Dizziness in peri- and postmenopausal women is associated with anxiety: a cross-sectional study

Background

Although dizziness is one of the most common symptoms of menopause, the underlying mechanism is not precisely known. Therefore, this study aimed to investigate the prevalence of, and the factors associated with, dizziness in peri- and postmenopausal women.

Methods

We conducted a cross-sectional study in which we analyzed the first-visit records of 471 Japanese women aged 40 to 65?years who enrolled in a health and nutrition education program at a menopause clinic. The prevalence of dizziness was estimated according to the participants’ responses to the Menopausal Health-Related Quality of Life Questionnaire. The background characteristics of age, menopause status, body composition, cardiovascular parameters, basal metabolism, and physical fitness; other menopausal symptoms, including vasomotor, insomnia, depression, and anxiety symptoms; and lifestyle characteristics were assessed for their associations with dizziness.

Results

The percentage of women who suffered from dizziness once a week or more frequently was 35.7%. Compared to the women without dizziness, those with the symptom were younger; had a higher body weight, body mass index, body fat percentage, muscle mass, and waist-to-hip ratio; had higher systolic pressure; were slower in reaction time; had higher physical and psychological symptom scores of menopause; exercised less regularly; and consumed less alcohol. A multivariate logistic regression analysis revealed that the anxiety symptom, which was evaluated by the Hospital Anxiety and Depression Scale, was the sole factor that was independently associated with dizziness (adjusted odds ratio 1.14; 95% confidence interval 1.08–1.20).

Conclusions

Dizziness is highly prevalent in Japanese peri- and postmenopausal women and it is associated with anxiety. The treatment of anxiety in this population might improve the symptom.

     

Crystallization and preliminary X-ray analysis of a DNA primase from hyperthermophilic archaeon Pyrococcus horikoshii.

At the initiation of chromosomal DNA replication, DNA primases synthesize short RNA primers, which are subsequently elongated by DNA polymerases. To understand the structural basis for the primer synthesis by archaeal/eukaryotic-type primases, the gene of the DNA primase from hyperthermophilic archaeon Pyrococcus horikoshii was cloned and overexpressed in Escherichia coli as a fusion protein with a hexa-histidine tag at its amino terminus. The recombinant DNA primase was purified and crystallized by the hanging-drop vapor diffusion method at 293 K, with polyethylene glycol 8000 as the precipitant. The crystals belong to the P3(2)21 space group with unit-cell parameters a = b = 77.8, c = 129.6 A, and alpha = beta = 90 degrees, gamma = 120 degrees. Crystals of the selenomethionine derivative were obtained by means of a cross-seeding method using native crystals. The data for the native and selenomethionine-substituted crystals were collected to 1.8 and 2.2 A resolution, respectively, with synchrotron radiation at SPring-8 under flash-frozen conditions at 100 K. The four wavelength MAD data provided a phase to determine the structure of the primase at 2.2 A resolution.     

Zoospore-specific antigen as a useful marker for molecular analysis of net formation in Hydrodictyon reticulatum (Chlorococcales, Chlorophyceae)

In the green alga Hydrodictyon reticulatum zoospores are arranged in a regular fashion to form an intricate hexagonal network during the asexual reproductive cycle. A monoclonal antibody which was raised against a homogenate of zoospores recognized a single poly‐peptide in zoospores with a molecular mass of 31 kDa. The antigenic polypeptide, which was designated Amy1, was localized within the cytoplasm of zoospores. The accumulation of Amy1 occurred concomitantly with the transition from multinuclear vegetative cells to mononuclear zoospores, and the degradation of Amy1 occurred concomitantly with the further development of zoospores. Amy1 was constantly expressed during the period of mononuclear zoospores. Thus, we conclude that Amy1 is a zoospore‐specific polypeptide. Using the anti‐Amy1 monoclonal antibody, we could easily distinguish between mononuclear zoospores and multinuclear vegetative net‐cells. This provides an important tool for analysing the molecular mechanisms involved in the hexagonal net formation by zoospores.     

Crystal structural characterization reveals novel oligomeric interactions of human voltage‐dependent anion channel 1

Voltage‐dependent anion channel 1 (VDAC1), which is located in the outer mitochondrial membrane, plays important roles in various cellular processes. For example, oligomerization of VDAC1 is involved in the release of cytochrome c to the cytoplasm, leading to apoptosis. However, it is unknown how VDAC1 oligomerization occurs in the membrane. In the present study, we determined high‐resolution crystal structures of oligomeric human VDAC1 (hVDAC1) prepared by using an Escherichia coli cell‐free protein synthesis system, which avoided the need for denaturation and refolding of the protein. Broad‐range screening using a bicelle crystallization method produced crystals in space groups C222 and P22₁2₁, which diffracted to a resolution of 3.10 and 3.15 Å, respectively. Each crystal contained two hVDAC1 protomers in the asymmetric unit. Dimer within the asymmetrical unit of the crystal in space group C222 were oriented parallel, whereas those of the crystal in space group P22₁2₁ were oriented anti‐parallel. From a model of the crystal in space group C222, which we constructed by using crystal symmetry operators, a heptameric structure with eight patterns of interaction between protomers, including hydrophobic interactions with β‐strands, hydrophilic interactions with loop regions, and protein–lipid interactions, was observed. It is possible that by having multiple patterns of interaction, VDAC1 can form homo‐ or hetero‐oligomers not only with other VDAC1 protomers but also with other proteins such as VDAC2, VDAC3 and apoptosis‐regulating proteins in the Bcl‐2 family.     

Characterization of lysine acetylation of a phosphoenolpyruvate carboxylase involved in glutamate overproduction in Corynebacterium glutamicum

Protein Nε‐acylation is emerging as a ubiquitous post‐translational modification. In Corynebacterium glutamicum, which is utilized for industrial production of l ‐glutamate, the levels of protein acetylation and succinylation change drastically under the conditions that induce glutamate overproduction. Here, the acylation of phosphoenolpyruvate carboxylase (PEPC), an anaplerotic enzyme that supplies oxaloacetate for glutamate overproduction was characterized. It was shown that acetylation of PEPC at lysine 653 decreased enzymatic activity, leading to reduced glutamate production. An acetylation‐mimic (KQ) mutant of K653 showed severely reduced glutamate production, while the corresponding KR mutant showed normal production levels. Using an acetyllysine‐incorporated PEPC protein, we verified that K653‐acetylation negatively regulates PEPC activity. In addition, NCgl0616, a sirtuin‐type deacetylase, deacetylated K653‐acetylated PEPC in vitro. Interestingly, the specific activity of PEPC was increased during glutamate overproduction, which was blocked by the K653R mutation or deletion of sirtuin‐type deacetylase homologues. These findings suggested that deacetylation of K653 by NCgl0616 likely plays a role in the activation of PEPC, which maintains carbon flux under glutamate‐producing conditions. PEPC deletion increased protein acetylation levels in cells under glutamate‐producing conditions, supporting the hypothesis that PEPC is responsible for a large carbon flux change under glutamate‐producing conditions.     

Calcification process dynamics in coral primary polyps as observed using a calcein incubation method

Calcification processes are largely unknown in scleractinian corals. In this study, live confocal imaging was used to elucidate the spatiotemporal dynamics of the calcification process in aposymbiotic primary polyps of the coral species Acropora digitifera. The fluorophore calcein was used as a calcium deposition marker and a visible indicator of extracellular fluid distribution at the tissue-skeleton interface (subcalicoblastic medium, SCM) in primary polyp tissues. Under continuous incubation in calcein-containing seawater, initial crystallization and skeletal growth were visualized among the calicoblastic cells in live primary polyp tissues. Additionally, the distribution of calcein-stained SCM and contraction movements of the pockets of SCM were captured at intervals of a few minutes. Our experimental system provided several new insights into coral calcification, particularly as a first step in monitoring the relationship between cellular dynamics and calcification in vivo. Our study suggests that coral calcification initiates at intercellular spaces, a finding that may contribute to the general understanding of coral calcification processes.     

Lower Serum Adiponectin Levels in African‐American Boys

Objective: To examine adiponectin, an adipocyte‐secreted hormone with anti‐inflammatory and insulin‐sensitizing effects, in relation to race or gender in younger subjects. Research Methods and Procedures: The relationship of adiponectin, quantitated by radioimmunoassay, to anthropometric and metabolic factors (fasting insulin, glucose, and leptin) and reproductive hormones was examined in 46 healthy African Americans (25 girls/21 boys) and 40 whites (20 girls/20 boys) ranging in age from 12 to 21 years. Results: There was no statistical difference in BMI or in BMI percentile among the four groups. Sums of skinfolds, but not skinfold percentile, were significantly lower in boys than girls (p = 0.001 and p = 0.896, respectively), whereas there was no difference between racial groups. Leptin was significantly greater in girls (p = 0.0002). There was no difference in fasting serum glucose, insulin, or homeostasis model assessment score among any of the groups. There was a significant negative univariate relationship between serum adiponectin and both BMI and BMI percentile for the entire group (p = 0.006 and p = 0.005). In a multivariate model, BMI percentile (p = 0.005) and the interaction between race and gender (p = 0.026) were significant predictors of serum adiponectin. In this model, African‐American boys had the lowest serum adiponectin level, 37% less than white boys, who had the highest adiponectin levels. Discussion: Serum adiponectin levels are reduced in young obese subjects (African Americans and whites) and are lower in African‐American boys than white boys. A lower adiponectin level in African‐American boys may predispose this group to a greater risk of diabetes and cardiovascular disease.     

Structural basis for the sequence-specific RNA-recognition mechanism of human CUG-BP1 RRM3

The CUG-binding protein 1 (CUG-BP1) is a member of the CUG-BP1 and ETR-like factors (CELF) family or the Bruno-like family and is involved in the control of splicing, translation and mRNA degradation. Several target RNA sequences of CUG-BP1 have been predicted, such as the CUG triplet repeat, the GU-rich sequences and the AU-rich element of nuclear pre-mRNAs and/or cytoplasmic mRNA. CUG-BP1 has three RNA-recognition motifs (RRMs), among which the third RRM (RRM3) can bind to the target RNAs on its own. In this study, we solved the solution structure of the CUG-BP1 RRM3 by hetero-nuclear NMR spectroscopy. The CUG-BP1 RRM3 exhibited a noncanonical RRM fold, with the four-stranded β-sheet surface tightly associated with the N-terminal extension. Furthermore, we determined the solution structure of the CUG-BP1 RRM3 in the complex with (UG)₃ RNA, and discovered that the UGU trinucleotide is specifically recognized through extensive stacking interactions and hydrogen bonds within the pocket formed by the β-sheet surface and the N-terminal extension. This study revealed the unique mechanism that enables the CUG-BP1 RRM3 to discriminate the short RNA segment from other sequences, thus providing the molecular basis for the comprehension of the role of the RRM3s in the CELF/Bruno-like family.     

Molecular hydrogen suppresses FcεRI-mediated signal transduction and prevents degranulation of mast cells

Molecular hydrogen ameliorates oxidative stress-associated diseases in animal models. We found that oral intake of hydrogen-rich water abolishes an immediate-type allergic reaction in mice. Using rat RBL-2H3 mast cells, we demonstrated that hydrogen attenuates phosphorylation of the FcεRI-associated Lyn and its downstream signal transduction, which subsequently inhibits the NADPH oxidase activity and reduces the generation of hydrogen peroxide. We also found that inhibition of NADPH oxidase attenuates phosphorylation of Lyn in mast cells, indicating the presence of a feed-forward loop that potentiates the allergic responses. Hydrogen accordingly inhibits all tested signaling molecule(s) in the loop. Hydrogen effects have been solely ascribed to exclusive removal of hydroxyl radical. In the immediate-type allergic reaction, hydrogen exerts its beneficial effect not by its radical scavenging activity but by modulating a specific signaling pathway. Effects of hydrogen in other diseases are possibly mediated by modulation of yet unidentified signaling pathways. Our studies also suggest that hydrogen is a gaseous signaling molecule like nitric oxide.