Miracle-dz/UniFAR-FTUs huggingface dataset:
Metformin Improves Metabolic Memory in High Fat Diet (HFD)-induced Renal Dysfunction*♦

Recently, we have shown that high fat diet (HFD) in vivo and in vitro generates metabolic memory by altering H3K36me2 and H3K27me3 on the promoter of FOXO1 (transcription factor of gluconeogenic genes) (Kumar, S., Pamulapati, H., and Tikoo, K. (2016) Mol. Cell. Endocrinol. 422, 233–242). Here we checked the hypothesis whether concomitant diet reversal and metformin could overcome HFD-induced metabolic memory and renal damage. Male adult Sprague-Dawley rats were rendered insulin-resistant by feeding high fat diet for 16 weeks. Then the rats were subjected to diet reversal alone and along with metformin for 8 weeks. Biochemical and histological markers of insulin resistance and kidney function were measured. Blood pressure and in vivo vascular reactivity to angiotensin II (200 ng kg−1) were also checked. Diet reversal could improve lipid profile but could not prevent renal complications induced by HFD. Interestingly, metformin along with diet reversal restored the levels of blood glucose, triglycerides, cholesterol, blood urea nitrogen, and creatinine. In kidney, metformin increased the activation of AMP-activated protein kinase (AMPK) and decreased inflammatory markers (COX-2 and IL-1β) and apoptotic markers (poly(ADP-ribose) polymerase (PARP) and caspase 3). Metformin was effective in lowering elevated basal blood pressure and acute change in mean arterial pressure in response to angiotensin II (Ang II). It also attenuated tubulointerstitial fibrosis and glomerulosclerosis induced by HFD feeding in kidney. Here we report, for the first time, that metformin treatment overcomes metabolic memory and prevents HFD-induced renal damage.
Psychiatric Computer Interviews: How Precise, Reliable And Accepted Are They?

Objective: Computer-assisted personal interviewing has been developed to help health care providers in gathering and processing information from the patients for diagnosis, treatment and intervention. Psychiatric service providers and patients, however, doubt this instrument in terms of the preciseness and reliability of the instruments because generally, psychiatric interviews rest on the interviewers' skills to create trust between patients and providers in order to go in-depth on sensitive issues. In this review, the existing literatures on the issue of reliability and precision of psychiatric computer interviews on patients' sensitive issues will be evaluated based on my work and experience in psychiatric care. Methods: Literature search on psychiatric computer interviews, which include patients and mental health professionals' attitude, which may include sensitive issue was conducted. Results: Patients prefer computer interviews rather than human interviews for revealing their sensitive issues while mental health professionals value human interviews and judgment more than computers. Computers have limitations in understanding human natural language, human interaction and non-verbal communication. Conclusion: It is recommended that the use of psychiatric computer interviews should be used under supervision of mental health professionals. ASEAN Journal of Psychiatry, Vol. 13 (1): January - June 2012: XX XX.
Down-Regulation of the Alternative Sigma Factor SigJ Confers a Photoprotective Phenotype to Anabaena PCC 7120

Alternative sigma factors belonging to Group 3 are thought to play an important role in the adaptation of cyanobacteria to environmental challenges by altering expression of genes needed for coping with such stresses. In this study, the role of an alternative sigma factor, SigJ, was analyzed in the filamentous nitrogen-fixing cyanobacterium, Anabaena sp. PCC 7120 by knocking down the expression of the sigJ gene (alr0277) employing an antisense RNA-mediated approach. In the absence of any stress, the knock-down (KD0277) or the wild-type strain both grew similarly. Upon exposure to high-intensity light, KD0277 showed substantially reduced bleaching of its pigments, higher photosynthetic activity and consequently better survival than the wild type. KD0277 also showed an enhanced accumulation of two carotenoids, which were identified as myxoxanthophyll and keto-myxoxanthophyll. Further, KD0277 was more tolerant to ammonium-triggered photodamage than the wild type. Moreover, PSII was better protected against photodamage in KD0277 than in the wild type. Down-regulation of sigJ in Anabaena PCC 7120, however, reduced its ability to cope with desiccation. This study demonstrates that down-regulation of the sigJ gene in Anabaena PCC 7120 differentially affects its ability to tolerate two environmentally relevant stresses, i.e. high-intensity light and desiccation.
Functional Requirement for Orai1 in Store-operated TRPC1-STIM1 Channels*

Orai1 and TRPC1 have been proposed as core components of store-operated calcium release-activated calcium (CRAC) and store-operated calcium (SOC) channels, respectively. STIM1, a Ca2+ sensor protein in the endoplasmic reticulum, interacts with and mediates store-dependent regulation of both channels. We have previously reported that dynamic association of Orai1, TRPC1, and STIM1 is involved in activation of store-operated Ca2+ entry (SOCE) in salivary gland cells. In this study, we have assessed the molecular basis of TRPC1-SOC channels in HEK293 cells. We report that TRPC1+STIM1-dependent SOCE requires functional Orai1. Thapsigargin stimulation of cells expressing Orai1+STIM1 increased Ca2+ entry and activated typical ICRAC current. STIM1 alone did not affect SOCE, whereas expression of Orai1 induced a decrease. Expression of TRPC1 induced a small increase in SOCE, which was greatly enhanced by co-expression of STIM1. Thapsigargin stimulation of cells expressing TRPC1+STIM1 activated a non-selective cation current, ISOC, that was blocked by 1 μm Gd3+ and 2-APB. Knockdown of Orai1 decreased endogenous SOCE as well as SOCE with TRPC1 alone. siOrai1 also significantly reduced SOCE and ISOC in cells expressing TRPC1+STIM1. Expression of R91WOrai1 or E106QOrai1 induced similar attenuation of TRPC1+STIM1-dependent SOCE and ISOC, whereas expression of Orai1 with TRPC1+STIM1 resulted in SOCE that was larger than that with Orai1+STIM1 or TRPC1+STIM1 but not additive. Additionally, Orai1, E106QOrai1, and R91WOrai1 co-immunoprecipitated with similar levels of TRPC1 and STIM1 from HEK293 cells, and endogenous TRPC1, STIM1, and Orai1 were co-immunoprecipitated from salivary glands. Together, these data demonstrate a functional requirement for Orai1 in TRPC1+STIM1-dependent SOCE.
Cytomegalovirus M45 Cell Death Suppression Requires Receptor-interacting Protein (RIP) Homotypic Interaction Motif (RHIM)-dependent Interaction with RIP1*

Herpesviruses such as cytomegaloviruses encode functions that modulate the innate response in diverse ways to counteract host sensing and delay host clearance during infection. The murine cytomegalovirus M45 protein interacts with receptor-interacting protein (RIP) 1 and RIP3 via a RIP homotypic interaction motif. Cell death suppression by M45 requires RIP homotypic interaction motif-dependent interaction with RIP1. This interaction also underlies the cell tropism role of M45 in preventing premature death of endothelial cells during murine cytomegalovirus infection. Thus, M45 is a viral inhibitor of RIP activation that provides a direct cell type-dependent replication benefit to the virus while modulating other biological processes signaling via the RIP1 adaptor such as activation of Toll-like receptor (TLR)3 as well as other mediators of cell death.
Intrinsic Van Der Waals Magnetic Materials from Bulk to the 2D Limit: New Frontiers of Spintronics

2D van der Waals (vdW) magnets, which present intrinsic ferromagnetic/antiferromagnetic ground states at finite temperatures down to atomic‐layer thicknesses, open a new horizon in materials science and enable the potential development of new spin‐related applications. The layered structure of vdW magnets facilitates their atomic‐layer cleavability and magnetic anisotropy, which counteracts spin fluctuations, thereby providing an ideal platform for theoretically and experimentally exploring magnetic phase transitions in the 2D limit. With reduced dimensions, the susceptibility of 2D magnets to a large variety of external stimuli also makes them more promising than their bulk counterpart in various device applications. Here, the current status of characterization and tuning of the magnetic properties of 2D vdW magnets, particularly the atomic‐layer thickness, is presented. Various state‐of‐the‐art optical and electrical techniques have been applied to reveal the magnetic states of 2D vdW magnets. Other emerging 2D vdW magnets and future perspectives on the stacking strategy are also given; it is believed that they will excite more intensive research and provide unprecedented opportunities in the field of spintronics.
Corporate Strategy and Shareholder Value during Decline and Turnaround

Purpose – The paper aims to assess the impact of corporate strategy on shareholder value in decline and turnaround situations.Design/methodology/approach – A sample of 45 turnaround firms was selected and matched against a control sample which did not face continuous decline over the time period studied. The impact of corporate strategy on shareholder value was tested using cumulative beta excess return measures to capture the long‐term basis of corporate strategy.Findings – The paper finds that the beta excess return measures captured the hypothesized relationships between strategy and shareholder value for the sample firms studied.Practical implications – Beta excess return measures are superior to case studies or event studies for identifying the long‐term effects of corporate strategy.Originality/value – Relatively few studies have compared the strategies of turnaround firms with a matched sample of non‐declining firms. The use of cumulative beta excess returns to assess long‐term valuation of corpora.
Antithrombin replacement and outcome in cardiac surgery

Background and objective: Antithrombin levels during cardiac surgery critically decrease, due to both hemodilution and consumption. This factor prompted the question of whether improved attenuation of hemostatic activation can be achieved by high dose treatment with antithrombin. The aim of this review is to present the currently available pre‐clinical and clinical data on the use of antithrombin in cardiac surgery. Methods: Review of the available literature searched using the terms ‘AT’ or ‘Antithrombin’ and ‘Cardiac surgery’ or ‘CPB’ or ‘Cardiopulmonary bypass’. Results: Antithrombin has been proposed in cardiac operations both as purified concentrates and as recombinant human preparations. The main clinical field where antithrombin supplementation is proposed is in case of heparine resistance (failure to achieve adequate anticoagulation following a standard heparin dose). However, other clinical scenarios have been investigated (modulation of inflammatory reaction; pulmonary vasodilation; prevention of thromboembolic complications). Conclusions: Many studies suggest that antithrombin supplementation during and after cardiac surgery may be beneficial to correct abnormally low values. One article found an association between low values of antithrombin activity at the end of the operation and adverse postoperative outcomes. However, a large prospective, randomized trial is still needed to finally set the role of antithrombin supplementation in cardiac surgery.
Solution Structure of Human Pex5·Pex14·PTS1 Protein Complexes Obtained by Small Angle X-ray Scattering

The Pex5p receptor recognizes newly synthesized peroxisomal matrix proteins which have a C-terminal peroxisomal targeting signal to the peroxisome. After docking to protein complexes on the membrane, these proteins are translocated across the membrane. The docking mechanism remains unclear, as no structural data on the multicomponent docking complex are available. As the interaction of the cargo-loaded Pex5p receptor and the peroxisomal membrane protein Pex14p is the essential primary docking step, we have investigated the solution structure of these complexes by small angle x-ray scattering and static light scattering. Titration studies yielded a 1:6 stoichiometry for the Pex5p·Pex14p complex, and low resolution structural models were reconstructed from the x-ray scattering data. The free full-length human Pex5p is monomeric in solution, with an elongated, partially unfolded N-terminal domain. The model of the complex reveals that the N terminus of Pex5p remains extended in the presence of cargo and Pex14p, the latter proteins being significantly intermingled with the Pex5p moiety. These results suggest that the extended structure of Pex5p may play a role in interactions with other substrates such as lipids and membrane proteins during the formation of functional multiprotein complexes.
Nonuniform channels in adsorbent monoliths

A model is introduced to account for nonuniform channel geometries in monolithic adsorbents. Based on nonisothermal operation, fully developed parabolic flow and the full three-dimensional convection-diffusion equation, the model is applied to the adsorption of dichloromethane from an air stream flowing through a binder-less activated carbon monolith. The equilibrium parameters and the effective diffusion coefficient for adsorption are obtained independently from gravimetric adsorption experiments. The nonuniform channel model is capable of predicting breakthrough curves as a function of feed gas flow rates up to dimensionless breakthrough concentrations of about 0.4-0.6, depending on the feed flow rate. Even though the variation of effective diffusion coefficient with both concentration and temperature has been tested, successful prediction over the whole range of concentration may require the incorporation of further aspects relating to the anisotropic nature of the carbon.
Apoptotic effect of Helicobacter pylori on oesophageal squamous‐cell carcinoma cells in vitro

Backbround The relationship between Helicobacter pylori (Hp) infection and oesophageal squamous‐cell carcinoma (ESCC) risk is still inconclusive. Our previous study found an inverse association between the two, but its mechanism is still unknown. Thus, we conducted in vitro studies to clarify the issue.
Identification of the C1q-binding Sites of Human C1r and C1s

The C1 complex of complement is assembled from a recognition protein C1q and C1s-C1r-C1r-C1s, a Ca2+-dependent tetramer of two modular proteases C1r and C1s. Resolution of the x-ray structure of the N-terminal CUB1-epidermal growth factor (EGF) C1s segment has led to a model of the C1q/C1s-C1r-C1r-C1s interaction where the C1q collagen stem binds at the C1r/C1s interface through ionic bonds involving acidic residues contributed by the C1r EGF module (Gregory, L. A., Thielens, N. M., Arlaud, G. J., Fontecilla-Camps, J. C., and Gaboriaud, C. (2003) J. Biol. Chem. 278, 32157–32164). To identify the C1q-binding sites of C1s-C1r-C1r-C1s, a series of C1r and C1s mutants was expressed, and the C1q binding ability of the resulting tetramer variants was assessed by surface plasmon resonance. Mutations targeting the Glu137-Glu-Asp139 stretch in the C1r EGF module had no effect on C1 assembly, ruling out our previous interaction model. Additional mutations targeting residues expected to participate in the Ca2+-binding sites of the C1r and C1s CUB modules provided evidence for high affinity C1q-binding sites contributed by the C1r CUB1 and CUB2 modules and lower affinity sites contributed by C1s CUB1. All of the sites implicate acidic residues also contributing Ca2+ ligands. C1s-C1r-C1r-C1s thus contributes six C1q-binding sites, one per C1q stem. Based on the location of these sites and available structural information, we propose a refined model of C1 assembly where the CUB1-EGF-CUB2 interaction domains of C1r and C1s are entirely clustered inside C1q and interact through six binding sites with reactive lysines of the C1q stems. This mechanism is similar to that demonstrated for mannan-binding lectin (MBL)-MBL-associated serine protease and ficolin-MBL-associated serine protease complexes.
Basic Clinical Radiobiology

1.Introduction: the significance of radiobiology and radiotherapy for cancer treatment 2. Irradiation-induced damage and the DNA damage response 3. Cell death after irradiation: how, when and why cells die 4. Quantitating cell kill and cell survival 5. Models of radiation response 5. Dose-response relationships in radiotherapy 6. LET and RBE 7. Tumour growth and response to radiation 8. Fractionation: the L-Q approach 9. The L-Q approach in clinical practice 10. Modified fractionation 11. Time factors in normal-tissue response to radiation 12. The dose-rate effect 13. Pathogenesis of normal-tissue side-effects 14. The volume effect in radiotherapy 15. The oxygen effect and fractionated radiotherapy 16. The tumour microenvironment and cellular hypoxia responses 17. Therapeutic approaches to tumor hypoxia 18. Combined radiotherapy and chemotherapy 19. Retreatment tolerance of normal tissues 20.Molecular image-guided radiotherapy with positron emission tomography 21. Molecular-targeted agents for enhancing tumour response 22. Biological response modifiers in the clinic: tumor 22. Biological response modifiers: normal tissue 23. Molecular targeting and patient individualization 24.Protons and other ions in radiotherapy 25. Second cancers after radiotherapy
Role of TLR4 for paclitaxel chemotherapy in human epithelial ovarian cancer cells

Background Paclitaxel has been reported to be a ligand to Toll like receptor 4 (TLR4). Myeloid differentiation factor 88(MyD88) was described as a myeloid differentiation primary response gene. TLR4 signalling owns two pathways: MyD88‐dependent and MyD88‐independent pathways. XIAP is a key member of the inhibitor of apoptosis protein family. Akt is a major downstream target of growth factor receptor tyrosine kinases, which negatively regulates apoptotic pathways through phosphorylation (pAkt). The aim of the present study is to investigate the role of TLR4 in paclitaxel resistance of ovarian cancer cells.
Mutation in the Heparan Sulfate Biosynthesis Enzyme EXT1 Influences Growth Factor Signaling and Fibroblast Interactions with the Extracellular Matrix*

Heparan sulfate (HS) chains bind and modulate the signaling efficiency of many ligands, including members of the fibroblast growth factor (FGF) and platelet-derived growth factor families. We previously reported the structure of HS synthesized by embryonic fibroblasts from mice with a gene trap mutation of Ext1 that encodes a glycosyltransferase involved in HS chain elongation. The gene trap mutation results in low expression of Ext1, and, as a consequence, HS chain length is substantially reduced. In the present study, Ext1 mutant and wild-type mouse embryonic fibroblasts were analyzed for the functional consequences of the Ext1 mutation for growth factor signaling and interaction with the extracellular matrix. Here, we show that the phosphorylation of ERK1/2 in response to FGF2 stimulation was markedly decreased in the Ext1 mutant fibroblasts, whereas neither PDGF-BB nor FGF10 signaling was significantly affected. Furthermore, Ext1 mutants displayed reduced ability to attach to collagen I and to contract collagen lattices, even though no differences in the expression of collagen-binding integrins were observed. Reintroduction of Ext1in the Ext1 mutant fibroblasts rescued HS chain length, FGF2 signaling, and the ability of the fibroblasts to contract collagen. These data suggest that the length of the HS chains is a critical determinant of HS-protein interactions and emphasize the essential role of EXT1 in providing specific binding sites for growth factors and extracellular matrix proteins.
A Longitudinal Study of Predictors of Housing Stability, Housing Quality, and Mental Health Functioning Among Single Homeless Individuals Staying in Emergency Shelters.

The current study examined risk and resilience factors at multiple levels that affect homeless individuals' ability to exit homelessness and achieve housing stability. It also examined the relationship between housing status, housing quality and mental health functioning. The methodology is a longitudinal study of single homeless individuals staying in emergency shelters in a medium-sized Canadian city who were followed for a 2 year period. Data were collected from participants at a baseline interview when they were homeless and at a 2-year follow-up. There were 329 participants interviewed at baseline and 197 (59.9%) participants interviewed at follow-up. Results from a structural equation modelling analysis found that having interpersonal and community resources were predictive of achieving housing stability. Specifically, having a larger social support network, access to subsidized housing, and greater income was related to achieving housing stability. On the other hand, having a substance use problem was a risk factor associated with a failure to achieving housing stability. Being female, feeling personally empowered, having housing that is perceived of being of higher quality were directly predictive of mental health functioning at follow-up. Findings are discussed in the context of previous research and their policy implications.
Why Does Disaster Recovery Work Influence Mental Health?: Pathways through Physical Health and Household Income.

Disaster recovery work increases risk for mental health problems, yet the mechanisms underlying this association are unclear. We explored links from recovery work to post-traumatic stress (PTS), major depression (MD), and generalized anxiety disorder (GAD) symptoms through physical health symptoms and household income in the aftermath of the Deepwater Horizon oil spill. As part of the NIEHS GuLF STUDY, participants (N = 10,141) reported on cleanup work activities, spill-related physical health symptoms, and household income at baseline, and mental health symptoms an average of 14.69 weeks (SD = 16.79) thereafter. Cleanup work participation was associated with higher physical health symptoms, which in turn were associated with higher PTS, MD, and GAD symptoms. Similar pattern of results were found in models including workers only and investigating the influence of longer work duration and higher work-related oil exposure on mental health symptoms. In addition, longer worker duration and higher work-related oil exposure were associated with higher household income, which in turn was associated with lower MD and GAD symptoms. These findings suggest that physical health symptoms contribute to workers' risk for mental health symptoms, while higher household income, potentially from more extensive work, might mitigate risk.