Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts

Background  

Radial chromosome positioning in interphase nuclei is nonrandom and can alter according to developmental, differentiation, proliferation, or disease status. However, it is not yet clear when and how chromosome repositioning is elicited.     

Role of Prolactin Receptors in Lymphangioleiomyomatosis

Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease caused by mutations in the tumor suppressor genes encoding Tuberous Sclerosis Complex (TSC) 1 and TSC2. The protein product of the TSC2 gene is a well-known suppressor of the mTOR pathway. Emerging evidence suggests that the pituitary hormone prolactin (Prl) has both endocrine and paracrine modes of action. Here, we have investigated components of the Prl system in models for LAM. In a TSC2 (+/-) mouse sarcoma cell line, down-regulation of TSC2 using siRNA resulted in increased levels of the Prl receptor. In human LAM cells, the Prl receptor is detectable by immunohistochemistry, and the expression of Prl in these cells stimulates STAT3 and Erk phosphorylation, as well as proliferation. A high affinity Prl receptor antagonist consisting of Prl with four amino acid substitutions reduced phosphorylation of STAT3 and Erk. Antagonist treatment further reduced the proliferative and invasive properties of LAM cells. In histological sections from LAM patients, Prl receptor immuno reactivity was observed. We conclude that the Prl receptor is expressed in LAM, and that loss of TSC2 increases Prl receptor levels. It is proposed that Prl exerts growth-stimulatory effects on LAM cells, and that antagonizing the Prl receptor can block such effects.     

Time of day effect on balance performance,functional capacities and risk of fall in women with rheumatoid arthritis

ABSTRACT

Objective: This study explored the time of day effect of balance performance, functional capacities and risk of fall in three different times in patients with rheumatoid arthritis (RA) and the association between these variations and those of RA symptoms.

Methods: A “discontinual” protocol, composed of three test sessions, carried out at 6 am, 2 pm and 10 pm was set up, in order to investigate the time of day effect of balance performance, functional capacities, risk of fall, stiffness, range of motion, swollen and painful joints in women with RA.

Results: Time Up and Go Test (TUGT), Functional Reach Test (FRT) and tinetti test scores were significantly higher (p < .01) at 6 am and at 10 pm compared to 2 pm. Stiffness, range of motion, swollen and painful joints values were significantly higher (p < .01) at 6 am and at 10 pm compared to 2 pm. A significant difference was observed on the stiffness, range of motion and swollen joints values between 6 am and 10 pm that were higher at 6 am (p < .05).

Using Pearson’s coefficient, correlations were found between RA symptom values; and TUGT, FRT and Tinetti test scores.

Conclusion: Results showed a time of day effect of balance performance, functional capacities and risk of falls in women with RA. This variation indicates an alteration of performance at 6 am and 10 pm. Fluctuations of stiffness, limited range of motion, swollen and painful joints noted are concomitant to those of balance performance, functional capacities, and risk of fall.

Abbreviations: RA: rheumatoid arthritis; H&O questionnaire: Horne and Ostberg questionnaire; PSQI: Pittsburgh sleep quality index; HAQ: health assessment questionnaire; SF-36: the short form-36; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; TUGT: Time Up and Go Test; FRT: Functional Reach Test     

Ataxia-telangiectasia: Linkage analysis in highly inbred Arab and Druze families and differentiation from an ataxia-microcephaly-cataract syndrome

Summary Ataxia-telangiectasia (A-T) is a progressive autosomal recessive disease featuring neurodegeneration, immunodeficiency, chromosomal instability, radiation sensitivity and a highly increased proneness to cancer. A-T is ethnically widespread and genetically heterogeneous, as indicated by the existence of four complementation groups in this disease. Several A-T-like genetic diseases share various clinical and cellular characteristics with A-T. By using linkage analysis to study North American and Turkish A-O families, the ATA (A-T, complementation group A) gene has been mapped to chromosome 11q23. A number of Israeli Arab A-T patients coming from large, highly inbred families were assigned to group A In one of these families, an additional autosomal recessive disease was identified, characterized by ataxia, hypotonia, microcephaly and bilateral congenital cataracts. In two patients with this syndrome, normal levels of serum immunoglobulins and alpha-fetoprotein, chromosomal stability in peripheral blood lymphocytes and skin fibroblasts, and normal cellular response to treatments with X-rays and the radiomimetic drug neocarzinostatin indicated that this disease does not share, with A-T, any additional features other than ataxia. These tests also showed that another patient in this family, who is also mentally retarded, is affected with both disorders. This conclusion was further supported by linkage analysis with 11q23 markers. Lod scores between A-O and these markers, cumulated over three large Arab families, were significant and confirmed the localization of the ATA gene to aq23. However, another Druze family unassigned to a specific complementation group, showed several recombinants between A-T and the same markers, leaving the localization of the A-T gene in this family open.     

Metabolic activities of the sugarbeet pathogens Fusarium solani (Mart.) Sacc. and Sclerotium rolfsii Sacc. under pyramin stress

Effects of different concentrations of active ingredient of the herbicide pyramin on metabolic activities of Fusarium solani and Sclerotium rolfsii were examined. High concentrations of this herbicide (1000 and 2000 g mL^-1 for F. solani and 100 and 200 g mL^-1 for S. rolfsii) had inhibitory effects on the metabolic activities of both fungi. These were demonstrated by significant decreases in growth, and increases in rates of CO₂ evolved, O₂ consumed and keto acids produced. These were accompanied by increased rates of sugar, nitrate and inorganic phosphorus absorption as well as lowered rates of synthesis of carbohydrates and insoluble nitrogenous (including protein) and phosphorus (including RNA-P and DNA-P) compounds. In addition, rates of excretion of both nitrogen and phosphorus fractions by the mycelial mats were increased.A concentration of 25 g mL^-1 exerted little or no effect on the metabolic activities of these fungi, although S. rolfsii was somewhat sensitive to this concentration.     

Identification of the glucose transporter in rat skeletal muscle

The glucose transporter in the plasma membrane of rat skeletal muscle has been identified by two approaches. In one, the transporter was detected as the polypeptide that was differentially labeled by photolysis with [³H]cytochalasin B in the presence of l- and d-glucose. [³H]Cytochalasin B is a high-affinity ligand for the transporter that is displaced by d-glucose. In the other, the transporter was detected by means of its reaction with rabbit antibodies against the purified glucose transporter from human erythrocytes. By both procedures, the transporter was found to be a polypeptide with a mobility corresponding to a molecular weight of 45,000–50,000 upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis.     

Choline derivatives and sodium fluoride protect acetylcholinesterase against irreversible inhibition and aging by DFP and paraoxon

A light addressable potentiometric sensor was used to measure acetylcholinesterase (AChE) activity in order to evaluate the protective effects of quaternary compounds and NaF against enzyme phosphorylation and aging by two organophosphates. The use of the immobilized AChE made possible the quick removal of reagents (i.e., organophosphate, 2-pralidoxime, and protectant), thereby permitting accurate determination of AChE activity before and after phosphorylation and aging. Paraoxon was 15-fold more potent in inhibiting AChE than DFP, while the percent aging following phosphorylation by diiso-propylfluorophosphate (DFP) was much higher. Sodium fluoride (NaF), the most effective protectant against phosphorylation and aging, and the quaternary ammonium compounds reduced significantly AChE inhibition by DFP and paraoxon, to similar degrees. Even though the percent AChE activity that was lost to aging was reduced by these agents, aging as a percent of phosphorylated AChE was not reduced. Thus, their major effect was in reducing the percent AChE phosphorylation, which consequently resulted in reduction of total aged AChE. The finding that quaternary ammonium compounds protect against phosphorylation is consonant with the proposed presence of the active site of AChE in an aromatic gorge.     

Population density and genetic diversity are positively correlated in wild felids globally

Aim

Insights into the biological and evolutionary traits of species, and their ability to cope with global changes, can be gained by studying genetic diversity within species. A cornerstone hypothesis in evolutionary and conservation biology suggests that genetic diversity decreases with decreasing population size, however, population size is difficult to estimate in threatened species with large distribution ranges, and evidence for this is limited to few species. To address this gap, we tested this hypothesis across multiple closely related species at a global scale using population density which is a more accessible measure.

Location

Global.

Time Period

Contemporary.

Major Taxa Studied

Wild felids in their natural habitats.

Methods

We obtained data from published estimates of population density assessed via camera trap and within-population genetic diversity generated from microsatellite markers on 18 felid species across 41 countries from 354 studies. We propose a novel method to standardize population density estimates and to spatially join data using K-means clustering. Linear mixed-effect modelling was applied to account for confounding factors such as body mass, generation length and sample size used for the genetic estimates.

Results

We found a significant positive correlation between population density and genetic diversity, particularly observed heterozygosity and allelic richness. While the confounding factors did not affect the main results, long generation length and large sample size were significantly associated with high genetic diversity. Body mass had no effect on genetic diversity, likely because large-bodied species were over-represented in our data sets.

Main Conclusions

Our study emphasizes how recent demographic processes shape neutral genetic diversity in threatened and small populations where extinction vortex is a risk. Although caution is needed when interpreting the small population density effect in our findings, our methodological framework shows promising potential to identify which populations require actions to conserve maximal genetic variation.