Spatiotemporal Changes in Plasmodium vivax msp142 Haplotypes in Southern Mexico: From the Control to the Pre-Elimination Phase

For 20 years, Plasmodium vivax has been the only prevalent malaria species in Mexico, and cases have declined significantly and continuously. Spatiotemporal genetic studies can be helpful for understanding parasite dynamics and developing strategies to weaken malaria transmission, thus facilitating the elimination of the parasite. The aim of the current contribution was to analyze P. vivax-infected blood samples from patients in southern Mexico during the control (1993–2007) and pre-elimination phases (2008–2011). Nucleotide and haplotype changes in the pvmsp142 fragment were evaluated over time. The majority of multiple genotype infections occurred in the 1990s, when the 198 single nucleotide sequences exhibited 57 segregating sites, 64 mutations, and 17 haplotypes. Nucleotide and genetic diversity parameters showed subtle fluctuations from across time, in contrast to the reduced haplotype diversity and the increase in the R2 index and Tajima’s D value from 2008 to 2011. The haplotype network consisted of four haplogroups, the geographical distribution of which varied slightly over time. Haplogroup-specific B-cell epitopes were predicted. Since only high-frequency and divergent haplotypes persisted, there was a contraction of the parasite population. Given that 84% of haplotypes were exclusive to Mesoamerica, P. vivax flow is likely circumscribed to this region, representing important information for parasite surveillance.

KIAA0319 influences cilia length, cell migration and mechanical cell–substrate interaction

Following its association with dyslexia in multiple genetic studies, the KIAA0319 gene has been extensively investigated in different animal models but its function in neurodevelopment remains poorly understood. We developed the first human cellular knockout model for KIAA0319 in RPE1 retinal pigment epithelia cells via CRISPR-Cas9n to investigate its role in processes suggested but not confirmed in previous studies, including cilia formation and cell migration. We observed in the KIAA0319 knockout increased cilia length and accelerated cell migration. Using Elastic Resonator Interference Stress Microscopy (ERISM), we detected an increase in cellular force for the knockout cells that was restored by a rescue experiment. Combining ERISM and immunostaining we show that RPE1 cells exert highly dynamic, piconewton vertical pushing forces through actin-rich protrusions that are surrounded by vinculin-rich pulling sites. This protein arrangement and force pattern has previously been associated to podosomes in other cells. KIAA0319 depletion reduces the fraction of cells forming these actin-rich protrusions. Our results suggest an involvement of KIAA0319 in cilia biology and cell–substrate force regulation.

The heritability of BMI varies across the range of BMI: a heritability curve analysis in a twin cohort

The heritability of traits such as body mass index (BMI), a measure of obesity, is generally estimated using family, twin, and increasingly by molecular genetic approaches. These studies generally assume that genetic effects are uniform across all trait values, yet there is emerging evidence that this may not always be the case. This paper analyzes twin data using a recently developed measure of heritability called the heritability curve. Under the assumption that trait values in twin pairs are governed by a flexible Gaussian mixture distribution, heritability curves may vary across trait values. The data consist of repeated measures of BMI on 1506 monozygotic (MZ) and 2843 like-sexed dizygotic (DZ) adult twin pairs, gathered from multiple surveys in older Finnish Twin Cohorts. The heritability curve and BMI value-specific MZ and DZ pairwise correlations were estimated, and these varied across the range of BMI. MZ correlations were highest at BMI values from 21 to 24, with a stronger decrease for women than for men at higher values. Models with additive and dominance effects fit best at low and high BMI values, while models with additive genetic and common environmental effects fit best in the normal range of BMI. Thus, we demonstrate that twin and molecular genetic studies need to consider how genetic effects vary across trait values. Such variation may reconcile findings of traits with high heritabilities and major differences in mean values between countries or over time.

DAF-2c signaling promotes taste avoidance after starvation in Caenorhabditis elegans by controlling distinct phospholipase C isozymes

Previously, we reported that DAF-2c, an axonal insulin receptor isoform in Caenorhabditis elegans, acts in the ASER gustatory neuron to regulate taste avoidance learning, a process in which worms learn to avoid salt concentrations experienced during starvation. Here, we show that secretion of INS-1, an insulin-like peptide, after starvation conditioning is sufficient to drive taste avoidance via DAF-2c signaling. Starvation conditioning enhances the salt-triggered activity of AIA neurons, the main sites of INS-1 release, which potentially promotes feedback signaling to ASER to maintain DAF-2c activity during taste avoidance. Genetic studies suggest that DAF-2c–Akt signaling promotes high-salt avoidance via a decrease in PLCβ activity. On the other hand, the DAF-2c pathway promotes low-salt avoidance via PLCε and putative Akt phosphorylation sites on PLCε are essential for taste avoidance. Our findings imply that animals disperse from the location at which they experience starvation by controlling distinct PLC isozymes via DAF-2c.

Cryopreservation of Anopheles stephensi embryos

The ability to cryopreserve mosquitoes would revolutionize work on these vectors of major human infectious diseases by conserving stocks, new isolates, lab-bred strains, and transgenic lines that currently require continuous life cycle maintenance. Efforts over several decades to develop a method for cryopreservation have, until now, been fruitless: we describe here a method for the cryopreservation of Anopheles stephensi embryos yielding hatch rates of ~ 25%, stable for > 5 years. Hatched larvae developed into fertile, fecund adults and blood-fed females, produced fully viable second generation eggs, that could be infected with Plasmodium falciparum at high intensities. The key components of the cryopreservation method are: embryos at 15–30 min post oviposition, two incubation steps in 100% deuterated methanol at − 7 °C and − 14.5 °C, and rapid cooling. Eggs are recovered by rapid warming with concomitant dilution of cryoprotectant. Eggs of genetically modified A. stephensi and of A. gambiae were also successfully cryopreserved. This enabling methodology will allow long-term conservation of mosquitoes as well as acceleration of genetic studies and facilitation of mass storage of anopheline mosquitoes for release programs.

Sample management: a primary critical starting point for successful omics studies

Biological samples collected from cohort studies are widely utilized in molecular genetic studies and are typically stored long term for future applications, such as omics analyses. The extent of sample availability is determined by proper sample handling, and it is of primary importance for successful omics studies. However, questions on whether samples in long-term storage are properly available for omics experiments has been raised, because the quality and availability of such samples remain unknown until their actual utilization. In that perspective, several guidelines for proper sample management have been suggested. In addition, several researchers assessed how improper management damages sample using mock sample and suggested a set of requirements for sample handling. In this review, we present several considerations for sample handling eligible for omics studies. Focusing on birth cohorts, we describe the types of samples collected from which omics data were generated. This review ultimately aims to provide proper guidelines for sample handling for successful human omics studies.

Mechanism of pyridoxine 5'-phosphate accumulation in PLPBP protein-deficiency

The pyridoxal 5'-phosphate (PLP)-binding protein (PLPBP) plays an important role in vitamin B 6 homeostasis. Loss of this protein in organisms such as Escherichia coli and humans disrupts the vitamin B 6 pool and induces intracellular accumulation of pyridoxine 5'-phosphate (PNP), which is normally undetectable in wild-type cells. The accumulated PNP could affect diverse metabolic systems through inhibition of some PLP-dependent enzymes. In this study, we investigated the as yet unclear mechanism of intracellular accumulation of PNP by the loss of PLPBP protein encoded by yggS in E. coli . Genetic studies using several PLPBP-deficient strains of E. coli lacking known enzyme(s) in the de novo or salvage pathway of vitamin B 6 , which includes pyridoxine (amine) 5'-phosphate oxidase (PNPO), PNP synthase, pyridoxal kinase, and pyridoxal reductase, demonstrated that neither the flux from the de novo pathway nor the salvage pathway solely contributed to the PNP accumulation caused by the PLPBP mutation. Studies with the strains lacking both PLPBP and PNPO suggested that PNP shares the same pool with PMP, and showed that PNP levels are impacted by PMP levels and vice versa . We show that disruption of PLPBP lead to perturb PMP homeostasis, which may result in PNP accumulation in the PLPBP-deficient strains. Importance A PLP-binding protein PLPBP from the conserved COG0325 family has recently been recognized as a key player in vitamin B 6 homeostasis in various organisms. Loss of PLPBP disrupts vitamin B 6 homeostasis and perturbs diverse metabolisms, including amino acid and α-keto acid metabolism. Accumulation of PNP is a characteristic phenotype of the PLPBP deficiency and is suggested to be a potential cause of the pleiotropic effects, but the mechanism of the PNP accumulation was poorly understood. In this study, we show that fluxes for PNP synthesis/metabolism are not responsible for the accumulation of PNP. Our results indicate that PLPBP is involved in the homeostasis of pyridoxamine 5'-phosphate, and its disruption may lead to the accumulation of PNP in PLPBP-deficiency.

A new case of scalp angiosarcoma revealed by eyelid edema

Cutaneous angiosarcoma is a rare and highly aggressive neoplasm with poor prognosis. Owing to its variable presentation, it may be a challenging clinical and histological diagnosis. Herein, we describe a particular case of cutaneous angiosarcoma of the head and neck in a 71-year-old male with skin type V who presented with solid, progressive eyelid edema. A histological examination of skin biopsies first concluded cutaneous metastasis of an undifferentiated carcinomatous tumor. Immunostaining was essential to reach the correct diagnosis. The treatment of cutaneous angiosarcoma remains unsatisfactory. We sincerely hope that the prognosis of cutaneous angiosarcoma will be improved with the use of targeted therapies based on current genetic studies as it has been for melanoma.

Genetic Structure and Forensic Feature of 38 X-Chromosome InDels in the Henan Han Chinese Population

Insertion/deletion (InDel) polymorphisms, as ideal forensic markers, show useful characteristics of both SNPs and STRs, such as low mutation rate, short amplicon size and general applicability of genotyping platform, and have been used in human identification, population genetics and biogeographic research in recent years. X-chromosome genetic markers are significant in population genetic studies and indispensable complements in some complex forensic cases. However, the population genetic studies of X-chromosome InDel polymorphisms (X-InDels) still need to be explored. In this study, the forensic utility of a novel panel including 38 X-InDel markers was evaluated in a sample of Han population from Henan province in China. It is observed that the heterozygosities ranged from 0.0054 to 0.6133, and the combined discrimination power was 1–9.18 × 10−17 for males and 1–7.22 × 10−12 for females respectively. The mean exclusion chance in trios and duos were 0.999999319 and 0.999802969 respectively. Multiple biostatistics methods, such as principal component analysis, genetic distances analysis, phylogenetic reconstruction, and structure analysis was used to reveal the genetic relationships among the studied Henan Han group and other 26 reference groups from 1,000 Genomes Project. As expected, the Henan Han population was clustered with East Asian populations, and the most intimate genetic relationships existed in three Han Chinese populations from Henan, Beijing and South China, and showed significant differences compared with other continental groups. These results confirmed the suitability of the 38 X-InDel markers both in individual identification and parentage testing in Han Chinese population, and simultaneously showed the potential application in population genetics.