Background
Genetic association studies for gastroschisis have highlighted several candidate variants. However, genetic basis in gastroschisis from noninvestigated heritable factors could provide new ...insights into the human biology for this birth defect. We aim to identify novel gastroschisis susceptibility variants by employing whole exome sequencing (WES) in a Mexican family with recurrence of gastroschisis.
Methods
We employed WES in two affected half‐sisters with gastroschisis, mother, and father of the proband. Additionally, functional bioinformatics analysis was based on SVS–PhoRank and Ensembl–Variant Effect Predictor. The latter assessed the potentially deleterious effects (high, moderate, low, or modifier impact) from exome variants based on SIFT, PolyPhen, dbNSFP, Condel, LoFtool, MaxEntScan, and BLOSUM62 algorithms. The analysis was based on the Human Genome annotation, GRCh37/hg19. Candidate genes were prioritized and manually curated based on significant phenotypic relevance (SVS–PhoRank) and functional properties (Ensembl–Variant Effect Predictor). Functional enrichment analysis was performed using ToppGene Suite, including a manual curation of significant Gene Ontology (GO) biological processes from functional similarity analysis of candidate genes.
Results
No single gene‐disrupting variant was identified. Instead, 428 heterozygous variations were identified for which SPATA17, PDE4DIP, CFAP65, ALPP, ZNF717, OR4C3, MAP2K3, TLR8, and UBE2NL were predicted as high impact in both cases, mother, and father of the proband. PLOD1, COL6A3, FGFRL1, HHIP, SGCD, RAPGEF1, PKD1, ZFHX3, BCAS3, EVPL, CEACAM5, and KLK14 were segregated among both cases and mother. Multiple interacting background modifiers may regulate gastroschisis susceptibility. These candidate genes highlight a role for development of blood vessel, circulatory system, muscle structure, epithelium, and epidermis, regulation of cell junction assembly, biological/cell adhesion, detection/response to endogenous stimulus, regulation of cytokine biosynthetic process, response to growth factor, postreplication repair/protein K63‐linked ubiquitination, protein‐containing complex assembly, and regulation of transcription DNA‐templated.
Conclusion
Considering the likely gene‐disrupting prediction results and similar biological pattern of mechanisms, we propose a joint “multifactorial model” in gastroschisis pathogenesis.
Heritable factors for gastroschisis have remained unexplained as the low‐frequency and rare variants have not yet been explored. Technological platforms such as NGS and WES could help in the understanding of the biological basis for gastroschisis. We identified multiple novel susceptibility genes involved in crucial GO biological processes possibly underlying gastroschisis. A joint “multifactorial model” is proposed for gastroschisis that might impact the normal ventral body wall closure as well as gastroschisis developmental process.
A geophysical and geochemical study was carried out in the Maneadero aquifer, Baja California, Mexico, with the aim of identifying potential recharge locations for reclaimed water (RW). This coastal ...aquifer shows a significant decline in water quality, both as a result of salinization and the pollution by nitrates. Total dissolved solids (TDS) in an extreme case increased from 4 g l⁻¹ in 2000 to 27 g l⁻¹ in 2011. Nitrate as N–NO₃, reaches 46 mg l⁻¹. Based on their geochemistry and location, four water-quality zones are identified: (a) fresh water with TDS ≈ 1 g l⁻¹ in the upper creeks, (b) mixture between seawater and freshwater in the coast-proximal sections, (c) water significantly enriched in nitrate below and adjacent to the town of Maneadero, and (d) brackish water with no signs of current interaction with freshwater. The 3D geophysics identifies the influence of modern recharge areas and also buried flow-paths down to at least 30 m depth. The locations best suitable for aquifer recharge are those with equal or higher TDS concentrations (>2.5 g l⁻¹) than RW, which are located at the brackish water zone and/or at the coastal limits of the mixing zones.
Skin wound repair requires the development of different kinds of biomaterials that must be capable of restoring the damaged tissue. Type I collagen and chitosan have been widely used to develop ...scaffolds for skin engineering because of their cell-related signaling properties such as proliferation, migration, and survival. Collagen is the major component of the skin extracellular matrix (ECM), while chitosan mimics the structure of the native polysaccharides and glycosaminoglycans in the ECM. Chitosan and its derivatives are also widely used as drug delivery vehicles since they are biodegradable and noncytotoxic. Regulation of the inflammatory response is crucial for wound healing and tissue regeneration processes; and, consequently, the development of biomaterials such as hydrogels with anti-inflammatory properties is very important and permissive for the growth of cells. In the last years, it has been shown that mesenchymal stem cells have clinical importance in the treatment of different pathologies, for example, skin injuries. In this paper, we describe the anti-inflammatory activity of collagen type 1/chitosan/dexamethasone hydrogel, which is permissive for the culture of human adipose-derived mesenchymal stem cells (hADMSC). Our results show that hADMSC cultured in the hydrogel are viable, proliferate, and secrete the anti-inflammatory cytokine interleukin-10 (IL-10) but not the inflammatory cytokine Tumor Necrosis Factor-alpha (TNF-α).
Familial hypercholesterolemia (FH) remains underdiagnosed and undertreated.
Report the results of the first years (2017-2019) of the Mexican FH registry.
There are 60 investigators, representing 28 ...federal states, participating in the registry. The variables included are in accordance with the European Atherosclerosis Society (EAS) FH recommendations.
To date, 709 patients have been registered, only 336 patients with complete data fields are presented. The mean age is 50 (36-62) years and the average time since diagnosis is 4 (IQR: 2-16) years. Genetic testing is recorded in 26.9%. Tendon xanthomas are present in 43.2%. The prevalence of type 2 diabetes is 11.3% and that of premature CAD is 9.8%. Index cases, male gender, hypertension and smoking were associated with premature CAD. The median lipoprotein (a) level is 30.5 (IQR 10.8-80.7) mg/dl. Statins and co-administration with ezetimibe were recorded in 88.1% and 35.7% respectively. A combined treatment target (50% reduction in LDL-C and an LDL-C <100 mg/dl) was achieved by 13.7%. Associated factors were index case (OR 3.6, 95%CI 1.69-8.73, P = .002), combination therapy (OR 2.4, 95%CI 1.23-4.90, P = .011), type 2 diabetes (OR 2.8, 95%CI 1.03-7.59, P = .036) and age (OR 1.023, 95%CI 1.01-1.05, P = .033).
The results confirm late diagnosis, a lower than expected prevalence and risk of ASCVD, a higher than expected prevalence of type 2 diabetes and undertreatment, with relatively few patients reaching goals. Recommendations include, the use of combination lipid lowering therapy, control of comorbid conditions and more frequent genetic testing in the future.
•Familial hypercholesterolemia remains underdiagnosed and undertreated in Mexico.•We present the results of the Mexican Familial Hypercholesterolemia Registry.•Over 60 investigators in 28 federal states participated in the registry.•We discuss the findings and challenges to overcome in this population.
Sediment cores from the Colorado River (CR) remnant delta were used to assess the changing sedimentation and pollutant deposition processes in response to extensive human manipulation of the river. ...The cores are formed of alternating layers of clays and silts, with isolated sandy horizons. The clayey units are interpreted as periods of flood flows into this low gradient and meandering estuary after dam construction in the United States. The geochemistry of these sediments is particular because of the association of MnO with CaO rather than with the Fe₂O₃-rich clays. Past pollution of the CR delta by As, and probably also Pb and Cu, is recorded in some cores. Enrichment factors (EFs) >1 for these elements and their statistical association suggest anthropogenic inputs. The most likely sources for these element enrichments (especially As) are the arsenate-based pesticides used intensively in the area during the first half of the 20th century. The transport of these elements from the nearby agricultural lands into the present river reaches appears to have been driven in part by flooding events of the CR. Flushing by river and tide flows appear to be responsible of a lower pollutant deposition in the CR compared to the adjacent Hardy River (HR). Arsenic in the buried clay units of the HR has concentrations above the probable toxic effect level (PEL) for dwelling organisms, with maximum concentrations of 30 μg g⁻¹. Excess ²¹⁰Pb activities (²¹⁰Pbxs) indicate that fluxes of this unsupported atmospheric isotope were not constant in this estuarine environment. However, the presence of ²¹⁰Pbxs does indicate that these sediments accumulated during the last ~100 years. Aproximate sediment ages were estimated from the correlation of historic flooding events with the interpretation of the stratigraphic record. They are in fair agreement with the reported onset of DDT metabolites at the bottom of one core.
BACKGROUND Ellis-van Creveld syndrome is an autosomal recessive chondro-ectodermal dysplasia characterized by disproportionate short stature, limb shortening, narrow chest, postaxial polydactyly and ...dysplastic nails and teeth. In addition, 60% of cases present congenital heart defects. Ellis-van Creveld syndrome is predominantly caused by mutations in the EVC or EVC2 (4p16) genes, with only a few cases caused by mutations in WDR35. CASE REPORT Here, we report on two Mexican families with patients diagnosed with Ellis-van Creveld syndrome. Family 1 includes four patients: three females of 15, 18, and 23 years of age and a 7-year old male. Family 2 has only one affected newborn male. All patients exhibited multiple features including hypodontia, dysplastic teeth, extra frenula, mild short stature, distal limb shortening, postaxial polydactyly of hands and feet, nail dystrophy, and knee joint abnormalities. Only two patients had an atrial septal defect. In all cases, molecular analysis by Sanger sequencing identified the same homozygous mutation in exon 12 of EVC, c.1678G>T, which leads to a premature stop codon. CONCLUSIONS The mutation c.1678G>T has been previously reported in another Mexican patient and it appears to be a recurrent mutation in Mexico which could represent a founder mutation. The large number of patients in this case allows the clinical variability and spectrum of manifestations present in individuals with Ellis-van Creveld syndrome even if they carry the same homozygous mutation in a same family.
Brown widow spider (BrWS) (
Latrodectus geometricus) venom produces intense systemic reactions such as cramps, harsh muscle nociceptive, nauseas, vomiting and hypertension. The proposed pathogenic ...mechanisms resulting in these accidents have principally been damages occurring at the nervous system. However, it is suspected that there is also damage of the adrenal glands, as a result of the experimental animal's clinical manifestations, which developed symptoms compatible with acute adrenal insufficiency. We have currently found that the adrenal gland is damaged by this venom gland homogenates (VGH) producing severe alterations on cortex cells resulting in death by acute adrenal insufficiency. In general, the ultrastructural study on the glands of mice under transmission electronic microscopy observations showed alterations in the majority of the intracellular membranes within 3 to 24
h. BrWSVGH also showed specific actions on extracellular matrix proteins such as fibronectin, laminin and fibrinogen. In addition, zymogram experiments using gelatin as substrates detected gelatinolytic activity. The molecular exclusion fractionation of crude BrWSVGH resulted in 15 fractions, of which F1 and F2 presented α/β-fibrinogenase and fibronectinolytic activities. Fractions F6, F14 and F15 showed only α-fibrinogenase activity; in contrast, the gelatinolytic action was only observed in fraction F11. Only metalloproteinase inhibitors abolished all these proteolytic activities. Our results suggest that adrenal cortex lesions may be relevant in the etiopathogenesis of severe brown widow spider envenoming. To our knowledge, this is the first report on adrenal gland damages, fibrinogenolytic activity and interrelations with cell-matrix adhesion proteins caused by
L.
geometricus VGH. The venom of this spider could be inducing hemostatic system damages on envenomed patients.
El presente artículo describe los fundamentos de los sistemas para dataciones radiométricas de procesos geológicos y ambientales ocurridos en el Cuaternario tardío (<500000 años), ...específicamente14C,210Pb y238U-234U-230Th. Se presenta al lector sobre los distintos tipos de especimenes que son susceptibles de ser fechados, así como las distintitas ventajas y limitaciones de cada uno de los sistemas geocronológicos.
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