Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal structure of human myo‐inositol monophosphatase 2, the product of the putative susceptibility gene for bipolar disorder, schizophrenia, and febrile seizures

The human IMPA2 gene, which encodes myo‐inositol monophosphatase 2 (IMPA2), is mapped onto 18p11.2, a susceptibility region for bipolar disorder. This chromosomal region has also been proposed to include a susceptibility locus for schizophrenia and febrile seizures. Here we report the crystal structures of human IMPA2 and its complex with calcium and phosphate ions. Human IMPA2 comprises an α–β protein with a five‐layered sandwich of α‐helices and β‐sheets (α–β–α–β–α). The crystal structure and analytical ultracentrifugation results indicated that IMPA2 exists as a dimer in solution. The overall structure of IMPA2 is similar to that of IMPA1, except for the loop regions. In IMPA1, the loop region (31–43) is located at the entrance of the active site cavity. In the corresponding region (42–54) of IMPA2, the residues are disordered and partially form an α‐helix. The structural difference in the opening of the active site cavity suggests that the substrate specificity differs between IMPA1 and IMPA2. The widely opened cavity of IMPA2 implies that the physiological substrate may be a larger compound than inositol monophosphate. The structure of IMPA2 complexed with Ca2+ revealed two metals and one phosphate binding sites, which were the same sites as in IMPA1 complexed with Mn2+ and phosphate, suggesting that the mechanism of the enzymatic reaction is similar to that of IMPA1. The crystal structures of human IMPA2 are useful for understanding the effect of nonsynonymous polymorphism reported in IMPA2, and will contribute to further functional analyses of IMPA2 that potentially predisposes to the vulnerabilities of bipolar disorder, schizophrenia, and febrile seizures. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Characterization of a novel gene, STAG1/PMEPA1, upregulated in renal cell carcinoma and other solid tumors

Using differential display–polymerase chain reaction, we identified a novel gene sequence, designated solid tumor–associated gene 1 (STAG1), that is upregulated in renal cell carcinoma (RCC). The full‐length cDNA (4839 bp) encompassed the recently reported androgen‐regulated prostatic cDNA PMEPA1, and so we refer to this gene as STAG1/PMEPA1. Two STAG1/PMEPA1 mRNA transcripts of approximately 2.7 and 5 kb, with identical coding regions but variant 3′ untranslated regions, were predominantly expressed in normal prostate tissue and at lower levels in the ovary. The expression of this gene was upregulated in 87% of RCC samples and also was upregulated in stomach and rectal adenocarcinomas. In contrast, STAG1/PMEPA1 expression was barely detectable in leukemia and lymphoma samples. Analysis of expressed sequence tag databases showed that STAG1/PMEPA1 also was expressed in pancreatic, endometrial, and prostatic adenocarcinomas. The STAG1/PMEPA1 cDNA encodes a 287‐amino‐acid protein containing a putative transmembrane domain and motifs that suggest that it may bind src homology 3– and tryptophan tryptophan domain–containing proteins. This protein shows 67% identity to the protein encoded by the chromosome 18 open reading frame 1 gene. Translation of STAG1/PMEPA1 mRNA in vitro showed two products of 36 and 39 kDa, respectively, suggesting that translation may initiate at more than one site. Comparison to genomic clones showed that STAG1/PMEPA1 was located on chromosome 20q13 between microsatellite markers D20S183 and D20S173 and spanned four exons and three introns. The upregulation of this gene in several solid tumors indicated that it may play an important role in tumorigenesis. ©2001 Wiley‐Liss, Inc.
Cognitive Unbinding in Sleep and Anesthesia

I read with great interest the Report “Breakdown of cortical effective connectivity during sleep” by M. Massimini et al. (30 Sept., p. [2228][1]). As in the field of sleep research, the traditional view in anesthesiology has been that the brain is somehow “shut off” under general anesthesia
Fluorophore‐binding RNA aptamers and their applications

Why image RNA? Of all the biological molecules, RNA exhibits the most diverse range of functions. Evidence suggests that transcription produces a wide range of noncoding RNAs (ncRNAs), both short (e.g., siRNAs, miRNAs) and long (e.g., telomeric RNAs) that regulate many aspects of gene expression, including the epigenetic processes that underlie cell fate determination, polarization, and morphogenesis. All these functions are realized through the exquisite temporal and spatial control of RNA expression levels and the stability of specific RNAs within well‐defined sub‐cellular compartments. Given the central importance of RNA in dictating cell behavior via gene‐related functions, there is a great demand for RNA imaging methods so as to determine the composition of the cellular ‘transcriptome’ and to acquire a complete spatial‐temporal profile of RNA localization. Recent advances in fluorophore‐binding RNA aptamers promise to provide exactly this knowledge, which can ultimately advance our understanding of cell function and behavior in conditions of health and disease, and in response to external stimuli. WIREs RNA 2016, 7:843–851. doi: 10.1002/wrna.1383
Directed forgetting of autobiographical memory in mild Alzheimer's disease

Using the autobiographical directed forgetting method (Barnier et al., 2007), the present paper addressed the intentional inhibitory processes of episodic and semantic autobiographical memory in Alzheimer's disease (AD). Mild AD patients and healthy elderly people were instructed to either forget or to continue remembering previously generated autobiographical events. In a later recall test they were asked to reconstruct the early-generated memories regardless of the forget/remember instruction. Autobiographical reconstruction was further distributed into episodic and semantic memories. Results showed no forget instruction effect on episodic or semantic autobiographical recall with AD patients, whereas healthy elderly people were able to inhibit only episodic autobiographical memories. The findings suggest an impairment of the intentional inhibitory processes in autobiographical memory with AD and a relative preservation of these mechanisms with normal ageing. They also demonstrate an earlier decline in the intentional inhibitory processes compared to the autobiographical deterioration in AD.
A day in the lives of APNs in the U.S.

ursing associations,state boards of nursing, and certification bodies routinely collect information that describes the professional activities of nurses in advanced practice. Traditionally, the focus of such surveys has been on demographic data about the nurses, their academic background, professional roles, functions, salaries, benefits, and the average number of hours worked and patients seen. Recent surveys of nurse practitioners (NPs) highlight the effects of rapid changes in the health care delivery system. In particular, scientific and technological advancements have enabled health care providers to treat and prolong the lives of individuals with chronic illness or disability.Also,a reduced length of patient hospital stay has been associated with the influence of managed care organizations and the high cost of inpatient care for individuals with complex or chronic illness. For nurses in advanced practice, these changes have resulted in health care roles that are relatively dynamic and often in a state of flux. In a role delineation study for pediatric nurse practitioners (PNPs), Brady and Neal found that 10% of their study population were employed in emergent care settings and inpatient units. They also reported that the practice of PNPs in office settings with a pediatrician was associated with a relatively greater level of management responsibility in the treatment of pediatric conditions and illnesses when compared with practice sites such as clinics or outpatient centers. Similarly, a pilot study of recent PNP graduates from six university programs by Jackson et al found that slightly less than half of the respondents were practicing in a primary care setting, and that more than one-third practiced in a specialty care setting. The reported role functions for these PNPs are now more likely to include case management, staff development, consultation, administration of programs or personnel,policy and program development, and implementation of research. Druss and colleagues, in their study on national trends in health care as provided by nonphysician clinicians (primarily NPs and physician assistants), reported that the extent of preventative and maternity care by these practitioners increased between 1987 and 1997. However, few details were given about the clinical content of these patient encounters. Moody, Smith and Glenn further described the practice patterns of NPs in Tennessee with an emphasis on the demographic characteristics and health problems of clients, and the therapeutic services offered by the NPs. Using an instrument adapted from the National Ambulatory Medical Care Survey, this study of 44 NPs revealed that the most frequent patient illnesses were hypertension, otitis media, upper respiratory infections and diabetes mellitus. Patient counseling and teaching were the most frequently Martha K. Swartz, PhDc, APRN, BC, PNP Margaret Grey, DrPH, CPNP, FAAN Janet D. Allan, PhD, RN, CS, FAAN Nancy Ridenour, PhD, RN, CS, FNC, FAAN Christine Kovner, PhD, RN, FAAN Patricia Hinton Walker, PhD, RN, FAAN Lucy Marion, PhD, RN, CS, FAAN
Electrospun nanofibre fibrinogen for urinary tract tissue reconstruction

The purpose of this study was to demonstrate that human bladder smooth muscle cells (HBSM) remodel electrospun fibrinogen mats. Fibrinogen scaffolds were electrospun and disinfected using standard methods. Scaffolds were seeded with 5 × 104 HBSM per scaffold. Cultures were supplemented with aprotinin concentrations of 0 KIU ml−1 (no aprotinin), 100 KIU ml−1 or 1000 KIU ml−1 and incubated with twice weekly media changes. Samples were removed for evaluation at 1, 3, 7 and 14 days. Cultured scaffolds were evaluated with a WST-1 cell proliferation assay, scanning electron microscopy and histology. Cell culture demonstrated that HBSM readily migrated into and initiated remodelling of the electrospun fibrinogen scaffolds by deposition of collagen. Proliferation was suppressed during this initial phase with respect to a 2D control due to cell migration. Histology confirmed that proliferation increased during the later stages of remodelling. Remodelling was slower at higher aprotinin concentrations. These results demonstrate that HBSM rapidly remodel an electrospun fibrinogen scaffold and deposit native collagen. The process can be modulated using aprotinin, a protease inhibitor. These initial findings indicate that there is tremendous potential for electrospun fibrinogen as a urologic tissue engineering scaffold with the ultimate goal of producing an implantable acellular product that would promote cellular in-growth and in situ tissue regeneration.
Immunological Evidence for the Existence of a Carrier Protein for Sucrose Transport in Tonoplast Vesicles from Red Beet (Beta vulgaris L.) Root Storage Tissue

Monoclonal antibodies were raised in mice against a highly purified tonoplast fraction from isolated red beet (Beta vulgaris L. ssp. conditiva) root vacuoles. Positive hybridoma clones and sub-clones were identified by prescreening using an enzyme-linked immunosorbent assay (ELISA) and by postscreening using a functional assay. This functional assay consisted of testing the impact of hybridoma supernatants and antibody-containing ascites fluids on basal and ATP-stimulated sugar uptake in vacuoles, isolated from protoplasts, as well as in tonoplast vesicles, prepared from tissue homogenates of red beet roots. Antibodies from four clones were particularly positive in ELISAs and they inhibited sucrose uptake significantly. These antibodies were specific inhibitors of sucrose transport, but they exhibited relatively low membrane and species specificity since uptake into red beet root protoplasts and sugarcane tonoplast vesicles was inhibited as well. Fast protein liquid chromatography assisted size exclusion chromatography on Superose 6 columns yielded two major peaks in the 55 to 65-kD regions and in the 110- to 130-kD regions of solubilized proteins from red beet root tonoplasts, which reacted positively in immunoglobulin-M(IgM)-specific ELISAs with anti-sugarcane tonoplast monoclonal IgM antibodies. Only reconstituted proteoliposomes containing polypeptides from the 55- to 65-kD band took up [14C]-sucrose with linear rates for 2 min, suggesting that this fraction contains the tonoplast sucrose carrier.
Functional Identification of Triterpene Methyltransferases from Botryococcus braunii Race B*

Background: Botryococcus braunii accumulates high levels of methylated triterpenes that contribute to the buoyancy of the algae and serve as highly valued chemical feedstocks. Results: AdoMet-dependent methyltransferases catalyzing successive and regio-specific methylations of squalene or botryococcene are identified. Conclusion: Methylation of squalene and botryococcene requires distinct methyltransferases. Significance: Substrate selectivity and successive cycles of regio-specific catalysis by triterpene methyltransferases from B. braunii are reported. Botryococcus braunii race B is a colony-forming, green algae that accumulates triterpene oils in excess of 30% of its dry weight. The composition of the triterpene oils is dominated by dimethylated to tetramethylated forms of botryococcene and squalene. Although unusual mechanisms for the biosynthesis of botryococcene and squalene were recently described, the enzyme(s) responsible for decorating these triterpene scaffolds with methyl substituents were unknown. A transcriptome of B. braunii was screened computationally assuming that the triterpene methyltransferases (TMTs) might resemble the S-adenosyl methionine-dependent enzymes described for methylating the side chain of sterols. Six sterol methyltransferase-like genes were isolated and functionally characterized. Three of these genes when co-expressed in yeast with complementary squalene synthase or botryococcene synthase expression cassettes resulted in the accumulation of mono- and dimethylated forms of both triterpene scaffolds. Surprisingly, TMT-1 and TMT-2 exhibited preference for squalene as the methyl acceptor substrate, whereas TMT-3 showed a striking preference for botryococcene as its methyl acceptor substrate. These in vivo preferences were confirmed with in vitro assays utilizing microsomal preparations from yeast overexpressing the respective genes, which encode for membrane-associated enzymes. Structural examination of the in vivo yeast generated mono- and dimethylated products by NMR identified terminal carbons, C-3 and C-22/C-20, as the atomic acceptor sites for the methyl additions to squalene and botryococcene, respectively. These sites are identical to those previously reported for the triterpenes extracted from the algae. The availability of closely related triterpene methyltransferases exhibiting distinct substrate selectivity and successive catalytic activities provides important tools for investigating the molecular mechanisms responsible for the specificities exhibited by these unique enzymes.
The carcinogenicity of compounds related to 2-acetylaminofluorene. II. Variations in the bridges and the 2-substituent.

Summary 1.The carcinogenic activities of fourteen compounds structurally related to 2-acetylaminofluorene and which differ principally in the nature of the bridges between the two aromatic rings have been determined in the rat. These compounds are the 2-acetylamino derivatives of 9-fluorenol, 9-fluorenone, phenanthrene, 9,10-dihydrophenanthrene, carbazole, pyrene, and dibenzothiophene; the 3-acetylamino derivatives of phenanthrene, carbazole, dibenzothiophene sulfone, and diphenylmethane; the 4-acetylamino derivatives of diphenylsulfide and biphenyl; and 1-acetylaminopyrene. 2.2-Acetylaminofluorene induced high incidences of liver tumors in the males and of mammary gland tumors in the females and moderate incidences of tumors of the ear duct and small intestinal epithelium in both sexes. 3.A fluorene nucleus appears to be required for strong carcinogenic activity toward the liver. 2-Acetylamino-9-fluorenol and 2-acetylamino-9-fluorenone had weak activity; the other compounds were inactive. 4.A biphenyl nucleus is apparently necessary for carcinogenic activity toward the mammary gland. 4-Acetylaminobiphenyl was as active as 2-acetylaminofluorene, and a number of compounds with bridges in the 2, 2′-positions were also active. 5.The requirements for carcinogenicity toward the ear duct and intestinal epithelium were intermediate between those of the liver and mammary gland; in general, a tricyclic derivative was necessary. 6.2-Acetylaminophenanthrene, in addition to inducing tumors of the mammary gland, ear duct, and intestinal epithelium, also had a moderate leukemogenic activity. When fed at higher levels, it induced a paralysis of the hind limbs. 7.7-Fluoro-2-acetylaminofluorene was much more active toward the liver of both male and female rats than 2-acetylaminofluorene. The activity toward the other tissues was not enhanced by this fluoro-substitution. 8.In agreement with the work of others 2-nitro-, 2-amino-, and 2-dimethylaminofluorene were less active than 2-acetylaminofluorene at the usual sites. In addition, 2-nitrofluorene induced a high incidence of squamous-cell carcinomas of the forestomach. 9.On histological examination a high proportion of the tumors induced by each compound and at all sites were found to be malignant. 10.The syntheses of the following new compounds are described: 2-acetylaminocarbazole and 7-fluoro-2-acetylaminofluorene.
Efficacy, Effectiveness and Efficiency in Mental Health Service Delivery

Objective: The aim of this paper is to review the status of treatments in psychiatry. Method: The criteria for good treatment are defined and then treatments in psychiatry are examined for efficacy, effectiveness and efficiency. Results: Alarge number of treatments were listed by Nathan and Gorman as having satisfied the criteria for efficacy: that is, they had been shown to be superior to placebo in randomised controlled trials. The problem of effectiveness (does the treatment still work when used by the average clinician with the average patient? ) is a general one in medicine, but the evidence in psychiatry is not outstanding. The problem of efficiency (what level of resources are required to produce benefit? ) is being addressed in a piecemeal fashion, and again this is no different to the situation in general medicine. Conclusions: Aconsiderable number of treatments have been shown to satisfy the criteria for efficacy. Effectiveness requires that psychiatrists apply such proven treatments and demonstrate benefit through the use of outcome measurement. A system that separated the health budget into segments for prevention, cure and care might ensure that these three goals were pursued equitably and efficiently.
The onset of tense marking in children at risk for specific language impairment.

PURPOSE The purpose of this study was to develop and evaluate measures reflecting the onset of tense marking for children between the ages of 2;0 (years;months) and 3;0. METHOD The validity of 4 cumulative measures of tense marker emergence and productivity was evaluated relative to existing measures of early grammatical development in a sample of 20 children followed longitudinally. Fourteen children were at risk for specific language impairment (AR-SLI group), and 6 children had low average language abilities (LA group). RESULTS All measures of onset were highly correlated with the traditional measures; however, children's progress toward mastery of grammatical tense marking was best explained by the productivity of their tense marking systems. Finally, the onset measures imposing productivity requirements best differentiated children in the LA group from those in the AR-SLI group. CONCLUSIONS The clinical implications for using the late onset of tense marking to improve the early identification of SLI are discussed.
STUDY OF PALMAR TYPE OF MEDIAN ARTERY AND ITS FATE

Address for Correspondence: Dr. Bhagya Shree, Senior Resident, Dept. of Anatomy, Guru Gobind Singh Medical College, Faridkot-151203, Punjab, India. Mob: 91-9463364664 E-Mail: drbhagyashree80@gmail.com *1 Senior Resident, Dept. of Anatomy, Guru Gobind Singh Medical College, Faridkot, Punjab, India. 2 Assistant Professor, Dept. of Anatomy, Guru Gobind Singh Medical College, Faridkot, Punjab, India. 3 Assistant Professor, Dept. of Forensic Medicine, Guru Gobind Singh Medical College, Faridkot, Punjab, India. 4 Professor & Head, Dept. of Anatomy, Dashmesh Institute of Research and Dental Sciences, Faridkot, Punjab, India. Background: The median artery is a transitory vessel that represents the arterial axis of the forearm during early embryonic life. When present, it appears mainly as two types: antebrachial and palmar. Context and purpose of the study: In the present study the objective was to investigate the occurrence and fate of palmar type of median artery. The study was conducted on 40 cadaveric upper extremities dissected in the department of Anatomy, Guru Gobind Singh Medical College, Faridkot, India. Results: In the present study, persistent median artery (palmar type) was seen in 2.5% of the limbs dissected. It was originating from the posterior aspect of the ulnar artery approximately 3.2 cm distal to the elbow joint. It pierced the median nerve (traversing from its medial to its lateral aspect) in the proximal third of the forearm. The artery then travelled lateral to the median nerve in rest of the forearm. Subsequently, it accompanied the median nerve into the palm passing deep to the flexor retinaculum. Finally, the artery terminated by completing the superficial palmar arch. In addition to the above described variant blood vessel, we also observed high division of median nerve into its medial and lateral branches. Clinical implications: When median artery is patent and reaches the hand, it forms the only arterial supply to the median nerve and damage to this artery could have serious effects. The aim of our study was to provide additional information about anomalous palmar type of median artery and its clinical implications.
Noninvasive Screening for Risk Factors of Type 2 Diabetes in Young, Rural, Caucasian Children

School nurses play an important role in identifying students who are at risk for Type 2 diabetes mellitus (T2DM). Few studies have screened Caucasian students, and none have targeted rural, low-income, elementary children. The five noninvasive risk factors used for this study were family history, high body mass index (BMI) for age/sex, racial/ethnic background, hypertension, and acanthosis nigricans. Two thirds of those screened (n = 299) had at least one of the five risk factors for T2DM. Seventeen students (5.6% of those screened) had three or more of the five risk factors and were considered at risk for T2DM. Fifteen percent (n = 43) had hypertension or prehypertension, and 18% (n = 53) were morbidly obese. Hypertension and acanthosis nigricans were significantly associated with being at risk in morbidly obese students. School nurses play an important role as frontline health professionals who are aware that risk factors for T2DM exist in all schools, regardless of students' age, size of community, or ethnic background.
Awash in information, patients face a lonely, uncertain road.

Now, just about out of options, Ms. Gaines faced an excruciating decision. Her lastditch chemotherapy regimen did seem to be working. Three medical oncologists thought she should stick with it. But two surgical oncologists thought she should first try cryosurgery, injecting liquid nitrogen into the tumors to shrink as many as possible, and then following up with chemotherapy, allowing it to be more effective.