Executive function predict the quality of life and negative emotion in older adults with diabetes: A longitudinal study.

AIMS: To investigate the influence of executive function (EF) on current and future quality of life (QoL) and negative emotion (NE) in older adults with diabetes. METHODS: A total of 128 older adults with diabetes were recruited. Independent variables (demographic information, health and medical conditions, cognitive function, life function) were collected in the first year. Dependent variables (QoL and NE) were collected for 3 years. Pearson's correlation coefficient analysis and stepwise multiple linear regression analysis were performed to identify the predictors of QoL and NE. RESULTS: EF was the strongest predictor for overall QoL and NE in all 3 years, and accounted for 23.0-36.2% and 11.1-17.1% of the variance, respectively. The second strongest predictor for overall QoL in all 3 years was pain interference, which accounted for 3.2-5.8% of the variance. Pain interference was also the second strongest predictor for NE in the second year, accounting for 5.5% of the variance. CONCLUSIONS: The present study revealed that EF is more predictive than pain for current and future QoL and NE in older adults with diabetes. We recommend that EF be included as an indicator for diabetes surveillance, and that prevention of EF decline be a part of diabetes management plans.

Geriatric syndromes and quality of life in older adults with diabetes.

AIM: To describe geriatric syndromes and their relationships with quality of life in older adults with diabetes. METHODS: Community-dwelling older adults (aged >60 years) with diabetes (n = 316) participated in the present study. Eight geriatric syndromes, including polypharmacy (number of medications), pain (Brief Pain Inventory), urinary incontinence (International Consultation on Incontinence Questionnaire), sleep disturbance (hours of sleep), lower cognitive level (Mini-Mental State Examination), falls, depressive symptoms (Geriatric Depression Scale short form) and functional limitation (Barthel Index and Instrumental Activity of Daily Living), were assessed. The WHOQOL-BREF Taiwan version was used to measure physical, psychological, social and environmental domains of quality of life. RESULTS: Polypharmacy was the most common geriatric syndrome (46.6%), followed by pain (41.5%). Participants with any of the geriatric syndromes, except for polypharmacy and sleep disturbance, had significantly poorer quality of life than those without. The Geriatric Depression Scale score was the only common and significant contributor to all four domains of quality of life, explaining 16~29% of the variance. Number of medications, pain level and cognitive level were also significant contributors, although they explained a small amount (<5%) of the variance. The number of geriatric syndromes (mode = 2) was significantly correlated with all four domains of quality of life (partial correlation r = -0.278~0.460, all P < 0.001). CONCLUSIONS: Geriatric syndromes, especially polypharmacy and pain, were common among older adults with diabetes. A greater number of geriatric syndromes or a higher Geriatric Depression Scale score were associated with poorer quality of life. Further studies focusing on combinations of different geriatric syndromes or comorbidities are required. Geriatr Gerontol Int 2019; 19: 518-524.

Gender differences in the relationship between walking activity and sleep disturbance among community-dwelling older adult with diabetes in Taiwan.

This study explored the gender differences in the relationship between walking activity and sleep disturbances. A cross-sectional study of 201 community-dwelling older adults with diabetes was conducted in southern Taiwan. Using the Taiwanese version of the International Physical Activity Questionnaire, self-administered short version (IPAQ-SS), information on physical activity and sleep disturbance conditions was collected. Among older female adults with diabetes, 54.2% reported sleep disturbance significantly higher than males (38.1%). Logistic regression analysis suggested that for women, in addition to the active group, older adults in the low-active, high-walking group exhibited a significantly lower rate of sleep disturbance than did those who walked less.

Insights into ParB spreading from the complex structure of Spo0J and parS.

Spo0J (stage 0 sporulation protein J, a member of the ParB superfamily) is an essential component of the ParABS (partition system of ParA, ParB, and parS)-related bacterial chromosome segregation system. ParB (partition protein B) and its regulatory protein, ParA, act cooperatively through parS (partition S) DNA to facilitate chromosome segregation. ParB binds to chromosomal DNA at specific parS sites as well as the neighboring nonspecific DNA sites. Various ParB molecules can associate together and spread along the chromosomal DNA. ParB oligomer and parS DNA interact together to form a high-order nucleoprotein that is required for the loading of the structural maintenance of chromosomes proteins onto the chromosome for chromosomal DNA condensation. In this report, we characterized the binding of parS and Spo0J from Helicobacter pylori (HpSpo0J) and solved the crystal structure of the C-terminal domain truncated protein (Ct-HpSpo0J)-parS complex. Ct-HpSpo0J folds into an elongated structure that includes a flexible N-terminal domain for protein-protein interaction and a conserved DNA-binding domain for parS binding. Two Ct-HpSpo0J molecules bind with one parS. Ct-HpSpo0J interacts vertically and horizontally with its neighbors through the N-terminal domain to form an oligomer. These adjacent and transverse interactions are accomplished via a highly conserved arginine patch: RRLR. These interactions might be needed for molecular assembly of a high-order nucleoprotein complex and for ParB spreading. A structural model for ParB spreading and chromosomal DNA condensation that lead to chromosome segregation is proposed.

SH2B1ß interacts with STAT3 and enhances fibroblast growth factor 1-induced gene expression during neuronal differentiation.

Neurite outgrowth is an essential process during neuronal differentiation as well as neuroregeneration. Thus, understanding the molecular and cellular control of neurite outgrowth will benefit patients with neurological diseases. We have previously shown that overexpression of the signaling adaptor protein SH2B1ß promotes fibroblast growth factor 1 (FGF1)-induced neurite outgrowth (W. F. Lin, C. J. Chen, Y. J. Chang, S. L. Chen, I. M. Chiu, and L. Chen, Cell. Signal. 21:1060-1072, 2009). SH2B1ß also undergoes nucleocytoplasmic shuttling and regulates a subset of neurotrophin-induced genes. Although these findings suggest that SH2B1ß regulates gene expression, the nuclear role of SH2B1ß was not known. In this study, we show that SH2B1ß interacts with the transcription factor, signal transducer, and activator of transcription 3 (STAT3) in neuronal PC12 cells, cortical neurons, and COS7 fibroblasts. By affecting the subcellular distribution of STAT3, SH2B1ß increased serine phosphorylation and the concomitant transcriptional activity of STAT3. As a result, overexpressing SH2B1ß enhanced FGF1-induced expression of STAT3 target genes Egr1 and Cdh2. Chromatin immunoprecipitation assays further reveal that, in response to FGF1, overexpression of SH2B1ß promotes the in vivo occupancy of STAT3-Sp1 heterodimers at the promoter of Egr1 and Cdh2. These findings establish a central role of SH2B1ß in orchestrating signaling events to transcriptional activation through interacting and regulating STAT3-containing complexes during neuronal differentiation.

LipL41, a hemin binding protein from Leptospira santarosai serovar Shermani.

Leptospirosis is one of the most widespread zoonotic diseases in the world. It is caused by the pathogen Leptospira that results in multiple-organ failure, in particular of the kidney. Outer membrane lipoprotein is the suspected virulence factor of Leptospira. In Leptospira spp LipL41 is one major lipoprotein and is highly conserved. Previous study suggests that LipL41 bears hemin-binding ability and might play a possible role in iron regulation and storage. However, the characterization of hemin-binding ability of LipL41 is still unclear. Here the hemin-binding ability of LipL41 was examined, yielding a K d = 0.59 ± 0.14 µM. Two possible heme regulatory motifs (HRMs), C[P/S], were found in LipL41 at (140)Cys-Ser and (220)Cys-Pro. The mutation study indicates that Cys140 and Cys220 might be cooperatively involved in hemin binding. A supramolecular assembly of LipL41 was determined by transmission electron microscopy. The LipL41 oligomer consists of 36 molecules and folds as a double-layered particle. At the C-terminus of LipL41, there are two tetratricopeptide repeats (TPRs), which might be involved in the protein-protein interaction of the supramolecular assembly.

Structures of Helicobacter pylori uridylate kinase: insight into release of the product UDP.

Uridylate kinase (UMPK; EC 2.7.4.22) transfers the γ-phosphate of ATP to UMP, forming UDP. It is allosterically regulated by GTP. Structures of Helicobacter pylori UMPK (HpUMPK) complexed with GTP (HpUMPK-GTP) and with UDP (HpUMPK-UDP) were determined at 1.8 and 2.5 Šresolution, respectively. As expected, HpUMPK-GTP forms a hexamer with six GTP molecules at its centre. Interactions between HpUMPK and GTP are made by the ß3 strand of the sheet, loop ß3α4 and the α4 helix. In HpUMPK-UDP, the hexameric symmetry typical of UMPKs is absent. Only four of the HpUMPK molecules bind UDP; the other two HpUMPK molecules are in the UDP-free state. The asymmetric hexamer of HpUMPK-UDP, which has an exposed dimer interface, may assist in UDP release. Furthermore, the flexibility of the α2 helix, which interacts with UDP, is found to increase when UDP is absent in HpUMPK-UDP. In HpUMPK-GTP, the α2 helix is too flexible to be observed. This suggests that GTP binding may affect the conformation of the α2 helix, thereby promoting UDP release.

Comparison of organic and inorganic germanium compounds in cellular radiosensitivity and preparation of germanium nanoparticles as a radiosensitizer.

PURPOSE: The aim of this work is to compare the radiosensitizing effect between organic and inorganic germanium compounds and to investigate whether nanometer-sized germanium particles can act as radiosensitizers. MATERIALS AND METHODS: Bis (2-carboxyethylgermanium) sesquioxide (Ge-132), germanium oxide (GeO(2)) and germanium nanoparticles were used in this study. Cell viability was determined by clonogenic survival assay. Cellular DNA damage was evaluated by alkaline comet assay, confocal microscopy and the cellular level of phospho-histone H2AX (gamma-H2AX). RESULTS: Nanometer-sized germanium particles were fabricated. They have a similar radiosensitizing effect as that of GeO(2). Conversely, Ge-132 did not enhance the radiosensitivity of cells. Comet assay was employed to evaluate the level of DNA damage and confirmed that inorganic germanium compounds enhanced cellular radiosensitivity. Notably, the comet assay indicated that the nanoparticle itself caused a higher level of DNA damage. The possibility that germanium nanoparticles per se caused DNA damage was ruled out when the cellular level of gamma-H2AX was examined. CONCLUSIONS: We demonstrated that inorganic but not organic germanium compounds exerted radiosensitizing effect in cells. Nanometer-sized germanium particles were fabricated and were able to enhance the radiosensitivity of cells. Confounding effect may occur when comet assay is used to estimate the level of DNA damage in the presence of germanium nanoparticles.