Miracle-dz/UniFAR-FTUs huggingface dataset:
Vanadium induces apoptosis and modulates the expressions of metallothionein, Ki‐67 nuclear antigen, and p53 during 2‐acetylaminofluorene‐induced rat liver preneoplasia

Our previous studies have shown that vanadium, a dietary micronutrient, has an inhibitory effect against experimentally induced rat hepatocarcinogenesis. In this study, we evaluated the role of vanadium on some potential protein expression markers of carcinogenesis, such as metallothionein (MT), an intracellular metal‐binding protein linked with cell proliferation and apoptosis, Ki‐67 nuclear antigen, and p53 tumor suppressor during 2‐acetylaminofluorene (2‐AAF)‐induced (0.05% in basal diet) rat liver preneoplasia. In a short‐term regimen, supplementation of vanadium at a dose of 0.5 ppm effectively suppressed the formation of DNA ‘comets’ (29.55%; P < 0.02), thereby indicating its nongenotoxicity at this particular dose. Vanadium administration throughout the study reduced relative liver weight (RLW), nodular incidence (57.15%), total number, and multiplicity (48.45%) with restoration of hepatic zinc (Zn), magnesium (Mg), selenium (Se), copper (Cu), iron (Fe), and calcium (Ca) contents when compared to the carcinogen control. Moreover, treatment with vanadium significantly abated the expressions of MT and Ki‐67, studied at four sequential time points. An increased immunopositivity of p53 protein (1.03 ± 0.23%; P < 0.02) was found in vanadium‐treated rat liver with an elevated apoptotic‐labeling index (AI; P < 0.001) as documented by TUNEL assay. Furthermore, a positive correlation between MT expression and Ki‐67 labeling along with a strong negative correlation between MT immunoreactivity and AI (r = −0.9000, P = 0.0004 at week 24) at various time intervals suggest that, vanadium‐mediated suppression of MT and Ki‐67 expressions may be associated with induction of apoptosis. The results thus provide evidence for the first time in support of the potential role of vanadium on induction of p53 and apoptosis with concurrent suppression of MT and Ki‐67 in order to have an understanding, in part, of the chemopreventive mechanism of this trace element in limiting neoplastic transformation in a defined model of experimental rat hepatocarcinogenesis. © 2004 Wiley‐Liss, Inc.
Engineering proteins with tunable thermodynamic and kinetic stabilities

It is widely recognized that enhancement of protein stability is an important biotechnological goal. However, some applications at least, could actually benefit from stability being strongly dependent on a suitable environment variable, in such a way that enhanced stability or decreased stability could be realized as required. In therapeutic applications, for instance, a long shelf‐life under storage conditions may be convenient, but a sufficiently fast degradation of the protein after it has performed the planned molecular task in vivo may avoid side effects and toxicity. Undesirable effects associated to high stability are also likely to occur in food‐industry applications. Clearly, one fundamental factor involved here is the kinetic stability of the protein, which relates to the time‐scale of the irreversible denaturation processes and which is determined to some significant extent by the free‐energy barrier for unfolding (the barrier that “separates” the native state from the highly‐susceptible‐to‐irreversible‐alterations nonnative states). With an appropriate experimental model, we show that strong environment‐dependencies of the thermodynamic and kinetic stabilities can be achieved using robust protein engineering. We use sequence‐alignment analysis and simple computational electrostatics to design stabilizing and destabilizing mutations, the latter introducing interactions between like charges which are screened out at high salt. Our design procedures lead naturally to mutating regions which are mostly unstructured in the transition state for unfolding. As a result, the large salt effect on the thermodynamic stability of our consensus plus charge‐reversal variant translates into dramatic changes in the time‐scale associated to the unfolding barrier: from the order of years at high salt to the order of days at low salt. Certainly, large changes in salt concentration are not expected to occur in biological systems in vivo. Hence, proteins with strong salt‐dependencies of the thermodynamic and kinetic stabilities are more likely to be of use in those cases in which high‐stability is required only under storage conditions. A plausible scenario is that inclusion of high salt in liquid formulations will contribute to a long protein shelf‐life, while the lower salt concentration under the conditions of the application will help prevent the side effects associated with high‐stability which may potentially arise in some therapeutic and food‐industry applications. From a more general viewpoint, this work shows that consensus engineering and electrostatic engineering can be readily combined and clarifies relevant aspects of the relation between thermodynamic stability and kinetic stability in proteins. Proteins 2008. © 2007 Wiley‐Liss, Inc.
DEVELOPMENTAL SUCCESS, STABILITY, AND PLASTICITY IN CLOSELY RELATED PARTHENOGENETIC AND SEXUAL LIZARDS (HETERONOTIA, GEKKONIDAE)

Abstract The developmental trajectory of an organism is influenced by the interaction between its genes and the environment in which it develops. For example, the phenotypic traits of a hatchling reptile can be influenced by the organism's genotype, by incubation temperature, and by genetically coded norms of reaction for thermally labile traits. The evolution of parthenogenesis provides a unique opportunity to explore such effects: a hybrid origin of this trait in vertebrates modifies important aspects of the genotype (e.g., heterozygosity, polyploidy) and may thus impact not only on the phenotype generally, but also on the ways in which incubation temperature affects expression of the phenotype. The scarcity of vertebrate parthenogenesis has been attributed to developmental disruptions, but previous work has rarely considered reaction norms of embryogenesis in this respect. We used closely related sexual and asexual races of the Australian gecko Heteronotia binoei, which include those with multiple origins of parthenogenesis, to explore the ways in which reproductive modes (sexual, asexual), incubation temperatures (24, 27, and 30°C), and the interaction between these factors affected hatchling phenotypes. The hatchling traits we considered included incubation period, incidence of deformities, hatchling survivorship, body size and shape, scalation (including fluctuating asymmetry), locomotor performance, and growth rate. Developmental success was slightly reduced (higher proportion of abnormal offspring) in parthenogenetic lineages although there was no major difference in hatching success. Incubation temperature affected a suite of traits including incubation period, tail length, body mass relative to egg mass, labial scale counts, running speed, growth rate, and hatchling survival. Our data also reveal an interaction between reproductive modes and thermal regimes, with the phenotypic traits of parthenogenetic lizards less sensitive to incubation temperature than was the case for their sexual relatives. Thus, the evolution of asexual reproduction in this species complex has modified both mean hatchling viability and the norms of reaction linking hatchling phenotypes to incubation temperature. Discussions on the reasons why parthenogenetic organisms are scarce in nature should take into account interactive effects such as these; future work could usefully try to tease apart the roles of parthenogenesis, its hybrid origin (and thus effects on ploidy and heterozygosity, etc.), and clonal selection in generating these divergent embryonic responses.
Anti-inflammatory and wound healing potential of cashew apple juice (Anacardium occidentale L.) in mice

Cashew apple is a tropical pseudofruit consumed as juice due to its excellent nutritional and sensory properties. In spite of being well known for its important antioxidant properties, the cashew apple has not been thoroughly investigated for its therapeutic potential. Thereby, this study evaluated the antioxidant capacity, anti-inflammatory, and wound-healing activities of cashew apple juice. Juices from ripe and immature cashew apples were analyzed for antioxidant, anti-inflammatory, and wound-healing properties. Those were evaluated in murine models of xylene-induced ear edema and wound excision. Swiss mice were treated with cashew juice by gavage. Edema thickness was measured and skin lesions were analyzed by planimetry and histology. Both antioxidant content and total antioxidant activity were higher in ripe cashew apple juice (RCAJ) than in unripe cashew apple juice (UNCAJ). The UNCAJ presented the main anti-inflammatory activity by a significant inhibition of ear edema (66.5%) when compared to RCAJ (10%). Moreover, UNCAJ also showed the best result for wound contraction (86.31%) compared to RCAJ (67.54%). Despite of higher antioxidant capacity, RCAJ did not promote better anti-inflammatory, and healing responses, which may be explained by the fact that treatment increased antioxidants level leading to a redox “imbalance” turning down the inflammatory response modulation exerted by reactive oxygen species (ROS). The results suggest that UNCAJ presents a greater therapeutic activity due to a synergistic effect of its phytochemical components, which improve the immunological mechanisms as well as an optimal balance between ROS and antioxidants leading to a better wound healing process.
Prevalence of nickel allergy among Finnish university students in 1995

Nickel allergy was studied in a sample of 1st‐year university students starting their studies in 1995. A total of 296 subjects (72%) of 413 invited participated in the clinical examination, and 284, 96 male and 188 female, were patch tested (69%). A history of nickel sensitization was enquired for. Prick tests and serum specific IgE levels were determined. Occurrence of atopic dermatitis, hand eczema, and current exposure to metals were recorded. Nickel allergy was encountered in 39% of all female students, in 42% of females with pierced skin, and in 14% of females without pierced skin. The corresponding figures for males were 3%, 7% and 3%. In the multiple regression analysis, the risk factors for nickel allergy were female sex (OR 8.1, p<0.01), current metal exposure at examination (OR 4.1, p<0.01) and skin piercing (OR 3.6, p<0.05). Positive prick tests or elevated IgE levels to common allergens were not significantly associated with nickel allergy. In female students, the prevalence of nickel allergy has increased from 13% in 1986 to 39%. The prevalence among males has remained low at 3%. The results indicate that, in addition to skin piercing, current metal contacts are important risk factors for nickel allergy. This finding gives support to the EU Nickel Directive.
Role of directional vacuum assisted breast biopsy in previously equivocal biopsies for breast masses suspicious for malignancy.

UNLABELLED Among percutaneous biopsy techniques, the vacuum assisted breast biopsy (VAB) obtains large tissue samples to alleviate some of the limitations associated with conventional percutaneous biopsy techniques. We aimed to determine the efficacy of VAB in previous equivocal biopsies using the mammotome device. MATERIALS AND METHODS A prospective non-randomized efficacy study was planned and executed on 43 patients (42 women, 1 man) whose previous FNAC and/or CNB of breast masses yielded inconclusive results or were suspicious for cancer. RESULTS VAB revealed malignancy in 31 (72%) of the 43 patients. Among them, 23 were diagnosed as infiltrative ductal carcinoma (IDC) on VAB, 20 underwent surgery and the final histopathological diagnosis was the same in 19 of them. One patient showed ductal carcinoma-in-situ (DCIS) only in the surgical specimen. Other malignancies included infiltrating lobular carcinoma (ILC) in 5 patients and one each of DCIS, non- Hodgkin lymphoma (NHL) and metastasis from lung cancer. Benign lesions were detected in 12 (28%) patients. These included 8 fibroadenomas, 2 fibrocystic disease and 1 each of mastitis and breast abscess. Four patients with fibroadenoma underwent surgical excision.
Comparison of various centroiding algorithms to determine the centroids of circular marks in images

Determining the centroids of circular marks is a problem that arises in many applications, for example, fluid mechanics, computer graphics, coordinate meteorology, statistics, etc. The accuracy of determining the centroids of circular marks in images is important for the overall accuracy of measurements. Therefore, the aim of the present work is to determine the centroids of these circular marks with reasonable accuracy. Artificial images were generated with the variation of image signal-to-noise ratio (SNR). First, the images were segmented using basic global thresholding method. Then different centroiding algorithms, namely, Center of Mass (CoM), Weighted Center of Mass (WCoM), Spath algorithm and Hough transform, were used, and RMS errors in centroid detection were compared. A circular mark with radius of 8 pixels (reported as commonly used value in literature) was used to study the effect of varying SNR. Results showed that CoM and WCoM techniques gave higher accuracy in centroid detection for high SNRs, whereas Hough transform performed better for low SNRs. However, Spath algorithm showed comparable errors to those of CoM and WCoM techniques for high SNRs and those of Hough transform for low SNRs. Hence, in overall sense, Spath algorithm is the most accurate algorithm for all SNRs.
Neuropsychological functioning, coping, and quality of life among returning war veterans.

PURPOSE The present research tested the hypothesis that action- and emotion-focused coping strategies would mediate the relationship between neuropsychological functioning and quality of life among a sample of returning Iraq/Afghanistan veterans. METHOD Veterans (N = 130) who served as part of the wars in Iraq and Afghanistan completed a diagnostic assessment of PTSD, a battery of questionnaires assessing coping style, traumatic brain injury (TBI), and quality of life, and neuropsychological tests measuring attention, learning and memory, working memory, inhibition, executive control, and visual motor coordination. RESULTS Executive control, immediate and delayed verbal recall, and visual motor coordination were associated with quality of life. However, after controlling for the effects of combat exposure, PTSD, and probable TBI, no measure of neuropsychological functioning was directly associated with quality of life. Mediation analyses indicated that delayed verbal recall influenced quality of life through its effect on action-focused coping. CONCLUSIONS Although replication is needed, these findings indicate that delayed verbal recall may indirectly influence quality of life among Iraq/Afghanistan veterans through its association with action-focused coping strategies. Psychologists who are working with veterans that are experiencing memory difficulties and poor quality of life may consider focusing on improving coping skills prior to rehabilitation of memory deficits. (PsycINFO Database Record
Generation after generation: Exploring the psychological impact of providing genetic services through a cascading approach

Purpose: The provision of genetic services often occurs in a cascading fashion within families experiencing inherited diseases. This study examines whether previous family experiences with genetic services influences levels of psychological well-being of family members receiving services later.Methods: Two hundred ninety-seven persons from 38 families with Lynch syndrome completed questionnaires before receiving genetic services. Baseline levels of test-related distress, depressive symptoms, and cancer worries were assessed in relationship to the (1) amount of time elapsed since services were provided to the index case and (2) generation of the family member relative to the index case.Results: Family members in the same generation as the index case experienced significant increases in test-related distress (P = 0.003) and cancer worry (P = 0.001) with increasing time between receipt of genetic test results by the index case and provision of services to family members. Change in the number of depressive symptoms was not significant (P = 0.17). Conclusion: The provision of genetic services through a cascading approach significantly increases distress and worry among family members within the same generation as the index case who receive services at increasingly distant time intervals. Additional research is needed to explore social influences after the introduction of genetic services.
Using communication to manage uncertainty about cervical cancer screening guideline adherence among Appalachian women

ABSTRACT Changes to the United States Preventive Services Task Force (USPSTF) recommendations for cervical cancer preventive services have led to patient confusion, especially in medically underserved populations. We investigated how patient uncertainty concerning cervical cancer screening guidelines is appraised and managed through communication with healthcare providers by conducting in-depth, face-to-face interviews with 24 adult women between the ages of 24 and 65 (m = 41, SD = 14) living in Appalachia Kentucky. In general, participants expressed a high degree of uncertainty about the updated cervical cancer screening guidelines and appraised this uncertainty as both a danger and an opportunity. Communication with healthcare providers served both to exacerbate and to mitigate patient uncertainty. The study identifies how healthcare providers may use the change in USPSTF guidelines as a “teachable moment” to productively counsel patients on the importance of timely screening, the typical progression of certain types of high-risk HPV (human papillomavirus) infection to cervical cancer, and the importance of follow-up care.
Space charge behaviours in polyethylene under combined AC and DC electric fields

Polyethylene has been one of the widely studied polymeric insulation materials. One of the major issues related to polymeric materials is the easy formation of space charge which may cause electric field enhancement. In this paper, a numerical simulation based on a bipolar charge injection/transport model is used to obtain characteristics of space charge in polyethylene under the combined AC and DC high voltage at room temperature. The bipolar charge injection/transport model, which is widely used in HVDC space charge simulation, is applied in this combined condition. The overall applied voltage, consisted of root mean square (RMS) values of 50 Hz AC voltage and DC voltage, is kept the same, while the DC component has been varied from 0 to 1. The simulated charge distributions present notable differences when DC offset is added compared with pure AC conditions. Besides, these differences become more significant when the offset ratio is increased. The total positive and negative charge amounts are calculated respectively by integrating the charge in the material, and a curve of net charge amount changing along with time is obtained.
Full Activation of PKB/Akt in Response to Insulin or Ionizing Radiation Is Mediated through ATM*

The gene mutated in ataxia telangiectasia, ATM, has been implicated in several cell functions such as cell cycle control and response to DNA damage and insulin. PKB/Akt has also been implicated in the cellular response to insulin, γ-radiation, and cell cycle control. Interestingly, lack of PKB/Akt function in vivo is able to mimic some phenotypic abnormalities associated with ataxia telangiectasia (AT). Here we show that ATM is a major determinant of full PKB/Akt activation in response to insulin or γ-radiation. This effect is mediated through the phosphatidylinositol 3-kinase domain of ATM that specifically affects Akt serine 473 phosphorylation. This conclusion was inferred from the results obtained in transient transfection assays using exogenous PKB/Akt and ATM in Cos cells. Moreover, the use of ATM inhibitors or small interfering RNA confirmed our observation. Further supporting these results, we also observed that biological responses tightly regulated by Akt, such as transcription factor of the forkhead family activity after insulin treatment or γ-radiation response, were altered in cell lines derived from AT patients and knockout mice for ATM in which phosphorylation in serine 473 was almost abolished. This study proposes new clues in the search of the unknown PDK2 and new explanations for the radiosensitivity or insulin intolerance described more than 30 years ago in AT patients.
Induction of Hypoglycemia Unawareness by Asymptomatic Nocturnal Hypoglycemia

Hypoglycemia has been incriminated as a possible factor responsible for development of the hypoglycemia unawareness phenomenon in patients with type I diabetes. Many patients with this condition, however, do not have a history of recent hypoglycemia. Because asymptomatic nocturnal hypoglycemia commonly occurs in type I diabetes, we tested the hypothesis that such episodes might be capable of inducing this phenomenon. Accordingly, autonomic and neuroglycopenic symptoms, counterregulatory hormone responses, and cognitive function were assessed during standardized insulin-induced hypoglycemia in 10 normal volunteer subjects on two occasions—once after induction of asymptomatic nocturnal hypoglycemia and once after control studies in which saline rather than insulin was infused overnight. Compared with control experiments, asymptomatic nocturnal hypoglycemia increased the threshold (required greater hypoglycemia for initiation) and reduced the magnitude of autonomic and neuroglycopenic symptoms, counterregulatory hormone responses, and cognitive dysfunction during subsequent hypoglycemia (all, P < 0.05). These results indicate that asymptomatic hypoglycemia may induce hypoglycemia unawareness and, thus, may explain why not every patient with this condition has a history of prior hypoglycemia. Our results therefore support the concept that in type I diabetes this phenomenon may be largely attributable to antecedent hypoglycemia.