Miracle-dz/UniFAR-FTUs huggingface dataset:
Specific Expression and Regulation of the New Melanoma Inhibitory Activity-related Gene MIA2 in Hepatocytes*

The novel human gene MIA2encoding a melanoma inhibitory activity (MIA) homologous protein was identified by a GenBankTM search. MIA2, together with MIA, OTOR, and TANGO, belongs to the novel MIA gene family sharing important structural features, significant homology at both the nucleotide and protein levels, and similar genomic organization. In situ hybridization, reverse transcriptase-PCR, and Northern blots presented a highly tissue-specific MIA2 expression pattern in the liver. Promoter studies analyzing transcriptional regulation of MIA2 revealed an HNF-1-binding site at position −236 controlling hepatocyte-specific expression. Mutation of the site led to a complete loss of promoter activity in HepG2 cell. Further sites detected in the MIA2 promoter were consensus binding sites for SMAD and STAT3, Consistently, stimulation of MIA2 mRNA expression occurred by treatment with interleukin-6, transforming growth factor-β, and conditioned medium from activated hepatic stellate cells. In accordance with these results, MIA2 mRNA was found to be increased in liver tissue of patients with chronic hepatitis C infection compared with controls. MIA2 mRNA levels were significantly higher in patients with severe fibrosis or inflammation than in patients with less severe fibrosis or inflammation. In summary our data indicate that MIA2 represents a potential novel acute phase protein and MIA2 expression responds to liver damage. The increased transcription in more severe chronic liver disease suggests that MIA2 may serve as a marker of hepatic disease activity and severity.
Congenital thrombocytopenia and radio‐ulnar synostosis: a new familial syndrome

The association of bone marrow failure and skeletal defects has been frequently noted, however, the genetic basis for most of these syndromes remains unclear. We describe a previously uncharacterized autosomal dominant syndrome of amegakaryocytic thrombocytopenia associated with radial‐ulnar synostosis. The clinical features of this syndrome appear to be distinct from other similar conditions, including Fanconi's anaemia and thrombocytopenia‐absent radii (TAR). The physical findings at diagnosis and clinical management of each case are detailed, as well as a discussion of this disorder in the context of other syndromes in which marrow failure and skeletal defects are prominent features. We also review recent developments in molecular genetics that may provide important clues to the underlying aetiology of this condition.
Shared Values, Social Trust, and the Perception of Geographic Cancer Clusters

Extensive scientific investigations often fail to identify specific carcinogens that have caused geographic clusters of cancer cases. In many such examples, public health officials and other experts have concluded that the cluster is not the result of a particular local environmental condition. Despite this conclusion by experts, concerned members of local communities often persist in believing that the cancer cluster was not random. The present study accounts for the persistence of this belief on the basis of two factors: (a) the tendency of the human mind to identify patterns (and causes), rather than randomness; and (b) a lack of social trust in public health experts. It was expected that perceived shared values evoke social trust. Individuals who conclude that public health experts share their values should be more likely to accept the experts’ conclusion that a cancer cluster reflects randomness, not a particular local cause. Individuals who trust authorities should be more inclined than individuals not having trust to accept that a geographic cluster of cancer cases is a coincidence. Data from Swiss students (N= 334) supported these expectations. Additionally, significant gender differences were observed. Females had less trust in authorities and perceived the cancer cluster as less likely to be a result of pure chance than did males. Practical implications of the results are discussed.
[Lymphoproliferative syndromes after renal transplantation].

UNLABELLED Following kidney transplantation, lymphoproliferative disorders (LD) are encountered at a frequency of 1%. The onset of these LD is correlated with the degree of immunosuppression. The mortality is elevated (> 50%) especially in late forms. Since 1984 we have performed two hundred and seventeen kidney transplantations. The patients received sequential quadruple-drug immunosuppressive therapy: antilymphocyte globulin (ALG), azathioprine, corticosteroids and cyclosporine. A diagnosis of LD was established in ten patients, four were of early onset (within twelve months of transplantation) and six late (after five to nine years). Rejection occurred in two patients, one of which was steroid resistant requiring ALG. Three LD arose from the graft hilum, four had a voluminous tumor mass with extranodal sites: the graft (1), stomach (2), gingiva (1), meninges (1), and bone marrow (1). Histologically there were eight cases of large-cell B lymphoma, 1 mononucleosis-like LD, and a MALT lymphoma. A search for EBV was positive seven times. Treatment consisted of decreasing immunosuppressive therapy only (1), combined with antiviral treatment (1), or with surgical removal of the graft (3), and/or chemotherapy (5). Nine patients are still alive, in complete remission, graft loss occurred in four cases. CONCLUSION In our series, we found a high frequency of LD. Despite 4 LD with a voluminous tumor mass and unfavorable histological prognosis requiring chemotherapy, all the LD in our series had a favorable outcome.
Clinal variation in body size and sexual dimorphism in an Indian fruit bat, Cynopterus sphinx (Chiroptera: Pteropodidae)

Geographic variation in body size and sexual dimorphism of the short-nosed fruit bat (Cynopterus sphinx) was investigated in peninsular India. Bats were sampled at 12 localities along a 1200 km latitudinal transect that paralleled the eastern flanks of the Western Ghats. The geographic pattern of variation in external morphology of C. sphinx conforms to the predictions of Bergmann's Rule, as indicated by a steep, monotonic cline of increasing body size from south to north. This study represents one of the first conclusively documented examples of Bergmann's Rule in a tropical mammal and confirms that latitudinal clines in body size are not exclusively restricted to temperate zone homeotherms. Body size was indexed by a multivariate axis derived from principal components analysis of linear measurements that summarize body and wing dimensions. Additionally, length of forearm was used as a univariate index of structural size to examine geographic variation in a more inclusive sample of bats across the latitudinal transect. Multivariate and univariate size metrics were strongly and positively correlated with body mass, and exhibited highly concordant patterns of clinal variation. Stepwise multiple regression on climatological variables revealed that increasing size of male and female C. sphinx was associated with decreasing minimum temperature, increasing relative humidity, and increasing seasonality. Although patterns of geographic size variation were highly concordant between the sexes, C. sphinx also exhibited a latitudinal cline in the magnitude and direction of sexual size dimorphism. The size differential reversed direction across the latitudinal gradient, as males averaged larger in the north, and females averaged larger in the south. The degree of female-biased size dimorphism across the transect was negatively correlated with body size of both sexes. Canonical discriminant analysis revealed that male- and female-biased size dimorphism were based on contrasting sets of external characters. Available data on geographic variation in the degree of polygyny in C. sphinx suggests that sexual selection on male size may play a role in determining the geographic pattern of sexual size dimorphism.
Association of vitamin D deficiency with incidence of type 2 diabetes in high-risk Asian subjects.

BACKGROUND Recent studies suggest an association between 25-hydroxyvitamin D [25(OH)D] and type 2 diabetes (T2D) risk. However, prospective studies investigating the relation between vitamin D inadequacy and incidence of T2D incorporating obesity and dynamic measures of insulin resistance (IR) and pancreatic β cell function are limited. OBJECTIVE We tested the hypothesis that baseline 25(OH)D is associated with the incidence of T2D in high-risk subjects for up to 5 y of follow-up, independently of obesity, baseline IR, and β cell function. DESIGN We recruited 1080 nondiabetic Korean subjects [mean ± SD age: 49.5 ± 11.4 y] based on the presence of one or more risk factors for T2D, including obesity, hypertension, dyslipidemia, and/or family history of T2D. We measured anthropometric and biochemical indicators, HOMA2-IR, and the insulinogenic index (IGI; calculated as change in insulin at 30 min/change in glucose at 30 min) from a 75-g oral-glucose-tolerance test. RESULTS Of the participants, 10.5% had a serum 25(OH)D deficiency (<10 ng/mL), 51.6% had an insufficiency (10.0-19.9 ng/mL), and 38.0% had a sufficiency (≥20 ng/mL), and the incidence of T2D at 32.3 ± 15.6 mo (±SD) declined accordingly: 15.9%, 10.2%, and 5.4%, respectively (P < 0.001). After adjustment for age, sex, blood pressure, lifestyles, family history, season, parathyroid hormone, and high-sensitivity C-reactive protein, the participants with 25(OH)D deficiency had an increased risk of T2D independently of BMI, HOMA2-IR, and IGI; the HRs were 2.06 (95% CI: 1.22, 3.49) for 25(OH)D 10-19.9 ng/mL compared with ≥20 ng/mL and 3.23 (95% CI: 1.66, 6.30) for 25(OH)D <10 ng/mL compared with ≥20 ng/mL. CONCLUSION The current prospective study suggests that vitamin D metabolism may play a role in T2D pathogenesis independently of known risk factors. This trial was registered at clinicaltrials.gov as NCT01508481.
Maternal Lipid Provisioning Mirrors Evolution of Reproductive Strategies in Direct-Developing Whelks

The energetic input that offspring receive from their mothers is a well-studied maternal effect that can influence the evolution of life histories. Using the offspring of three sympatric whelks: Cominella virgata (one embryo per capsule); Cominella maculosa (multiple embryos per capsule); and Haustrum scobina (multiple embryos per capsule and nurse-embryo consumption), we examined how contrasting reproductive strategies mediate inter- and intraspecific differences in hatchling provisioning. Total lipid content (as measured in μg hatchling−1 ± SE) was unrelated to size among the 3 species; the hatchlings of H. scobina were the smallest but had the highest lipid content (33.8 ± 8.1 μg hatchling−1). In offspring of C. maculosa, lipid content was 6.6 ± 0.4 μg hatchling−1, and in offspring of C. virgata, it was 21.7 ± 3.2 μg hatchling−1. The multi-encapsulated hatchlings of C. maculosa and H. scobina were the only species that contained the energetic lipids, wax ester (WE) and methyl ester (ME). However, the overall composition of energetic lipid between hatchlings of the two Cominella species reflected strong affinities of taxonomy, suggesting a phylogenetic evolution of the non-adelphophagic development strategy. Inter- and intracapsular variability in sibling provisioning was highest in H. scobina, a finding that implies less control of allocation to individual hatchlings in this adelphophagic developer. We suggest that interspecific variability of lipids offers a useful approach to understanding the evolution of maternal provisioning in direct-developing species.
Gastrointestinal outbreaks associated with Norwalk virus in restaurants in Vancouver, British Columbia.

The Vancouver Coastal Health Authority (VCHA) investigated an Indian restaurant in Vancouver when two groups of people reported becoming ill after consuming meals from the vegetarian buffet there on 12 April, 2002. In the first group, seven of nine office workers became ill 30 to 43 hours (median 34 hours) after eating lunch on that day. Symptoms included nausea, vomiting, diarrhea, fever, prostration, headache, stomach pain, and aching joints. Foods consumed were yoghurt, curry, chick peas, kidney beans and potatoes, lentils, cauliflower and potatoes, green peas and paneer cheese, naan bread, rice, and gulabjamun (a dessert). The duration of illness ranged from 6 hours to 96 hours (median 48 hours).
Pulse Pressure Variation Adjusted by Respiratory Changes in Pleural Pressure, Rather Than by Tidal Volume, Reliably Predicts Fluid Responsiveness in Patients With Acute Respiratory Distress Syndrome*

Objectives:1) To evaluate the ability of pulse pressure variation adjusted by respiratory changes in pleural pressure to predict fluid responsiveness compared with pulse pressure variation alone. 2) To identify factors explaining the poor performance of pulse pressure variation in acute respiratory distress syndrome. Design:Prospective study. Setting:Forty-bed university hospital general ICU. Patients:Ninety-six mechanically ventilated acute respiratory distress syndrome patients requiring fluid challenge. Interventions:Fluid challenge, 500 mL saline over 20 minutes. Measurements and Main Results:Before fluid challenge, esophageal pressure was measured at the end-inspiratory and end-expiratory occlusions. Change in pleural pressure was calculated as the difference between esophageal pressure measured at end-inspiratory and end-expiratory occlusions. Hemodynamic measurements were obtained before and after the fluid challenge. Patients were ventilated with tidal volume 7.0 ± 0.8 mL/kg predicted body weight. The fluids increased cardiac output by greater than 15% in 52 patients (responders). Adjusting pulse pressure variation for changes in pleural pressure (area under the receiver operating characteristic curve, 0.94 [0.88–0.98]) and the ratio of chest wall elastance to total respiratory system elastance (area under the receiver operating characteristic curve, 0.93 [0.88–0.98]) predicted fluid responsiveness better than pulse pressure variation (area under the receiver operating characteristic curve, 0.78 [0.69–0.86]; all p < 0.01). The gray zone approach identified a range of pulse pressure variation/changes in pleural pressure values (1.94–2.1) in 3.1% of patients for whom fluid responsiveness could not be predicted reliably. On logistic regression analysis, two independent factors affected the correct classification of fluid responsiveness at a 12% pulse pressure variation cutoff: tidal volume (adjusted odds ratio 1.57/50 mL; 95% CI, 1.05–2.34; p = 0.027) and chest wall elastance/respiratory system elastance (adjusted odds ratio, 2.035/0.1 unit; 95% CI, 1.36–3.06; p = 0.001). In patients with chest wall elastance/respiratory system elastance above the median (0.28), pulse pressure variation area under the receiver operating characteristic curve was 0.94 (95% CI, 0.84–0.99) compared with 0.76 (95% CI, 0.61–0.87) otherwise (p = 0.02). Conclusions:In acute respiratory distress syndrome patients, pulse pressure variation adjusted by changes in pleural pressure is a reliable fluid responsiveness predictor despite the low tidal volume (< 8 mL/kg). The poor predictive ability of pulse pressure variation in acute respiratory distress syndrome patients is more related to low chest wall elastance/respiratory system elastance ratios than to a low tidal volume.
Correlates of mood disturbance in women with breast cancer: patterns over time.

AIM This study examined factors associated with mood disturbance prior to, during and after adjuvant therapy. BACKGROUND Breast cancer is the most common cancer in women worldwide. Mood disturbance affects between 20% and 30% of women with breast cancer and is associated with other debilitating symptoms. However, factors associated with mood disturbance across the breast cancer diagnosis-treatment trajectory are not clearly understood. METHOD A stress-coping framework guided this longitudinal study. A convenience sample of 49 American women with newly diagnosed breast cancer aged 37-77 years completed questionnaires assessing age, optimism, disease stage, type of adjuvant therapy, lymph node status, emotional support, aid (tangible) support, perceived stress and mood disturbance. Data were collected over an 18-month period in 2002-2003 at three time points: prior to, during and after adjuvant therapy. Descriptive statistics, Pearson's correlation and multiple regression were used. FINDINGS At all three time points, higher stress was significantly related to greater mood disturbance. Perceived stress mediated the relationship between (1) emotional support and mood disturbance prior to and after adjuvant therapy and between (2) aid support and mood disturbance during adjuvant therapy. In addition, the type of support that was most important to mood disturbance varied over time. Emotional support was related to reduced mood disturbance prior to and after adjuvant therapy, whereas aid support was most important during adjuvant therapy. CONCLUSIONS Nurses may use this information to develop interventions that bolster appropriate types of support to reduce stress and ultimately lower mood disturbance. Further research across cultures is needed.
Unconventional Mode of Attachment of the Ruminococcus flavefaciens Cellulosome to the Cell Surface

ABSTRACT Sequence extension of the scaffoldin gene cluster from Ruminococcus flavefaciens revealed a new gene (scaE) that encodes a protein with an N-terminal cohesin domain and a C terminus with a typical gram-positive anchoring signal for sortase-mediated attachment to the bacterial cell wall. The recombinant cohesin of ScaE was recovered after expression in Escherichia coli and was shown to bind to the C-terminal domain of the cellulosomal structural protein ScaB, as well as to three unknown polypeptides derived from native cellulose-bound Ruminococcus flavefaciens protein extracts. The ScaB C terminus includes a cryptic dockerin domain that is unusual in its sequence, and considerably larger than conventional dockerins. The ScaB dockerin binds to ScaE, suggesting that this interaction occurs through a novel cohesin-dockerin pairing. The novel ScaB dockerin was expressed as a xylanase fusion protein, which was shown to bind tenaciously and selectively to a recombinant form of the ScaE cohesin. Thus, ScaE appears to play a role in anchoring the cellulosomal complex to the bacterial cell envelope via its interaction with ScaB. This sortase-mediated mechanism for covalent cell-wall anchoring of the cellulosome in R. flavefaciens differs from those reported thus far for any other cellulosome system.
Food Safety Challenges—A Pakistan's Perspective

Biological, chemical, and physical contamination of foods is a terrifying threat for the health and economic growth in developing societies. Rampantly available literature on foodborne illnesses especially diarrhea among children exclusively depicts the intensified disease burden associated with foodborne illness in the underdeveloped economies. Prevalence of many pathogens in several foods is commonplace in Pakistan. Precise estimates for foodborne illnesses in Pakistan are hard to make because of the absence of any monitoring, surveillance, and infection control. Poor processing and storage of milk, cereal grains, and nuts are a major cause of aflatoxin contamination and mold proliferation. Numerous studies manifest a multitude of foods to be contaminated with heavy metals. Escalating population growth limits the economic potential of the individual and the state through a tendency among the traders and manufacturers to intentionally debase food commodities offered for sale to make profit at the cost of their quality and safety. Therefore, a growing trend of adulteration in foods during the recent past, particularly adulteration of milk, poses a pressing challenge for the government. This review is a concerted attempt to elucidate the prevailing food safety scenario in Pakistan. Information derived from local and related international studies will be presented to clearly depict a picture of food safety in Pakistan. It is proposed that an extensive food safety infrastructure leading to a safer supply of foods needs to be devised, designed, and implemented.
Lode Gold Deposits and Archean Mantle Plume–Island Arc Interaction, Abitibi Subprovince, Canada

In combination with seismic interpretations and geochronological constraints, the association of juvenile arc‐type low‐Ti tholeiitic basalts with komatiites in the southeastern Abitibi subprovince, Canada, supports a history of subduction step back following Late Archean mantle plume–island arc interaction. The resulting paired collision zones preserved abundant komatiites and numerous massive sulphide deposits and established the critical metallogenic features to concentrate the majority of Canada's Precambrian gold resources in a small area of the southern Abitibi subprovince.
Radiation dosimetry results for zevalin radioimmunotherapy of rituximab‐refractory non‐hodgkin lymphoma

Zevalin consists of a murine anti‐CD20 monoclonal antibody (ibritumomab) conjugated to the linker‐chelator tiuxetan, which securely chelates indium‐111 (111In) for imaging and dosimetry and yttrium‐90 (90Y) for radioimmunotherapy (RIT). Previous trials involving rituximab‐naïve patients have demonstrated excellent targeting of Zevalin to CD20+ B‐cell non‐Hodgkin lymphoma with minimal uptake in normal organs. The purpose of this trial was to perform 111In‐Zevalin imaging in patients with rituximab‐refractory tumors to determine normal organ dosimetry.
Initiation and termination of DNA transfer at F plasmid oriT

DNA sequences within the F plasmid transfer origin (oriT) were tested for their ability to initiate or terminate conjugal transfer. Mutant and wild‐type oriT elements were cloned as direct repetitions flanking the rpsL gene on a pBR322‐based plasmid, and the frequency of deletion of this segment during matings sponsored by F’lac (F42) with streptomycin‐resistant recipients was measured. Shortened oriT elements that lacked adjacent TraM‐binding sites allowed efficient initiation and termination. Some truncated orir segments lacking the TraM‐binding sites and the TraY‐binding site, sbyA, initiated transfer inefficiently, but nevertheless promoted efficient termination. Removal of TraM‐, TraY‐, and IHF‐binding sites severely reduced both nicking and termination. Point mutations that previously had been reported to prevent nicking caused reduced levels of both initiation and termination. These results indicate that regions of oriT supporting initiation are more extensive than those needed for termination, although some regions are required for both. Moreover, termination can be effective for some mutant loci that do not support efficient nicking.