Adolescent Verbal Memory as a Psychosis Endophenotype: A Genome-Wide Association Study in an Ancestrally Diverse Sample

Verbal memory impairment is one of the most prominent cognitive deficits in psychosis. However, few studies have investigated the genetic basis of verbal memory in a neurodevelopmental context, and most genome-wide association studies (GWASs) have been conducted in European-ancestry populations. We conducted a GWAS on verbal memory in a maximum of 11,017 participants aged 8.9 to 11.1 years in the Adolescent Brain Cognitive Development Study®, recruited from a diverse population in the United States. Verbal memory was assessed by the Rey Auditory Verbal Learning Test, which included three measures of verbal memory: immediate recall, short-delay recall, and long-delay recall. We adopted a mixed-model approach to perform a joint GWAS of all participants, adjusting for ancestral background and familial relatedness. The inclusion of participants from all ancestries increased the power of the GWAS. Two novel genome-wide significant associations were found for short-delay and long-delay recall verbal memory. In particular, one locus (rs9896243) associated with long-delay recall was mapped to the NSF (N-Ethylmaleimide Sensitive Factor, Vesicle Fusing ATPase) gene, indicating the role of membrane fusion in adolescent verbal memory. Based on the GWAS in the European subset, we estimated the SNP-heritability to be 15% to 29% for the three verbal memory traits. We found that verbal memory was genetically correlated with schizophrenia, providing further evidence supporting verbal memory as an endophenotype for psychosis.

A novel ATPase gene, Ab-atps, plays an important role in the interaction of rice and white tip nematode, Aphelenchoides besseyi

Plant kinases containing the LysM domain play important roles in pathogen recognition and self-defense reactions. And it could recognize microbe-associated molecules including chitin and other polypeptides. The white tip nematode Aphelenchoides besseyi is a migratory parasitic nematode that infects plant shoots. It is distributed over almost all rice-producing areas and causes up to 50% economic losses. The rice OsRLK3 gene was a defense-related LysM kinase gene of rice. This study showed that the rice LysM kinase OsRLK3 could be induced by flg22, jasmonic acid, salicylic acid, and chitin. An interaction gene, Ab-atps from A. besseyi, was identified by screening the interaction between the rice gene OsRLK3 and an A. besseyi cDNA library using yeast two-hybrid screening. Ab-atps is a novel ATP synthase gene with a full length of 1341 bp, coding for 183 amino acids. The mRNA of Ab-atps was located in the esophagus and reproductive system of A. besseyi. The expression of Ab-atps was assessed at different developmental stages of the nematode and found to be the highest in the juvenile, followed by the egg, female, and male. Reproduction was significantly decreased in nematodes treated with Ab-atps double-stranded RNA (dsRNA) (p < 0.05). Transient expression experiments showed that Ab-ATPS-GFP was distributed in the nucleus, cytoplasm, and cell membrane, and Ab-ATPS-GFP triggered plant cell death. OsRLK3 was expressed significantly higher at 0.5 day and 1 day (p < 0.05) in rice plants inoculated with nematodes treated with Ab-atps dsRNA and gfp dsRNA for 0.5–7 days, respectively. Further, OsRLK3 expression under Ab-atps dsRNA treatment was significantly lower than with gfp dsRNA treatment at 0.5 day (p < 0.05) and significantly higher than with gfp dsRNA treatment at 1 day (p < 0.05). These results suggest that rice OsRLK3 could interact with A. besseyi Ab-atps, which plays an important role in growth, reproduction, and infection of the nematode. Our findings provide a theoretical basis to further understand the parasitic strategy of A. besseyi and its interaction mechanism with host plants, suggesting new ideas and targets for controlling A. besseyi.

RNA interference-mediated tolerance to whitefly (Bemisia tabaci) in genetically engineered tomato

Whitefly (Bemisia tabaci) is a polyphagous insect that causes huge damage in several horticultural crops, including tomato, by sucking nutrients from the phloem and transmitting viruses. Whiteflies are particularly difficult to manage and the use of chemicals remains the common practice, which causes the development of insecticidal resistance. Thus, there is considerable interest in the introduction of whitefly resistance by classical and molecular breeding. Here, we explored the concept of using an RNA interference construct to silence a v-ATPase gene in whiteflies interacting with transgenic tomato plants that express siRNA molecules corresponding to a fragment from the B. tabaci vATPase. PCR analyses revealed the presence of both ΔATPase and nptII transgenes in all transgenic lines. siRNA expressing lines were challenged against whitefly and revealed a mortality rate of 57.1% in transgenic line 4.4.1, while in the control the mortality was 7.6%. Mortality of 2nd instar nymphs was higher on the transgenic plants and the development of 3rd instar nymphs was slightly longer than on the control plants. Although the attraction of insects was not significantly different between treatments, the number of eggs laid by the insects on the transgenic plants was significantly lower, compared to the controls. RT-qPCR revealed a decreased expression level of endogenous v-ATPase gene in whiteflies feeding on transgenic plants. No unexpected effect was observed on the non-target insects Myzus persicae or Tuta absoluta. Results presented here may form the foundation for the generation of elite tomato varieties resistant to whitefly, a devastating insect pest.

The Effect of Eight Weeks of Training on Positive and Negative Slopes with Royal Jelly Consumption on MGMT and ATPase Gene Expression Levels in the Hippocampus Tissue of Trimethyltin-Induced Alzheimer’s Rats

Background: Alzheimer’s disease (AD) is a common disease in the elderly that is associated with impaired metabolism and biology of the hippocampus. Although the role of exercise and natural antioxidants in improving the disease has been reported, the role of muscle contraction-related physical activity along with royal jelly (RJ) consumption is not yet well understood. Objectives: This study aimed to investigate the effect of eight weeks of training on positive slope (ETPS) and negative slope (ETNS) with royal jelly (RJ) consumption on O-6-methylguanine DNA methyltransferase (MGMT) and ATPase gene expression levels in the hippocampus tissue of trimethyltin (TMT)-induced AD rats. Methods: In this experimental trial, 36 male Sprague-Dawley AD rats (induced with 8 mg/kg TMT) were divided into (1) control + normal saline/royal jelly solvent) (Sh); (2) ETPS; (3) ETNS; (4) ETPS + RJ; (5) ETNS + RJ, and (6) RJ groups. Six rats were placed in the healthy control (HC) group. Then the training groups trained on ( + 15 and -15) slopes for eight weeks, five sessions per week, and each session lasted 60 minutes at a speed of 16 m/min. The royal jelly (RJ) groups received 100 mg/kg royal jelly per day by intraperitoneal injection. Results: ETNS, ETPS, ETPS + RJ, and ETNS + RJ increased MGMT gene expression (P ≥ 0.05). ETPS and ETPS + RJ also increased ATPase gene expression (P ≥ 0.05). However, RJ had no significant effect on increasing MGMT and ATPase gene expression in the hippocampus tissue of AD rats (P ≥ 0.05). Conclusions: It seems that the improvement of DNA damage markers and energy levels depends on the type of contraction. Although training on positive and negative slopes with royal jelly consumption has an interactive effect on DNA repair markers, training on a positive slope and royal jelly consumption has an interactive effect on ATPase gene expression.

3, 5-Di-tert-butylphenol Combat Against Streptococcus Mutans Via Impedes Acidogenicity, Acidurance and Biofilm Formation

Streptococcus mutans is a common pathogen present in oral cavity and it cause dental caries for all aged group of people, in particular, children’s. S. mutans have several virulence factors such as acidogenecity, aciduricity, adhesion and biofilm formation. These virulence factors are working together and lead to initiate development of caries in tooth surface. The present study aimed to investigate the anticariogenic potential of 3, 5-Di-tert-butylphenol (3, 5-DTBP) against S. mutans. 3, 5-DTBP biofilm inhibitory concentration (BIC) was found at 100 µg/ml concentration without any lethal effect on the growth. Moreover, 3, 5- DTBP significantly reduced water soluble and water insoluble glucans production, in concurrence with downregulation of gtfBC genes. Moreover, acidogenicity associated virulence factors such as lactate dehydrogenase and enolase enzymatic production was arrested upon 3, 5-DTBP treatment. In addition, 3, 5-DTBP greatly reduced acidtolerance ability through impedes of F1F0-ATPase. Gene expression analysis unveiled the downregulation of gtfB, gtfC, gtfD, vicRK, comDE, gbpB, smu0630 and relA upon 3, 5-DTBP treatment. The present study paves the way for exhibiting 3, 5-DTBP as a promising therapeutic agent to control S. mutans infections.

Probing the Energetic Metabolism of Resting Cysts under Different Conditions from Molecular and Physiological Perspectives in the Harmful Algal Blooms-Forming Dinoflagellate Scrippsiella trochoidea

Energetic metabolism is essential in maintaining the viability of all organisms. Resting cysts play important roles in the ecology of dinoflagellates, particularly for harmful algal blooms (HABs)-causative species. However, the energetic metabolism underlying the germination potency maintenance of resting cysts of dinoflagellate have been extremely scarce in studies from physiological and, particularly, molecular perspectives. Therefore, we used the cosmopolitan Scrippsiella trochoidea as a representative of HABs-forming and cyst-producing dinoflagellates in this work to obtain novel insights into the molecular mechanisms, regulating the energetic metabolism in dinoflagellate resting cysts, under different physical condition. As the starting step, we established a cDNA subtractive library via suppression subtractive hybridization (SSH) technology, from which we screened an incomplete sequence for the β subunit of ATP synthase gene (β-F1-ATPase), a key indicator for the status of cell’s energetic metabolism. The full-length cDNA of β-F1-ATPase gene from S.trochoidea (Stβ-F1-ATPase) was then obtained via rapid amplification of cDNA ends (RACE) (Accession: MZ343333). Our real-time qPCR detections, in vegetative cells and resting cysts treated with different physical conditions, revealed that (1) the expression of Stβ-F1-ATPase in resting cysts was generally much lower than that in vegetative cells, and (2) the Stβ-F1-ATPase expressions in the resting cysts under darkness, lowered temperature, and anoxia, and during an extended duration of dormancy, were significantly lower than that in cysts under the condition normally used for culture-maintaining (a 12 h light:12 h dark cycle, 21 °C, aerobic, and newly harvested). Our detections of the viability (via Neutral Red staining) and cellular ATP content of resting cysts, at the conditions corresponding to the abovementioned treatments, showed that both the viability and ATP content decreased rapidly within 12 h and then maintained at low levels within the 4-day experimentation under all the three conditions applied (4 °C, darkness, and anoxia), which are well in accordance with the measurements of the transcription of Stβ-F1-ATPase. These results demonstrated that the energy consumption of resting cysts reaches a low, but somehow stable, level within a short time period and is lower at low temperature, darkness, and anoxia than that at ambient temperature. Our work provides an important basis for explaining that resting cysts survive long-term darkness and low temperature in marine sediments from molecular and physiological levels.

Genotypic and Phenotypic Characterization of Highly Alkaline-Resistant Carnobacterium maltaromaticum V-Type ATPase from the Dairy Product Based on Comparative Genomics

Although Carnobacterium maltaromaticum derived from dairy products has been used as a lactic acid bacterium industrially, several studies have reported potential pathogenicity and disease outbreaks. Because strains derived from diseased fish and dairy products are considered potentially virulent and beneficial, respectively, their genotypic and phenotypic characteristics have attracted considerable attention. A genome-wide comparison of 30 genome sequences (13, 3, and 14 strains from diseased aquatic animals, dairy products, and processed food, respectively) was carried out. Additionally, one dairy and two nondairy strains were incubated in nutrient-rich (diluted liquid media) and nutrient-deficient environments (PBS) at pH 10 to compare their alkaline resistance in accordance with different nutritional environments by measuring their optical density and viable bacterial cell counts. Interestingly, only dairy strains carried 11 shared accessory genes, and 8 genes were strongly involved in the V-type ATPase gene cluster. Given that V-type ATPase contributes to resistance to alkaline pH and salts using proton motive force generated via sodium translocation across the membrane, C. maltaromaticum with a V-type ATPase might use nutrients in food under high pH. Indeed, the dairy strain carrying the V-type ATPase exhibited the highest alkaline resistance only in the nutrient-rich environment with significant upregulation of V-type ATPase expression. These results suggest that the gene cluster of V-type ATPase and increased alkaline resistance of dairy strains facilitate adaptation in the long-term ripening of alkaline dairy products.

Plasma Membrane H+-ATPase SmPHA4 Negatively Regulates the Biosynthesis of Tanshinones in Salvia miltiorrhiza

Salvia miltiorrhiza Bunge has been widely used in the treatment of cardiovascular and cerebrovascular diseases, due to the pharmacological action of its active components such as the tanshinones. Plasma membrane (PM) H+-ATPase plays key roles in numerous physiological processes in plants. However, little is known about the PM H+-ATPase gene family in S. miltiorrhiza (Sm). Here, nine PM H+-ATPase isoforms were identified and named SmPHA1–SmPHA9. Phylogenetic tree analysis showed that the genetic distance of SmPHAs was relatively far in the S. miltiorrhiza PM H+-ATPase family. Moreover, the transmembrane structures were rich in SmPHA protein. In addition, SmPHA4 was found to be highly expressed in roots and flowers. HPLC revealed that accumulation of dihydrotanshinone (DT), cryptotanshinone (CT), and tanshinone I (TI) was significantly reduced in the SmPHA4-OE lines but was increased in the SmPHA4-RNAi lines, ranging from 2.54 to 3.52, 3.77 to 6.33, and 0.35 to 0.74 mg/g, respectively, suggesting that SmPHA4 is a candidate regulator of tanshinone metabolites. Moreover, qRT-PCR confirmed that the expression of tanshinone biosynthetic-related key enzymes was also upregulated in the SmPHA4-RNAi lines. In summary, this study highlighted PM H+-ATPase function and provided new insights into regulatory candidate genes for modulating secondary metabolism biosynthesis in S. miltiorrhiza.

Homology between the flagellar export apparatus and ATP synthetase: evidence from synteny predating the Last Universal Common Ancestor

Evidence of homology between proteins in the ATP synthetase and the bacterial flagellar motor (BFM) has been accumulating since the 1980s. Specifically, the BFM’s Type 3 Secretion System (T3SS) export apparatus FliH, FliI, and FliJ are considered homologous to FO-b + F1-δ, F1-α/β, and F1-γ, and have similar structure and interactions. We review the discoveries that advanced the homology hypothesis and then conduct a further test by examining gene order in the two systems and their relatives. Conservation of gene order, or synteny, is often observed between closely related prokaryote species, but usually degrades with phylogenetic distance. As a result, observed conservation of synteny over vast phylogenetic distances can be evidence of shared ancestral coexpression, interaction, and function. We constructed a gene order dataset by examining the order of fliH, fliI, and fliJ genes across the phylogenetic breadth of flagellar and nonflagellar T3SS. We compared this to published surveys of gene order in the F1FO-ATP synthetase, its N-ATPase relatives, and the bacterial/archaeal V- and A-type ATPases. Strikingly, the fliHIJ gene order was deeply conserved, with the few exceptions appearing derived, and exactly matching the widely conserved F-ATPase gene order atpFHAG, coding for subunits b-δ-α-γ. The V/A-type ATPases have a similar conserved gene order shared for homologous components. Our results further strengthen the argument for homology between these systems, and suggest a rare case of synteny conserved over billions of years, dating back to well before the Last Universal Common Ancestor (LUCA).