Miracle-dz/UniFAR-FTUs huggingface dataset:
Protrudin Regulates Endoplasmic Reticulum Morphology and Function Associated with the Pathogenesis of Hereditary Spastic Paraplegia*

Background: Certain hereditary spastic paraplegia (HSP)-related proteins possess hairpin domains and regulate the morphology of the endoplasmic reticulum (ER) network. Results: Protrudin possesses a hairpin domain and interacts with HSP-related proteins. Conclusion: Protrudin regulates ER morphology and function. Significance: Mutant protrudin produced in certain individuals with HSP is prone to form microaggregates that induce ER stress. Protrudin is a membrane protein that regulates polarized vesicular trafficking in neurons. The protrudin gene (ZFYVE27) is mutated in a subset of individuals with hereditary spastic paraplegia (HSP), and protrudin is therefore also referred to as spastic paraplegia (SPG) 33. We have now generated mice that express a transgene for dual epitope-tagged protrudin under control of a neuron-specific promoter, and we have subjected highly purified protrudin-containing complexes isolated from the brain of these mice to proteomics analysis to identify proteins that associate with protrudin. Protrudin was found to interact with other HSP-related proteins including myelin proteolipid protein 1 (SPG2), atlastin-1 (SPG3A), REEP1 (SPG31), REEP5 (similar to REEP1), Kif5A (SPG10), Kif5B, Kif5C, and reticulon 1, 3, and 4 (similar to reticulon 2, SPG12). Membrane topology analysis indicated that one of three hydrophobic segments of protrudin forms a hydrophobic hairpin domain similar to those of other SPG proteins. Protrudin was found to localize predominantly to the tubular endoplasmic reticulum (ER), and forced expression of protrudin promoted the formation and stabilization of the tubular ER network. The protrudin(G191V) mutant, which has been identified in a subset of HSP patients, manifested an increased intracellular stability, and cells expressing this mutant showed an increased susceptibility to ER stress. Our results thus suggest that protrudin contributes to the regulation of ER morphology and function, and that its deregulation by mutation is a causative defect in HSP.
The impact of maternal behavior on children's pain experiences: an experimental analysis.

OBJECTIVE To provide an experimental investigation of the impact of maternal behavior on children's pain experiences. METHOD Participants were 120 healthy children (60 boys, 60 girls) between the ages of 8 and 12 years and their mothers. Mothers were randomly assigned and trained to interact with their children in one of three ways while the children were exposed to lab-induced cold pressor pain: (1) a pain-promoting interaction, (2) a pain-reducing interaction, and (3) a no training control group. Training was based on behaviors presumed to have the expected impact, as based on correlational studies reported in the literature. Children's pain experiences during the cold pressor were assessed using self-reports of intensity and affect, coding of facial activity, tolerance, and heart rate responsiveness. RESULTS Girls whose mothers interacted with them in the pain-promoting manner reported more pain than daughters of mothers in the control group, who in turn reported more pain than girls whose mothers interacted with them in the pain-reducing manner. This effect was not significant for boys. Maternal interaction type had no effect on children's pain affect, facial activity, tolerance, or heart rate. CONCLUSIONS Results indicate that maternal behavior can have a direct impact on their daughters' subjective reports of pain. These data support the importance of social learning factors in influencing children's pain experiences.
Genetic association of vitamin D receptor polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese

Background: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two autoimmune diseases of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. Vitamin D has been shown to exert multiple immunomodulatory effects, which acts through its own receptor (VDR). Polymorphisms of VDR had been implicated in several autoimmune diseases. In the present study, the association between Chinese patients with AIH, PBC and the polymorphisms in exon 2, intron 8 and exon 9 of vitamin D receptor genes was studied.
Community based retrospective study of sex in infant mortality in India

Abstract Objective To determine whether the imbalance in the sex ratio in India can be explained by less favourable treatment of girls in infancy. Design Analysis of results of verbal autopsy reports over a five year period. Setting Community health project in urban India. Main outcome measures Deaths from all causes in infants aged less than 1 year. Results The sex ratio at birth was 869 females per 1000 males. The mean infant mortality was 1.3 times higher in females than in males (72 v 55 per 1000). Diarrhoea was responsible for 22% of deaths overall, though twice as many girls died from diarrhoea. There were no significant differences in the numbers of deaths from causes such as birth asphyxia, septicaemia, prematurity, and congenital anomalies. In 10% of deaths there was no preceding illness and no satisfactory cause was found. Three out of every four such deaths were in girls. Conclusions The excess number of unexplained deaths and deaths due to treatable conditions such as diarrhoeal disease in girls may be because girls are regarded and treated less favourably in India.
Sensitivity of Whole-Body Dosimetry to Channel Model Parameters

Impact of channel model parameters on the whole-body specific absorption rate (SAR) is studied. Closed-form expressions are derived for the mean value and the standard deviation of the SAR, taking into account the random nature of the channel parameters. Total sensitivity indices of the SAR with respect to the channel parameters are derived. They are estimated using a Monte-Carlo approach. Noninfluential channel parameters are identified. They are then suppressed from channel models for dosimetry purpose.
Molecular and Pharmacological Characterization of GABAA Receptor α1 Subunit Knockout Mice

GABAA receptors mediate fast inhibitory neurotransmission in the central nervous system (CNS), and approximately half of these receptors contain α1 subunits. GABAA receptor α1 subunits are important for receptor assembly and specific pharmacological responses to benzodiazepines. Plasticity in GABAA receptor α1 subunit expression is associated with changes in CNS excitability observed during normal brain development, in animal models of epilepsy, and upon withdrawal from alcohol and benzodiazepines. To examine the role of α1 subunit-containing GABAA receptors in vivo, we characterized receptor subunit expression and pharmacological properties in cerebral cortex of knockout mice with a targeted deletion of the α1 subunit. The mice are viable but exhibit an intention tremor. Western blot analysis confirms the complete loss of α1 subunit peptide expression. Stable adaptations in the expression of several GABAA receptor subunits are observed in the fifth to seventh generations, including decreased expression of β2/3 and γ2 subunits and increased expression of α2 and α3 subunits. There was no change in α4, α5, or δ subunit peptide levels in cerebral cortex. Knockout mice exhibit loss of over half of GABAA receptors measured by [3H]muscimol, [3H]2-(3-carboxyl)-3-amino-6-(4-methoxyphenyl)-pyridazinium bromide ([3H]SR-95531), andt-butylbicyclophosphoro[35S]thionate ([35S]TBPS) binding. [3H]Ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate ([3H]Ro15-4513) binding is reduced by variable amounts in different regions across brain. GABAA receptor α1−/− mice lose all high-affinity [3H]zolpidem binding and about half of [3H]flunitrazepam binding in the cerebral cortex. The potency and maximal efficacy of muscimol-stimulated36Cl− uptake in cerebral cortical synaptoneurosomes are reduced in α1−/− mice. Furthermore, knockout mice exhibit increased bicuculline-induced seizure susceptibility compared with wild-type mice. These data emphasize the significance of α1 subunit expression and its involvement in the regulation of CNS excitability.
Metformin-3-hydroxyflavone , A New Schiff Base Complex Modulates the Activities of Carbohydrate Regulatory Enzymes in High Fat Diet Fed-Low Dose Streptozotocin Induced Type 2 Diabetes in Experimental Rats

T2DM is a multifaceted endocrine disorder arises due to insulin resistance coupled with insufficient secretion of insulin from the pancreatic β-cells. Its prevalence is increasing alarmingly worldwide due to genetic and environmental factors. Among the various oral antidiabetic drugs widely used for the treatment of T2DM, metformin is considered as the first line of treatment to T2DM and backbone for combination therapy. However, at higher doses metformin induced lactic acidosis in addition to vitamin B12 deficiency. In order to circumvent the toxicity of metformin at high doses, an attempt has been made to synthesize a new metformin-3-hydroxyflavone complex. The Schiff base complex synthesized was characterized by various spectral studies such as FT-IR, Mass, 1 H NMR and 13 C NMR. The effect of oral administration of metformin-3-hydroxyflavone complex at a concentration of 20 mg/kg.b. w. /rat/day to high fat diet fed-low dose STZ induced type 2 diabetes in rats was evaluated. The biochemical alterations such as fasting blood glucose, hemoglobin, glycosylated hemoglobin, plasma insulin and c-peptide observed in the diabetic rats were restored to near normal after treatment with the Schiff base complex. Additionally, the complex treatment regulates the activity of carbohydrate and glycogen metabolizing enzymes. The efficacy of the complex was comparable with metformin which was administration at a relatively high dose of 50 mg/kg.b. w. /rat/day. The data obtained evidenced the regulatory properties of metformin-3-hydroxyflavone complex in maintaining normoglycemia in experimental type 2 diabetes.
Laparoscopic Colorectal Resections: A Simple Predictor Model and a Stratification Risk for Conversion to Open Surgery

BACKGROUND: The advantages associated with the laparoscopic approach are lost when conversion is required. Available predictive models have failed to show external validation. Body surface area is a recently described risk factor not included in these models. OBJECTIVE: The aim of this study was to develop a clinical rule including body surface area for predicting conversion in patients undergoing elective laparoscopic colorectal surgery. DESIGN: This was a prospective cohort study. SETTING: This study was conducted at a single large tertiary care institution. PATIENTS: Nine hundred sixteen patients (mean age, 63.9; range, 14–91 years; 53.2% female) who underwent surgery between January 2004 and August 2011 were identified from a prospective database. MAIN OUTCOME MEASURES: Conversion rate was analyzed related to age, sex, obesity, disease location (colon vs rectum), type of disease (neoplastic vs nonneoplastic), history of previous surgery, and body surface area. A predictive model for conversion was developed with the use of logistic regression to identify independently associated variables, and a simple clinical prediction rule was derived. Internal validation of the model was performed by using bootstrapping. RESULTS: The conversion rate was 9.9% (91/916). Rectal disease, large patient size, and male sex were independently associated with higher odds of conversion (OR, 2.28 95%CI, 1.47–3.46]), 1.88 [1.1–3.44], and 1.87 [1.04–3.24]). The prediction rule identified 3 risk groups: low risk (women and nonlarge males), average risk (large males with colon disease), and high risk (large males with rectal disease). Conversion rates among these groups were 5.7%, 11.3%, and 27.8% (p < 0.001). Compared with the low-risk group, ORs for average- and high-risk groups were 2.17 (1.30–3.62, p = 0.004) and 6.38 (3.57–11.4, p < 0.0001). LIMITATIONS: The study was limited by the lack of external validation. CONCLUSION: This predictive model, including body surface area, stratifies patients with different conversion risks and may help to inform patients, to select cases in the early learning curve, and to evaluate the standard of care. However, this prediction rule needs to be externally validated in other samples (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A137).
The Need for a Dualist Application of Public and Private Law in Great Britain Following the Use of “Flame Trolling” During the 2011 UK Riots: A Review and Model

Since time immemorial, the legal systems of Great Britain have often been spoken of highly as pinnacles of democracy. However, the split between criminal law and tort law have often caused problems where the police has often focused on the prosecution of people in poverty and where only the wealthy can afford to use the system. This chapter discusses the extent and limitations of existing measures to tackle computer-related crime, particularlywith regardsto the abusive kind of Internet Trolling, namely “flame trolling. ” The chapter recommends further research to establish whether it should be the case that in a society based on dualism that criminal and civil cases should be held at the same time, and that in both instances those being accused of an offence or tort should be allowed to bring a counter-claim. It is discussed that in such a system the cases that would be brought are where there is a clear victim who had no part in the offence against them, such as murder, rape, theft and burglary, which are usually carefully planned and orchestrated acts.
Wavelet based descriptors for soil moisture estimation using SAR data

This paper presents a wavelet based descriptors for soil moisture estimation using Synthetic Aperture Radar data. The single look complex SAR image is transformed using complex stationary wavelet transform, which is constructed using a complex filter bank. The wavelet coefficients are grouped together using spatial relationships and Fourier based descriptors are preformed within wavelet domain across different subbands. The wavelet based descriptors were compared with the ground measurements and a good correlation was achieved.
Bargaining for Gender Equality in the Australian Public Service

The concept of ‘equality bargaining’ emerged in Europe and the United Kingdom in the 1990s as an important method to advance women's interests at work. This paper examines ‘equality bargaining’ in the Australian context using a detailed case study of bargaining in an Australian public service agency. In this particular case, increased family provisions were successfully negotiated. The main determinant of successful equality bargaining was found to be the mainstreaming of a suite of provisions in the union's centralised log of claims which aim to achieve equality for female employees. Potentially, the findings from this case study have wider implications for enterprise bargaining in Australia, and suggest how unions can progress an equality agenda.
Price Clustering Asymmetries in Limit Order Flows

We explore the relation between limit order price clustering and price efficiency. We find that executed sell limit orders cluster more frequently on round increments than buy limit orders and that this asymmetry in clustering is consistent with the well documented asymmetry in price response to marketable orders. Additionally, we find that the degree of clustering is positively related to volatility and that asymmetry in clustering depends on whether stock prices are rising or falling - sell limit orders cluster more frequently as prices are rising, while buy limit order cluster more as prices are declining. Our results indicate that predictable patterns in limit order pricing contribute to short-run deviations from price efficiency.
Use and Non-Use Values in an Applied Bioeconomic Model of Fisheries and Habitat Connections

ABSTRACT In addition to indirect support to fisheries, marine habitats also provide non-use benefits often overlooked in most bioeconomic models.We expand a dynamic bioeconomic fisheries model where presence of natural habitats reduces fishing cost via aggregation effects and provides non-use benefits. The theoretical model is illustrated with an application to cold-water corals in Norway where two fishing methods are considered—destructive bottom trawl and non-destructive coastal gear. Non-use values of cold-water corals in Norway are estimated using a discrete choice experiment. Both the theoretical model and its empirical applications demonstrate how non-use values impact optimal fishing practices. JEL Codes: Q22, Q28, Q57.
Current Chemotherapy and Potential New Targets in Uterine Leiomyosarcoma

A variety of chemotherapeutic agents have been used for treating recurrent or advanced stage uterine leiomyosarcoma (ULMS). The response rates of these current agents are disappointing, with partial response rates varying from 0% to 33%, and complete response rates varying from 0% to 8%. Recent studies have documented many molecular changes in ULMSs. Prominent amongst these are gains of growth factors C-MYC, Bcl-2, K-ras, and Ki-67, and losses in tumor suppressors p16, p53, Rb1, ING2 and D14S267. Various techniques that have been used to target these molecules are presented. Targeting specific therapies at these underlying molecular changes could potentially yield better response rates with fewer side effects.
Modulation of biofilms of Pseudomonas aeruginosa by quinolones

The interaction between four fluoroquinolones (ciprofloxacin, norfloxacin, pefloxacin, and ofloxacin) and biofilms of Pseudomonas aeruginosa in wells of microtiter plates and on segments of vascular catheters were studied in an in vitro model of vascular catheter colonization. Subinhibitory concentrations (one-half, one-fourth, and one-eight of the MIC) of the fluoroquinolones reduced the adherence of P. aeruginosa to 30 to 33, 44 to 47, and 61 to 67% of that of controls, respectively. The addition of high concentrations of the fluoroquinolones (12.5 and 400 micrograms/ml) to preformed biofilms (grown for 48 h at 37 degrees C) decreased the adherence of P. aeruginosa to 69 to 77 and 39 to 60% of that of controls, respectively. In an in vitro model of vascular catheter colonization, subinhibitory concentrations (one-half, one-fourth, and one-eight of the MIC) of fluoroquinolones reduced the number of adherent bacteria to 21 to 23, 40 to 46, and 55 to 70% of that of the controls, respectively. Scanning electron microscopy demonstrated a significant reduction in glycocalyx formation and adherent bacteria in the presence of pefloxacin at one-half to one-eight of the MIC. Vascular catheter segments precolonized with P. aeruginosa for 24 h and exposed to the fluoroquinolones at 4 to 25 times the MIC (50 micrograms/ml) for 2 h showed <5% growth of adherent cells compared with controls. No adherent organisms were cultured in the presence of 8 to 50 times the MIC (100 micrograms/ml). Scanning electron microscopy studies of preformed biofilms exposed to pefloxacin verified the results obtained by culture. These data show that subinhibitory concentrations of ciprofloxacin, norfloxacin, pefloxacin, and ofloxacin inhibit the adherence of P. aeruginosa to plastic surfaces and vascular catheters. Clinically achievable concentrations of fluoroquinolones (50 to 100 micrograms/ml) were able to eradicate preformed biofilms on vascular catheters.
The Adenosine Transporter, mENT1, Is a Target for Adenosine Receptor Signaling and Protein Kinase Cϵ in Hypoxic and Pharmacological Preconditioning in the Mouse Cardiomyocyte Cell Line, HL-1

Brief exposure of the heart to hypoxia results in less cellular damage after subsequent hypoxia, an effect known as preconditioning (PC). PC has been widely studied but is still not fully understood. Adenosine (Ado), adenosine receptors, and protein kinase C (PKC) have been implicated as integral components of PC. Adenosine (nucleoside) transporters (NTs) facilitate flux of Ado across cell membranes, but their role in PC is unknown. Therefore, we used the murine cardiomyocyte cell line, HL-1, and asked if there was feedback regulation of NTs by Ado, Ado receptors, and PKC following either hypoxic or pharmacological PC. Activation (by specific agonists) of A1 or A3 Ado receptors or PKC resulted in PC in HL-1. The A1 (but not A3) receptor is coupled to PKCϵ, and activation of PKCϵ (by specific peptide agonist) resulted in PC. Moreover, PKCϵ stimulates Ado uptake via the predominant NT in HL-1, mouse equilibrative nucleoside transporter 1 (mENT1). Studies in primary neonatal mouse cardiomyocytes confirmed our observations in HL-1 cells. Hypoxic challenge led to a rapid increase in, and efflux of, intracellular Ado from cells, which was blocked by NT inhibitors (dipyridamole/nitrobenzylthioinosine). Moreover, NT inhibition during hypoxia or PC was highly protective, suggesting that Ado loss contributes to decreased cell viability. Our data suggest that hypoxic challenge causes an efflux of Ado via ENTs, activation of A1 and/or A3 receptors, signaling through PKCϵ, and activation of ENT1. Since Ado is required for ATP synthesis on reperfusion, this feedback regulation of mENT1 would promote reuptake of Ado.
Myeloid Bmal1 deletion increases monocyte recruitment and worsens atherosclerosis

BMAL1, the nonredundant transcription factor in the core molecular clock, has been implicated in cardiometabolic diseases in mice and humans. BMAL1 controls the cyclic trafficking of Ly6chi monocytes to sites of acute inflammation. Myeloid deficiency of Bmal1 also worsens chronic inflammation in diet‐induced obesity. We studied whether myeloid Bmal1 deletion promotes atherosclerosis by enhancing monocyte recruitment to atherosclerotic lesions. By generating Bmal1FloxP/FloxP;LysMCre mice on the Apoe−/− background, we showed that Bmal1 deletion in myeloid cells increased the size of atherosclerotic lesions. Bmal1 deficiency in monocytes and macrophages resulted in an increased total number of lesional macrophages in general and Ly6chi infiltrating monocyte‐macrophages in particular, accompanied by skewed M2 to M1 macrophage phenotype. Ly6chi and/or Ly6cl° monocyte subsets in blood, spleen, and bone marrow were not altered. Cell tracking and adoptive transfer of Ly6chi monocytes showed Bmal1 deficiency induced more trafficking of Ly6chi monocytes to atherosclerotic lesions, preferential differentiation of Ly6chi monocytes into M1 macrophages, and increased macrophage content and lesion size in the carotid arteries. We demonstrated that Bmal1 deficiency in macrophages promotes atherosclerosis by enhancing recruitment of Ly6chi monocytes to atherosclerotic lesions. —Huo, M. , Huang, Y. , Qu, D. , Zhang, H. , Wong, W. T. , Chawla, A. , Huang, Y. , Tian, X. Y. Myeloid Bmal1 deletion increases monocyte recruitment and worsens atherosclerosis. FASEB J. 31, 1097–1106 (2017). www.fasebj. org