Miracle-dz/UniFAR-FTUs huggingface dataset:
Results of Balloon Atrial Septostomy as Preparation for Surgical Correction in Transposition of Great Arteries

Balloon atrial septostomy (BAS) is a palliative procedure performed in the preoperative management of patients with transposition of great arteries (TGA), to improve the mixing of blood between the 2 systems. This report describes experience at the Clínica Cardiovascular Santa Maria in Medellin, Colombia. Between 2002 and 2010, 22 patients with TGA underwent BAS. Patient age at the time of the procedure was 21 days on average; 68% of patients were male. Average weight was 2.96 kg and interatrial gradient was between 4 and 12 mm Hg. The average systemic oxygen saturation at the beginning of the procedure was 60%, with a final saturation of 90%. Z5 atrioseptostomy balloons were used in 18 patients (81%), using Rashkind technique; Tyshak balloon catheters were used in 3 patients (13%) with the Shrivastava technique; and static high-pressure peripheral angioplasty balloons were used in 3 patients (13%). Two patients underwent BAS with 2 types of balloons. Although there were no complications clearly attributable to the procedure, 14% of patients had evidence of focal brain injury on the postoperative magnetic resonance image. Six patients died (27%), 5 of them because of postoperative complications and 1 because of infectious complications at another institution. All postoperative deaths occurred before 2006. The BAS is a safe technique for preoperative stabilization of patients with TGA.
The Interaction of Prp2 with a Defined Region of the Intron Is Required for the First Splicing Reaction

ABSTRACT In Saccharomyces cerevisiae, the 3′ splice site is not required for the first catalytic reaction of splicing. We have previously reported that at least 24 nucleotides downstream of the branch point is required for the first reaction to take place, but the precatalytic spliceosome forms efficiently on the truncated pre-mRNA with only 5 nucleotides retained downstream of the branch point. The factors that mediate this length-dependent control of the first catalytic step are not known. We show here that Prp2 can be recruited to the spliceosome without interacting with pre-mRNA when the 3′ tail is short. Prp2 interacts with the intron when the 3′ tail is extended, which results in destabilization of Prp2 and, consequently, progression of the first reaction. An RNA segment at 23 to 33 nucleotides downstream of the branch point is necessary and sufficient for the ATP-dependent action of Prp2. We also show that Prp2 directly interacts with the carboxyl-terminal fragment of Brr2 by pulldown assays. We propose that Prp2 is recruited to the spliceosome via interaction with Brr2 and is spatially positioned to interact with this specific region of the pre-mRNA, which stimulates the ATPase activity of Prp2 to promote the progression of the first catalytic step.
Enhanced Cardiac Akt/Protein Kinase B Signaling Contributes to Pathological Cardiac Hypertrophy in Part by Impairing Mitochondrial Function via Transcriptional Repression of Mitochondrion-Targeted Nuclear Genes

ABSTRACT Sustained Akt activation induces cardiac hypertrophy (LVH), which may lead to heart failure. This study tested the hypothesis that Akt activation contributes to mitochondrial dysfunction in pathological LVH. Akt activation induced LVH and progressive repression of mitochondrial fatty acid oxidation (FAO) pathways. Preventing LVH by inhibiting mTOR failed to prevent the decline in mitochondrial function, but glucose utilization was maintained. Akt activation represses expression of mitochondrial regulatory, FAO, and oxidative phosphorylation genes in vivo that correlate with the duration of Akt activation in part by reducing FOXO-mediated transcriptional activation of mitochondrion-targeted nuclear genes in concert with reduced signaling via peroxisome proliferator-activated receptor α (PPARα)/PGC-1α and other transcriptional regulators. In cultured myocytes, Akt activation disrupted mitochondrial bioenergetics, which could be partially reversed by maintaining nuclear FOXO but not by increasing PGC-1α. Thus, although short-term Akt activation may be cardioprotective during ischemia by reducing mitochondrial metabolism and increasing glycolysis, long-term Akt activation in the adult heart contributes to pathological LVH in part by reducing mitochondrial oxidative capacity.
DNA Polymerase POLN Participates in Cross-Link Repair and Homologous Recombination

ABSTRACT All cells rely on DNA polymerases to duplicate their genetic material and to repair or bypass DNA lesions. In humans, 16 polymerases have been identified, and each bears specific functions in genome maintenance. We identified here the recently discovered polymerase POLN to be involved in repair of DNA cross-links. Such DNA lesions are highly toxic and are believed to be repaired by the sequential activity of nucleotide excision repair, translesion synthesis, and homologous recombination mechanisms. By functionally assaying its role in these processes, we unraveled an unexpected involvement of POLN in homologous recombination. Moreover, we obtained evidence for physical and functional interaction of POLN with factors belonging to the Fanconi anemia pathway, a master regulator of cross-link repair. Finally, we show that POLN interacts and cooperates in DNA repair with the helicase HEL308, which shares a common origin with POLN in the Drosophila mus308 gene. Our data indicate that this novel polymerase-helicase complex participates in homologous recombination repair and is essential for cellular protection against DNA cross-links.
Prevention and treatment of experimental crescentic glomerulonephritis by blocking tumour necrosis factor-alpha.

BACKGROUND The mechanisms controlling progression of glomerulonephritis are poorly understood, but there is increasing evidence that tumour necrosis factor-alpha (TNF-alpha) plays a central role in many aspects of glomerular inflammation and scarring. We investigated the role of TNF-alpha in an experimental model of crescentic glomerulonephritis in Wistar Kyoto (WKY) rats by continuously blocking endogenous TNF-alpha, using its soluble receptor sTNFr p55, both before and after establishment of nephritis. METHODS Glomerulonephritis was induced by a single intravenous injection of 0.1 ml nephrotoxic serum. In the first experiment, rats were pre-treated with sTNFr p55 2 mg/kg intraperitoneally 1 hour before induction of nephritis and on a daily basis thereafter until day 4. In the second experiment, a similar protocol was followed, but treatment with sTNFr p55 was continued until day 10. In the third experiment, treatment with sTNFr p55 was delayed until 4 days after induction of nephritis and continued until day 10. The effects of treatment on renal function, renal histology, cellular infiltration, activation and proliferation, and IL-1beta expression were assessed by standard methods. RESULTS In the first experiment, short-term treatment with sTNFr p55 caused a marked reduction in albuminuria and fibrinoid necrosis. It also reduced glomerular cell infiltration, activation and proliferation. In the second experiment, prolonged treatment with sTNFr p55 caused a sustained reduction in albuminuria and all histological and cellular parameters of glomerular inflammation; in particular it completely prevented the development of crescents. In the third experiment, delayed therapy of established nephritis with sTNFr p55 significantly reduced albuminuria and glomerular inflammation, including the prevalence of crescent formation. In both long-term experiments, there was less glomerular expression of IL-1beta and lower serum concentrations of IL-beta in sTNFr p55-treated rats. CONCLUSIONS This study shows that neutralization of endogenous TNF-alpha is effective in preventing acute glomerular inflammation and crescent formation, and in treating established disease, in a rat model of crescentic nephritis. These results may have therapeutic implications for human glomerulonephritis.
Pathways for Holliday Junction Processing during Homologous Recombination in Saccharomyces cerevisiae

ABSTRACT The Saccharomyces cerevisiae Rmi1 protein is a component of the highly conserved Sgs1-Top3-Rmi1 complex. Deletion of SGS1, TOP3, or RMI1 is synthetically lethal when combined with the loss of the Mus81-Mms4 or Slx1-Slx4 endonucleases, which have been implicated in Holliday junction (HJ) resolution. To investigate the causes of this synthetic lethality, we isolated a temperature-sensitive mutant of the RMI1 strain, referred to as the rmi1-1 mutant. At the restrictive temperature, this mutant phenocopies an rmi1Δ strain but behaves like the wild type at the permissive temperature. Following a transient exposure to methyl methanesulfonate, rmi1-1 mutants accumulate unprocessed homologous recombination repair (HRR) intermediates. These intermediates are slowly resolved at the restrictive temperature, revealing a redundant resolution activity when Rmi1 is impaired. This resolution depends on Mus81-Mms4 but not on either Slx1-Slx4 or another HJ resolvase, Yen1. Similar results were also observed when Top3 function was impaired. We propose that the Sgs1-Top3-Rmi1 complex constitutes the main pathway for the processing of HJ-containing HRR intermediates but that Mus81-Mms4 can also resolve these intermediates.
Cellular and Molecular Immunology

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Iterative Multi-Level Soft Frequency Reuse With Load Balancing for Heterogeneous LTE-A Systems

This paper deals with the planning of two-layer long-term evolution-advanced cellular systems, taking both the co-tier and cross-tier interference into account. In particular, we propose the novel multi-level soft frequency reuse (MSFR) scheme, where the users in three different regions of a macro/micro cell adopt distinct frequency segments and different transmission power levels. The optimization of power control parameters and cell association with MSFR results in a non-convex problem. We present the iterative-MSFR (I-MSFR) scheme, where the main optimization problem is divided into two sub-problems that can be subsequently solved by means of classical optimization methods. Finally, we propose two simplified schemes that achieve a comparable performance as I-MSFR in terms of utility, cell capacity, and outage conditions. I-MSFR and the simplified schemes have shown better performance than other schemes in the literature.
GUIDE TO AUTOANTIBODY TESTING IN PERIPHERAL NEUROPATHIES

BACKGROUND–Many autoantibodies with reactivity to glycoconjugate components of peripheral nerve have been described in the last two decades. Serum autoantibodies to gangliosides and glycoproteins have received the most attention and have been implicated in a variety of sensory and motor neuropathy syndromes. Detection of these autoantibodies raises the possibility that the peripheral nerve disturbance is immune-mediated and that immunosuppressive therapy may be of benefit. REVIEW SUMMARY–This review summarizes the peripheral nerve syndromes associated with autoantibodies to glycoconjugates. The potential role for these autoantibodies in diagnosing peripheral nerve syndromes as well as predicting treatment response and immunopathogenesis is discussed. Autoantibody panels promoted by commercial laboratories for the evaluation of peripheral neuropathies are analyzed. CONCLUSIONS–Despite the fact that a pathogenic role for many peripheral nerve autoantibodies remains in question, several have evolved into helpful serologic markers for certain neuropathy syndromes. A rational approach to autoantibody testing in routine practice is presented, with an argument that testing should be individualized and tailored to the clinical setting, avoiding the use of larger screening panels.
Role of MicroRNA 30a Targeting Insulin Receptor Substrate 2 in Colorectal Tumorigenesis

ABSTRACT MicroRNAs (miRNAs) are dysregulated in many types of malignant diseases, including colorectal cancer. miRNA 30a (miR-30a) is a member of the miR-30 family and has been implicated in many types of cancers. In this study, we determined the expression of miR-30a in human colon cancer tissues and cell lines. miR-30a was found to be significantly downregulated in both the tissues and cell lines. Furthermore, overexpression of miR-30a inhibited, while silencing of miR-30a promoted, cell proliferation, migration, and invasion in vitro. Consistently, stable overexpression of miR-30a suppressed the growth of colon cancer cell xenografts in vivo. Moreover, bioinformatic algorithms and luciferase reporter assays revealed that insulin receptor substrate 2 (IRS2) is a direct target of miR-30a. Further functional studies suggested that repression of IRS2 by miR-30a partially mediated the tumor suppressor effect of miR-30a. In addition, miR-30a inhibited constitutive phosphorylation of Akt by targeting IRS2. Additionally, clinicopathological analysis indicated that miR-30a has an inverse correlation with the staging in patients with colon cancer. Taken together, our study provides the first evidence that miR-30a suppressed colon cancer cell growth through inhibition of IRS2. Thus, miR-30a might serve as a promising therapeutic strategy for colon cancer treatment.
Analysis of the Result Treated with Locking Compression Plate-Distal Tibia and Zimmer Periarticular Locking Plate in Distal Tibia Fracture

118 통신저자:이 준 영 광주시 동구 필문대로 365, 조선대학교병원 정형외과 Tel:062-220-3147ᆞFax:062-226-3379 E-mail:leejy88@chosun.ac. kr 접수: 2012. 7. 27 심사(수정): 2013. 1. 7 게재확정: 2013. 1. 7 Address reprint requests to:Jun-Young Lee, M.D. Department of Orthopaedic Surgery, Chosun University Hospital, 365 Pilmun-daero, Dong-gu, Gwangju 501-717, Korea Tel:82-62-220-3147ᆞFax:82-62-226-3379 E-mail:leejy88@chosun.ac. kr 경골 원위부 골절에서 Locking Compression Plate-Distal Tibia와 Zimmer Periarticular Locking Plate의 치료 결과 비교
New golden era of chelation therapy in thalassaemia: the achievement and maintenance of normal range body iron stores. Response to Kontoghiorghes et al

We have given a general description of the chelation therapy prescribed. With combination therapy it would be too complicated and not necessarily of clinical value to describe all the changes in either the dose of desferrioxamine (DFO) or the frequency of its weekly infusions. Obviously, when patients do reduce their hepatic iron to normal levels, adjustments to the frequency and dosage of DFO are made. We have indicated that what is important in patients is the individual tailoring of their chelation therapy. Drs Kolnagou and Kontoghiorghes commented: ‘the rate for achieving normalization of the body iron store range levels using the deferiprone (L1)/DFO combination could be <4 years’
Pastoral Teams and Parish Collaboratives: A Case Study of Diocesan Reorganization

Over 70% of dioceses in the United States made significant structural changes from 1995–2000. These reorganization efforts addressed a series of challenges identified by diocesan pastoral planners, principally a continuing decline in the participation by Catholics in their parishes, fewer priests and religious available for parochial service, and a widening gap between existing resources and the costs of pastoral services.1 The reorganization model most f requently used included large-scale closings and merging of parishes.2 Planning studies soon demonstrated, however, that these changes were often insufficient. During the decade from 2000–2010, U.S. dioceses further reduced the total number of parishes by 7.1%. 3 T H E J U R I S T 7 2 ( 2 0 1 2 ) 3 3 4 – 3 7 6
HSP105 Recruits Protein Phosphatase 2A To Dephosphorylate β-Catenin

ABSTRACT The Wnt/β-catenin pathway causes accumulation of β-catenin in the cytoplasm and its subsequent translocation into the nucleus to initiate the transcription of the target genes. Without Wnt stimulation, β-catenin forms a complex with axin (axis inhibitor), adenomatous polyposis coli (APC), casein kinase 1α (CK1α), and glycogen synthase kinase 3β (GSK3β) and undergoes phosphorylation-dependent ubiquitination. Phosphatases, such as protein phosphatase 2A (PP2A), interestingly, also are components of this degradation complex; therefore, a balance must be reached between phosphorylation and dephosphorylation. How this balance is regulated is largely unknown. Here we show that a heat shock protein, HSP105, is a previously unidentified component of the β-catenin degradation complex. HSP105 is required for Wnt signaling, since depletion of HSP105 compromises β-catenin accumulation and target gene transcription upon Wnt stimulation. Mechanistically, HSP105 depletion disrupts the integration of PP2A into the β-catenin degradation complex, favoring the hyperphosphorylation and degradation of β-catenin. HSP105 is overexpressed in many types of tumors, correlating with increased nuclear β-catenin protein levels and Wnt target gene upregulation. Furthermore, overexpression of HSP105 is a prognostic biomarker that correlates with poor overall survival in breast cancer patients as well as melanoma patients participating in the BRIM2 clinical study.
Hemodynamic Profile of Mild Pregnancy Induced Hypertension

An echocardiographic assessment of hemodynamics was performed in normotensive pregnant women, and in two categories of patients with mild pregnancy-induced hypertension (PIH): those with preeclampsia (PE, proteinuria 0.3g/24 hours) (n=23) and those with gestational hypertension (GH, proteinuria < 0.3g/24 hours) (n=22). The purpose of the study was to establish whether the two subsets of patients with PIH differ in respect to hemodynamics. Patients with PE had significantly lower stroke volume index and cardiac index than patients with GH, and normotensive pregnant women. Despite similar values of mean blood pressure, patients with PE had systemic vascular resistances higher than GH patients. In the PE group mean fetal weight was lower and the incidence of small for gestational age infants was higher than in the GH group.The differences in hemodynamic profile in patients with preeclampsia and in woman with gestational hypertension suggest that they represent two distinct pathophysiologic entities. PIH with.
Plk3 Interacts with and Specifically Phosphorylates VRK1 in Ser342, a Downstream Target in a Pathway That Induces Golgi Fragmentation

ABSTRACT Golgi fragmentation is a process that is necessary to allow its redistribution into daughter cells during mitosis, a process controlled by serine-threonine kinases. This Golgi fragmentation is activated by MEK1 and Plk3. Plk3 is a kinase that is a downstream target in the Golgi fragmentation pathway induced by MEK1 or by nocodazole. In this work, we have identified that Plk3 and VRK1 are two consecutive steps in this signaling pathway. Plk3 interacts with VRK1, forming a stable complex detected by reciprocal immunoprecipitations and pull-down assays; VRK1 colocalizes with giantin in the Golgi apparatus, as Plk3 also does, forming clearly detectable granules. VRK1 does not phosphorylate Plk3, but Plk3 phosphorylates the C-terminal region of VRK1 in Ser342. VRK1 with substitutions in S342 is catalytically active but blocks Golgi fragmentation, indicating that its specific phosphorylation is necessary for this process. The induction of Golgi fragmentation by MEK1 and Plk3 can be inhibited by kinase-dead VRK1, the knockdown of VRK1 by siVRK1, kinase-dead Plk3, or PD98059, a MEK1 inhibitor. The Plk3-VRK1 kinase module might represent two consecutive steps of a signaling cascade that participates in the regulation of Golgi fragmentation.
Quantitative Analysis of Chromosome Condensation in Fission Yeast

ABSTRACT Chromosomes undergo extensive conformational rearrangements in preparation for their segregation during cell divisions. Insights into the molecular mechanisms behind this still poorly understood condensation process require the development of new approaches to quantitatively assess chromosome formation in vivo. In this study, we present a live-cell microscopy-based chromosome condensation assay in the fission yeast Schizosaccharomyces pombe. By automatically tracking the three-dimensional distance changes between fluorescently marked chromosome loci at high temporal and spatial resolution, we analyze chromosome condensation during mitosis and meiosis and deduct defined parameters to describe condensation dynamics. We demonstrate that this method can determine the contributions of condensin, topoisomerase II, and Aurora kinase to mitotic chromosome condensation. We furthermore show that the assay can identify proteins required for mitotic chromosome formation de novo by isolating mutants in condensin, DNA polymerase ε, and F-box DNA helicase I that are specifically defective in pro-/metaphase condensation. Thus, the chromosome condensation assay provides a direct and sensitive system for the discovery and characterization of components of the chromosome condensation machinery in a genetically tractable eukaryote.
Anaphase-Promoting Complex/Cyclosome Participates in the Acute Response to Protein-Damaging Stress

ABSTRACT The ubiquitin E3 ligase anaphase-promoting complex/cyclosome (APC/C) drives degradation of cell cycle regulators in cycling cells by associating with the coactivators Cdc20 and Cdh1. Although a plethora of APC/C substrates have been identified, only a few transcriptional regulators are described as direct targets of APC/C-dependent ubiquitination. Here we show that APC/C, through substrate recognition by both Cdc20 and Cdh1, mediates ubiquitination and degradation of heat shock factor 2 (HSF2), a transcription factor that binds to the Hsp70 promoter. The interaction between HSF2 and the APC/C subunit Cdc27 and coactivator Cdc20 is enhanced by moderate heat stress, and the degradation of HSF2 is induced during the acute phase of the heat shock response, leading to clearance of HSF2 from the Hsp70 promoter. Remarkably, Cdc20 and the proteasome 20S core α2 subunit are recruited to the Hsp70 promoter in a heat shock-inducible manner. Moreover, the heat shock-induced expression of Hsp70 is increased when Cdc20 is silenced by a specific small interfering RNA (siRNA). Our results provide the first evidence for participation of APC/C in the acute response to protein-damaging stress.
Elektrophysiologische Methoden sind der Magnetresonanztomographie beim Nachweis von Hirnstammläsionen überlegen

Electrophysiologic methods are superior to Magnetic Resonance lmaging in the detection of small brainstem lesions Twenty-eight patients with isolated cranial nerve palsies of sudden onset (3rd nerve: 18 patients. 4th nerve: one patient, 6th nerve: 6 patients. vestibular , nerve: 3 patients) had abnormal electro-oculographic ' and/or masseter reflex findings indicating a causative I brainstem lesion. Improvement or rccovery of the respective cranial nerve palsy was always accompanied by improvement or recovery of pathologic electrophysiologic findings, which strongly indicates their functional significance. Magnetic resonance imaging, however. revealed corresponding brainstem lesion in only five patients (four with 3rd and one with 6th nerve palsy). Electrophysiologic methods are superior to magnetic resonance imaging in detecting small brain-stem lesions.