Miracle-dz/UniFAR-FTUs huggingface dataset:
Selenoergothionein as a Potential Inhibitor against Amyloid ÃÂ²-Protein(AÃÂ²): Docking and Molecular Dynamics Studies

Alzheimer‘s disease (AD) is a progressive neurodegenerative disorder, encircling the deterioration of cognitive functions and behavioral changes, characterized by the aggregation of amyloid β-protein (Aβ) into fibrillar amyloid plaques in elected areas of the brain with the lipid-carrier protein apolipoprotein E (apoE), the microtubule associated protein tau, and the presynaptic protein α-synuclein. High levels of fibrillary Aβ, the main constituent of senile plaques, are deposited in the AD brain that outcome in the thrashing of synapses, neurons and destruction of neuronal role. Aβ is derived from the amyloid precursor protein through sequential protein cleavage by aspartyl protease, β-secretase and presenilin-dependent β-secretase triggering a spill of events such as oxidative damage, neurotoxicity, and inflammation that contributes to the progression of AD. Therefore the Aβ protein may be a target for anti-Alzheimer drugs. Aβ proteinwas retrieved from the Protein data bankand energy minimized and subjectedto molecular dynamic simulations using NAMD 2.9 software with CHARMM27 force field inwater. The Aβ protein structure was energy minimized by 25,000 steps for 500 ps and pretend 100,000 steps for 2ns.The ergothionein and selenoergothionein, which were found to exhibit amyloid inhibitory effect, were selected and the 3D structure files of those compounds were retrieved from Zinc database. The two compounds were then dockedinto the active site of Aβ protein with AutoDock Vina in PyRx Virtual Screening tool.The two compounds were showed best binding energies of -9.8, and -7.9 kcal/mol correspondingly. The binding interactions of compounds with active site of Aβ proteinmodel suggested that the amino acid residues (SER8, GLN15, and LYS16) play a key role for drug design.The predicted pharmalogical properties of two compounds, among them selenoergothionein is well within the range of a drug molecule with good ADME profile. Therefore, would be interesting towards progress of persuasive inhibitor against Aβ protein.
Robust guaranteed cost control for sampled-data systems with parametric uncertainties

This paper investigates the problem of robust guaranteed control for sampled-data systems with time-varying norm-bounded parametric uncertainties in the state matrix and input matrix. Attention is focused on the design of a causal dynamic output feedback sampled-data controller which guarantees the asymptotical stability of the closed-loop system and the quadratic performance index less than a certain bound for all admissible uncertainties. Sufficient condition for the solvability of the problem is presented in terms of a set of linear matrix inequalities (LMIs). It is shown that the desired guaranteed cost controller can be constructed by solving certain LMIs. An illustrative example is given to demonstrate the effectiveness of the proposed method.
Sporadic fatal insomnia: A case study

A 58‐year‐old man died after a 27‐month illness characterized by insomnia, confirmed by polysomnography. He was homozygous for methionine at codon 129 of the prion gene but had no mutation in the prion gene. Neuropathology showed thalamic and olivary atrophy and no spongiform changes. Paraffin‐embedded tissue blotting demonstrated abnormal prion protein in the brain. This is the first case of the sporadic form of fatal familial insomnia with demonstration of the disorder by polysomnography. Ann Neurol 2000;48:665–668
Different roles of individual N-linked oligosaccharide chains in folding, assembly, and transport of the simian virus 5 hemagglutinin-neuraminidase

The role of N-linked glycosylation in protein maturation and transport has been studied by using the simian virus 5 hemagglutinin-neuraminidase (HN) protein, a model class II integral membrane glycoprotein. The sites of N-linked glycosylation on HN were identified by eliminating each of the potential sites for N-linked glycosylation by oligonucleotide-directed mutagenesis on a cDNA clone. Expression of the mutant HN proteins in eucaryotic cells indicated that four sites are used in the HN glycoprotein for the addition of N-linked oligosaccharide chains. These functional glycosylation sites were systematically eliminated in various combinations from HN to form a panel of mutants in which the roles of individual carbohydrate chains and groups of carbohydrate chains could be analyzed. Alterations in the normal glycosylation pattern resulted in the impairment of HN protein folding and assembly which, in turn, affected the intracellular transport of HN. The severity of the consequences on HN maturation depended on both the number of deleted carbohydrate sites and their position in the HN molecule. Analysis of the reactivity pattern of HN conformation-specific monoclonal antibodies with the mutant HN proteins indicated that one specific carbohydrate chain plays a major role in promoting the correct folding of HN. Another carbohydrate chain, which is not essential for the initial folding of HN was found to play a role in preventing the aggregation of HN oligomers. The HN molecules which were misfolded, owing to their altered glycosylation pattern, were retained in the endoplasmic reticulum. Double-label immunofluorescence experiments indicate that misfolded HN and folded HN are segregated in the same cell. Misfolded HN forms disulfide-linked aggregates and is stably associated with the resident endoplasmic reticulum protein, GRP78-BiP, whereas wild-type HN forms a specific and transient complex with GRP78-BiP during its folding process.
Conversion Without Hysteria: A Case Report and Review of the Literature

The term ‘conversion’ implies a correlation between conversion symptoms, hysteria, and hysterical personality. A clinical case of conversion related to chronic post-traumatic disorder, with paranoid features, was successfully treated by anti-psychotic drugs; it illustrates the non-specific nature of conversion symptoms. Mechanic's concept of ‘illness behaviour’ is a frame-work that meets the need for a broader understanding of conversion symptoms.
Determination of effective tip geometries in Kelvin probe force microscopy on thin insulating films on metals

In scanning probe techniques, accurate height measurements on heterogeneous surfaces are a major requirement. Different electrostatic potentials of various materials have a significant influence on the measured force/current and therefore a direct influence on the tip–sample distance. Kelvin probe force microscopy (KPFM) is based on a dynamic compensation of the electrostatic force while performing non-contact atomic force microscopy measurements. Thus, the influence of the electrostatic potentials can be minimized and accurate height measurements become possible. Here, the study of ultra-thin alkali halide films on Cu(111) investigated by KPFM is presented. This work is focused on the interface between areas of bare Cu(111) and the first layers of salt. The compensation of the electrostatic potential allow us to determine layer heights with high accuracy. The second objective was to elaborate on the characterization of tip geometries across suitable nanostructures. Simulations of measured images are performed with different input parameters, which gives a direct estimation of the effective tip radius and geometry used for the measurements.
A Hospital-Based Treatment Programme for Male Mentally Handicapped Offenders

The paper describes a special hospital-based treatment programme for male mentally handicapped offenders, comprising a package of practical and personal skills training coupled with a socialisation programme based on token-economy strategies within a controlled and structured environment. Twenty patients admitted to the programme and followed up after discharge for an average of 3.3 years were studied in detail. All had committed serious or persistent offences and showed a high level of psychosocial pathology. A good or fair response to the treatment programme was made by 85%, and 65% were judged well adjusted or reasonably well adjusted at last follow-up contact. A good outcome was associated with more than two years' in-patient care, a good response to the treatment programme and stable residential placement, regular occupation and regular supervision and support in the community. Offenders against the person (sex and assault) had a better prognosis than and showed other interesting differences from property offenders (property and arson).
The mechanisms of sarcoplasmic reticulum Ca2+ release in toad pacemaker cells

1 The mechanisms of sarcoplasmic reticulum (SR) Ca2+ release in pacemaker cells from the sinus venosus of the cane toad (Bufo marinus) were studied. Single, isolated cells were voltage clamped using a nystatin‐perforated patch. Ionic currents and intracellular Ca2+ concentration ([Ca2+]i) were recorded simultaneously. 2 Depolarizations of 300 ms duration from a holding potential of −55 mV produced an inward current which had a bell‐shaped relationship with voltage. Inward current first appeared at about −45 mV, reached a maximum of −343 ± 46 pA at −15 mV and reversed at +45 mV. In contrast the amplitude of the increase in [Ca2+]i caused by depolarization (Ca2+ transient) increased monotonically with the increasing depolarization. At −15 mV the amplitude of the Ca2+ transient was 243 ± 33 nm and at +45 mV it was 411 ± 43 nm. 3 The inward current produced by depolarizations to −5 mV was largely eliminated by the L‐type Ca2+ channel blocker nifedipine (10 μM) while 37 ± 7% of the Ca2+ transient persisted. A significantly larger proportion of the Ca2+ transient (56 ± 5%) remained at +85 mV in the presence of nifedipine. 4 The SR Ca2+ pump inhibitor 2,5‐di(tert‐butyl)‐1,4‐hydroquinone (10 μm), which causes depletion of the SR Ca2+, reduced the amplitude of the Ca2+ transient to 34 ± 1% of control, irrespective of the voltage. 5 Brief exposure to extracellular Ca2+‐free solution abolished the Ca2+ transients caused by depolarization while the caffeine‐induced Ca2+ release persisted. 6 Tetrodotoxin (1 μm) had no effect on the amplitude of the depolarization‐induced Ca2+ transient, although it reduced the fast component of the inward current. In contrast, Ni2+ (5 mm) abolished the Ca2+ transients at any given voltage. Ni2+ also abolished spontaneous Ca2+ transients. 7 In conclusion, in toad pacemaker cells Ca2+ release from SR contributes approximately 66% of the Ca2+ involved in the Ca2+ transient and requires extracellular Ca2+ influx to trigger its release. The L‐type Ca2+ channels and Na+‐Ca2+ exchange are major sources of Ca2+ influx under physiological conditions.
The presentation of newly-diagnosed diabetic patients in Uganda.

We assessed the clinical characteristics of newly-diagnosed diabetic patients presenting to the Mulago Hospital Diabetic Clinic for the first time between 1 January 1993 and 10 August 1994. There were 252 patients: 117 men and 135 women. Mean age at onset of diabetes was 45 years (range 2-87 years) and peak incidence was at 40-49 years. Body mass index (BMI) was available in only 71 patients, of whom 53.5% (33.8% female, 19.7% male) were overweight (BMI > 25 in women, in > 27 men) and 11.3% (8.5% men, 2.8% women) were underweight (BMI < 20). Obesity was more marked in young women. Almost all patients presented with the classical symptoms of diabetes, and the majority were severely hyperglycaemic. A family history of diabetes was identified in 16%. Concurrent illnesses at diagnosis of diabetes were unusual. Sepsis was commonest (11.9%), followed by malaria (7.8%), tuberculosis (1.2%), AIDS (1.2%) and pancreatitis (0.8%). Peripheral neuropathy was present in 46.4% of patients, hypertension (BP > 150/100) in 27.3%, impotence in 22.2% of the men, proteinuria in 17.1%, ischaemic heart disease in 4.8%, foot ulcers in 4.0% and cataracts in 3.2%. Insulin was the most commonly prescribed treatment (52.8%); 31% of patients received oral hypoglycaemic agents, only 15.1% were managed on diet only, and 1.2% opted for herbal medicine.
Use of Web and Phone Survey Modes to Gather Data from Adults about Their Young Adult Children

Mode effects on responses to survey items may introduce bias to data collected using multiple modes of administration. The present study examines data from 704 surveys conducted as part of a longitudinal study in which parents and their children had been surveyed at multiple prior time points. Parents of 22-year-old study participants were randomly assigned to one of two mixed-mode conditions: (1) web mode first followed by the offer of an interviewer-administered telephone mode; or (2) telephone mode first followed by the offer of the web mode. Comparison of responses by assigned condition on 12 measures showed one statistically significant difference. Analyses that modeled differences by completed mode and the interaction between assigned condition and completed mode found significant differences on six measures related to completed mode. None of the differences indicated that more socially desirable responses were given in interviewer-administered surveys.
Design and synthesis of benzopyran-based inhibitors of the hypoxia-inducible factor-1 pathway with improved water solubility

Abstract While progress has been made in treating cancer, cytotoxic chemotherapeutic agents are still the most widely used drugs and are associated with severe side-effects. Drugs that target unique molecular signalling pathways are needed for treating cancer with low or no intrinsic toxicity to normal cells. Our goal is to target hypoxic tumours and specifically the hypoxia inducible factor (HIF) pathway for the development of new cancer therapies. To this end, we have previously developed benzopyran-based HIF-1 inhibitors such as arylsulfonamide KCN1. However, KCN1 and its earlier analogs have poor water solubility, which hamper their applications. Herein, we describe a series of KCN1 analogs that incorporate a morpholine moiety at various positions. We found that replacing the benzopyran group of KCN1 with a phenyl group with a morpholinomethyl moiety at the para positions had minimal effect on potency and improved the water solubility of two new compounds by more than 10-fold compared to KCN1, the lead compound.
Augmented production of chemokines by the interaction of type II collagen-reactive T cells with rheumatoid synovial fibroblasts.

OBJECTIVE To determine the impact of type II collagen (CII)-reactive T cells on the production of chemokines in the joints of patients with rheumatoid arthritis (RA). METHODS T cell proliferative responses to bovine CII were assayed in synovial fluid (SF) mononuclear cells and peripheral blood mononuclear cells. CII-stimulated T cells were cocultured with fibroblast-like synoviocytes (FLS). The expression of interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1 alpha (MIP-1 alpha) in the sera, SF, and supernatant of the CII-stimulated T cells and FLS coculture was measured by enzyme-linked immunosorbent assays. RESULTS The levels of IL-8, MCP-1, and MIP-1 alpha in SF were significantly higher than those in paired sera of RA patients. IL-8, MCP-1, and MIP-1 alpha levels in SF were strongly correlated with T cell responses to CII. When FLS were cocultured with CII-stimulated T cells, the production of IL-8, MCP-1, and MIP-1 alpha was significantly increased. This increase correlated well with the T cell proliferative response to CII. Chemokine production by coculture of CII-stimulated T cells and FLS was mediated mainly by direct cell-cell contact through CD40 ligand-CD40 engagement. CONCLUSION Our data indicate that the presence of CII-reactive T cells in RA joints can increase the production of chemokines such as IL-8, MCP-1, and MIP-1 alpha through interaction with FLS. This chemokine production is mediated by cell-cell contact, including CD40 ligand-CD40 engagement. These results suggest that CII-reactive T cells play a crucial role in the amplification and perpetuation of the inflammatory process in the rheumatoid synovium.
Age-Related Changes in Glucose Transporter-One mRNA Structure and Function

Abstract To determine the molecular mechanisms of age-related changes in the expression of glucose transporter 1 (GLUT-1) mRNA in cerebral tissue, male Fischer 344 rats at 4,12, and 24 months of age were studied. The GLUT-1 mRNA in cerebral tissue was not significantly different among the various age groups. The in vitro translatability of GLUT-1 mRNA of 24-month-old rats (0.867 + 0.066 arbitrary units) was significantly lower than that in 4-month-old (1.403 + 0.153) P < 0.01 or 12-month-old rats (1.387 + 0.122) P < 0.01. The poly (A) tail length of GLUT-1 mRNA decreased from 200-350 nt in 4-month-old rats to only 50-100 nt in 24-month-old rats. Twelve-month-old rats also showed reduced poly (A) tail lengths. The poly (A) tail of G3PDH mRNA was not altered with age. The changes in GLUT-1 mRNA translatability did not correlate with GLUT-1 content in total cerebral tissue homogenate or in isolated cerebral microvessels, suggesting that GLUT-1 protein turnover is altered with age. It is concluded that aging is associated with significant changes in the structure and function of GLUT-1 mRNA.
Progression in Behavioral Variant Frontotemporal Dementia

DESIGN, SETTING, AND PARTICIPANTS Longitudinal cohort study performed in a specialist tertiary FTD research clinic. Fifty-eight consecutive patients were followed up longitudinally from January 1, 2008, through December 31, 2013, and classified as having possible, probable, or definite BVFTD at presentation and latest review. Final follow-up was completed on December 31, 2013, and data were analyzed from January 1 to August 1, 2014.
Genetic Transformation of the Relapsing Fever Spirochete Borrelia hermsii: Stable Integration and Expression of Green Fluorescent Protein from Linear Plasmid 200

ABSTRACT Tick-borne relapsing fever (TBRF) is a spirochetal disease caused by at least 15 different Borrelia species. It is a serious human health concern in regions of endemicity throughout the world. Transmission to humans occurs through the bites of infected Ornithodoros ticks. In North America, the primary Borrelia species associated with human disease are B. hermsii and B. turicatae. Direct demonstration of the role of putative TBRF spirochete virulence factors in the disease process has been hindered by the lack of a genetic manipulation system and complete genome sequences. Expanding on recent developments in these areas, here we demonstrate the successful generation of a clone of B. hermsii YOR that constitutively produces green fluorescent protein (GFP) (B. hermsii YOR::kan gfp). This strain was generated through introduction of a kan-gfp cassette into a noncoding region of the 200-kb B. hermsii linear plasmid lp200. Genetic manipulation did not affect the growth rate or trigger the loss of native plasmids. B. hermsii YOR::kan gfp retained infectivity and elicited host seroconversion. Stable production of GFP was demonstrated both in vitro and in vivo. This study represents a significant step forward in the development of tools that can be employed to study the virulence mechanisms of TBRF spirochetes.
Cysteine Is Not the Sulfur Source for Iron-Sulfur Cluster and Methionine Biosynthesis in the Methanogenic Archaeon Methanococcus maripaludis*

Three multiprotein systems are known for iron-sulfur (Fe-S) cluster biogenesis in prokaryotes and eukaryotes as follows: the NIF (nitrogen fixation), the ISC (iron-sulfur cluster), and the SUF (mobilization of sulfur) systems. In all three, cysteine is the physiological sulfur source, and the sulfur is transferred from cysteine desulfurase through a persulfidic intermediate to a scaffold protein. However, the biochemical nature of the sulfur source for Fe-S cluster assembly in archaea is unknown, and many archaea lack homologs of cysteine desulfurases. Methanococcus maripaludis is a methanogenic archaeon that contains a high amount of protein-bound Fe-S clusters (45 nmol/mg protein). Cysteine in this archaeon is synthesized primarily via the tRNA-dependent SepRS/SepCysS pathway. When a ΔsepS mutant (a cysteine auxotroph) was grown with 34S-labeled sulfide and unlabeled cysteine, <8% of the cysteine, >92% of the methionine, and >87% of the sulfur in the Fe-S clusters in proteins were labeled, suggesting that the sulfur in methionine and Fe-S clusters was derived predominantly from exogenous sulfide instead of cysteine. Therefore, this investigation challenges the concept that cysteine is always the sulfur source for Fe-S cluster biosynthesis in vivo and suggests that Fe-S clusters are derived from sulfide in those organisms, which live in sulfide-rich habitats.
Catecholamine Synthesizing Enzyme Activity in Brainstem Areas from Victims of Sudden Infant Death Syndrome

In order to investigate whether central catecholaminergic neurons are altered in sudden infant death syndrome (SIDS), the activities of dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) were determined in nine brainstem areas from 19 victims of totally unexplained SIDS (tSIDS), 9 victims of partially unexplained SIDS (pSIDS) and 8 control infants. The distinction between tSIDS and pSIDS was made according to the results of the autopsy. They were totally negative for the tSIDS victims, while minor pathological alterations were found in pSIDS victims. In both tSIDS and pSIDS victims, the PNMT activity was significantly decreased in the medullary C2m and C21 areas and in the nucleus medullae oblongatae centralis. In the C21 area only DBH activity was decreased. Further, in the nucleus ambiguus PNMT activity was decreased in tSIDS, while DBH was lowered in pSIDS victims. No significant modifications were found in the areas from the dorso-lateral pons (locus coeruleus, Kolliker Fuse and parabrachialis nuclei). Thus, in the two groups of SIDS victims the capacity to synthesize adrenaline was decreased in some medullary areas. It is considered that these biochemical alterations are related to the abnormal central respiratory and arousal control, which is thought to be present in SIDS.
Providing Diabetes Self-Management Support in Rural Primary Care Clinics With Nurse Partners

This study examined the roles and effectiveness of nurse partner–provided diabetes self-management (DSM) support in five rural primary care clinics. There were two to nine providers and one nurse partner in each clinic; nurses were licensed practical nurses (LPNs) in all but one clinic. Interviews with providers and observations of patient interactions assessed nurse roles, clinic processes, and communication patterns. Using immersion-crystallization methods, three major themes explained nurse partner role variation: “gatekeeper” role of providers, compression of time and space within clinic work flow, and nurses’ educational background and experience. While nurses’ education and experience were important, clinics where providers facilitated nurse participation in DSM support through focused communication and commitment of time and space most effectively integrated DSM support into their practice. Some quantitative measures improved; notably glycated hemoglobin level and patients’ frequency of blood glucose measurement. Study findings provide guidance on using nurses in primary care clinics to provide DSM.