Miracle-dz/UniFAR-FTUs huggingface dataset:
The fragile genes FHIT and WWOX are inactivated coordinately in invasive breast carcinoma

FHIT and WWOX are a tumor suppressor and a candidate suppressor that encompass the FRA3B and FRA16D fragile sites at chromosomes 3p14.2 and 16q23.3–24.1, respectively. Reduced or absent Fhit expression has been reported in two‐thirds of invasive breast tumors in association with adverse prognostic factors. Loss of 16q has been reported frequently in low‐grade, invasive breast tumors.
Mechanisms Regulating Spontaneous Contractions in the Bovine Epididymal Duct1

Abstract Muscular autorhythmicity provides propulsion of spermatozoa through the epididymal duct, thereby ensuring sperm maturation. In the present study, the mechanisms underlying the bovine epididymal spontaneous phasic contractions (SCs) were analyzed by using muscle-tension recording and patch-clamp techniques. SCs were recorded from the caput, the corpus, and the proximal cauda region and found to be predominantly myogenic in origin. Removal of the luminal fluid induced a burstlike contraction pattern, and removal of the epithelium, a complete loss of SCs. Application of nifedipine, but not heparin and cyclopiazonic acid, suppressed SCs, indicating that influx of Ca2+ through L-type Ca2+ channels, but not Ca2+ release from intracellular stores, was crucial for maintaining SCs. The prostaglandin-endoperoxide synthase 2 (PTGS2) inhibitor NS-398 caused a region-dependent decrease in SCs and tone. These effects were mimicked by the mitogen-activated protein kinase (MAPK) kinase inhibitor PD-98059. Similarly, the prostaglandin F2alpha (PGF2alpha)-receptor antagonist AL-8810 reduced SC generation, whereas PGF2alpha induced SC-like activity in epithelium-denuded segments. Cell-isolation experiments revealed the existence of three morphologically different types of contractile cells, which also showed distinct biophysical properties: typical smooth muscle cells in the cauda, myofibroblast-like cells all along the duct, and atypical muscle cells (ATMs) with filament-like spurs in all regions with SCs. These data suggest that the bovine epididymal autorhythmicity is based on an epithelial PTGS2-dependent release of (an) excitatory prostaglandin(s) and a MAPK-dependent activation of L-type Ca2+ channels in the contractile cells. ATM cells may provide electrical coupling between myofibroblasts, which is essential for the generation of regular myogenic activity.
Characterization of Neurophysiologic Alerts During Anterior Cervical Spine Surgery

Study Design. A retrospective review of neurophysiologic alerts during anterior cervical surgery. Objectives. To examine incidence and types of neurophysiologic alerts and their correlation with new postoperative neurologic deficits after anterior cervical discectomy or corpectomy procedures. Summary of Background Data. Although multimodality neurophysiologic monitoring has been shown to predict iatrogenic neurologic injuries in scoliosis surgeries, their role in degenerative or trauma-related anterior cervical spine surgery is still unclear. Materials and Methods. We retrospectively reviewed 1,445 patients who underwent anterior cervical discectomy or corpectomy and arthrodesis with neurophysiologic monitoring that included transcranial electrical motor-evoked potentials (tceMEP), somatosensory-evoked potentials (SSEP), and spontaneous electromyography (EMG). Intraoperative alerts were analyzed for type, perceived cause, actions taken to reverse or minimize the possible spinal cord injury, and any new postoperative neurologic deficits. Results. There were 267 (18.4%) procedures that had either minor (spontaneous, sustained EMG) or major (tceMEP/SSEP amplitude reduction) alerts. Patients who underwent corpectomies had 28% increased risk of having a major neurophysiologic alert compared with those who had discectomies. Diagnosis of cervical spondylotic myelopathy or trauma increased the risk of having a major neurophysiologic alert 30% and 76%, respectively, compared with cervical radiculopathy. Eight surgeries were aborted due to persistent tceMEP/SSEP amplitude loss, but none resulted in new postoperative neurologic deficits. Two patients had halo-vest applied due to early termination of surgery. One of these patients ultimately could not receive definitive surgical stabilization. Discussion and Conclusion. Diagnosis of cervical spondylotic myelopathy or trauma and cervical corpectomy procedures increase the risk for having major intraoperative alerts. In case of persistent tceMEP/SSEP amplitude loss, consider delaying potentially harmful interventions, such as premature termination of the procedure or methylprednisolone infusion, until a new neurologic deficit is verified with an awake-clinical examination.
N-methyl-D-aspartate increases acetylcholine release from rat striatum and cortex: its effect is augmented by choline.

We examined the effects of N-methyl-D-aspartate (NMDA), a glutamate agonist, and of glutamate itself, on acetylcholine (ACh) release from superfused rat striatal slices. In a Mg(++)-free medium, NMDA (32-1000 microM) as well as glutamate (1 mM) increased basal ACh release by 35 to 100% (all indicated differences, P less than .05), without altering tissue ACh or choline contents. This augmentation was blocked by Mg++ (1.2 mM) or by MK-801 (10 microM). Electrical stimulation (15 Hz, 75 mA) increased ACh release 9-fold (from 400 to 3660 pmol/mg of protein): this was enhanced (to 4850 pmol/mg of protein) by NMDA (100 microM). ACh levels in stimulated slices fell by 50 or 65% depending on the absence or presence of NMDA. The addition of choline (40 microM) increased ACh release both basally (570 pmol/mg of protein) and with electrical stimulation (6900 pmol/mg of protein). In stimulated slices choline acted synergistically with NMDA, raising ACh release to 10,520 pmol/mg of protein. The presence of choline also blocked the fall in tissue ACh. No treatment affected tissue phospholipid or protein levels. NMDA (32-320 microM) also augmented basal ACh release from cortical but not hippocampal slices. Choline efflux from striatal and cortical (but not hippocampal) slices decreased by 34 to 50% in Mg(++)-free medium. These data indicate that NMDA-like drugs may be useful, particularly in combination with choline, to enhance striatal and cortical cholinergic activity. ACh release from rat hippocampus apparently is not affected by NMDA receptors.
Mutations in the human ATP‐binding cassette transporters ABCG5 and ABCG8 in sitosterolemia

Phytosterolemia or Sitosterolemia is a rare autosomal recessive disorder characterized by highly elevated plasma levels of plant sterols and cholesterol as a consequence of hyperabsorption and impaired biliary secretion of sterols. The disease is caused by mutations in two half size ATP‐binding cassette transporters, ABCG5 and ABCG8. We have analyzed the genomic sequence of ABCG5 and ABCG8 in five well‐characterized patients with Sitosterolemia. In the first patient we found a heterozygous mutation in exon 8 of the ABCG5 gene leading to a premature termination of the protein (Arg408Ter). This German patient is the first European showing a mutation of the ABCG5 gene. In a second patient we found a novel heterozygous mutation in exon 5 of ABCG8 (c.584T>A; Leu195Gln). Both patients were heterozygous for the identified mutation, but no mutation could be identified on the other chromosome. In three further analyzed patients we found mutations in exons 7, 9 and 11 of the ABCG8 gene, respectively, of which two result in a premature termination signal for translation products. One of these patients was compound heterozygous (Trp361Ter and Arg412Ter), the other was homozygous for Trp361Ter. The third patient was homozygous for an amino acid exchange (Gly574Arg). In conclusion this report describes one novel mutation affecting a highly conserved amino acid and two previously identified mutations in the ABCG8 gene. In addition, we identified for the first time a mutation in the ABCG5 gene of a European Sitosterolemia patient. © 2002 Wiley‐Liss, Inc.
Syndrome specificity and behavioural disorders in young adults with intellectual disability: cultural differences in family impact.

BACKGROUND This study examined whether behaviour problems and adaptive behaviour of low functioning young adults, and well-being of their families, varied by diagnostic syndrome [intellectual disability (ID) only, cerebral palsy, Down syndrome, autism], as well as by cultural group. METHODS Behaviour disorders in young adults with moderate to severe ID were assessed from information provided by 282 caregivers during in-home interviews. The sample consisted of 150 Anglo participants, and 132 Latino, primarily Spanish-speaking, participants drawn from Southern California. RESULTS Behaviour disorders and maternal well-being showed the same pattern across disability syndromes. Autism was associated with the highest scores in multiple behaviour problem areas as well as maternal reports of lower well-being. Down syndrome was associated with the lowest behaviour problem scores and the highest maternal well-being. When behaviour problems were controlled for, diagnostic groups accounted for no additional variance in maternal stress or depression. The pattern of behaviour problems and well-being did not differ by sample (Anglo vs. Latino), although level on well-being measures did. Latina mothers reported significantly higher depression symptoms and lower morale, but also higher positive impact from their child than did Anglo mothers. CONCLUSIONS Caregivers of young adults with autism report more maladaptive behaviour problems and lower personal well-being, or stress, relative to other diagnostic groups, regardless of cultural group. However, cultural differences exist in caregiver reports of depression, morale, and positive perceptions. Implications for service provision aimed at families of children with challenging behaviour problems are discussed in the context of culture.
ENTREPRENEURSHIP EDUCATION IN TERTIARY INSTITUTIONS IN NIGERIA: RELEVANCE, CHALLENGES AND STRATEGIES

This paper discusses the need for entrepreneurship education in tertiary Institutions in Nigeria. The spate of youth restiveness and graduate unemployment in recent times have compelled the Federal government to search for immediate but lasting solution to the scenario, hence the introduction of entrepreneurial studies across disciplines in higher institutions of learning in Nigeria. The introduction of entrepreneurial teaching and learning especially in Universities, Polytechnics and Colleges of Education is a new development in the education system. It is hoped that it will assist graduates become self employed rather than searching for non-existent paid employment. This paper therefore argues that entrepreneurship education will equip students in tertiary institutions with job specific skills for self employment. The objectives and strategies for re-designing entrepreneurship education are also discussed. The paper recommends that educational programmes at all levels of education should be functional and dedicated to the acquisition of job specific skills capable of generating self employment for the recipient.
mRNA structures influencing translation in the yeast Saccharomyces cerevisiae

The mRNA sequence and structures that modify and are required for translation of iso-1-cytochrome c in the yeast Saccharomyces cerevisiae were investigated with sets of CYC1 alleles having alterations in the 5' leader region. Measurements of levels of CYC1 mRNA and iso-1-cytochrome c in strains having single copies of altered alleles with nested deletions led to the conclusion that there is no specific sequence adjacent to the AUG initiator codon required for efficient translation. However, the nucleotides preceding the AUG initiator codon at positions -1 and -3 slightly modified the efficiency of translation to an order of preference similar to that found in higher cells. In contrast to large effects observed in higher eucaryotes, the magnitude of this AUG context effect in S. cerevisiae was only two- to threefold. Furthermore, introduction of hairpin structures in the vicinity of the AUG initiator codon inhibited translation, with the degree of inhibition related to the stability and proximity of the hairpin. These results with S. cerevisiae and published findings on other organisms suggest that translation in S. cerevisiae is more sensitive to secondary structures than is translation in higher eucaryotes.
Nuclear Hat1p Complex (NuB4) Components Participate in DNA Repair-linked Chromatin Reassembly*

Chromatin is disassembled and reassembled during DNA repair. To assay chromatin reassembly accompanying DNA double strand break repair, ChIP analysis can be used to monitor the presence of histone H3 near the lesion. The chromatin assembly factor Asf1p, as well as the acetylation of histone H3 lysine 56, have been shown to promote chromatin reassembly when DNA double strand break repair is complete. Using Gal-HO-mediated double strand break repair, we have tested each of the components of the nuclear Hat1p-containing type B histone acetyltransferase complex (NuB4) and have found that they can affect repair-linked chromatin reassembly but that their contributions are not equivalent. In particular, deletion of the catalytic subunit, Hat1p, caused a significant defect in chromatin reassembly. In addition, loss of the histone chaperone Hif1p, when combined with an allele of H3 that mutates lysines 14 and 23 to arginine, has a pronounced effect on chromatin reassembly that is similar to that observed in an asf1Δ. The role of Hat1p and Hif1p is at least partially redundant with the role of Asf1p. Consistent with a more prominent role for Hif1p in chromatin reassembly than either Hat1p or Hat2p, Hif1p exists in complex(es) independent of Hat1p and Hat2p and influences the activity of an H3-specific histone acetyltransferase activity. Our data directly demonstrate the role of the nuclear HAT1 complex (NuB4) components in DNA repair-linked chromatin reassembly.
Heat shock factor can activate transcription while bound to nucleosomal DNA in Saccharomyces cerevisiae

After each round of replication, new transcription initiation complexes must assemble on promoter DNA. This process may compete with packaging of the same promoter sequences into nucleosomes. To elucidate interactions between regulatory transcription factors and nucleosomes on newly replicated DNA, we asked whether heat shock factor (HSF) could be made to bind to nucleosomal DNA in vivo. A heat shock element (HSE) was embedded at either of two different sites within a DNA segment that directs the formation of a stable, positioned nucleosome. The resulting DNA segments were coupled to a reporter gene and transfected into the yeast Saccharomyces cerevisiae. Transcription from these two plasmid constructions after induction by heat shock was similar in amount to that from a control plasmid in which HSF binds to nucleosome-free DNA. High-resolution genomic footprint mapping of DNase I and micrococcal nuclease cleavage sites indicated that the HSE in these two plasmids was, nevertheless, packaged in a nucleosome. The inclusion of HSE sequences within (but relatively close to the edge of) the nucleosome did not alter the position of the nucleosome which formed with the parental DNA fragment. Genomic footprint analyses also suggested that the HSE-containing nucleosome was unchanged by the induction of transcription. Quantitative comparisons with control plasmids ruled out the possibility that HSF was bound only to a small fraction of molecules that might have escaped nucleosome assembly. Analysis of the helical orientation of HSE DNA in the nucleosome indicated that HSF contacted DNA residues that faced outward from the histone octamer. We discuss the significance of these results with regard to the role of nucleosomes in inhibiting transcription and the normal occurrence of nucleosome-free regions in promoters.
Overexpression of metabolic markers PKM2 and LDH5 correlates with aggressive clinicopathological features and adverse patient prognosis in tongue cancer

Pyruvate kinase M2 (PKM2) and lactate dehydrogenase 5 (LDH5) are two metabolic and oncogenic markers of cancer. In this study, we sought to investigate their expression patterns and prognostic value in tongue squamous cell carcinoma (TSCC).
Household Over-Indebtedness and Financial Vulnerability in Korea: Evidence from Credit Bureau Data

Financial soundness in the household sector matters for financial stability and for the real economy. The level of household debt in Korea raises concern about the financial soundness of the household sector due to its size, growth rate and quality. Against this backdrop, we assess the financial vulnerability of borrowers based on an analysis of credit bureau (CB) data, in which the actual credit activities of most individuals are recorded at a high frequency in Korea. We construct over-indebtedness indicators from the CB data and then assess the predictability of forthcoming defaults. Based on the over-indebtedness indicators, we show how borrowers are distributed in terms of over-indebtedness and how the over-indebted differ from average borrowers in terms of their characteristics. Furthermore, we show how the aggregate credit risk in the household sector would change under macroeconomic distress by analyzing how each borrower’s credit quality would be affected by adverse shocks. The findings of this paper may contribute to assessing household debt vulnerability and to enhancing regulatory and supervisory practices for financial stability.
Women from Africa living with HIV in London: a descriptive study

There are no studies that have examined the particular needs and experiences of African women living with HIV in the UK at a time when they represent an increasingly large proportion of the UK HIV epidemic. This study explores the illness biographies and daily lives of HIV-positive African women receiving treatment in London. Sixty-two women from 11 African countries attending HIV specialist clinics in five London hospitals participated in self-completion questionnaires and in depth semi-structured interviews. Using a narrative approach, women were asked to talk about their HIV status in the broader context of their life history. Important differences exist within this group based mainly on nationality, income, education level and legal status in the UK. However, marked similarities also emerged which were related in part to their situation as migrants and were compounded by their illness. Stigma, both actual and perceived, had a profound impact on women's lives, making control of information about their situation a matter of acute concern. This had an effect on how women accessed health services and voluntary sector agencies. The resilience of women in dealing with difficulties in their lives was strengthened by religious belief. Such similarities and differences need to be properly understood by health and social care professionals if they are to offer the most appropriate care for this growing population of patients.
Primary lateral sclerosis: Upper‐motor‐predominant amyotrophic lateral sclerosis with frontotemporal lobar degeneration – immunohistochemical and biochemical analyses of TDP‐43

Primary lateral sclerosis (PLS) is clinically defined as a disorder selectively affecting the upper motor neuron (UMN) system. However, recently it has also been considered that PLS is heterogeneous in its clinical presentation. To elucidate the association of PLS, or disorders mimicking PLS, with 43‐kDa TAR DNA‐binding protein (TDP‐43) abnormality, we examined two adult patients with motor neuron disease, which clinically was limited almost entirely to the UMN system, and was followed by progressive frontotemporal atrophy. In the present study, the distribution and severity, and biochemical profile of phosphorylated TDP‐43 (pTDP‐43) in the brains and spinal cords were examined immunohistochemically and biochemically. Pathologically, in both cases, frontotemporal lobar degeneration with ubiquitin inclusions (FTLD‐U) was evident, with the most severe degeneration in the motor cortex. An important feature in both cases was the presence of Bunina bodies and/or ubiquitin inclusions, albeit very rarely, in the well preserved lower motor neurons. The amygdala and neostriatum were also affected. pTDP‐43 immunohistochemistry revealed the presence of many positively stained neuronal cytoplamic inclusions (NCIs) and dystrophic neurites/neuropil threads in the affected frontotemporal cortex and subcortical gray matter. By contrast, such pTDP‐43 lesions, including NCIs, were observed in only a few lower motor neurons. pTDP‐43 immunoblotting revealed that fragments of ∼25‐kDa were present in the cortices, but not in the spinal cord in both cases. Genetically, neither of the patients had any mutation in the TDP‐43 gene. In conclusion, we consider that although PLS may be a clinically significant disease entity, at autopsy, the majority of such clinical cases would present as upper‐motor‐predominant amyotrophic lateral sclerosis with FTLD‐TDP.
Studies on ampicillin resistant plasmid of Streptococcus mutans isolated from dental caries patients

Dental caries is a well known major oral health problem in most countries. The multifactorial etiology of the disease includes multiple bacterial species, S. mutans is the main pathogen associated with the disease. Streptococcus mutans is recognized as the main pathogen of dental caries in human beings. One of the important virulence properties of S. mutans is their ability to form biofi lms on tooth surfaces which make them a primary an etiological agent in dental caries. This bacterium allows the colonization of other microorganisms resulting in dental plaque. Recently multi drug resistant species of S. mutans were identifi ed from the dental caries patients against many commercial antibiotics. Several therapeutic agents are available to treat or prevent tooth decay, but none of them showed complete sensitivity and have signifi cantly infl uenced the disease’s global burden. Totally, fi fty extracted tooth samples with chronic dental caries were selected for this study. The effectivity of caries was determined by the caries susceptibility test. S. mutans, the predominant cariogens were isolated from dental caries patients. Ten antibiotics (Penicillin-G, Ampicillin, Cefaclor, Tetracycline, Erythromycin, Chloramphenicol, Ciprofl oxacin, Amoxicillin, Vancomycin and Kanamycin) were used for antibiotic susceptibility test, among Ampicillin showed 70% resistant proved against to the strains of S.mutans. The plasmid of the isolates has specifi c antibiotic resistance against antibiotics like ampicillin and it has cell wall breaking capacity. R-plasmid (Resistant plasmid) was obtained from Ampicillin resistant strains of S. mutans from extracted tooth samples of dental caries disease. The molecular weight of the isolates were (KK2, 3 and KK4, 5) 800bp and 700bp respectively.
Association of Angiotensin-Converting Enzyme Insertion(I)/Deletion (D) Genotype in Alzheimer's Disease Patients of North Indian Population

ABSTRACT Several lines of evidence support for the role of angiotensin-converting enzyme (ACE) in Alzheimer's disease (AD) patients. Most human genetic studies have focussed on ACE insertion (I)/deletion (D) polymorphism and have yielded conflicting results. We have evaluated the association of ACE polymorphism with serum ACE activity in 95 AD patients and 110 healthy controls from north Indian population. In Alzheimer's patients a higher frequency of D allele was detected (I/D ratio 0.53:0.47) compared with the control group (I/D ratio 0.54:0.45), the difference being not statistically significant (p > .05). AD patients were found to be more homozygous for the D allele (26.3%) compared with controls (20.8%). The observed genotype distribution was in agreement with Hardy- Weinberg equilibrium. We observed that the D/D genotype is more in patients with a higher serum ACE activity. The D allele and the D/D genotype in AD patients may influence increased risk of cognitive impairment.