Miracle-dz/UniFAR-FTUs huggingface dataset:
Peroxisome Proliferator-Activated Receptor γ and Growth Inhibition by Its Ligands in Uterine Endometrial Carcinoma

Purpose: In this study, we evaluated the correlation between endometrial carcinoma and peroxisome proliferator-activated receptor γ (PPARγ) expression and assessed whether PPARγ ligands influence carcinoma growth. Experimental Design: We examined the presence and cellular distribution of PPARγ protein in 42 normal endometria, 32 endometria with hyperplasia, and 103 endometria with endometrial carcinoma by immunohistochemistry. We then compared PPARγ mRNA expression in endometrial carcinoma with that in normal endometria using real-time reverse transcription-PCR. We subsequently confirmed expression of PPARγ mRNA by real-time reverse transcription-PCR and PPARγ protein by immunoblotting in endometrial carcinoma cell lines (Ishikawa, Sawano, and RL95-2 cells). We further examined the effects of PPARγ agonist 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a naturally occurring PPARγ ligand, to these endometrial carcinoma cell lines. We also examined the status of apoptosis and p21 mRNA expression of these endometrial carcinoma cell lines following addition of 15d-PGJ2. Results: PPARγ immunoreactivity was detected in 11 of 23 (48%) of proliferative-phase endometrium, 14 of 19 (74%) of secretory-phase endometrium, 27 of 32 (84%) of endometrial hyperplasia, and 67 of 103 (65%) of carcinoma cases. PPARγ immunoreactivity was significantly lower in endometrial carcinoma than in secretory-phase endometrium (P = 0.012) and endometrial hyperplasia (P = 0.006). There was a significant positive association between the status of PPARγ and p21 expression in endometrial carcinoma (P < 0.0001). There was a significant negative association between the body mass index and PPARγ labeling index of carcinoma tissue in the patients with endometrial carcinoma (P < 0.0001). PPARγ mRNA was expressed abundantly in normal endometria but not in endometrial carcinoma. We showed that PPARγ agonist 15d-PGJ2 inhibited cell proliferation and induced p21 mRNA of endometrial carcinoma cell lines. Conclusion: We showed the expression of PPARγ in human endometrial carcinoma and the effects of PPARγ ligand in endometrial carcinoma cells. These findings suggest that a PPARγ ligand, 15d-PGJ2, has antiproliferative activity against endometrial carcinoma.
New Evidence on News-Driven Business Cycles

We study the Beaudry and Portier (2006)-hypothesis of delayed-technology diffusion and newsdriven business cycles. For German data on TFP and stock prices we find qualitatively similar empirical evidence. Quantitatively, however, an impulse response analysis suggests that a substantial part of the total TFP response is immediate rather than delayed. We relate this to disembodied technological change and noisy data on TFP. Nevertheless, we confirm the technology interpretation of structural shocks by showing that they are Granger-causal for data on patents granted by the German patent agency.
Intracellular acidification delays hormonal G2/M transition and inhibits G2/M transition triggered by thiophosphorylated MAPK in Xenopus oocytes

Xenopus oocyte maturation is analogous to G2/M transition and characterized by germinal vesicle breakdown (GVBD), spindle formation, activation of MPF and Mos‐Xp42Mpk1 pathways. It is accompanied prior to GVBD by a transient increase in intracellular pH. We determined that a well known acidifying compound, NH4Cl, delayed progesterone‐induced GVBD in a dose‐dependent manner. GVBD50 was delayed up to 2.3‐fold by 10 mM NH4Cl. Cyclin B2 phosphorylation, Cdk1 Tyr15 dephosphorylation as well as p39Mos accumulation, Xp42Mpk1 and p90Rsk phosphorylation induced by progesterone were also delayed by incubation of oocyte in NH4Cl. The delay induced by NH4Cl was prevented by injection of MOPS buffer pH 7.7. In contrast to acidifying medium, alkalyzing treatment such as Tris buffer pH 9 injections, accelerated GVBD, MPF and Xp42Mpk1 activation, indicating that pHi changes control early steps of G2/M dynamics. When injected in an immature recipient oocyte, egg cytoplasm triggers GVBD through MPF auto‐amplification, independently of protein synthesis. In these conditions, GVBD and Xp42Mpk1 activation were delayed by high concentration of NH4Cl, which never prevented or delayed MPF activation. Strickingly, NH4Cl strongly inhibited thiophosphorylated active MAPK‐induced GVBD and MPF activation. Nevertheless, Tris pH 9 did not have any effects on egg cytoplasm‐ or active MAPK‐induced GVBD. Taken together, our results suggest that dynamic of early events driving Xp42Mpk1 and MPF activation induced by progesterone may be negatively or positively regulated by pHi changes. However Xp42Mpk1 pathway was inhibited by acidification alone. Finally, MPF auto‐amplification loop was not sensitive to pHi changes. J. Cell. Biochem. 98: 287–300, 2006. © 2006 Wiley‐Liss, Inc.
Quality of life of Nigerian informal caregivers of community-dwelling stroke survivors.

BACKGROUND Caregivers play important roles in the collaborative efforts that characterize successful stroke rehabilitation, and their quality of life (QoL) may have implications for outcome of care. AIM This study explored the QoL of caregivers of community-dwelling stroke survivors in north-eastern Nigeria. METHODS Fifty-nine caregivers of community-dwelling stroke survivors attending physiotherapy out-patients departments of two government hospitals in the city of Maiduguri participated in the study. Information on participants' age, gender, employment status, educational background, relationship with the stroke patient, and time after onset of stroke were obtained through interview, while their QoL was assessed with WHOQoLBREF questionnaire. Demographic and QoL data were summarized with descriptive statistics, and influence of caregivers and care recipients' factors on QoL was analysed using Kruskal-Wallis test. RESULTS Majority of caregivers were males (55.9%) and provided care for their parents (69.5%) who had suffered stroke within 1 year prior to study (72.9%). Mean scores on all QoL domains were above average with the physical domain recording the lowest scores. Caregivers' factors of age, educational background and employment, and duration poststroke onset were significantly associated with domains of QoL. CONCLUSION Although QoL of stroke caregivers was fair across domains, the physical domain recorded the lowest mean scores. Older age, lack of formal education, unemployment and caring for stroke patients within the second year poststroke were associated with lower QoL scores. Information from this study may aid in identifying those caregivers who require support programmes and care the most.
Patterns of Striatal Degeneration in Frontotemporal Dementia

Behavioral variant frontotemporal dementia and semantic dementia have been associated with striatal degeneration, but few studies have delineated striatal subregion volumes in vivo or related them to the clinical phenotype. We traced caudate, putamen, and nucleus accumbens on magnetic resonance images to quantify volumes of these structures in behavioral variant frontotemporal dementia, semantic dementia, Alzheimer disease, and healthy controls (n=12 per group). We further related these striatal volumes to clinical deficits and neuropathologic findings in a subset of patients. Behavioral variant frontotemporal dementia and semantic dementia showed significant overall striatal atrophy compared with controls. Moreover, behavioral variant frontotemporal dementia showed panstriatal degeneration, whereas semantic dementia featured a more focal pattern involving putamen and accumbens. Right-sided striatal atrophy, especially in the putamen, correlated with the overall behavioral symptom severity and with specific behavioral domains. At autopsy, patients with behavioral variant frontotemporal dementia and semantic dementia showed striking and severe tau or TAR DNA-binding protein of 43 kDa pathology, especially in ventral parts of the striatum. These results demonstrate that ventral striatum degeneration is a prominent shared feature in behavioral variant frontotemporal dementia and semantic dementia and may contribute to the social-emotional deficits common to both disorders.
Connexin dynamics in the privileged wound healing of the buccal mucosa

Wound closure is fundamental to maintaining tissue homeostasis; a plethora of processes and signals must be coordinated, and gap junctions play a critical role. Some tissues exhibit privileged healing, such as buccal mucosa, repairing more rapidly, but gap junction connexin dynamics during wound healing in such tissues have not been investigated. To determine connexin changes during this rapid healing process, incisional wounds were made in the cheeks of mice and microscopically observed. We discovered that buccal mucosa wound edge keratinocytes do not form a thin tongue of migratory cells like epidermis; instead, a wedge of cells rapidly moves into the wound. The dorsal surfaces of opposing sides of the wounds then touch and join in a “V,” which subsequently fills up with cells to form a “delta” that remodels into a flat sheet. Immunostaining showed that connexin26, connexin30, and connexin43 are expressed at significantly higher levels in the buccal mucosa than the epidermis and that, unlike the skin, all three are rapidly down‐regulated at the wound edge within 6 hours of wounding. This rapid down‐regulation of all three connexins may in part underlie the rapid healing of the buccal mucosa.
Calculation of esophageal variceal wall tension by ultrasonic microprobe and noninvasive pressure measurements.

OBJECTIVE To calculate esophageal variceal wall tension by sonographic and noninvasive pressure measurements and to study the role of esophageal variceal wall tension in predicting the likelihood of esophageal variceal rupture. METHODS In 28 patients with esophageal varices, a 20 MHz ultrasonographic transducer was used to image esophageal varices; the radius and wall thickness of the varices were calculated. Esophageal variceal pressure measurements were obtained noninvasively. The correlation between the esophageal wall tension and esophageal variceal pressure gradient were studied. RESULTS There was a linear correlation between the esophageal wall tension and the variceal pressure gradient after curve fitting (r=0.87, p < 0.05). CONCLUSION Esophageal variceal wall tension is an important parameter in predicting variceal rupture.
Troponin T and beta-myosin mutations have distinct cardiac functional effects in hypertrophic cardiomyopathy patients without hypertrophy.

AIMS The validity of genotype:phenotype correlation studies in human hypertrophic cardiomyopathy (HCM) has recently been questioned, yet animal models and in vitro studies suggest distinct effects for different mutations. The aims of this study were to investigate whether distinct HCM-mutations have different consequences for cardiac structure and function in the absence of the confounding effects of hypertrophy. METHODS AND RESULTS Individuals aged 20-65 belonging to 21 R92W(TNNT2), R403W(MYH7), or A797T(MYH7) mutation-bearing families were investigated with 2D, M-mode, and Doppler echocardiography. Cardiac structural and functional parameters were compared between prehypertrophic mutation-carriers and their non-carrier family members, with concomitant adjustment for appropriate covariates. Findings were evaluated against existing animal and in vitro functional data. The distinct functional effect of the R92W(TNNT) mutation was a relative increase in systolic functional parameters, that of the A797T(MYH7) mutation was reduced diastolic function, while the R403W(MYH7) mutation reduced both systolic and diastolic function. The observed early effects of the R92W(TNNT2) mutation mechanistically fit with prolonged force-transients precipitated by increased Ca(2+) sensitivity of the thin filament, and that of the MYH7 mutations with local ATP depletion. CONCLUSION Evaluation of the impact of the mutations on cardiac structure and function in prehypertrophic mutation-carriers, relative to the baseline norm provided by their non-carrier family members, best recapitulated existing animal and in vitro functional data, while inclusion of mutation-carriers with hypertrophy obscured such findings. The results prompt speculation that timely treatment aimed at ameliorating Ca(2+) sensitivity for R92W(TNNT2)-carriers, and energy depletion for MYH7 mutation-carriers, may offer a plausible approach for preventing progression from a preclinical into a decompensated state.
Identification of a sequence within U5 required for human immunodeficiency virus type 1 to stably maintain a primer binding site complementary to tRNA(Met)

Initiation of reverse transcription of human immunodeficiency virus type 1 (HIV-1) occurs by extension from the 3' end of a cellular tRNA complexed to the primer binding site (PBS) located near the 5' end of the viral RNA genome. Although the PBSs for all naturally occurring HIV-1 viruses are complementary to the 3'-terminal 18 nucleotides of tRNA(Lys)3, we identified an HIV-1 virus which contained a PBS complementary to the 3' nucleotides of tRNA(Met); the PBS of this virus was not stable upon extended culture and reverted back to the wild type (S.-M. Kang, J. K. Wakefield, and C. D. Morrow, Virology 222:401-414, 1996). To further characterize the virus with a PBS complementary to tRNA(Met), a DNA fragment encompassing the PBS and U5 region from this proviral genome was substituted for the same region in the infectious HIV-1 proviral clone [named pHXB2(AC-Met)]. Three additional proviral genomes were also created: pHXB2(Met), which is isogenic with pHXB2 except for the PBS complementary to tRNA(Met); pHXB2(Met-AC-Met), which contains the PBS sequence complementary to the 3'-terminal nucleotides and the sequence upstream of this PBS in U5 complementary to the anticodon region of tRNA(Met); and pHXB2(Met-C-Met), which contains two G-to-C changes predicted to disrupt complementarity within the tRNA(Met) anticodon region. Viruses derived from the transfection of these proviral genomes were infectious, although the appearance of the viruses was delayed compared to that of the wild-type virus. PCR amplification and DNA sequence analysis of the PBS regions from proviral genomes revealed that the PBSs from viruses derived from pHXB2(Met) and pHXB2(AC-Met) reverted back to the wild type by days 16 and 44 postcoculture, respectively. Two new, novel mutant viruses were identified among viruses derived from pHXB2(Met-C-Met) at day 35 postcoculture: one contained a PBS complementary to tRNA(Lys)1,2, while the second maintained a PBS complementary to tRNA(Met) but contained a 26-nucleotide deletion in U5 upstream of the anticodon-complementary region. By day 125 postcoculture, the PBS in the virus from this culture had reverted back to the wild type, complementary to tRNA(Lys)3. In contrast, the viruses derived from pHXB2(Met-AC-Met) stably maintained a PBS complementary to tRNA(Met) during the 125-day culture period examined. The results of these studies support the idea that HIV-1 can maintain a PBS complementary to alternative tRNAs provided that the appropriate complementarity exists between the U5-PBS region of the viral RNA genome and the tRNA molecule used to initiate reverse transcription.
Immunological tolerance to a defined myelin basic protein antigen administered intrathymically.

To explore the mechanisms responsible for the development of tolerance to allografts after intrathymic (IT) injection of alloantigen, the well-defined model of experimental autoimmune encephalomyelitis (EAE), which mimics the human autoimmune disease multiple sclerosis, was used. This inflammatory neurologic syndrome is initiated by myelin basic protein (MBP)-reactive CD4+ T lymphocytes restricted to self-MHC class II molecules. Naive adult, EAE-susceptible Lewis (RT1(1) rats were treated IT, i.v. , or i.p. with a single dose (100 micrograms) of guinea pig-myelin basic protein (GP-MBP 1-176) in PBS plus 1 ml rabbit anti-rat lymphocyte serum i.p. Twenty-one days later, all rats were challenged by intradermal hind footpad injections of 50 micrograms GP-MBP in PBS emulsified in CFA. Only IT, but not i.p. or i.v. , administration of GP-MBP plus anti-lymphocyte serum conferred marked resistance to a subsequent systemic challenge of GP-MBP, as demonstrated by the prevention of weight loss and paralysis characteristic of EAE. The IT administration dramatically decreased the size and number of histologic perivascular infiltrates observed per visual field in spinal cord of the tolerant animals and decreased GP-MBP-specific T lymphocyte in vitro proliferation (p < 0.01), whereas proliferation to a nonspecific mitogen (Con A) was not altered. With the addition of rIL-2, the decreased Ag-specific proliferative responses of IT-treated animals increased to control levels. Adoptive transfer of 100 x 10(6) splenocytes from tolerant hosts i.v. to naive syngeneic Lewis rats challenge with 100 micrograms GP-MBP in CFA had no effect on clinical or histologic EAE. Exposure of MBP to maturing thymocytes results in functionally immunounresponsive lymphocytes and prevention of autoimmune EAE.
Can a 'single hit' cause limitations in language development? A comparative study of Swedish children with hearing impairment and children with specific language impairment.

BACKGROUND Studies of language in children with mild-to-moderate hearing impairment (HI) indicate that they often have problems in phonological short-term memory (PSTM) and that they have linguistic weaknesses both in vocabulary and morphosyntax similar to children with specific language impairment (SLI). However, children with HI may be more likely than children with SLI to acquire typical language skills as they get older. It has been suggested that the more persisting problems in children with SLI are due to a combination of factors: perceptual, cognitive and/or linguistic. AIMS The main aim of this study was to explore language skills in children with HI in comparison with children with SLI, and how children with both HI and language impairment differ from those with non-impaired spoken language skills. METHODS & PROCEDURES PSTM, output phonology, lexical ability, receptive grammar and verb morphology were assessed in a group of children with mild-to-moderate HI (n = 11) and a group of children with SLI (n = 12) aged 5 years 6 months to 9 years 0 months. OUTCOMES & RESULTS The HI group tended to score higher than the SLI group on the language measures, although few of the differences were significant. The children with HI had their most obvious weaknesses in PSTM, vocabulary, receptive grammar and inflection of novel verbs. The subgroup of children with HI (five out of 10) who also showed evidence of grammatical output problems was significantly younger than the remaining children with HI. Correlation analysis showed that the language variables were not associated with age, whereas hearing level was associated with PSTM. CONCLUSIONS Children with HI are at risk for at least a delay in lexical ability, receptive grammar and grammatical production. The problems seen in the HI group might be explained by their low-level perceptual deficit and weak PSTM. For the SLI group the impairment is more severe. From a clinical perspective an important conclusion is that the language development in children with even mild-to-moderate HI deserves attention and support.
The salt tolerance of the freshwater snail Melanoides tuberculata ( Mollusca , Gastropoda ) , a bioinvader gastropod

Melanoides tuberculata (Müller, 1774) (Gastropoda: Thiaridae) is a freshwater gastropod native to Africa and Asia. It is a bioinvader of remarkable ecological capabilities presenting euryoic and highly adaptable to eutrophic conditions, M. tuberculata has also been found in estuarine environments. The first occurrence of the species in South America was reported from Brazil, in the late 60’s. The current literature documents a broader distribution of M. tuberculata in the rivers and reservoirs of the Brazilian north and northeast as well as in the Brazilian middle-west. The aim of this study is to analyze the salt tolerance of M. tuberculata, comparing the effects of salinity variation on adults and juveniles collected from a eutrophic lentic system in Bahia State (Brazil). Survival tests based on salinity exposure shows that the 50% survival salt concentration (salt LC50) for adults is 22.82‰ (CI= 20.46‰-25.19‰) and that the LC50 for juveniles was 21.56‰ (CI= 20.06‰-23.07‰). Activity tests show that the snails tested are motionless at salt concentrations of 30‰ or greater. This study provides new empirical information on the population characteristics of M. tuberculata in Brazil and also contributes to the understanding of physiological stress, ecological capabilities and dispersal strategies in bioinvader species.
Is the Association between Cigarette Smoking and Breast Cancer Modified by Genotype? A Review of Epidemiologic Studies and Meta-analysis

Epidemiologic studies have examined the association between cigarette smoking and breast cancer risk according to genotype with increasing frequency, commensurate with the growing awareness of the roles genes play in detoxifying or activating chemicals found in cigarette smoke and in preventing or repairing the damage caused by those compounds. To date, ∼50 epidemiologic studies have examined the association between smoking and breast cancer risk according to variation in genes related to carcinogen metabolism, modulation of oxidative damage, and DNA repair. Some of the findings presented here suggest possible effect modification by genotype. In particular, 14 epidemiologic studies have tended to show positive associations with long-term smoking among NAT2 slow acetylators, especially among postmenopausal women. Summary analyses produced overall meta–relative risk (RR) estimates for smoking of 1.2 [95% confidence interval (95% CI), 1.0-1.5] for rapid acetylators and 1.5 (95% CI, 1.2-1.8) for slow acetylators. After stratification by menopausal status, the meta-RR for postmenopausal slow acetylators was 2.4 (95% CI, 1.7-3.3), whereas similar analyses for the other categories showed no association. In addition, summary analyses produced meta-RRs for smoking of 1.1 (95% CI, 0.8-1.4) when GSTM1 was present and 1.5 (95% CI, 1.1-2.1) when the gene was deleted. Overall, however, interpretation of the available literature is complicated by methodologic limitations, including small sample sizes, varying definitions of smoking, and difficulties involving single nucleotide polymorphism selection, which likely have contributed to the inconsistent findings. These methodologic issues should be addressed in future studies to help clarify the association between smoking and breast cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(4):602–11)
Robust Combination of Model Selection Methods for Prediction

One important goal of regression analysis is prediction. In recent years, the idea of combining different statistical methods has attracted an increasing atten- tion. In this work, we propose a method, l1-ARM (adaptive regression by mixing), to robustly combine model selection methods that performs well adaptively. In numerical work, we consider the LASSO, SCAD, and adaptive LASSO in represen- tative scenarios, as well as in cases of randomly generated models. The l1-ARM automatically performs like the best among them and consequently provides a bet- ter estimation/prediction in an overall sense, especially when outliers are likely to occur.