Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective interference with class I major histocompatibility complex presentation of the major immediate-early protein following infection with human cytomegalovirus

Responses of cytotoxic T-cells (Tc) to human cytomegalovirus (CMV) represent the predominant mechanism by which hosts resist CMV infection. The CMV major immediate-early protein (IE) is present throughout the virus replicative cycle. Studies were performed to determine whether Tc specific for IE effectively lyse CMV-infected targets and are thus capable of providing protective immunity against infection. After in vitro stimulation of peripheral blood mononuclear cells with CMV-infected autologous fibroblasts, Tc specific for IE were not readily detectable in CMV-reactive polyclonal Tc lines. However, after stimulation of peripheral blood mononuclear cells with cells selectively expressing IE, weak but detectable IE-specific Tc responses were observed. The frequency of IE-specific Tc clones derived from cultures stimulated with IE-expressing cells was 50 to 100 times lower than the frequency of Tc clones specific for other CMV proteins isolated from cultures stimulated with CMV-infected cells. All of the IE-specific Tc clones, which efficiently lysed targets selectively expressing IE, demonstrated minimal lysis of CMV-infected fibroblasts, despite abundant IE expression in these target cells. In contrast to these results with IE, other viral proteins were efficiently presented during all phases of CMV infection. These data suggest that CMV has evolved a unique mechanism for selectively limiting the presentation of the potentially immunogenic IE protein, which may preclude IE-specific Tc from providing protective immunity to CMV infection.
Outcomes of Cleft Lip Repair for Internationally Adopted Children

Background: Large numbers of international children with cleft lip–cleft palate are adopted in the United States; many underwent their first operation before arrival. Methods: The authors reviewed records of internationally adopted children with cleft lip–cleft palate treated by one surgeon over 25 years. This study focused on anatomical types, frequency/methods of repair, correction of unrepaired deformities, and secondary procedures in this country. Results: Of 105 internationally adopted children with cleft lip–cleft palate, 91 percent were Asian; 75 percent had labial or labiopalatal closure in their native country. Of repaired unilateral cleft lips, 43 percent required complete revision, 49 percent required minor revisions, and 8 percent required no revision. All repaired bilateral cleft lips were revised; 90 percent were complete and 10 percent were minor. “Delayed” primary nasal correction was always necessary in both unilateral and bilateral forms. Labial closure was scheduled first in young infants with an unrepaired unilateral defect, whereas palatal closure took precedence in older children. Premaxillary setback and palatoplasty were scheduled first in older children with unrepaired bilateral cleft lip–cleft palate. Of children arriving with repaired palate, 43 percent required a pharyngeal flap. Conclusions: Whenever cleft lip–cleft palate is repaired in another country, revision rates are high for both unilateral and bilateral types. Nevertheless, primary closure in the native country may increase the likelihood for adoption. Traditional surgical protocols often are altered for an adoptee with an unrepaired cleft lip–cleft palate, particularly the sequence of labial and palatal closure, depending on the child's age and type of defect.
Smurf2 Is a Ubiquitin E3 Ligase Mediating Proteasome-dependent Degradation of Smad2 in Transforming Growth Factor-β Signaling* 210

Smads are important intracellular signaling effectors for transforming growth factor-β (TGF-β) and related factors. Proper TGF-β signaling requires precise control of Smad functions. In this study, we have identified a novel HECT class ubiquitin E3 ligase, designated Smurf2, that negatively regulates Smad2 signaling. In both yeast two-hybrid and in vitro binding assays, we found that Smurf2 could interact with receptor-activated Smads (R-Smads), including Smad1, Smad2, and Smad3 but not Smad4. Ectopic expression of Smurf2 was sufficient to reduce the steady-state levels of Smad1 and Smad2 but not Smad3 or Smad4. Significantly, Smurf2 displayed preference to Smad2 as its target for degradation. Furthermore, Smurf2 exhibited higher binding affinity to activated Smad2 upon TGF-β stimulation. The ability of Smurf2 to promote Smad2 destruction required the HECT catalytic activity of Smurf2 and depended on the proteasome-dependent pathway. Consistent with these results, Smurf2 potently reduced the transcriptional activity of Smad2. These data suggest that a ubiquitin/proteasome-dependent mechanism is important for proper regulation of TGF-β signaling.
Immunobiology of Chronic Lung Allograft Dysfunction: New Insights from the Bench and Beyond

The first successful human lung transplants were performed in the 1980s. Since that time lung transplantation has been a therapeutic modality for end‐stage pulmonary diseases. However, chronic rejection, known as obliterative bronchiolitis (OB)/bronchiolitis obliterans syndrome (BOS), is the key reason why the 5‐year survival is only 50%, which is significantly worse than most other solid organ transplants. Recent studies have provided exciting advances that are beginning to be translated into findings in humans. This review will highlight the current advances in understanding the mechanisms of OB/BOS in lung transplant recipients.
Functional Analysis of a Mutant Sulfonylurea Receptor, SUR1-R1420C, That Is Responsible for Persistent Hyperinsulinemic Hypoglycemia of Infancy*

The ATP-sensitive potassium (KATP +) channel is crucial for the regulation of insulin secretion from the pancreatic β-cell, and mutations in either the sulfonylurea receptor type 1 (SUR1) or Kir6.2 subunit of this channel can cause persistent hyperinsulinemic hypoglycemia of infancy (PHHI). We analyzed the functional consequences of the PHHI missense mutation R1420C, which lies in the second nucleotide-binding fold (NBF2) of SUR1. Mild tryptic digestion of SUR1 after photoaffinity labeling allowed analysis of the nucleotide-binding properties of NBF1 and NBF2. Labeling of NBF1 with 8-azido-[α-32P]ATP was inhibited by MgATP and MgADP with similar K i for wild-type SUR1 and SUR1-R1420C. However, the MgATP and MgADP affinities of NBF2 of SUR1-R1420C were about 5-fold lower than those of wild-type SUR1. MgATP and MgADP stabilized 8-azido-ATP binding at NBF1 of wild-type SUR1 by interacting with NBF2, but this cooperative nucleotide binding was not observed for SUR1-R1420C. Studies on macroscopic currents recorded in inside-out membrane patches revealed that the SUR1-R1420C mutation exhibits reduced expression but does not affect inhibition by ATP or tolbutamide or activation by diazoxide. However, co-expression with Kir6.2-R50G, which renders the channel less sensitive to ATP inhibition, revealed that the SUR1-R1420C mutation increases the EC50 for MgADP activation from 74 to 197 μm. We suggest that the lower expression of the mutant channel and the reduced affinity of NBF2 for MgADP may lead to a smaller KATP + current in R1420C-PHHI β-cells and thereby to the enhanced insulin secretion. We also propose a new model for nucleotide activation of KATP + channels.
FXYD 1 is an MeCP 2 target gene overexpressed in the brains of Rett syndrome patients and Mecp 2-null mice

Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR, USA, School of Medicine Graduate Program, Department of Cell and Developmental Biology, Neurological Sciences Institute, Division of Developmental Pediatrics, Oregon Health and Science University, Portland, OR, USA, Department of Neurology, Kennedy Krieger Institute and Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA
The impact of insecticide‐treated bednets on malaria and anaemia in pregnancy in Kassena‐Nankana district, Ghana: a randomized controlled trial

The impact of insecticide‐treated bednet use on malaria and anaemia in pregnancy was assessed, as a supplementary study, in a major WHO/TDR‐supported bednet trial in northern Ghana between July 1994 and April 1995. The study area was divided into 96 clusters of compounds, with 48 clusters being randomly allocated to intervention. All pregnant women were included in the study but the focus was on primigravidae and secundigravidae. 1961 pregnant women were recruited into the study – 1033 (52.7%) in the treated bednet group and 928 (47.3%) in the no net group. 1806 (92.1%) had blood taken for malaria microscopy and haemoglobin determination in the third trimester. Pregnancy outcomes were reported for 847 women. The characteristics of women in intervention and control groups were comparable. The odds ratios, with 95% confidence interval (CI), for different study endpoints were, for Plasmodium falciparum parasitaemia – 0.89 (0.73, 1.08), for anaemia – 0.88 (0.70, 1.09), for low birthweight (LBW) – 0.87 (0.63, 1.19), indicating no benefit for treated bednet use. Effective net use by parity varied from 42% in primigravidae to 63% in multigravidae, in spite of free nets and insecticide impregnation. The main reasons for not using a net were warm weather and perceived absence of mosquito biting. Chloroquine use in pregnancy was low and comparable in both groups. Implications of findings for malaria control in pregnancy and further research are discussed.
Volatility Spillover from Oil to Food and Agricultural Raw Material Markets

The upward movement in oil and food prices in the 2000s has attracted interest in the information transmission mechanism between the two markets. This paper investigates the volatility spillover between oil, food consumption item, and agricultural raw material price indexes for the period January 1980 to April 2008. The results of the Cheung-Ng procedure show that variation in oil prices does not Granger cause the variance in food and agricultural raw material prices. Since there is no volatility spillover from oil markets to food and agricultural raw material markets, investors can benefit from risk diversification. However, there is bi-directional spillover between agricultural raw material and food markets.
Increased sensitivity of dopamine receptors and recurrence of affective psychosis after childbirth.

OBJECTIVE--To test the hypothesis that affective psychosis after childbirth is associated with an altered sensitivity to dopaminergic stimulation. DESIGN--Prospective study of pregnant women at high risk of developing an affective psychosis after childbirth. Clinical assessments in pregnancy and after delivery were made by using a semistructured interview (schedule for affective disorders and schizophrenia) and psychiatric illnesses were categorised according to operational criteria (research diagnostic criteria). SETTING--Obstetric and psychiatric departments in and around Greater London. SUBJECTS--29 pregnant women with a history of bipolar or schizoaffective psychosis and 47 control pregnant women. Of these, 16 from each group participated in a growth hormone challenge test and the results for 15 women in each group were analysed. INTERVENTIONS--On the fourth day postpartum women participating in the hormone challenge test were given a subcutaneous injection of a small dose (0.005 mg/kg) of the dopamine agonist apomorphine. MAIN OUTCOME MEASURES--Growth hormone secretion in response to apomorphine as an index of the functional state of hypothalamic dopamine receptors. RESULTS--Eight of the 15 women at risk of psychosis subsequently had a recurrence of illness (five bipolar, one schizomanic, and two major depressive illnesses); these women had significantly greater growth hormone responses to apomorphine than the seven at risk women who remained well and the 15 controls, and there were no significant differences between groups in average baseline growth hormone concentrations. The mean (SD) concentrations for women with recurrence, women at risk who remained well, and control women respectively were: average baseline concentrations 1.06 (1.14), 1.44 (1.39), and 0.90 (1.34) mU/l; peak increase in concentrations 13.68 (12.95), 3.46 (4.68), and 3.40 (3.83) mU/l (between group difference p less than 0.05); average increase in concentrations 6.74 (7.01), 1.78 (3.39), and 1.40 (2.05) mU/l (p less than 0.05). CONCLUSIONS--The onset of affective psychosis after childbirth was associated with increased sensitivity of dopamine receptors in the hypothalamus and possibly elsewhere in the brain. Such changes may be triggered by the sharp fall in circulating oestrogen concentrations after delivery.
Natural History of Brainstem Cavernous Malformations

OBJECTIVE To review the natural history and determine the rates of intra- and extralesional hemorrhaging of brainstem cavernous malformations (cavernomas) monitored by one neuro-ophthalmology service. METHODS A record review of all patients with brainstem cavernomas who were evaluated by a neuro-ophthalmology service between 1987 and 1999 was performed. We recorded the clinical symptoms and Rankin disability grade at presentation, during the worst clinical episode, and at the last follow-up examination. Magnetic resonance imaging scans were reviewed for evidence of intralesional hemorrhage (a bleeding episode), edema, or venous anomalies, and the cavernoma size was assessed. RESULTS Thirty-seven patients (age range, 6–73 yr; mean age at presentation, 37.5 yr) underwent a mean of 4.9 years of follow-up monitoring. At presentation, there were 27 bleeding events and 8 nonhemorrhagic events; 2 patients did not exhibit symptoms. Patients who were at least 35 years of age exhibited a lower risk of bleeding episodes (odds ratio, 0.15; 95% confidence interval, 0.1–0.4). Cavernomas of at least 10 mm were associated with a higher risk of bleeding episodes (odds ratio, 3.48; 95% confidence interval, 1.3–9.4). Thirty-nine bleeding episodes occurred in 31 patients, yielding a bleeding rate of 2.46%/yr. There were eight rebleeding episodes, yielding a rebleeding rate of 5.1%/yr. Three patients experienced extralesional bleeding episodes; all of these patients experienced rebleeding. Of the 39 follow-up magnetic resonance imaging scans, the cavernoma size was unchanged in 66.7%, smaller in 18%, and larger in 15%. At the last follow-up examination, the mean Rankin grade was 1.0 for all patients, 0.6 for the 25 nonsurgically treated patients, and 1.4 for the 12 surgically treated patients. CONCLUSION Rebleeding is not more common among patients who first present with bleeding, and it often has little effect on the neurological status of patients. Significant morbidity attributable to a brainstem cavernoma occurred in 8% of patients during follow-up monitoring of medium duration.
Preserving data and key privacy in Data Aggregation for Wireless Sensor Networks

Reliable and trustful data aggregation is needed for most application in Wireless Sensor Networks. In this paper, we propose a new approach to attain data and key privacy protection in data aggregation called Preserving Data and Key Privacy in Data Aggregation for Wireless Sensor Networks (PDKP). Existing privacy preserving protocol provide more computational and communicational overhead in the sensor nodes. It increases the consumption of energy among the nodes. In our scheme, the encrypted content of the data is shared without revealing the data and key to other nodes by using simple technique. It preserves the key and data from an adversary with less computational and communication overhead. The base station can identify the distrustful groups related to the set of group aggregates and the retransmission of data is performed only for the abnormal data sensing intermediate nodes. It preserves the various security issues such as data freshness, data integrity, data confidentiality in data aggregation. Our simulation result showed that implementation of PDKP reduces the communication overhead and increases energy efficiency.
Endogenous cyclo‐oxygenase activity regulates mouse gastric surface pH

In the stomach, production of prostaglandins by cyclo‐oxygenase (COX) is believed to be important in mucosal defence. We tested the hypothesis that endogenous COX activity is required for protective gastric surface pH control. Intact stomachs of anaesthetized mice were perfused with a weakly buffered solution (150 mmNaCl+ 4 mm Homopipes) at pH values from 2.5 to 7.0. Gastric effluents were collected to measure pH and estimate amounts of acid or alkali secretion in nanomoles secreted per minute. A switch from net acid to net alkali secretion was seen in response to acidifying luminal pH with an apparent ‘set point’ between pH 4 and 5. At luminal pH 3, the net alkali secretion (12.7 ± 2.8 nmol OH− equivalents min−1) was abolished (2.2 ± 1.7 nmol OH− min−1) by the non‐specific COX inhibitor indomethacin (5 mg kg−1 I.P.). Similar inhibition was observed using a COX‐1 inhibitor (SC‐560; 10 mg kg−1 I.P.), but not a COX‐2 inhibitor (NS‐398; 10 mg kg−1 I.P.). Subsequent treatment with 16,16‐dimethyl prostaglandin E2 (dm‐PGE2; 1 mg kg−1 I.P.) rescued the alkali secretion (21.8 ± 2.7 nmol OH− min−1). In either the absence or presence of the H+,K+‐ATPase inhibitor omeprazole (60 mg kg−1 I.P.), indomethacin blocked similar amounts of net alkali secretion (10.5 ± 2.7 and 16.4 ± 3.4 nmol OH− min−1, respectively). We also used in vivo confocal microscopy to examine pH near the mucosal surface. The gastric mucosal surface of anaesthetized mice was exposed and mucosal surface pH was imaged using the fluorescence intensity ratio of Cl‐NERF as a pH indicator. Results showed a switch from a continuous net acid to net alkali secretion by the stomach in response to changing superfusate pH from 5 to 3. At luminal pH 3, the relatively alkaline surface pH (4.3 ± 0.1) was acidified (3.6 ± 0.2) by indomethacin, and subsequent dm‐PGE2 restored surface pH (4.2 ± 0.2). We conclude that the pre‐epithelial alkaline layer is regulated by endogenous COX activity.
Hepatitis E in the south west of France in individuals who have never visited an endemic area

A total of 431 consecutive patients from the Midi Pyrenees area with acute hepatitis with unknown etiology in 2001–2002 were tested for the presence of immunoglobulin G‐class (IgG) anti‐hepatitis E virus (HEV) antibodies. Forty‐six (10.7%) had anti‐HEV IgG, and the results were questionable for a further 17 (3.9%). Real time PCR based on TaqMan detection was used to identify HEV genome fragments in the serum of patients with positive or questionable anti‐HEV serology. HEV RNA was found in 25.4% of cases. All amplification products were sequenced and analyzed. Phylogenetic analysis revealed that all the strains were genotype 3. In conclusion, virological and epidemiological data indicate that genotype 3 viruses are circulating in the south west part of France (Midi‐Pyrenees) in patients with acute hepatitis and who have not visited recently areas in which HEV is endemic. J. Med. Virol. 74:419–424, 2004. © 2004 Wiley‐Liss, Inc.
Screening of Body Mass Index (BMI) and Blood Pressure in Egyptian School Children

Background: Childhood overweight and obesity are global problems that are on the rise. Obesity in children appears to increase the risk of subsequent morbidity, whether or not obesity persists into adulthood. Outcomes related to childhood obesity include hypertension, type 2 diabetes mellitus, dyslipidemia, left ventricular hypertrophy, non-alcoholic steatohepatitis, obstructive sleep apnea and orthopedic and psychosocial problems. For this we aimed to study BMI & BP among Egyptian children. Methods: A cross sectional study on 816 students (425 boys & 391 girls), aged 6 to 18 years (mean age 11.4 ±2.8 years), almost of the same socioeconomic status. Anthropometric measurement (weight, height BMI & SDS), blood pressure four blood pressure measurements were calculated: Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure. Questionnaire for some variables as family history of obesity, hypertension and smoking, salty diet, physical activity of children were studied to all children. Results: Prevalence of obesity and overweight was (1.5% & 2.9%), prehypertension and hypertension (1.1% & 10.5%) with no stastical significant difference among both sex. BMI SDS was positively correlated with age, SBP, MAP & pulse pressure. The risk of developing hypertension in obese children was 1.7 higher than the risk in non obese children (Odds ratio=1.7, CI 0.4-8.0). Conclusion: Given the presence of an increase of BMI SDS with age in our study, the elevated B.P values with age can be attributable to a parallel change in BMI. So children with elevated blood pressure and high BMI will be confronted with problem of hypertension and obesity as adult with all their morbidities.
Practical Variance Reduction via Regression for Simulating Diffusions

The well-known variance reduction methods—the method of importance sampling and the method of control variates—can be exploited if an approximation of the required solution is known. Here we employ conditional probabilistic representations of solutions together with the regression method to obtain sufficiently inexpensive (although rather rough) estimates of the solution and its derivatives by using the single auxiliary set of approximate trajectories starting from the initial position. These estimates can effectively be used for significant reduction of variance and further accurate evaluation of the required solution. The developed approach is supported by numerical experiments.
Microsatellite markers derived from bay scallop Argopecten irradians expressed sequence tags

When data mining was performed on the National Center for Biotechnology Information database, a total of 2038 sequences from five different expressed sequence tag libraries were registered. Eighty sequences (3.9%) were found to contain 91 microsatellites. Clustering analysis indicated that 23 sequences of these expressed sequence tags fell into five clusters and that the remaining 57 sequences were independent. The di- and tri-nucleotide repeat motifs accounted for approximately 62.1% of the total microsatellites. The most abundant dinucleotide microsatellite was TA, followed by GA and CA, and the trinucleotide microsatellites GAT and GGT showed a high abundance. Nineteen sequences representing di-, tri-, tetra- and penta-nucleotides motifs were chosen for the design of polymerase chain reaction (PCR) primers. Of primer pairs, 16 successfully amplified scorable PCR products and 11 revealed polymorphism, with the average polymorphic information content value of 0.5082 and 3.1 alleles per locus. A transferability analysis on three other related scallop species, Chlamys farreri, Chlamys nobilis and Patinopecten yessoenssis, showed that only 1 of 16 primer pairs could amplify PCR products with the expected size in Chlamys nobilis.