregnancy may both play a role in the etiology of congenital anorectal malformations (ARM). However, it is unclear, whether the medication use or the underlying condition would be responsible. Therefore, our aim was to unravel the role of maternal chronic respiratory diseases from that of antiasthmatic medication in the etiology of ARM. Methods: We obtained 412 ARM patients and 2,137 population-based controls from the Dutch AGORA data- and biobank. We used maternal questionnaires and follow-up telephone interviews to obtain information on chronic respiratory diseases, antiasthmatic medication use, and potential confounders. Multivariable logistic regression analyses were performed to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). RESULTS: We observed higher risk estimates among women with chronic respiratory diseases with and without medication use (1.4 [0.8–2.7] and 2.0 [0.8–5.0]), both in comparison to women without a chronic respiratory disease and without medication use. Furthermore, increased ORs of ARM were found for women using rescue medication (2.4 [0.8–7.3]) or a combination of maintenance and rescue medication (2.5 [0.9–6.7]). In addition, increased risk estimates were observed for women having nonallergic triggers (2.5 [1.0–6.3]) or experiencing exacerbations during the periconceptional period (3.5 [1.4–8.6]). CONCLUSIONS: Although the 95% CIs of most associations include the null value, the risk estimates all point towards an association between uncontrolled chronic respiratory disease, instead of antiasthmatic medication use, with ARM in offspring. Further in-depth studies towards mechanisms of this newly identified risk factor are warranted

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Cardiovascular health check in the elderly in one general practice

BACKGROUND: Prevention of cardiovascular disease in the elderly is becoming increasingly important. GPs are in a unique position to initiate preventive interventions in this age group. However, it is not clear which strategy a GP should follow to identify patients at increased cardiovascular risk-case finding or screening. OBJECTIVE: We aimed to assess the value of a single cardiovascular health check compared with a normal care case finding and to investigate the diagnostic or therapeutic consequences of detecting new cardiovascular risk indicators. METHODS: In 1991, 1002 persons aged 60 years and over, enlisted in one general practice, were invited. Of the 805 subjects who responded (80%), the cardiovascular risk profile was determined by a research physician. The proportion of newly detected cardiovascular risk indicators was the main outcome measure. A risk indicator was considered newly detected when it was not mentioned in the GP's summary of the patient record, which had been checked by the patient for its completeness. The patient records of participants with newly detected hypertension, diabetes or hypercholesterolaemia were systematically reviewed to detect diagnostic and therapeutic interventions by the GP. RESULTS: In 25.1% of the participants, one or more cardiovascular risk indicators were found which were previously unknown to the GP, including 38 (4.7%) cases of hypertension, 82 (10%) cases of isolated systolic hypertension, 14 (1.7%) cases of diabetes mellitus and 63 (7.8%) cases of hypercholesterolaemia. On the basis of these findings, the GP initiated therapeutic interventions in almost all subjects with newly detected diabetes. However, reports of newly detected hypertension or high cholesterol levels were usually not followed by an intervention. CONCLUSION: A single cardiovascular health check in the elderly can detect a considerable number of risk indicators that are unknown to a patient's GP. In most cases, however, the detection of hypertension or cholesterol > or = 6.5 mmol/l did not lead to interventions by the GP. More efforts are needed to ensure that the beneficial effects of these interventions are not limited to participants in clinical trials but can be extended to patients in general practice