Miracle-dz/UniFAR-FTUs huggingface dataset:
GRID: A Novel Grb-2-Related Adapter Protein That Interacts with the Activated T Cell Costimulatory Receptor CD28

Adapter proteins such as Grb2 play a central role in the formation of signaling complexes through their association with multiple protein binding partners. These interactions are mediated by specialized domains such as the well-characterized Src homology SH2 and SH3 motifs. Using yeast three-hybrid technology, we have identified a novel adapter protein, expressed predominantly in T lymphocytes, that associates with the activated form of the costimulatory receptor, CD28. The protein is a member of the Grb2 family of adapter proteins and contains an SH3-SH2-SH3 domain structure. A unique glutamine/proline-rich domain (insert domain) of unknown function is situated between the SH2 and N-terminal SH3 domains. We term this protein GRID for Grb2-related protein with insert domain. GRID coimmunoprecipitates with CD28 from Jurkat cell lysates following activation of CD28. Using mutants of CD28 and GRID, we demonstrate that interaction between the proteins is dependent on phosphorylation of CD28 at tyrosine 173 and integrity of the GRID SH2 domain, although there are also subsidiary stabilizing contacts between the PXXP motifs of CD28 and the GRID C-terminal SH3 domain. In addition to CD28, GRID interacts with a number of other T cell signaling proteins, including SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa), p62dok, and RACK-1 (receptor for activated protein kinase C-1). These findings suggest that GRID functions as an adapter protein in the CD28-mediated costimulatory pathway in T cells.
Mice Lacking Osteopontin Show Normal Development and Bone Structure but Display Altered Osteoclast Formation In Vitro

We have used homologous recombination in embryonic stem cells to generate mice with a targeted disruption of the osteopontin (Opn, or Spp1, for secreted phosphoprotein 1) gene. Mice homozygous for this disruption fail to express osteopontin (OPN) as assessed at both the mRNA and protein level, although an N‐terminal fragment of OPN is detectable at extremely low levels in the bones of −/− animals. The Opn−/− mice are fertile, their litter size is normal, and they develop normally. The bones and teeth of animals not expressing OPN are morphologically normal at the level of light and electron microscopy, and the skeletal structure of young animals is normal as assessed by radiography. Ultrastructurally, proteinaceous structures normally rich in OPN, such as cement lines, persist in the bones of the Opn−/− animals. Osteoclastogenesis was assessed in vitro in cocultures with a feeder layer of calvarial osteoblast cells from wild‐type mice. Spleen cells from Opn−/− mice cells formed osteoclasts 3‐ to 13‐fold more frequently than did control Opn+/+ cells, while the extent of osteoclast development from Opn−/− bone marrow cells was about 2‐ to 4‐fold more than from the corresponding wild‐type cells. Osteoclast development occurred when Opn−/− spleen cells were differentiated in the presence of Opn−/− osteoblasts, indicating that endogenous OPN is not required for this process. These results suggest that OPN is not essential for normal mouse development and osteogenesis, but can modulate osteoclast differentiation.
Randomised trial of hysterectomy, endometrial laser ablation, and transcervical endometrial resection for dysfunctional uterine bleeding

Abstract Objective: To evaluate the effectiveness and safety of endometrial laser ablation and transcervical resection of the endometrium compared with hysterectomy in the surgical treatment of women with dysfunctional uterine bleeding. Design: Prospective randomised controlled trial. Setting: Gynaecology department of a large teaching hospital. Subjects: 204 women who would otherwise have been undergoing hysterectomy for menorrhagia were recruited between August 1990 and March 1992 and randomly allocated to hysterectomy (n=99) or conservative (hysteroscopic) surgery (transcervical resection (n=52) and laser ablation (n=53)). Main outcome measures: Operative complications, postoperative recovery, relief of menstrual and other symptoms, patient satisfaction with treatment after six and 12 months. Results - Women treated by hysteroscopic surgery had less early morbidity and a significantly shorter recovery period than those treated by hysterectomy (median time to full recovery 2-4 weeks v 2-3 months, P<0.001). Twelve months later 17 women in the hysteroscopy group had had a hysterectomy, 11 for continuing symptoms; 11 women had had a repeat hysteroscopic procedure; 45 were amenorrhoeic or had only a brown discharge; and 35 had light periods. Dysmenorrhoea and premenstrual symptoms improved in most women in both groups. After 12 months 89% (79/89) in the hysterectomy group and 78% (75/96) in the hysteroscopy group were very satisfied with the effect of surgery (P<0.05); 95% (85/89) and 90% (86/96) thought that there had been an acceptable improvement in symptoms, and 72% (64/89) and 71% (68/96) would recommend the same operation to others. Conclusions: Hysteroscopic endometrial ablation was superior to hysterectomy in terms of operative complications and postoperative recovery. Satisfaction after hysterectomy was significantly higher, but between 70% and 90% of the women were satisfied with the outcome of hysteroscopic surgery. Hysteroscopic surgery can be recommended as an alternative to hysterectomy for dysfunctional uterine bleeding.
Phytochrome Induces Rapid PIF5 Phosphorylation and Degradation in Response to Red-Light Activation1[W][OA]

The phytochrome (phy) family of sensory photoreceptors (phyA–phyE in Arabidopsis thaliana) induces changes in target-gene expression upon light-induced translocation to the nucleus, where certain members interact with selected members of the constitutively nuclear basic helix-loop-helix transcription factor family, such as PHYTOCHROME-INTERACTING FACTOR3 (PIF3). Previous evidence indicates that the binding of the photoactivated photoreceptor molecule to PIF3 induces rapid phosphorylation of the transcription factor in the cell prior to its degradation via the ubiqitin-proteosome system. To investigate whether this apparent primary signaling mechanism can be generalized to other phy-interacting partners, we have examined the molecular behavior of a second related phy-interacting member of the basic helix-loop-helix family, PIF5, during early deetiolation, immediately following initial exposure of dark-grown seedlings to light. The data show that red light induces very rapid phosphorylation and subsequent degradation (t1/2 < 5 min) of PIF5 via the proteosome system upon irradiation. Photobiological and genetic evidence indicates that the photoactivated phy molecule acts within 60 s to induce this phosphorylation of PIF5, and that phyA and phyB redundantly dominate this process, with phyD playing an apparently minor role. Collectively, the data support the proposal that the rapid phy-induced phosphorylation of PIF3 and PIF5 may represent the biochemical mechanism of primary signal transfer from photoactivated photoreceptor to binding partner, and that phyA and phyB (and possibly phyD) may signal to multiple, shared partners utilizing this common mechanism.
Mixing in a Moderately Sheared Salt-Fingering Layer

AbstractMixing due to sheared salt fingers is studied by means of direct numerical simulations (DNS) of a double-diffusively unstable shear layer. The focus is on the “moderate shear” case, where shear is strong enough to produce Kelvin–Helmholtz (KH) instability but not strong enough to produce the subharmonic pairing instability. This flow supports both KH and salt-sheet instabilities, and the objective is to see how the two mechanisms work together to flux heat, salt, and momentum across the layer.For observed values of the bulk Richardson number Ri and the density ratio Rρ, the linear growth rates of KH and salt-sheet instabilities are similar. These mechanisms, as well as their associated secondary instabilities, lead the flow to a fully turbulent state. Depending on the values of Ri and Rρ, the resulting turbulence may be driven mainly by shear or mainly by salt fingering. Turbulent mixing causes the profiles of temperature, salinity, and velocity to spread; however, in salt-sheet-dominated cases, t.
OMAmer: tree-driven and alignment-free protein assignment to subfamilies outperforms closest sequence approaches

Assigning new sequences to known protein families and subfamilies is a prerequisite for many functional, comparative and evolutionary genomics analyses. Such assignment is commonly achieved by looking for the closest sequence in a reference database, using a method such as BLAST. However, ignoring the gene phylogeny can be misleading because a query sequence does not necessarily belong to the same subfamily as its closest sequence. For example, a hemoglobin which branched out prior to the hemoglobin alpha/beta duplication could be closest to a hemoglobin alpha or beta sequence, whereas it is neither. To overcome this problem, phylogeny-driven tools have emerged but rely on gene trees, whose inference is computationally expensive. Here, we first show that in multiple animal datasets, 19 to 68% of assignments by closest sequence are misassigned, typically to an over-specific subfamily. Then, we introduce OMAmer, a novel alignment-free protein subfamily assignment method, which limits over-specific subfamily assignments and is suited to phylogenomic databases with thousands of genomes. OMAmer is based on an innovative method using subfamily-informed k-mers for alignment-free mapping to ancestral protein subfamilies. Whilst able to reject non-homologous family-level assignments, we show that OMAmer provides better and quicker subfamily-level assignments than approaches relying on the closest sequence, whether inferred exactly by Smith-Waterman or by the fast heuristic DIAMOND. OMAmer is available from the Python Package Index (as omamer), with the source code and a precomputed database available at https://github.com/DessimozLab/omamer.
Developmental and spinal cord injury‐induced changes in nitric oxide‐mediated inhibition in rat urinary bladder

During postnatal development large amplitude spontaneous activity of the neonatal rat bladder changes to a low amplitude adult pattern of activity that leads to improved storage function. Previously, we have shown that spontaneous activity in neonatal rat bladder strips is inhibited by activation of the nitric oxide (NO)–cGMP signaling pathway. In the present experiments we determined if this inhibitory pathway is altered during postnatal development or spinal cord injury.
Aortic intracardiac echocardiography-guided septal puncture during mitral valvuloplasty.

AIMS Transoesophageal echocardiography (TEE) and venous intracardiac echocardiography (ICE) are traditionally used to visualize the interatrial septum (IAS) and the tenting effect of the fossa ovalis in patients undergoing percutaneous balloon mitral valvuloplasty (PBMV). The aim of the present study was to assess the comparative efficacy and safety of arterial (intra-aortic) ICE and venous ICE, compared with TEE (traditional approach), in the patients undergoing PBMV. METHODS AND RESULTS TEE, aortic ICE, and venous ICE were consecutively performed in 50 patients (40 ± 9 years, 86% female). The images of intracardiac structures were obtained from both aortic and right atrial loci. The IAS was visualized using TEE, aortic ICE, and venous ICE. The mean mitral valve area was 1.14 ± 0.2 cm(2), and the mean left atrial volume index was 57.5 ± 12 mL/m(2). The mean size of the visualized septal length was 48 ± 5 mm by TEE, 51 ± 5 mm by aortic ICE, and 33 ± 6 mm by venous ICE. The Bland-Altman test indicated that the 95% limits of agreement for the measurement of septal diameter ranged from -11.0 to +5.9 mm (mean -2.5 mm) between TEE and aortic ICE, -2.8 to +33.5 mm (mean +15.3 mm) between TEE and venous ICE, and -36.6 to +0.8 mm (mean -17.9 mm) between venous and aortic ICE. Standard venous ICE generally tended to yield smaller values compared with TEE and aortic ICE for the measurement of septal length. Furthermore, the view of fossa ovalis and 'tenting effect' was optimal in 11 patients on venous ICE; however, the fossa ovalis and tip of the needle were well visualized in all patients on aortic ICE (P < 0.001). There were no major complications with the use of aortic ICE. CONCLUSION Aortic ICE is a superior alternative to venous ICE and facilitates trans-septal puncture in patients with mitral stenosis.
The Consequences of Swim, Cycle, and Run Performance on Overall Result in Elite Olympic Distance Triathlon

This study examined the consequences of performance in swim, cycle, and run phases on overall race finish in an elite "draft legal" Olympic distance (OD) triathlon. The subjects were 24 male athletes grouped by rank order into the top 50 % (n = 12) and bottom 50 % (n = 12) of the race population. Swimming velocity (m x s (-1)), cycling speed (km x h (-1)), and running velocity (m x s (-1)) were measured at regular intervals using a global positioning system, chip timing system, and video analysis. Actual rank after each stage and overall was obtained from the race results and video analysis. The top 50 % athletes overall swam faster over the first 400 m of the swim phase (p > 0.05). Their swim ranking was lower (p < 0.01) than the bottom 50 % athletes after this stage. There were no significant differences in actual race position between the groups after the cycle. However, the bottom 50 % athletes after the swim stage cycled faster (p < 0.01) at 13.4 km of the cycle. Speed at 13.4 km of the cycle stage was inversely correlated (r = 0.60, p < 0.01) to running performance. Performance (rank and velocity) in the running stage was highly correlated with overall race result (r = 0.86 and - 0.53, respectively, both p > 0.01). It appears that inferior swimming performance can result in a tactic that involves greater work in the initial stages of the cycle stage of elite OD racing, and may influence subsequent running performance.
[Effect of losartan on lung fibrosis in neonatal rats with hyperoxia-induced chronic lung disease].

OBJECTIVE In addition to regulating blood pressure, angiotensin II is involved in lung fibrogenesis. This study aimed to explore the effect of losartan, an angiotensin II type 1 receptor antagonist, on lung fibrosis in neonatal rats with hyperoxia-induced chronic lung disease (CLD) and its possible mechanisms. METHODS Neonatal Wistar rats were randomly divided into four groups within 24 hrs after birth: room air exposure, hyperoxia exposure (85%-90% O2), hyperoxia exposure + losartan, and hyperoxia exposure + placebo. Losartan (5 mg/kg/d) or placebo was administered beginning on the 6th day after birth. After 7, 14 and 21 days of exposure, 8 rats in each group were sacrificed. Lung histological changes were evaluated by hematoxylin-eosin staining. Levels of hydroxyproline (HYP), superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissues were determined by spectroscopy. RESULTS Hyperoxia exposure resulted in decreased alveolar septation, enlarged terminal air space, increased collagen deposition, pulmonary hemorrhage, and pulmonary consolidation. In the hyperoxia exposure + losartan group, the alveolar septum became thinner and lung fibrosis was alleviated, but the alveolar space was not obviously deflated and the number of secondary septum was not increased. Hyperoxia exposure increased significantly the HYP contents in lung tissues 14 and 21 days after exposure. Addition of losartan to the hyperoxia exposure resulted in decreased HYP contents (471.46 +/- 30.63 mu g/kg vs 545.15 +/- 34.90 mu g/kg for hypoxia alone; P < 0.01) after 21 days of exposure. SOD activity increased 7 days after hyperoxia exposure and then decreased to levels similar to the air exposure group. MDA levels increased to a peak at 7 days and remained at higher levels through 21 days of exposure when compared with the air exposure group (P < 0.01). Losartan treatment significantly increased SOD activities (82.94 +/- 4.62 U/mg protein vs 67.78 +/-8.02 U/mg protein; P < 0.01) and decreased MDA levels (30.54 +/- 5.89 nmol/mg protein vs 48.75 +/- 8.09 nmol/mg protein, P < 0.01) compared with the hyperoxia exposure group 21 days after exposure. CONCLUSIONS Losartan attenuated lung fibrosis in neonatal rats with hyperoxia-induced CLD, possibly through an increase of antioxidase enzyme activity and reduction of lipid peroxidation.
The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome.

BACKGROUND People with Gilbert's syndrome have mild, chronic unconjugated hyperbilirubinemia in the absence of liver disease or overt hemolysis. Hepatic glucuronidating activity, essential for efficient biliary excretion of bilirubin, is reduced to about 30 percent of normal. METHODS We sequenced the coding and promoter regions of the gene for bilirubin UDP-glucuronosyltransferase 1 (bilirubin/uridine diphosphoglucuronate-glucuronosyltransferase 1)--the only enzyme that contributes substantially to bilirubin glucuronidation--in 10 unrelated patients with Gilbert's syndrome, 16 members of a kindred with a history of Crigler-Najjar syndrome type II, and 55 normal subjects. RESULTS The coding region of the gene for the enzyme was normal in the 10 patients with Gilbert's syndrome. These patients were homozygous for two extra bases (TA) in the TATAA element of the 5' promoter region of the gene (A(TA)7TAA rather than the normal A(TA)6TAA). The presence of the longer TATAA element resulted in the reduced expression of a reporter gene, encoding firefly luciferase, in a human hepatoma cell line. The frequency of the abnormal allele was 40 percent among the normal subjects. The 3 men in the control group who were homozygous for the longer TATAA element had significantly higher serum bilirubin levels than the other 52 normal subjects (P = 0.009). Among the kindred with a history of Crigler-Najjar syndrome type II, only the six heterozygous carriers who had a longer TATAA element on the structurally normal allele had mild hyperbilirubinemia, characteristic of Gilbert's syndrome. CONCLUSIONS Reduced expression of bilirubin UDP-glucuronosyltransferase 1 due to an abnormality in the promoter region of the gene for this enzyme appears to be necessary for Gilbert's syndrome but not sufficient for the complete manifestation of the syndrome.
Thermoregulation and heat loss prevention after birth and during neonatal intensive-care unit stabilization of extremely low-birthweight infants.

Extremely low-birthweight infants have inefficient thermoregulation due to immaturity and may exhibit cold body temperatures after birth and during their first 12 hours of life. Hypothermia in these infants can lead to increased morbidity and mortality. Anecdotal notes made during our recent study revealed extremely low-birthweight infants' temperatures decreased with caregiver procedures such as umbilical line insertion, intubations, obtaining chest x-rays, manipulating intravenous lines, repositioning, suctioning, and taking vital signs during the first 12 hours of life. Therefore, nursing interventions should be undertaken to prevent heat loss during these caregiver procedures. Nurses can improve the thermal environment for extremely low-birthweight infants by prewarming the delivery room and placing the infant in a plastic bag up to the neck during delivery room stabilization to prevent heat loss. JOGNN, 36, 280-287; 2007. DOI: 10.1111/J.1552-6909.2007. 00149.x.
Age-adjusted charlson comorbidity index score as predictor of prolonged postoperative ileus in patients with colorectal cancer who underwent surgical resection

Comorbidities had considerable effects on the development of postoperative ileus (POI). The primary aim of the present study was to determine the influence of the age-adjusted Charlson comorbidity index (ACCI) score on the risk of prolonged POI in patients with colorectal cancer who underwent surgical resection. Using the electronic Hospitalization Summary Reports, we identified 11,397 patients with colorectal cancer who underwent surgical resection from 2013 through 2015. Logistic regression models were applied to evaluate the effect of the ACCI score on the risk of prolonged POI. The ACCI score had a positive graded association with the risk of prolonged POI in both colon and rectal cancer (P for trend < 0.05). Among patients with rectal cancer, after adjusting for potential confounders, those with an ACCI score of 4–5 had a 108% higher risk of prolonged POI than those with an ACCI score of 0–1 (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.09–3.98), and those with an ACCI score of ≥ 6 had a 130% higher risk (OR, 2.30; 95% CI, 1.08–4.89). Among patients with colon cancer, those with an ACCI score of ≥ 6 had a 47% greater risk of prolonged POI than those with an ACCI score of 0–1 (OR, 1.47; 95% CI, 1.07–2.02). These findings suggested that a higher ACCI score was an independent predictor of the development of prolonged POI.
Discharge education to promote self-management following cardiovascular surgery: An integrative review

Background: Nurses have a key role in teaching cardiovascular (CV) surgical patients to manage their post-surgical care after discharge. There is evidence that effective patient teaching contributes to improved quality of life, decreased anxiety and depression and fewer post-CV surgery emergency department visits and hospital readmissions. Despite this, there are no guidelines or standards for how best to educate CV surgical patients for discharge. Aim: To conduct a literature review of published research on discharge education for CV surgical patients to inform guidelines for educating CV surgical patients. Method: An exhaustive search of CINAHL, Medline, Web of Science, Cochrane Database of Systematic Reviews, and ERIC was executed using the following search terms: cardiovascular, cardiac, cardio*, heart, surg*, transplant, discharge, self-manage*, teach*, educat*, preop*, patient, care. In addition, an ancestry search of all reference lists was completed. Studies were included if they were published between 2007 and 2012 and focused on preoperative CV surgery adult patient education. Results: The search yielded 20 studies, 12 were excluded because they did not meet the inclusion/exclusion criteria. Eight studies were included in the final review. Three studies reported statistically significant decreases in reported anxiety and depression and increased subjective health. Four studies had mixed results with both positive and neutral findings. No studies reported negative findings in relation to preoperative education. Conclusion: Patients and staff identified that patient education is essential. Standardized educational tools are appropriate as they can spare resources, but are only effective if used in conjunction with individualized education.