Association between salivary flow rate and depressive symptoms with adjustment for genetic and family environmental factors in Japanese twin study

Clinical Oral Investigations - The association between salivary flow rate (SFR) and depressive symptoms have been inconclusive. The present study aimed to investigate the association between SFR...     

Tissue nonautonomous effects of fat body methionine metabolism on imaginal disc repair in Drosophila

Regulatory mechanisms for tissue repair and regeneration within damaged tissue have been extensively studied. However, the systemic regulation of tissue repair remains poorly understood. To elucidate tissue nonautonomous control of repair process, it is essential to induce local damage, independent of genetic manipulations in uninjured parts of the body. Herein, we develop a system in Drosophila for spatiotemporal tissue injury using a temperature-sensitive form of diphtheria toxin A domain driven by the Q system to study factors contributing to imaginal disc repair. Using this technique, we demonstrate that methionine metabolism in the fat body, a counterpart of mammalian liver and adipose tissue, supports the repair processes of wing discs. Local injury to wing discs decreases methionine and S-adenosylmethionine, whereas it increases S-adenosylhomocysteine in the fat body. Fat body-specific genetic manipulation of methionine metabolism results in defective disc repair but does not affect normal wing development. Our data indicate the contribution of tissue interactions to tissue repair in Drosophila, as local damage to wing discs influences fat body metabolism, and proper control of methionine metabolism in the fat body, in turn, affects wing regeneration.Tissue repair is the necessary ability of an organism to maintain tissue homeostasis. The self-repair mechanisms of injured tissues have been extensively studied (1, 2). The homeostatic mechanisms of tissue repair, on the other hand, are not confined to the damaged tissues, but rather involve organismal regulation with contributions from multiple systems, including the circulatory, nervous, and endocrine systems. The importance of interactions between damaged tissue and other tissues has been suggested. For example, nerve-derived factor is essential for limb regeneration in the newt and axolotl (3, 4). Studies of parabiosis, the fusion of two organisms that consequently share a vascular system, revealed that regenerative ability was affected by internal environmental conditions based on the circulation of body fluids (5, 6). However, the molecular mechanisms of tissue nonautonomous regulation of the repair process are only beginning to be understood.Drosophila is a useful model animal for studying tissue interactions because of the availability of tissue-specific gene manipulation systems, such as the Gal4/Upstream Activation Sequence (UAS) system (7) or the Q system (8, 9). In Drosophila larvae, the epithelial sheets of imaginal discs are known to have a remarkable ability to repair massive tissue damage. A classic example is their regenerative capacity following surgical ablation (10–12). To overcome the technical difficulties of surgical ablation/regeneration experiments, a system was established for studying imaginal discs repair following genetic ablation, using a Gal4/UAS/Gal80^ts system (13). Despite the great advantages provided by this system, the use of Gal80^ts limits the manipulation of genes with UAS constructs to only the ablating cells at the time of ablation. One strategy for overcoming this problem is to conduct tissue ablation independent of the Gal4/UAS/Gal80^ts system, which allows for utilization of the Gal4/UAS system to manipulate gene expression in uninjured parts of the body. In the present study, we established a cell ablation system using a temperature-sensitive form of the diphtheria toxin A domain (DtA^ts) (14). It has been demonstrated that DtA^ts is active at low temperatures (18 °C) and induces cell death through nuclease activity, but is inactivated at high temperatures (29 °C) (14, 15). Inducing DtA^ts expression by using the Q system enabled us to manipulate Gal4/UAS-mediated gene expression in other organs, independent of the temporal tissue damage in wing discs.Several studies using Drosophila have demonstrated that damaged tissues send signals to surrounding tissues. Cytokine signaling from UV-damaged epidermal cells mediates nociceptive sensitization in larvae (16). Disc injury caused by aseptic wounds leads to production of Unpaired 3 (Upd3), an IL-6 like cytokine in the hemocytes and fat body, which triggers hemocyte proliferation, probably to accelerate clearance of injured cells (17). Hemocyte ablation, however, had no effect on wound closure in the injured larval epidermis (18), raising the question in terms of the functional contribution of hemocytes to tissue repair. In addition, damaged imaginal discs secrete Drosophila insulin-like peptide 8 (Dilp8), which inhibits ecdysone biosynthesis in the ring gland and arrests developmental processes, probably to gain time for repair (19, 20).We previously revealed that local necrosis in adult wings resulted in reduced levels of systemic S-adenosylmethionine (SAM) through the up-regulation of glycine N-methyltransferase (gnmt) in the fat body (21). This report is an example of systemic regulation of SAM metabolism in the fat body on epithelial damage. SAM is a metabolite present in all living cells; it plays various roles, including that of a precursor for transmethylation, transsulfuration, and polyamine biosynthesis (22). It is produced by sole SAM synthase (Sams) from the essential amino acid methionine (Met) and ATP, and SAM levels are strongly regulated by Gnmt in Drosophila fat body (21, 22). Gnmt consumes excess SAM and produces S-adenosylhomocysteine (SAH), which is further metabolized to homocysteine (Hcy). Changes in SAM levels in response to necrotic tissue led us to hypothesize that tissue damage in larval discs also affects methionine metabolism in the fat body, which turned out to be the case in the present study using DtA^ts-ablation system. We further tested whether the modulation of methionine metabolism in the fat body could affect imaginal disc repair in a tissue nonautonomous manner. Our study indicated that proper control of methionine metabolism in the fat body is crucial for repair of wing discs, highlighting the significance of systemic regulation for epithelial tissue repair.     

The relationship between body mass index and uric acid: a study on Japanese adult twins

Objectives

The present study aimed to investigate the association between body mass index (BMI) and uric acid (UA) using the twin study methodology to adjust for genetic factors.

Methods

The association between BMI and UA was investigated in a cross-sectional study using data from both monozygotic and dizygotic twins registered at the Osaka University Center for Twin Research and the Osaka University Graduate School of Medicine. From January 2011 to March 2014, 422 individuals participated in the health examination. We measured height, weight, age, BMI, lifestyle habits (Breslow’s Health Practice Index), serum UA, and serum creatinine. To investigate the association between UA and BMI with adjustment for the clustering of a twin within a pair, individual-level analyses were performed using generalized linear mixed models (GLMMs). To investigate an association with adjustment for genetic and family environmental factors, twin-pair difference values analyses were performed.

Results

In all analysis, BMI was associated with UA in men and women. Using the GLMMs, standardized regression coefficients were 0.194 (95 % confidence interval: 0.016–0.373) in men and 0.186 (95 % confidence interval: 0.071–0.302) in women. Considering twin-pair difference value analyses, standardized regression coefficients were 0.333 (95 % confidence interval: 0.072–0.594) in men and 0.314 (95 % confidence interval: 0.151–0.477) in women.

Conclusions

The present study shows that BMI was significantly associated with UA, after adjusting for both genetic and familial environment factors in both men and women.     

Association between subjective memory complaints and depressive symptoms after adjustment for genetic and family environmental factors in a Japanese twin study

Objectives

The aim of this study was to investigate the association between subjective memory complaints (SMCs) and depressive symptoms, with and without adjustment for genetic and family environmental factors.

Methods

We conducted a cross-sectional study using twins and measured SMCs and depressive symptoms as outcomes and explanatory variables, respectively. First, we performed regression analyses using generalized estimating equations to investigate the associations between SMCs and depressive symptoms without adjustment for genetic and family environmental factors (individual-level analyses). We then performed regression analyses for within-pair differences using monozygotic (MZ) and dizygotic (DZ) twin pairs and MZ twin pairs to investigate these associations with adjustment for genetic and family environmental factors by subtracting the values of one twin from those of co-twin variables (within-pair level analyses). Therefore, differences between the associations at individual- and within-pair level analyses suggested confounding by genetic factors.

Results

We included 556 twins aged ≥20 years. In the individual-level analyses, SMCs were significantly associated with depressive symptoms in both males and females [standardized coefficients: males, 0.23 (95 % CI 0.08–0.38); females, 0.35 (95 % CI 0.23–0.46)]. In the within-pair level analyses using MZ and same-sex DZ twin pairs, SMCs were significantly associated with depressive symptoms. In the within-pair level analyses using the MZ twin pairs, SMCs were significantly associated with depressive symptoms [standardized coefficients: males, 0.32 (95 % CI 0.08–0.56); females, 0.24 (95 % CI 0.13–0.42)].

Conclusions

This study suggested that SMCs were significantly associated with depressive symptoms after adjustment for genetic and family environmental factors.

     

Genetic Factors Explain the Association Between Pain Catastrophizing and Chronic Widespread Pain

This study aimed to clarify whether there are shared genetic and/or environmental factors explaining the strong link between pain catastrophizing (PC) and chronic widespread pain (CWP). Data were available for N = 1,109 female twins from TwinsUK. Information on self-reported CWP and PC was subject to variance component twin analysis. Heritabilities were 40% for PC and 77% for CWP. The genetic correlation between PC and CWP was .40%, whereas no evidence of an environmental correlation could be detected (.0). According to the best-fitting additive genetic, non-shared environmental (AE) Cholesky model, an additive genetic factor loading on PC as well as CWP, as well as an additive genetic factor loading on CWP alone was found. In terms of environmental influences, 2 individual environmental factors could be identified, loading separately on PC and CWP. Overall, the results add to the knowledge on the nature of CWP and the basis of its close relationship with PC by suggesting a shared genetic etiological structure. The findings highlight a potential avenue for future research and may provide useful insight for the clinical management of pain and pain coping.

Common Genetic Factors Influence Hand Strength,Processing Speed,and Working Memory

Background

It is important to detect cognitive decline at an early stage, especially before onset of mild cognitive impairment and dementia. Processing speed and working memory are aspects of cognitive function that are associated with cognitive decline. Hand strength is an inexpensive, easily measurable indicator of cognitive decline. However, associations between hand strength, processing speed, and working memory have not been studied. In addition, the genetic and environmental structure of the association between hand strength and cognitive decline is unclear. We investigated phenotypic associations between hand strength, processing speed, and working memory and examined the genetic and environmental structure of the associations between phenotypes.

Methods

Hand strength, processing speed (digit symbol performance), and working memory (digit span performance) were examined in monozygotic and dizygotic twin pairs. Generalized estimating equations were used to identify phenotypic associations, and structural equation modeling was used to investigate the genetic and environmental structure of the association.

Results

Generalized estimating equations showed that hand strength was phenotypically associated with digit symbol performance but not with digit span performance. Structural equation modeling showed that common genetic factors influenced hand strength and digit symbol and digit span performance.

Conclusions

There was a phenotypic association between hand strength and processing speed. In addition, some genetic factors were common to hand strength, processing speed, and working memory.Key words: hand strength, processing speed, working memory, twin study, cognitive decline     

A digest from evidence-based Clinical Practice Guideline for Polycystic Kidney Disease 2020

Clinical and Experimental Nephrology -     

Genome-wide association study for white coat effect in Japanese middle-aged to elderly people: The HOMED-BP study

Background: White coat effect (WCE), the blood pressure (BP) difference between clinical and non-clinical settings, can lead to clinical problems such as misdiagnosis of hypertension. Etiology of WCE has been still unclear, especially from genetic aspects. The present article investigated association between genome-wide single nucleotide polymorphisms (SNPs) and WCE in patients with essential hypertension.

Methods: The present cross-sectional analyses were based on 295 Japanese essential hypertensive outpatients aged ≧40 years enrolled in randomized control study, Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study, who were not taking antihypertensive medications before the randomization. Home and clinic BP were measured. WCE was defined by subtracting home BP from clinic BP. Genotyping was conducted with 500K DNA microarray chips. Association between genome-wide SNPs and WCE were analyzed. For replication (p < 10^–4), we analyzed participants from Ohasama study who took no antihypertension medications and whose SNPs were collected.

Results: Genome-wide SNPs were not significantly associated with WCE of systolic and diastolic BP after corrections of multiple comparisons (p < 2 × 10^–7). We found suggestive SNPs associated with WCE of systolic and diastolic BP (p < 10^–4). However, the consistent results were not obtained in the replication study.

Conclusion: The present article showed no significant association between genome-wide SNPs and WCE. Since there were several suggestive SNPs associated with WCE, the present study warrants a further study with bigger sample size for investigating the genetic influence on WCE.