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PubMed2004

Targeted deletion of BMK1/ERK5 in adult mice perturbs vascular integrity and leads to endothelial failure.

Big mitogen-activated protein kinase 1 (BMK1), also known as ERK5, is a member of the MAPK family. Genetic ablation of BMK1 in mice leads to embryonic lethality, precluding the exploration of pathophysiological roles of BMK1 in adult mice. We generated a BMK1 conditional mutation in mice in which disruption of the BMK1 gene is under the control of the inducible Mx1-Cre transgene. Ablation of BMK1 in adult mice led to lethality within 2-4 weeks after the induction of Cre recombinase. Physiological analysis showed that the blood vessels became abnormally leaky after deletion of the BMK1 gene. Histological analysis revealed that, after BMK1 ablation, hemorrhages occurred in multiple organs in which endothelial cells lining the blood vessels became round, irregularly aligned, and, eventually, apoptotic. In vitro removal of BMK1 protein also led to the death of endothelial cells partially due to the deregulation of transcriptional factor MEF2C, which is a direct substrate of BMK1. Additionally, endothelial-specific BMK1-KO leads to cardiovascular defects identical to that of global BMK1-KO mutants, whereas, surprisingly, mice lacking BMK1 in cardiomyocytes developed to term without any apparent defects. Taken together, the data provide direct genetic evidence that the BMK1 pathway is critical for endothelial function and for maintaining blood vessel integrity.

Animals↗

PubMed2001

Microsatellite instability occurs in distinct subtypes of pediatric but not adult central nervous system tumors.

Length alterations in microsatellite repeats, termed microsatellite instability (MSI), are found in 10-15% of sporadic colon, endometrial, and gastric cancers harboring defects in DNA mismatch repair (MMR) genes We used the microsatellite markers Big Adenine Tract (BAT) 26 and BAT-25 from the reference panel of five markers recommended by the National Cancer Institute to evaluate the incidence of MSI in 206 central nervous system tumors. We screened 102 pediatric and 104 adult cases representing 165 astrocytic and 41 nonastrocytic tumors. The overall incidence of MSI was 8% (16 of 206). All 16 tumors with MSI were found in pediatric rather than adult patients. MSI was associated with two distinct subtypes of pediatric tumors occurring in 27% (12 of 45) of WHO grade III and grade IV astrocytomas and 24% (4 of 17) of gangliogliomas We evaluated the difference in clinicopathological and genetic features among 45 high-grade pediatric astrocytomas by MSI status. The median survival for pediatric patients with MSI (n = 12) was 8 months compared with 15 months for those patients without MSI (n = 33; P = 0.18). The frequency of p53 gene mutations was 13% for pediatric patients with MSI (n = 8) compared with 47% for those patients without MSI (n = 19; P = 0.19). These results revealed a trend between MSI status and prog nosis and MSI status and frequency of p53 gene mutations. Our data suggest that pediatric high-grade astrocytomas can be attributed to two different genetic pathways: a MMR-deficient pathway and a MMR proficient pathway.

Adolescent↗

PubMedDate not supplied

Causes of blindness among adult Jordanians: a hospital-based study.

PURPOSE: To assess the causes of blindness among adults aged 20 years and over who attended two big general ophthalmic clinics in Jordan. PATIENTS AND METHODS: This hospital-based study was undertaken at Jordan University Hospital in Amman (the capital of Jordan) and Princess Basma Teaching Hospital which is affiliated with Jordan University of Science and Technology in Irbid, the third largest city in the country. A total of 2732 patients seen consecutively over 26 months were examined and the ophthalmic findings were recorded. Using standard Snellen charts, subjects were placed in one of three categories according to their best corrected visual acuity: (1) unilateral blindness: less than 6/60 in the worst eye, 6/60 or more in the better eye; (2) moderate bilateral blindness: less than 6/60 in the worst eye, less than 6/60 to 3/60 or more the better eye; and (3) severe bilateral blindness: less than 3/60 in both eyes. RESULTS: Of the totalpatients seen, 373 were blind according to the selection criteria. Among 248 patients with unilateral blindness, diabetic retinopathy, cataract and trauma were the leading causes. Among the 81 patients with moderate bilateral blindness, diabetic retinopathy and cataract were the leading causes. Diabetic retinopathy and glaucoma were the leading causes in patients with severe bilateral blindness. CONCLUSIONS: These data could be used in planning blindness prevention and treatment programs while awaiting a national survey on the prevalence and causes of blindness in Jordan.

Adult↗

PubMed2005

[Occurrence of lice (Anoplura) in rodents from Lover Silesia].

BACKGROUND: The data on the lice of small mammals, which can be the vectors of some human pathogens, are rather scarce in Poland. MATERIAL: During 2001-2004 an investigation of the lice of rodents was undertaken in the area of Lover Silesia. The research was concentrated on habitat in Masyw Slezy (about 35 km from Wrocław, popular recreational area) and on two habitats in Wrocław: in Osobowice (irrigation fields) and Mokry Dwór (water-bearing ground). 105 rodents belonging to three species: Apodemus agrarius (35), Apodemus flavicolis (30) and Clethrionomys glareolus (40) were examined. RESULTS: On 13 individuals of rodents 68 lice (Anoplura) of 3 species were found: Hoplopleura affinis (Burmeister, 1839)--21 females and 8 male, H. acanthopus (Burmeister, 1839)--2 females and Polyplax serrata (Burmeister, 1839)--22 females, 11 male and 4 nymphs. The prevalence of lice infestation was 12.4%; A. agrarius was the most infected rodent (prevalence 25%). The most numerous lice were P. serrata. This species was recorded on A. agrarius (11.4%) and A. flavicolis (3.3%) collected in Wrocław, and on C. glareolus (2.5%) collected in Masyw Slezy. Only single individuals of P. serrata were found on Apodemus (the mean intensity was 1.25). A big collection (17 females, 11 males and 3 nymphs) was gathered on C. glareolus. H. affinis was found only on a typical host A. agrarius (14.3%) collected in both habitats in Wrocław (mean intensity 4.75). H. acanthopus was found only on C. glareolus (prevalence 5.0%). No mixed infestation was recorded. Higer infestation of hosts was in habitats of Wrocław than in Masyw Slezy.

Animals↗

PubMed1998

Comparison of mutant frequencies and types of mutations induced by thiotepa in the endogenous Hprt gene and transgenic lacI gene of Big Blue rats.

The utility of the lacI transgene of Big Blue rats as a reporter of in vivo mutation was evaluated by comparing the frequency and types of mutations induced by thiotepa in the transgene and the endogenous Hprt gene. Transgenic rats were given i.p. injections of 1.4 mg/kg of thiotepa three times per week over a period of 4 weeks (a total dose of 16.8 mg/kg); 1 week after the last injection, mutation assays were performed on spleen lymphocytes isolated from the animals. Thiotepa treatment increased the lacI mutant frequency from 34.8 +/- 4.1 x 10(-6) in control animals to 140.9 +/- 64.8 x 10(-6) (p = 0.0020) and the Hprt mutant frequency from 3.5 +/- 1.5 x 10(-6) to 41.1 +/- 23.2 x 10(-6) (p = 0.0028). Sequence analysis of lacI mutant DNA and Hprt mutant cDNA produced similar overall mutation patterns: G:C-->T:A transversion was the most common base pair substitution (32% of independent mutations in the lacI gene and 28% of Hprt mutations), and deletions and insertions accounted for 34% of mutations in the lacI gene and 28% in the Hprt gene. The majority of thiotepa-induced base pair substitutions in the Hprt gene occurred with the mutated purine on the non-transcribed DNA strand, while no strand-related bias was found for mutations in the lacI gene. Substitutions at G:C base pairs in the lacI gene, but not in the Hprt gene, were found disproportionately in CpG sites. In addition, multiplex polymerase chain reaction analysis of genomic DNA from the Hprt mutants indicated that 34% had relatively large deletions; none of these deletions was detected by the cDNA analysis. The results indicate that the frequency of thiotepa-induced mutants in Big Blue rats was 2.8-fold greater in the lacI gene than in the Hprt gene. Although the Hprt gene recovered a fraction of large deletions not found among the lacI mutants, the effects of transcription-coupled DNA repair in the Hprt gene and the targeting of base pair substitutions to G:C base pairs in CpG sites may have contributed to the higher mutant frequencies induced by thiotepa in the lacI transgene compared with the Hprt gene.

Animals↗

PubMed2003

[Drugs use among adolescents: results from the National Survey on Addictions, 1998].

OBJECTIVE: The aim of this paper is to describe drug and associated factors use among adolescents (12 to 17 years of age). MATERIAL AND METHODS: Data come from the recent Encuesta Nacional de Adicciones, 1998 (National Survey on Addictions) undertaken in urban areas of Mexico. A probabilistic, multi-stage, stratified cluster sampling design was used to select the study population. The sampling unit was the individual in each household. Statistical analysis consisted of the estimation of prevalences of drug use, with 95% confidence intervals. Associations were analyzed using logistic regressions models. RESULTS: Excluding tobacco and alcohol, 3.57% of males and 0.6% of females have used one or more drugs; 2.14% and 0.45% used them in the 12 months previous to the survey, and 1.4% and 0.3% in the previous 30 days, respectively. Marihuana was the drug more often used by males (2.4%) and females (0.45%), followed by inhaled solvents (1.08% and 0.20%), and cocaine (0.99% and 0.22%), respectively. The risk of using illicit drugs was associated to being male, having dropped out from school, perceiving availability, drug use by family and friends, social tolerance among friends, and symptoms of depression. CONCLUSIONS: Adolescents between 12 to 17 years of age are exposed to increasing drug use. The rates of drug use have risen, especially in the northern region of Mexico and in the big urban areas (Tijuana, Mexico City and Guadalajara). These findings emphasize the need to develop campaigns to detect emotional problems. Preventive measures should provide appropriate care to prevent drug use as a mechanism to cope with such emotional conflicts. Also, more intense preventive interventions should be targeted to adolescents with a high probability of developing drug abuse.

Adolescent↗

PubMed2000

Tissue endothelin-converting enzyme activity correlates with cardiovascular risk factors in coronary artery disease.

BACKGROUND: Endothelin-converting enzymes (ECEs) are the key enzymes in endothelin-1 (ET-1) generation. However, their pathophysiological role in patients with cardiovascular disease remains elusive. METHODS AND RESULTS: Vascular reactivity to big endothelin-1 (bigET-1; 10(-9) to 10(-7) mol/L) and ET-1 (10(-9) to 10(-7) mol/L) were examined in the internal mammary artery (IMA, n=33) and saphenous vein (SV, n=27) of patients with coronary artery disease with identified cardiovascular risk factors. Vascular ECE activity was determined by conversion of exogenously added bigET-1 to ET-1. Tissue contents of bigET-1 and ET-1 were measured by radioimmunoassay. In addition, the effects of LDL and oxidized LDL on ECE-1 protein levels were determined by Western blot analysis in human IMA endothelial cells. In the IMA, vascular ECE activity showed an inverse correlation with serum LDL levels (r=-0.76; P<0.01) and systolic and diastolic blood pressure and a positive correlation with fibrinogen (r=0.58; P<0.05). In the SV, fibrinogen was the only parameter to be correlated with vascular ECE activity. Vascular tissue content of bigET-1 was attenuated in the IMA of patients with hyperfibrinogenemia but increased in patients with elevated systolic blood pressure and increased serum LDL levels (P<0.05). Most interestingly, LDL and oxidized LDL downregulated ECE-1 protein levels in human IMA endothelial cells (P<0.05). CONCLUSIONS: These data demonstrate, for the first time, that vascular ECE activity is (1) inversely correlated with serum LDL levels and blood pressure and (2) positively associated with fibrinogen in human vascular tissue. Hence, ECE-1 activity may modulate cardiovascular risk in patients with coronary artery disease.

Aspartic Acid Endopeptidases↗

PubMed1994

Potential independent factors of variability of biological status and reproductive history of Yucatecan women.

In this paper, we report the results of the application of principal component analysis (PCA) in a study of the human ecology of rural-to-urban migrantion in Yucatan, Mexico. Socioeconomic, reproductive and anthropometric data from 216 women 32 years of age or older, were obtained in 1989-1990. Seventeen socioeconomic, demographic and environmental properties of the families of such women, plus migrant status, were employed in a PCA, which yielded five independent factors, explaining 57.1% of the total variance of such properties. These factors were employed to made a multiple regression analysis on 19 anthropometric and 21 reproductive traits, age adjusted. According to the multiple regression of women's biological status to independent factors, we found that in better living conditions (Factor 3), women are heavier, taller, with more body surface and subcutaneous fat in the trunk and in the upper extremity, than in worse living conditions. Better educational level of wife and husband (Factor 2) is associated with lower number of pregnancies and alive born children, as well as less reproductive losses. Women living in families with higher income (Factor 4), have a younger age at the first pregnancy, older age at the last pregnancy, greater number of pregnancies, alive born children and alive offspring at the interview, and they experience less reproductive losses in relation to the number of pregnancies. This fact suggests that for the families in this sample, big families are a strategy to cope with poverty and uncertainty in employment and income. Our results are discussed against the reports in the literature.

Adult↗

PubMed1996

[Use of mini-septopal in trauma surgery of the hand. Experimental and clinical studies].

The antibiotics application in treatment of infections makes necessary that they are present in the focus of infection in concentration which is enough to fight back bacteria responsible for the symptoms of disease. Concentration higher then MIC is especially difficult to obtain in tissue with poor blood supply.c. in the cortical bone. Many attempts has been made to find proper method to obtain high antibiotic concentration in the infection focus without overloading the rest of the organism. In the years 1972-1973 Klemm in Frankfurt/Main had first very promising results treating bone infections by filling bone cavities after proper surgical debridement with hand-made beads made of bone cement with gentamicin. This method has been developed by the E. MERCK company which started to produce drug as Septopal. Very good results of treatment using this form of antibiotic created natural demand for this method also in hand surgery, where big sized Septopal beads couldn't be used. E. MERCK company has provided us with Septopal Mini Chains where small ellipsoids are gathered in 10- or 20 elements chains. Starting investigations on SMC application the following aims of experimental and clinical studies has been pointed out: observation of tissue reaction for the implanted ellipsoids, studies on gentamicin releasing velocity and its concentration in the implantation site as well as in the tissues of peripheral organs, observation of the potential toxicity and observation of the ellipsoids structure in the scanning electron microscopy, evaluation of usefulness of the SMC in the treatment of bone and soft tissue infections and in prophylactics in high risk wounds treatment, evaluation of its efficiency in comparison with gentamicin-resisted bacterial strains. Statistical analysis of results has proved very high efficiency of this form of drug by obtaining very high local antibiotic concentration even 100 times higher then after parenteral application. No toxic reactions has been noticed. In the Department of Traumatology Medical Academy in Wrocław in the years 1983-1991 Septopal Mini Chains has been applied in 76 cases and very good results-complete healing has been obtained in 83% of patients. These data allow us to evaluate very high the usefulness of the Septopal Mini Chains as very good, new method of bone and soft tissue infection treatment in the area of hand.

Animals↗

PubMed1996

A pseudo-particle approach for studying protein-ligand models truncated to their active sites.

A molecular dynamics method has been developed to describe the structural and dynamic properties of protein-ligand complexes that are truncated to their active sites. The active site is comprised of the ligand and discontinuous, positionally unrestrained peptide chains. This truncated active-site complex is surrounded by big unspecific pseudo-particles representing the complete protein and the solvent. Thus, knowledge of the folding of the outer parts of the protein is not required, and the method can be applied to protein models, derived from homology modeling. The method has been tested using ligand complexes of adenylate kinase, retinol binding protein, HIV-1 protease, and human leucocyte antigen. Comparisons with their crystal structures and with results from time-demanding simulations of the whole complexes in explicit water solvent show that the ligand binding properties are conserved. Most of the hydrogen bonds between the ligand and the active-site residues are reproduced and, furthermore, the simulation time is reduced.

Amino Acid Sequence↗

PubMed1988

An amphibian two-domain 'big' neurophysin: conformational homology with the mammalian MSEL-neurophysin/copeptin intermediate precursor shown by trypsin-sepharose proteolysis.

A 'big' frog (Rana esculenta) neurophysin, encompassing sequences homologous to mammalian MSEL-neurophysin and copeptin, has been passed through a trypsin-Sepharose column in order to compare its conformation with that of the two-domain intermediate precursor isolated from guinea pig. Whereas the polypeptide possesses 8 arginine residues, only two cleavages were observed located in a putative inter-domain sequence (at Arg-94 and Arg-114). Because free vasotocin has been isolated from the frog, it is assumed that pro-vasotocin has a three-domain conformation similar to that of pro-vasopressin but processing in amphibians involves only one step rather than two steps as in mammals.

Amino Acid Sequence↗

PubMed1993

Enzyme immunometric assay for endothelin using tandem monoclonal antibodies.

Seven distinct mouse monoclonal antibodies (mAbs) directed against human endothelin-1 (ET-1) have been obtained. On the basis of specificity studies performed with competitive immunoassays and of complementary binding studies, these mAbs were classified in two groups. mAbs of group A (Endo-4, -5, -6 and -10) were shown to be directed against the N terminal loop while those of group B (Endo-2, -8 and -18) recognized the C terminal part of the peptide. A pair of monoclonal antibodies with optimal properties for a two-site immunometric assay were selected and the test was performed in 96-well microtiter plates coated with one mAb (Endo-18), while another mAb (Endo-4) covalently labeled with enzyme acetylcholinesterase was used as tracer. Under optimal conditions, the assay appeared to be very sensitive since concentrations as low as 1 pg/ml could be significantly detected. The precision was also very good with a coefficient of variation below 10% from 3 to 250 pg/ml. The assay was specific for mature endothelin presenting no cross-reactivity with the precursor Big ET-1. On the other hand, strong cross-reactivity was observed with other ET-1-related peptides, including ET-2, ET-3, VIC peptide and sarafotoxin 6-b. The assay permitted specific determination of ET-1 in supernatants of cultured endothelial cells and the validity of the test was demonstrated by HPLC fractionation experiments. In addition, the assay also appeared to be suitable for direct determination of ET-1 in plasma. Studies performed with plasma from healthy subjects revealed that circulating levels of ET-1 are below or close to the detection limit of the method (< 8 pg/ml).

Amino Acid Sequence↗

PubMed2006

Response of male BUT big 6 turkeys to varying amino acid feeding programs.

Dietary protein is a major cost contributor in turkey nutrition. Therefore, a feeding trial with male BUT Big 6 turkeys to 154 d of age was conducted to examine how live performance and economics are affected when dietary amino acid levels are altered in different phases. Six dietary treatments were run with treatment 1 as the control in which balanced protein levels were according to recommendations during all 6 phases. Treatments 2 through 6 used combinations of balanced protein (based on lysine) that ranged from 90 to 120% of those used in treatment 1. The combinations for the 6 phases of feeding were 120, 120, 120, 120, 90, and 90% for treatment 2; 120, 120, 120, 100, 90, and 90% for treatment 3; 120, 120, 100, 100, 90, and 90% for treatment 4; 120, 120, 120, 120, 100, and 100% for treatment 5; and 90, 90, 90, 100, 100, and 100 for treatment 6. Final BW was highest in treatment 4 and lowest in treatment 2 (P < 0.05), whereas final BW were intermediate and statistically not different in treatments 1, 3, 5, and 6. Breast meat yield was highest in treatment 5 and lowest in treatments 2 and 3 (P < 0.05). Mortality seemed to be reduced in treatment 6 compared with treatments 2, 3, and 5 (P < 0.10). Performance data in combination with economic simulations suggested that the feeding regimens of treatments 4 or 6 might be alternative strategies to treatment 1 to improve overall profitability.

Amino Acids↗

PubMed2005

Biochemical effects of lead, zinc, and cadmium from mining on fish in the Tri-States District of northeastern Oklahoma, USA.

We assessed the exposure of fish from the Spring and Neosho Rivers in northeast Oklahoma, USA, to lead, zinc, and cadmium from historical mining in the Tri-States Mining District (TSMD). Fish (n = 74) representing six species were collected in October 2001 from six sites on the Spring and Neosho Rivers influenced to differing degrees by mining. Additional samples were obtained from the Big River, a heavily contaminated stream in eastern Missouri, USA, and from reference sites. Blood from each fish was analyzed for Pb, Zn, Cd, Fe, and hemoglobin (Hb). Blood also was analyzed for delta-aminolevulinic acid dehydratase (ALA-D) activity. The activity of ALA-D, an enzyme involved in heme synthesis, is inhibited by Pb. Concentrations of Fe and Hb were highly correlated (r = 0.89, p < 0.01) across all species and locations and typically were greater in common carp (Cyprinus carpio) than in other taxa. Concentrations of Pb, Zn, and Cd typically were greatest in fish from sites most heavily affected by mining and lowest in reference samples. The activity of ALA-D, but not concentrations of Hb or Fe, also differed significantly (p < 0.01) among sites and species. Enzyme activity was lowest in fish from mining-contaminated sites and greatest in reference fish, and was correlated negatively with Pb in most species. Statistically significant (p < 0.01) linear regression models that included negative terms for blood Pb explained as much as 68% of the total variation in ALA-D activity, but differences among taxa were highly evident. Positive correlations with Zn were documented in the combined data for channel catfish (Icralurus punctatus) and flathead catfish (Pylodictis olivaris), as has been reported for other taxa, but not in bass (Micropterus spp.) or carp. In channel catfish, ALA-D activity appeared to be more sensitive to blood Pb than in the other species investigated (i.e., threshold concentrations for inhibition were lower). Such among-species differences are consistent with previous studies. Enzyme activity was inhibited by more than 50% relative to reference sites in channel catfish from several TSMD sites. Collectively, our results indicate that Pb is both bioavailable and active biochemically in the Spring-Neosho River system.

Animals↗

PubMed2004

Diagnosis and treatment of polypoid lesions of the gallbladder: report of 194 cases.

BACKGROUND: With the wide use of B-ultrasonography in recent years, the polypoid lesion of the gallbladder (PLG) has been one of the most common diseases detected in biliary surgery. This study was to investigate the diagnostic method and operative indications of PLG. METHODS: The clinical and pathological data of 194 patients with PLG who had received operation at our hospital from January 1994 to September 2002 were analyzed retrospectively. Categorized data were analyzed by the chi-square test. RESULTS: All the patients received preoperative B-ultrasonography. 185 of the 194 PLG patients were diagnosed as having cholecystic polyp, and 9 adenomas. Among the 42 patients who received CT, 6 showed early gallbladder cancer. Pathologically, cholesterol polyps were mostly multiple lesions (64.7%) with a mean diameter of 3.86+/-2.2 mm in 136 patients. Of 16 patients with adenomas, 10 had a tumor diameter of more than 10 mm (62.5%). In 11 patients with gallbladder carcinoma, 7 were accompanied with gallbladder stone (63.6%). In addition, inflammatory polyps and adenomyomas were found in 25 and 6 patients respectively. CONCLUSIONS: B-ultrasonography is the most effective diagnostic method for detecting PLG. When large or irregular lesions are found, CT should be performed in order to avoid missing of gallbladder carcinoma. Operative indications for PLG include: a maximal tumor diameter of more than 10 mm; an over 50-year-old patient with a widebase and a single polyp lesion; a wide-base lesion or a lesion showing a tendency to enlargement; co-existing gallbladder stone or cholecystitis; a patient without other diseases but obvious clinical features and failure of general management; big or long pedicels or polyps at the neck of the gallbladder for preventing the empty of the gallbladder and a history of biliary colic; and PLG with irregularly thickened local gallbladder wall.

Adult↗

PubMed1999

Tandem-base mutations occur in mouse liver and adipose tissue preferentially as G:C to T:A transversions and accumulate with age.

Tandem-base mutations (TBM) are associated with ultraviolet light and other mutagens. Herein, we report an age- and tissue-specific difference in the frequency of spontaneous TBM in Big Blue transgenic mice. A total of 390 mutants from liver and adipose tissue contained 17 and 4 TBM, respectively, while no TBM were detected in 683 mutants from six other tissues. There was a proportional increase in the frequency of TBM in liver with age (29 days postconception to 25 months of age). Nine TBM (43%) were GG to TT transversions that preferentially occurred at specific sites. The remaining 12 mutants contained at least one transversion mutation each. We speculate that the increase of TBM in liver and adipose tissue with age is due to chronic mutagen exposure, perhaps derived from fat in the diet.

Adipose Tissue↗

PubMed2005

Resilience in relation to personality and intelligence.

Resilience is a construct of increasing interest, but validated scales measuring resilience factors among adults are scarce. Here, a scale named the Resilience Scale for Adults (RSA) was crossvalidated and compared with measures of personality (Big Five/5PFs), cognitive abilities (Raven's Advanced Matrices, Vocabulary, Number series), and social intelligence (TSIS). All measures were given to 482 applicants for the military college. Confirmatory factor analyses confirmed the fit of the five-factor model, measuring 'personal strength', 'social competence', 'structured style', 'family cohesion' and 'social resources'. Using Big Five to discriminate between well adjusted and more vulnerable personality profiles, all resilience factors were positively correlated with the well adjusted personality profile. RSA-personal strength was most associated with 5PFs-emotional stability, RSA-social competence with 5PFs-extroversion and 5PFs-agreeableness, as well as TSIS-social skills, RSA-structured style with 5PFs-conscientiousness. Unexpectedly but interestingly, measures of RSA-family cohesion and RSA-social resources were also related to personality. Furthermore, the RSA was unrelated to cognitive abilities. This study supported the convergent and discriminative validity of the scale, and thus the inference that individuals scoring high on this scale are psychologically healthier, better adjusted, and thus more resilient.

Adaptation, Psychological↗

PubMed2003

Differential role of MEK5alpha and MEK5beta in BMK1/ERK5 activation.

Big mitogen-activated protein kinase 1/extracellular-regulated kinase 5 (BMK1/ERK5) is regulated sequentially by a series of upstream MAP kinase kinases (MEKs) in a signaling cascade. MEKs activate their downstream MAPK by phosphorylation of threonine and tyrosine in the T- X-Y motif. MEK5 is the upstream BMK1 kinase and exists as naturally occurring splice variants, MEK5alpha and MEK5beta. The full-length MEK5 (MEK5alpha) is 89 amino acids longer than MEK5beta at the N terminus, but the precise functional difference between the two splice variants is not known. Dual phosphorylation site mutation of MEK5alpha (Ser-311 --> Asp and Thr- 315 --> Asp; MEK5alpha(S311D/T315D)) activated BMK1, but the corresponding dual phosphorylation sites mutant of MEK5beta could not induce BMK1 kinase activation or nuclear translocation. Furthermore, MEK5beta inhibited epidermal growth factor-induced BMK1 activation and MEK5alpha(S311D/T315D)-induced MEF2 transcriptional activity. Both MEK5alpha and MEK5beta individually co-immunoprecipitated with BMK1, but the presence of MEK5beta prevented association of MEK5alpha with BMK1 suggesting a mechanistic basis for the dominant-negative behavior of MEK5beta on BMK1 activation. The ratio of MEK5alpha to MEK5beta expression was higher in cancer cell lines, and overexpression of MEK5beta-inhibited serum-induced DNA synthesis. These data suggest that alternative splicing of MEK5alpha and MEK5beta may play a critical role in BMK1 activation and subsequent cell proliferation.

Active Transport, Cell Nucleus↗