Human genetics and molecular genomics of Chiari malformation type 1.

Chiari malformation type 1 (CM1) is the most common structural brain disorder involving the craniocervical junction, characterized by caudal displacement of the cerebellar tonsils below the foramen magnum into the spinal canal. Despite the heterogeneity of CM1, its poorly understood patho-etiology has led to a 'one-size-fits-all' surgical approach, with predictably high rates of morbidity and treatment failure. In this review we present multiplex CM1 families, associated Mendelian syndromes, and candidate genes from recent whole exome sequencing (WES) and other genetic studies that suggest a significant genetic contribution from inherited and de novo germline variants impacting transcription regulation, craniovertebral osteogenesis, and embryonic developmental signaling. We suggest that more extensive WES may identify clinically relevant, genetically defined CM1 subtypes distinguished by unique neuroradiographic and neurophysiological endophenotypes.

Risk assessment of 3-MCPD esters and glycidyl esters from the formulas for infants and young children up to 36 months of age.

Esters of 2-monochloropropane-1,2-diol (2-MCPD), 3- monochloropropane-1,2-diol (3-MCPD), and glycidol are present in infant formulas, follow-on foods and similar compositions. They arise mainly from the vegetable oil content and may cause harmful effects in consumers. The contents of these substances in formulas were determined indirectly by converting the esters to the free form, followed by derivatization and analysis by gas chromatography-tandem mass spectrometry (GC-MS/MS). The validation results demonstrate that the method had sufficient specificity and adequate accuracy. The limits of detection (LOD) and limits of quantification (LOQ) for each of 2-MCPDE, 3-MCPDE, and GE were 1.5 and 5 µg/kg, respectively. Formula intake by children up to 36 months of age was surveyed, and the data was used to assess the risks due to 3-MCPD esters (3-MCPDE) and glycidyl esters (GE). The mean exposure dose of 3-MCPDE for different age groups ranged from 0.51 to 1.13 µg/kg bw per day. The corresponding mean GE exposure ranged from 0.031 to 0.069 µg/kg bw per day. Neither mean values nor the percentile 95% values of 3-MCPDE exposure doses exceed the recommended provisional maximum tolerable daily intake (PMTDI).

Genetic dysregulation of an endothelial Ras signaling network in vein of Galen malformations.

To elucidate the pathogenesis of vein of Galen malformations (VOGMs), the most common and severe congenital brain arteriovenous malformation, we performed an integrated analysis of 310 VOGM proband-family exomes and 336,326 human cerebrovasculature single-cell transcriptomes. We found the Ras suppressor p120 RasGAP ( RASA1 ) harbored a genome-wide significant burden of loss-of-function de novo variants (p=4.79×10 -7 ). Rare, damaging transmitted variants were enriched in Ephrin receptor-B4 ( EPHB4 ) (p=1.22×10 -5 ), which cooperates with p120 RasGAP to limit Ras activation. Other probands had pathogenic variants in ACVRL1 , NOTCH1 , ITGB1 , and PTPN11 . ACVRL1 variants were also identified in a multi-generational VOGM pedigree. Integrative genomics defined developing endothelial cells as a key spatio-temporal locus of VOGM pathophysiology. Mice expressing a VOGM-specific EPHB4 kinase-domain missense variant exhibited constitutive endothelial Ras/ERK/MAPK activation and impaired hierarchical development of angiogenesis-regulated arterial-capillary-venous networks, but only when carrying a "second-hit" allele. These results illuminate human arterio-venous development and VOGM pathobiology and have clinical implications.

Target Capture Reveals the Complex Origin of Vietnamese Ginseng.

The global market of the medicinal plant ginseng is worth billions of dollars. Many ginseng species are threatened in the wild and effective sustainable development initiatives are necessary to preserve biodiversity at species and genetic level whilst meeting the demand for medicinal produce. This is also the case of Panax vietnamensis Ha & Grushv., an endemic and threatened ginseng species in Vietnam that is locally cultivated at different scales and has been the object of national breeding programs. To investigate the genetic diversity within cultivated and wild populations of P. vietnamensis we captured 353 nuclear markers using the Angiosperm-353 probe set. Genetic diversity and population structure were evaluated for 319 individuals of Vietnamese ginseng across its area of distribution and from wild and a varying range of cultivated areas. In total, 319 individuals were sampled. After filtering, 1,181 SNPs were recovered. From the population statistics, we observe high genetic diversity and high genetic flow between populations. This is also supported by the STRUCTURE analysis. The intense gene flow between populations and very low genetic differentiation is observed regardless of the populations' wild or cultivated status. High levels of admixture from two ancestral populations exist in both wild and cultivated samples. The high gene flow between populations can be attributed to ancient and on-going practices of cultivation, which exist in a continuum from understorey, untended breeding to irrigated farm cultivation and to trade and exchange activities. These results highlight the importance of partnering with indigenous peoples and local communities and taking their knowledge into account for biodiversity conservation and sustainable development of plants of high cultural value.

Quantification, serovars, and antibiotic resistance of salmonella isolated from retail raw chicken meat in Vietnam.

The objectives of this study were to quantify Salmonella counts on retail raw poultry meat in Vietnam and to phenotypically characterize (serovars and antibiotic resistance) the isolates. A total of 300 chicken carcasses were collected from two cities and two provinces in Vietnam. Salmonella counts on the samples were determined according to the most-probable-number (MPN) method of the U.S. Department of Agriculture, Food Safety and Inspection Service (USDA-FSIS). A total of 457 isolates were serotyped and tested for antibiotic susceptibility. Overall, 48.7% of chicken samples were Salmonella positive with a count of 2.0 log MPN per carcass. There were no significant differences (P > 0.05) in log MPN per carcass by the study variables (market type, storage condition, and chicken production system). There was a significant difference (P < 0.05) in Salmonella-positive prevalence by chicken production system. Among the 22 Salmonella serovars identified, Albany was the most frequent (34.1%), followed by Agona (15.5%) and Dabou (8.8%). Resistance to at least one antibiotic was common (i.e., 73.3%), with high resistance to tetracycline (59.1%) and ampicillin (41.6%). Resistance to three antibiotics was the most frequently found multidrug resistance profile (17.7%, n = 81); the profile that was resistant to the highest number of drugs was resistant to nine antibiotics (0.7%, n = 3). Only Salmonella Albany posed phenotypic resistance to ceftriaxone (a drug of choice to treat severe cases of salmonellosis). The data revealed that, whereas Salmonella prevalence on raw poultry was high (48.7%), counts were low, which suggests that the exposure risk to Salmonella is low. However, improper storage of raw chicken meat and cross-contamination may increase Salmonella cell counts and pose a greater risk for infection. These data may be helpful in developing risk assessment models and preventing the transmission of foodborne Salmonella from poultry to humans in Vietnam.

Prevalence of Salmonella on chicken carcasses from retail markets in Vietnam.

This study was conducted to estimate the prevalence of Salmonella on chicken carcasses collected from six regions in Vietnam. A total of 1,000 whole, dressed chicken carcasses were collected from five cities and seven provinces across the six regions in Vietnam. Of these, 900 samples were collected from wet markets and 100 from supermarkets. All samples were analyzed for the presence of Salmonella according to a method recommended by the U. S. Department of Agriculture, Food Safety and Inspection Service. The overall Salmonella prevalence was 45.9%. There was no significant difference (P > 0.05) in Salmonella prevalence by (i) location (Ha Noi city, 51.1%; Hai Phong city, 45.6%; Da Nang and Can Tho cities, 45.5%; Bac Ninh province and Ho Chi Minh city, 44.7%; Dong Nai province, 44.6%; Ha Tinh province, 44.4%; Phu Tho province, 43.8%; Lao Cai province, 43.5%; Kien Giang province, 41.9%; and Lam Dong province, 40.9%), (ii) market type (wet market, 46.2%; supermarket samples, 43.0%), and (iii) storage temperature at retail (ambient storage, 46.4%; chilled storage, 45.1%). Hence, Salmonella presence on poultry meat in Vietnam was not associated with a specific city or province, market type, or storage temperature at retail. Strategies to reduce Salmonella levels on raw poultry in Vietnam should be undertaken to improve the safety of poultry products and reduce the incidence of human salmonellosis from poultry consumption.