Maternal obesity and long-term neuropsychiatric morbidity of the offspring

Archives of Gynecology and Obstetrics - To evaluate the long-term pediatric neuropsychiatric morbidity of children born to obese patients. A population-based cohort analysis was performed comparing...     

Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase

It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute G_i/o-coupled receptor activation inhibits the activity of several AC isozymes, including Ca²⁺/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report that both acute μ-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin sensitive. In addition, we show that proteins that interfere with the activity of {ie195-2} subunits ({ie195-3} scavengers) strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation of AC-VIII. Based on these results, we suggest that {ie195-4} is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.     

Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1

Aurora-A is a centrosomal serine-threonine kinase that regulates mitosis. Over-expression of Aurora-A has been found in a wide range of tumors and has been implicated in oncogenic transformation. However, how Aurora-A over-expression contributes to promotion of carcinogenesis remains elusive. Immunohistochemical analysis of breast tumors revealed that over-expressed Aurora-A is not restricted to the centrosomes but is also found in the cytoplasm. This over-expressed Aurora-A appeared to be phosphorylated on Thr288, which is known to be required for its enzymatic activation. In analogy to Aurora-A's role in oocyte maturation and the early embryonic cell cycle, here we investigated whether ectopically over-expressed Aurora-A can similarly stimulate polyadenylation of mRNA in human somatic cultured cells by interacting with a human ortholog of cytoplasmic polyadenylation element binding protein, h-CPEB. In vitro experiments revealed that Aurora-A binds directly to, and phosphorylates, h-CPEB. We found that polyadenylation of mRNA tails of cyclin B1 and Cdk1 was synergistically stimulated when Aurora-A and h-CPEB were over-expressed, and they were further promoted in the presence of an Aurora-A activator Ajuba. Our results suggest a function of ectopically over-expressed Aurora-A that might be relevant for carcinogenesis.     

Detection of human glioma-associated antigen by rat monoclonal antibody raised against syngeneic rat glioma cells

A monoclonal antibody termed "FR77" was obtained from a hybridoma clone established by fusion between P3x63Ag8.653 mouse myeloma cells and spleen cells of a Fischer F344 rat hyperimmune to syngeneic 9L/R3 glioma cells. Immunoperoxidase staining of various cultured cells showed that FR77 was reactive to both rat and human glioma cells, but was not reactive with other nonglioma cells. Immunohistochemical examination of paraffin-embedded or cryostat-frozen sections of various human tissues revealed that FR77 was strongly reactive with glioblastoma, grade III astrocytoma, and craniopharyngioma; partially reactive with intracerebral primitive neuroectodermal tumor, pineoblastoma, and desmoplastic medulloblastoma; and weakly reactive with low-grade astrocytoma. It was not reactive with other types of brain tumors and normal human tissues tested. The FR77-defined antigen was observed to be predominantly localized in the cytoplasm of antigen-bearing cells as suggested by the immunostaining pattern, but part of it was also expressed on the cell surface of glioma cells as demonstrated by a complement-mediated cytotoxic test. Fractionation of the antigenic component and periodic acid treatment of tumor tissue bearing the FR77-defined antigen indicated that the antigen is of a neutral glycolipid nature and that the antigenic determinant to FR77 is present on its sugar portion.     

L-Glutamine Supplementation Enhances Strength and Power of Knee Muscles and Improves Glycemia Control and Plasma Redox Balance in Exercising Elderly Women

We investigated the effects of oral L-glutamine (Gln) supplementation, associated or not with physical exercises, in control of glycemia, oxidative stress, and strength/power of knee muscles in elderly women. Physically active (n = 21) and sedentary (n = 23) elderly women aged 60 to 80 years were enrolled in the study. Plasma levels of D-fructosamine, insulin, reduced (GSH) and oxidized (GSSG) glutathione, iron, uric acid, and thiobarbituric acid-reactive substances (TBARs) (lipoperoxidation product), as well as knee extensor/flexor muscle torque peak and average power (isokinetic test), were assessed pre- and post-supplementation with Gln or placebo (30 days). Higher plasma D-fructosamine, insulin, and iron levels, and lower strength/power of knee muscles were found pre-supplementation in the NPE group than in the PE group. Post-supplementation, Gln subgroups showed higher levels of GSH, GSSG, and torque peak, besides lower D-fructosamine than pre-supplementation values. Higher muscle average power and plasma uric acid levels were reported in the PE + Gln group, whereas lower insulin levels were found in the NPE + Gln than pre-supplementation values. TBARs levels were diminished post-supplementation in all groups. Gln supplementation, mainly when associated with physical exercises, improves strength and power of knee muscles and glycemia control, besides boosting plasma antioxidant capacity of elderly women.     

Prevalence and Associated Factors of Sarcopenia in Singaporean Adults—The Yishun Study

ObjectivesTo describe the normative values of sarcopenia among community-dwelling adults (≥21 years of age); compare the prevalence of sarcopenia using Asian Working Group for Sarcopenia criteria, 2014 (AWGS2014), Asian Working Group for Sarcopenia criteria, 2019 (AWGS2019), and European Working Group on Sarcopenia in Older People criteria, 2018 (EWGSOP2) guidelines; and identify factors associated with sarcopenia.DesignParticipants were recruited through random sampling. Sarcopenia assessments were performed using a dual-energy x-ray absorptiometry scan (muscle mass), handgrip test (muscle strength), and usual walking test (physical performance). Questionnaires were administered to evaluate lifestyle and cognition.Setting and ParticipantsIn total, 542 community-dwelling Singaporeans were recruited (21?90 years old, 57.9% women).MethodsWe assessed anthropometry, body composition, and questionnaire-based physical and cognitive factors, and estimated sarcopenia prevalence according to the AWGS2014, AWGS2019, and EWGSOP2 recommendations, and examined associations using logistic regression.ResultsAccording to AWGS2019, the Singapore population-adjusted sarcopenia prevalence was 13.6% (men 13.0%; women 14.2%) overall, and 32.2% (men 33.7%, women 30.9%) in those aged 60 years and above. The cut-offs derived from young adult reference group for low appendicular lean mass index were 5.28 kg/m2 for men and 3.69 kg/m2 for women (lower than AWGS recommended cut-off); for gait speed it was 0.82 m/s, (AWGS2019 recommended cut-off 1.0 m/s, AWGS2014 cut-off was 0.8 m/s); and for handgrip strength it was 27.9 kg/m2 for men and 16.7 kg/m2 for women (close to AWGS2019 recommendation). Age, sex, marital status, alcoholism, physical activity, body mass index, waist circumference, and global cognition were associated with sarcopenia (P < .05).Conclusions and ImplicationsThis is the first study to provide reference values of muscle mass, strength, and gait speed across the adult lifespan of Singaporeans. Using AWGS2019 criteria, sarcopenia is prominent in older age (32.2% in ≥60 years old), but it is already nontrivial (6.9%) among young and middle-age persons. Multidomain lifestyle modifications addressing muscle strength, cognition, and nutrition over the adult lifespan are important to delay the development of sarcopenia.     

Vaccination with chimeric protein induces protection in murine model against ascariasis

An estimated 400 million people are infected by parasites of the genus Ascaris and the existing control measures are inefficient. Vaccine development using B cell antigens is a promising strategy for increased protection against this parasite. The present study aimed at developing a chimeric protein capable of conferring protection against infection by Ascaris sp. For this purpose, we performed B-cell epitope predictions on previously described vaccine candidate proteins from Ascaris suum and the corresponding peptides were used to construct a chimeric protein. Female BALB / c mice were immunized subcutaneously in three doses at 10 day intervals with a vaccine formulation comprised of the chimeric protein together with monophosphoryl lipid A (MPLA). Control groups included protein alone, MPLA, or PBS. After challenge infection, animals vaccinated with chimeric protein plus MPLA showed a reduction of 73.54% of larval load in the lung compared to control group animals. Animals immunized with chimeric protein plus MPLA also display higher IgG response and a reduction in lung inflammation. Our study highlights how chimeric proteins containing more than one B cell epitope can enhance immune protection against helminthic infection and offer new approaches to the development of Ascaris vaccines.     

Reduced tumorigenicity and cell motility of a gastric-carcinoma cell-line by introduction of wild-type p53 gene

Wild-type or mutant human p53 gene was transfected into a human gastric carcinoma cell line MKN-1 which shares a mutant p53 allele. Transfected wild-type p53 reduced the colony forming efficiency and tumorigenicity of MKN-1 cells. However, no difference in expression of cell adhesion molecule, oncogenes and growth factors was observed among parent, wild-type p53 and mutant p53 transfectants. In motility assay, the wild-type p53 transfectants relative to the parental or mutant p53 transfectants exhibited a decreased motility, and HGF had a greater effect on the motility of the mutant p53 transfectants, but very little effect on the motility of either the parental or wild-type transfectants. In invasion assay, mutant p53 transfectants revealed the increased invasion ability into collagen gel. These results suggest that allele loss and point mutation of p53 gene may play a critical role not only in growth but also in invasion of gastric carcinoma cells.