bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the protein Z–dependent protease inhibitor
Authors: Han Xin , Fiehler Ryan , Broze George J.
Published: October 2019

Protein Z-dependent protease inhibitor (ZPI) is a 72-kd member of the serpin superfamily of proteinase inhibitors that produces rapid inhibition of factor Xa in the presence of protein Z (PZ), procoagulant phospholipids, and Ca++ (t1/2 less than 10 seconds). The rate of factor Xa inhibition by ZPI is reduced more than 1000-fold in the absence of PZ. The factor Xa–ZPI complex is not stable to sodium dodecyl sulfate–polyacrylamide gel electrophoresis, but is detectable by alkaline–polyacrylamide gel electrophoresis. The combination of PZ and ZPI dramatically delays the initiation and reduces the ultimate rate of thrombin generation in mixtures containing prothrombin, factor V, phospholipids, and Ca++. In similar mixtures containing factor Va, however, PZ and ZPI do not inhibit thrombin generation. Thus, the major effect of PZ and ZPI is to dampen the coagulation response prior to the formation of the prothrombinase complex. Besides factor Xa, ZPI also inhibits factor XIa in the absence of PZ, phospholipids, and Ca++. Heparin (0.2 U/mL) enhances the rate (t1/2 = 25 seconds vs 50 seconds) and the extent (99% vs 93% at 30 minutes) of factor XIa inhibition by ZPI. During its inhibitory interaction with factor Xa and factor XIa, ZPI is proteolytically cleaved with the release of a 4.2-kd peptide. The N-terminal amino acid sequence of this peptide (SMPPVIKVDRPF) establishes Y387 as the P1 residue at the reactive center of ZPI. ZPI activity is consumed during the in vitro coagulation of plasma through a proteolytic process that involves the actions of factor Xa with PZ and factor XIa.
Platelet release of trimolecular complex components MT1-MMP/TIMP2/MMP2: involvement in MMP2 activation and platelet aggregation
Authors: Kazes Isabelle , Elalamy Ismaı̈l , Sraer Jean-Daniel , Hatmi Mohamed , Nguyen Geneviève
Published: October 2019

Matrix metalloproteinase 2 (MMP2) has been reported to be secreted by collagen-stimulated platelets, and active MMP2 has been shown to play a role in platelet aggregation. It has been demonstrated that MMP2 activation is dependent on the complex (membrane type 1 [MT1]-MMP/tissue inhibitor of MMP2 [TIMP2]) receptor and MMP2. We have investigated human platelets as a possible source of MT1-MMP, and we have studied its role in MMP2 activation and in platelet aggregation. Gelatin zymograms showed the existence of MMP2 at proforms (68 kd) and activated-enzyme forms (62-59 kd) in supernatants of resting and activated platelets, respectively. No gelatinolytic activity was associated with the platelet pellet after aggregation, suggesting a total release of MMP2 during cell activation. By Western blot analysis in nonreduced conditions, MT1-MMP was found on resting platelet membranes in 2 forms–the inactive 45-kd form and an apparent 89-kd form, which totally disappeared under reduced conditions. After platelet degranulation, only the 45-kd form was detected. Reverse transcription–polymerase chain reaction experiments showed the expression in platelets of messenger RNA encoding for MMP2, MT1-MMP, and TIMP2. Flow cytometry analysis showed that MT1-MMP, MMP2, and TIMP2 expressions were enhanced at the activated platelet surface. MMP inhibitors, recombinant TIMP2, and synthetic BB94 inhibited collagen-induced platelet aggregation in a concentration-dependent manner, indicating the role of activated MT1-MMP in the modulation of platelet function. In conclusion, our results demonstrate the expression of the trimolecular complex components (MT1-MMP/TIMP2/MMP2) by blood platelets as well as the ability of MMP inhibitors to modulate the aggregating response.
Role of SCL/Tal-1, GATA, and Ets transcription factor binding sites for the regulation of Flk-1 expression during murine vascular development
Authors: Kappel Andreas , Schlaeger Thorsten M. , Flamme Ingo , Orkin Stuart H. , Risau Werner , Breier Georg
Published: October 2019

The receptor tyrosine kinase Flk-1 is essential for embryonic blood vessel development and for tumor angiogenesis. To identify upstream transcriptional regulators of Flk-1, the gene regulatory elements that mediate endothelium-specific expression in mouse embryos were characterized. By mutational analysis, binding sites for SCL/Tal-1, GATA, and Ets transcription factors located in theFlk-1 enhancer were identified as critical elements for the endothelium-specific Flk-1 gene expression in transgenic mice. c-Ets1, a transcription factor that is coexpressed withFlk-1 during embryonic development and tumor angiogenesis, activated the Flk-1 promoter via 2 binding sites. One of these sites was required for Flk-1 promoter function in the embryonic vasculature. These results provide the first evidence that SCL/Tal-1, GATA, and Ets transcription factors act upstream ofFlk-1 in a combinatorial fashion to determine embryonic blood vessel formation and are key regulators not only of the hematopoietic program, but also of vascular development.
Impaired function of circulating HIV-specific CD8+ T cells in chronic human immunodeficiency virus infection
Authors: Shankar Premlata , Russo Melissa , Harnisch Brooke , Patterson Mark , Skolnik Paul , Lieberman Judy
Published: October 2019

The functional status of circulating human immunodeficiency (HIV)-specific CD8 T cells in chronically infected subjects was evaluated. By flow cytometry, only 5 of 7 subjects had detectable CD8 T cells that produced IFN-γ after stimulation with HIV-infected primary CD4 T cells. In 2 subjects, the frequency of IFN-γ–producing cells increased 4-fold when IL-2 was added to the culture medium; in another subject, IFN-γ–producing cells could be detected only after IL-2 was added. IFN-γ–producing cells ranged from 0.4% to 3% of CD8 T cells. Major histocompatibility complex–peptide tetramer staining, which identifies antigen-specific T cells irrespective of function, was used to evaluate the proportion of HIV-specific CD8 T cells that may be nonfunctional in vivo. CD8 T cells binding to tetramers complexed to HIV gag epitope SLYNTVATL and reverse transcriptase epitope YTAFTIPSI were identified in 9 of 15 and 5 of 12 HLA-A2–expressing seropositive subjects at frequencies of 0.1% to 1.1% and 0.1 to 0.7%, respectively. Freshly isolated tetramer-positive cells expressed a mixed pattern of memory and effector markers. On average, IFN-γ was produced by less than 25% of tetramer-positive CD8 T cells after stimulation with the relevant gag or reverse transcriptase peptide. In all subjects tested, freshly isolated CD8 T cells were not cytolytic against peptide-pulsed B lymphoblastoid cell line or primary HIV-infected CD4 T-cell targets. Exposure to IL-2 enhanced the cytotoxicity of CD8 T cells against primary HIV-infected CD4 targets in 2 of 2 subjects tested. These results suggest that a significant proportion of HIV-specific CD8 T cells may be functionally compromised in vivo and that some function can be restored by exposure to IL-2.
Elevated soluble MUC1 levels and decreased anti-MUC1 antibody levels in patients with multiple myeloma
Authors: Treon Steven P. , Maimonis Peter , Bua Deborah , Young Gloria , Raje Noopur , Mollick Joseph , Chauhan Dharminder , Tai Yu-Tzu , Hideshima Teru , Shima Yoshihito , Hilgers Jo , von Mensdorff-Pouilly Silvia , Belch Andrew R. , Pilarski Linda M. , Anderson Kenneth C.
Published: October 2019

Soluble MUC1 (sMUC1) levels are elevated in many MUC1+cancers. We and others have shown that MUC1 is expressed on multiple myeloma (MM) plasma cells and B cells. In this study, we measured sMUC1 levels in bone marrow (BM) plasma from 71 MM patients and 21 healthy donors (HDs), and in peripheral blood (PB) plasma from 42 MM patients and 13 HDs using an immunoassay that detects the CA27.29 epitope of MUC1. sMUC1 levels were found to be significantly greater (mean 31.76 U/mL, range 5.69 to 142.48 U/mL) in MM patient BM plasma versus HD BM plasma (mean 9.68 U/mL, range 0.65 to 39.83 U/mL) (P < .001). Importantly, BM plasma sMUC1 levels were related to tumor burden because sMUC1 levels were significantly higher for MM patients with active disease (34.62 U/mL, range 5.69 to 142.48 U/mL) versus MM patients with minimal residual disease (16.16 U/mL, range 5.7 to 56.68 U/mL) (P = .0026). sMUC1 levels were also elevated in the PB plasma of MM patients (32.79 U/mL, range 4.15 to 148.84 U/mL) versus HDs (18.47 U/mL, range 8.84 to 42.49) (P = .0052). Lastly, circulating immunglobulin M (IgM) and IgG antibodies to MUC1 were measured in 114 MM patients and 31 HDs, because natural antibodies to MUC1 have been detected in patients with other MUC1-bearing malignancies. These studies demonstrated lower levels of circulating IgM (P < .001) and IgG (P = .078) antibodies to MUC1 in MM patients compared with HDs. Our data therefore show that in MM patients, sMUC1 levels are elevated and correlate with disease burden, whereas anti-MUC1 antibody levels are decreased.
Bone marrow transplantation corrects osteopetrosis in the carbonic anhydrase II deficiency syndrome
Authors: McMahon Corrina , Will Andrew , Hu Peiyi , Shah Gul N. , Sly William S. , Smith Owen P.
Published: October 2019

Carbonic anhydrase II (CAII), found in renal tubules, brain, and osteoclasts, is critical in acid-base homeostasis and bone remodeling. Deficiency of CAII gives rise to a syndrome of osteopetrosis, renal tubular acidosis (RTA), and cerebral calcification with associated developmental delay. It is inherited in an autosomal recessive fashion and found most frequently in the Mediterranean region and the Middle East. We report 2 related Irish families with clinically severe CAII deficiency in whom the gene mutation has been fully elucidated. Two children, one from each family, have undergone allogeneic bone marrow transplantation because of severe progressive visual and hearing loss. The older 2 children had already developed cerebral calcification and marked visual loss at the time of diagnosis and were treated symptomatically. Post-transplantation evaluation at 2 and 3 years demonstrates histologic and radiologic resolution of their osteopetrosis with stabilization of hearing and vision. Both children remain developmentally delayed and continue to have RTA, and the older child has now developed cerebral calcification. Allogeneic bone marrow stem cell replacement cures the osteoclast component of CAII deficiency and retards the development of cerebral calcification, but it appears to have little or no effect on the renal lesions.
Human homologues of Delta-1 and Delta-4 function as mitogenic regulators of primitive human hematopoietic cells
Authors: Karanu Francis N. , Murdoch Barbara , Miyabayashi Tomoyuki , Ohno Mitsuhara , Koremoto Masahide , Gallacher Lisa , Wu Dongmei , Itoh Akira , Sakano Seiji , Bhatia Mickie
Published: October 2019

Delta-mediated Notch signaling controls cell fate decisions during invertebrate and murine development. However, in the human, functional roles for Delta have yet to be described. This study reports the characterization of Delta-1 and Delta-4 in the human. Human Delta-4 was found to be expressed in a wide range of adult and fetal tissues, including sites of hematopoiesis. Subsets of immature hematopoietic cells, along with stromal and endothelial cells that support hematopoiesis, were shown to express Notch and both Delta-1 and Delta-4. Soluble forms of human Delta-1 (hDelta-1) and hDelta-4 proteins were able to augment the proliferation of primitive human hematopoietic progenitors in vitro. Intravenous transplantation of treated cultures into immune-deficient mice revealed that hDelta-1 is capable of expanding pluripotent human hematopoietic repopulating cells detected in vivo. This study provides the first evidence for a role of Delta ligands as a mitogenic regulator of primitive hematopoietic cells in the human.
Thoracic positron emission tomography using18F-fluorodeoxyglucose for the evaluation of residual mediastinal Hodgkin disease
Authors: Weihrauch Martin R. , Re Daniel , Scheidhauer Klemens , Ansén Sascha , Dietlein Markus , Bischoff Stefanie , Bohlen Heribert , Wolf Jürgen , Schicha Harald , Diehl Volker , Tesch Hans
Published: October 2019

Residual mediastinal masses are frequently observed in patients with Hodgkin disease (HD) after completed therapy, and the discrimination between active tumor tissue and fibrotic residues remains a clinical challenge. We studied the diagnostic value of metabolic imaging by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in detecting active mediastinal disease and predicting relapse. Twenty-eight HD patients with a residual mediastinal mass of at least 2 cm after initial therapy or after salvage chemotherapy were prospectively assigned to 29 examinations with FDG PET and were evaluated as 29 “subjects.” Patients were monitored for at least 1 year after examination and observed for signs of relapse. Median follow-up was 28 months (range, 16 to 68 months). A PET-negative mediastinal tumor was observed in 19 subjects, of whom 16 stayed in remission and 3 relapsed. Progression or relapse occurred in 6 of 10 subjects with a positive PET, whereas 4 subjects remained in remission. The negative predictive value (negative PET result and remission) at 1 year was 95%, and the positive predictive value (positive PET result and relapse) was 60%. The disease-free survival for PET-negative and PET-positive patients at 1 year was 95% and 40%, respectively. The difference was statistically significant. A negative FDG PET indicates that an HD patient with a residual mediastinal mass is unlikely to relapse before 1 year, if ever. On the other hand, a positive PET result indicates a significantly higher risk of relapse and demands further diagnostic procedures and a closer follow-up.
Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment
Authors: Janowska-Wieczorek Anna , Majka Marcin , Kijowski Jacek , Baj-Krzyworzeka Monika , Reca Ryan , Turner A. Robert , Ratajczak Janina , Emerson Steven G. , Kowalska M. Anna , Ratajczak Mariusz Z.
Published: October 2019

Because human CD34+ and murine Sca-1+hematopoietic stem–progenitor cells (HSPCs) express platelet-binding sialomucin P-selectin (CD162) and integrin Mac-1 (CD11b–CD18) antigen, it was inferred that these cells might interact with platelets. As a result of this interaction, microparticles derived from platelets (PMPs) may transfer many platelet antigens (CD41, CD61, CD62, CXCR4, PAR-1) to the surfaces of HSPCs. To determine the biologic significance of the presence of PMPs on human CD34+ and murine Sca-1+ cells, their expressions on mobilized peripheral blood (mPB) and on nonmobilized PB- and bone marrow (BM)–derived CD34+ cells were compared. In addition, the effects of PMPs on the proliferation of CD34+ and Sca-1+ cells and on adhesion of HSPCs to endothelium and immobilized SDF-1 were studied. Finally, the hematopoietic reconstitution of lethally irradiated mice receiving transplanted BM mononuclear cells covered or not covered with PMPs was examined. It was found that PMPs are more numerous on mPB than on BM CD34+cells, do not affect the clonogenicity of human and murine HSPCs, and increase adhesion of these cells to endothelium and immobilized SDF-1. Moreover, murine BM cells covered with PMPs engrafted lethally irradiated mice significantly faster than those not covered, indicating that PMPs play an important role in the homing of HSPCs. This could explain why in a clinical setting human mPB HSPCs (densely covered with PMPs) engraft more rapidly than BM HSPCs (covered with fewer PMPs). These findings indicate a new role for PMPs in stem cell transplantation and may have clinical implications for the optimization of transplantations.
Immature mouse dendritic cells enter inflamed tissue, a process that requires E- and P-selectin, but not P-selectin glycoprotein ligand 1
Authors: Pendl Gunther G. , Robert Caroline , Steinert Meike , Thanos Renate , Eytner Ruth , Borges Eric , Wild Martin K. , Lowe John B. , Fuhlbrigge Robert C. , Kupper Thomas S. , Vestweber Dietmar , Grabbe Stephan
Published: October 2019

Inflammatory processes are associated with the rapid migration of dendritic cells (DCs) to regional lymph nodes and depletion of these potent antigen-presenting cells (APCs) from the inflamed tissue. This study examined whether sites of cutaneous inflammation can be repopulated with DCs from a pool of immature DCs circulating in the blood. In adoptive transfer experiments with ex vivo–generated radioactively labeled primary bone marrow–derived DCs injected into mice challenged by an allergic contact dermatitis reaction, immature DCs were actively recruited from the blood to sites of cutaneous inflammation, whereas mature DCs were not. Immature, but not mature, DCs were able to adhere specifically to immobilized recombinant E- and P-selectin under static as well as under flow conditions. P-selectin–dependent adhesion of immature DCs correlates with their higher level of expression of the carbohydrate epitope cutaneous lymphocyte-associated antigen (CLA) and is blocked by a novel inhibitory antibody against mouse P-selectin glycoprotein ligand 1 (PSGL-1). Surprisingly, however, emigration of immature DCs into inflamed skin is retained in the presence of this anti–PSGL-1 antibody and is also normal when immature DCs are generated from fucosyltransferase (Fuc-T) Fuc-TVII–deficient mice. By contrast, emigration of wild-type immature DCs is reduced by adhesion-blocking anti–E- and P-selectin antibodies, and immature DCs generated ex vivo from Fuc-TVII/Fuc-TIV double-deficient mice emigrate poorly. Thus, fucosylated ligands of the endothelial selectins, determined in part by Fuc-TIV, and independent of PSGL-1, are required for extravasation of DCs into sites of cutaneous inflammation.
METTL3-mediated N6-methyladenosine modification is critical for epithelial-mesenchymal transition and metastasis of gastric cancer
Authors: Yue Ben , Song Chenlong , Yang Linxi , Cui Ran , Cheng Xingwang , Zhang Zizhen , Zhao Gang
Published: October 2019

Background

As one of the most frequent chemical modifications in eukaryotic mRNAs, N6-methyladenosine (m6A) modification exerts important effects on mRNA stability, splicing, and translation. Recently, the regulatory role of m6A in tumorigenesis has been increasingly recognized. However, dysregulation of m6A and its functions in tumor epithelial-mesenchymal transition (EMT) and metastasis remain obscure.

Methods

qRT-PCR and immunohistochemistry were used to evaluate the expression of methyltransferase-like 3 (METTL3) in gastric cancer (GC). The effects of METTL3 on GC metastasis were investigated through in vitro and in vivo assays. The mechanism of METTL3 action was explored through transcriptome-sequencing, m6A-sequencing, m6A methylated RNA immunoprecipitation quantitative reverse transcription polymerase chain reaction (MeRIP qRT-PCR), confocal immunofluorescent assay, luciferase reporter assay, co-immunoprecipitation, RNA immunoprecipitation and chromatin immunoprecipitation assay.

Results

Here, we show that METTL3, a major RNA N6-adenosine methyltransferase, was upregulated in GC. Clinically, elevated METTL3 level was predictive of poor prognosis. Functionally, we found that METTL3 was required for the EMT process in vitro and for metastasis in vivo. Mechanistically, we unveiled the METTL3-mediated m6A modification profile in GC cells for the first time and identified zinc finger MYM-type containing 1 (ZMYM1) as a bona fide m6A target of METTL3. The m6A modification of ZMYM1 mRNA by METTL3 enhanced its stability relying on the “reader” protein HuR (also known as ELAVL1) dependent pathway. In addition, ZMYM1 bound to and mediated the repression of E-cadherin promoter by recruiting the CtBP/LSD1/CoREST complex, thus facilitating the EMT program and metastasis.

Conclusions

Collectively, our findings indicate the critical role of m6A modification in GC and uncover METTL3/ZMYM1/E-cadherin signaling as a potential therapeutic target in anti-metastatic strategy against GC.
Transplantation of bone marrow derived macrophages reduces markers of neuropathology in an APP/PS1 mouse model
Authors: Costa-Marques Luís , Arnold Katrin , Pardon Marie-Christine , Leovsky Christiane , Swarbrick Samantha , Fabian Claire , Stolzing Alexandra
Published: October 2019

Background

We investigated early hallmarks of putative therapeutic effects following systemic transplantation of bone marrow derived macrophages (BM-M) in APP/PS1 transgenic mice.

Method

BM-M were transplanted into the tail vein and the animals analysed 1 month later.

Results

BM-M transplantation promoted the reduction of the amyloid beta [37-42] plaque number and size in the cortex and hippocampus of the treated mice, but no change in the more heavily modified pyroglutamate amyloid beta E3 plaques. The number of phenotypically ‘small’ microglia increased in the hippocampus. Astrocyte size decreased overall, indicating a reduction of activated astrocytes. Gene expression of interleukin 6 and 10, interferon-gamma, and prostaglandin E receptor 2 was significantly lower in the hippocampus, while interleukin 10 expression was elevated in the cortex of the treated mice.

Conclusions

BM-M systemically transplanted, promote a decrease in neuroinflammation and a limited reversion of amyloid pathology. This exploratory study may support the potential of BM-M or microglia-like cell therapy and further illuminates the mechanisms of action associated with such transplants.
Aquaglyceroporins but not orthodox aquaporins are involved in the cryotolerance of pig spermatozoa
Authors: Delgado-Bermúdez Ariadna , Llavanera Marc , Fernández-Bastit Leira , Recuero Sandra , Mateo-Otero Yentel , Bonet Sergi , Barranco Isabel , Fernández-Fuertes Beatriz , Yeste Marc
Published: October 2019

Background

Aquaporins (AQPs) are a family of transmembrane water channels that includes orthodox AQPs, aquaglyceroporins (GLPs) and superAQPs. AQP3, AQP7, AQP9 and AQP11 have been identified in boar sperm, and they are crucial for sperm maturation and osmoregulation. Water exchange is an important event in cryopreservation, which is the most efficient method for long-term storage of sperm. However, the freeze-thaw process leads to sperm damage and a loss of fertilizing potential. Assuming that the quality of frozen-thawed sperm partially depends on the regulation of osmolality variations during this process, AQPs might play a crucial role in boar semen freezability. In this context, the aim of this study was to unravel the functional relevance of the different groups of AQPs for boar sperm cryotolerance through three different inhibitors.

Results

Inhibition of different groups of AQPs was found to have different effects on boar sperm cryotolerance. Whereas the use of 1,3-propanediol (PDO), an inhibitor of orthodox AQPs and GLPs, decreased total motility (P < 0.05), it increased post-thaw sperm viability, lowered membrane lipid disorder and increased mitochondrial membrane potential (MMP) (P < 0.05). When acetazolamide (AC) was used as an inhibitor of orthodox AQPs, the effects on post-thaw sperm quality were restricted to a mild increase in MMP in the presence of the intermediate concentration at 30 min post-thaw and an increase in superoxide levels (P < 0.05). Finally, the addition of phloretin (PHL), a GLP inhibitor, had detrimental effects on post-thaw total and progressive sperm motilities, viability and lipid membrane disorder (P < 0.05).

Conclusions

The effects of the different inhibitors suggest that GLPs rather than orthodox AQPs are relevant for boar sperm freezability. Moreover, the positive effect of PDO on sperm quality suggests a cryoprotective role for this molecule.
A Role for Oncostatin M in the Impairment of Glucose Homeostasis in Obesity
Authors: Piquer-Garcia Irene , Campderros Laura , Taxerås Siri D , Gavaldà-Navarro Aleix , Pardo Rosario , Vila María , Pellitero Silvia , Martínez Eva , Tarascó Jordi , Moreno Pau , Villarroya Joan , Cereijo Rubén , González Lorena , Reyes Marjorie , Rodriguez-Fernández Silvia , Vives-Pi Marta , Lerin Carles , Elks Carrie M , Stephens Jacqueline M , Puig-Domingo Manel , Villarroya Francesc , Villena Josep A , Sánchez-Infantes David
Published: October 2019

Context

Oncostatin M (OSM) plays a key role in inflammation, but its regulation and function during obesity is not fully understood.

Objective

The aim of this study was to evaluate the relationship of OSM with the inflammatory state that leads to impaired glucose homeostasis in obesity. We also assessed whether OSM immunoneutralization could revert metabolic disturbances caused by a high-fat diet (HFD) in mice.

Design

28 patients with severe obesity were included and stratified into two groups: (1) glucose levels <100 mg/dL and (2) glucose levels >100 mg/dL. White adipose tissue was obtained to examine OSM gene expression. Human adipocytes were used to evaluate the effect of OSM in the inflammatory response, and HFD-fed C57BL/6J mice were injected with anti-OSM antibody to evaluate its effects.

Results

OSM expression was elevated in subcutaneous and visceral fat from patients with obesity and hyperglycemia, and correlated with Glut4 mRNA levels, serum insulin, homeostatic model assessment of insulin resistance, and inflammatory markers. OSM inhibited adipogenesis and induced inflammation in human adipocytes. Finally, OSM receptor knockout mice had increased Glut4 mRNA levels in adipose tissue, and OSM immunoneutralization resulted in a reduction of glucose levels and Ccl2 expression in adipose tissue from HFD-fed mice.

Conclusions

OSM contributes to the inflammatory state during obesity and may be involved in the development of insulin resistance.
Radiographer non-medical prescribing: independence and implications for practice
Authors: Cain Michelle
Published: October 2019

Non-medical prescribing is not a new initiative in healthcare. The modernisation of the NHS, strained workforces in radiotherapy and clinical oncology and the recognition that the role of the radiographer extends across the entire patient pathway has motivated development of therapeutic radiographer roles. For advanced, expert and consultant radiographers, this includes non–medical, supplementary, and independent prescribing authority. Limitations in current prescribing legislation have the potential to negatively impact these services. However, the overall benefits of non-medical prescribing for the patient, professional and entire workforce are undeniable. Radiographer non-medical prescribing is pertinent to the maintenance and continued improvement of cancer services.
GDPR: one year on…
Authors: Skipper Richard
Published: October 2019

GDPR recently celebrated its first anniversary, but there is still confusion in schools about data duties and obligations. Richard Skipper provides clarity on some common problems
The parents who misuse and abuse social media
Authors: Foran Kaley
Published: October 2019

The best way to deal with inappropriate social media use by parents is to proactively set expectations, and to be clear on how you will respond to incidents of abuse or misuse. Kaley Foran explains what you can do if an issue does arise
User-generated content gatekeeping on the radio: Displacing control to technology
Authors: Zelenkauskaite Asta
Published: October 2019

This study focuses on user-generated content (UGC) via Facebook and mobile texting selection and allocation for broadcast. Based on the premises of Gatekeeping theory in traditional mass media content selection, this study asks how social media messages, solicited by the radio station, are filtered out for the programmes. Based on semi-structured interviews with the Italian commercial radio station’s staff, participant observation and a content analysis of the UGC messages, the study scrutinizes institutional decision-making processes. The radio station’s selection of UGC exhibits efforts to maintain control over the streams of incoming UGC content. As expected, UGC manual content selection or automated content matching is geared towards efficiency. Also, in this study only 33 per cent of messages have been selected for broadcast. UGC gatekeeping has also presented evidence of displacement of control within the radio station. Rather than shifting control to audiences, radio stations displaced control to technology-assisted gatekeeping. While the study showed a ‘widening’ of the gates in terms of content (there was no differentiation in selecting messages directed to the radio station or to the overall audience members), shift of control to the audiences remains an ideal rather than reality.
True crime podcasting: Journalism, justice or entertainment?
Authors: Boling Kelli S.
Published: October 2019

This study examines true crime podcasts with a critical/cultural lens to explore how podcasts are impacting the true crime genre, public opinion and the criminal justice system. Four in-depth qualitative interviews with true crime podcast producers offer insight into both the political economy of podcasts and effective audience engagement. Ultimately, this study argues that true crime podcasts are impacting the criminal justice system in unprecedented ways and that the future of this emerging media could challenge both criminal justice and media reform. Practical implications for genre-specific media are also discussed.
Kindergarten of the Air: From Australia to the world
Authors: Griffen-Foley Bridget
Published: October 2019

This article considers the radio programme for kindergarten-aged children that the Australian Broadcasting Commission (ABC) launched during the Second World War and continued to broadcast until 1985. Kindergarten of the Air, thought to be the ‘first of its kind in the world’, was to inspire interest from, and similar programmes throughout, the British empire and beyond. The article examines the imperial and international broadcasting networks that enabled the exchange of ideas and initiatives within the field of educational broadcasting, and the export of one of Australia’s most successful radio initiatives, while also considering the willingness of the British Broadcasting Corporation (BBC) to be influenced by a dominion broadcaster.
Secretion of growth hormone in children with familial dwarfism
Authors: Kasatkina E. P. , Ibragimova G. V. , Soltakhanov E. M.
Published: October 2019

Thirty-two patients with familial dwarfism were examined. Stimulated and spontaneous secretion of growth hormone was studied in all of them. Stimulated secretion was assessed in two standard pharmacologic tests, spontaneous one was examined during the first 3 h of night sleep. Analysis of the results showed an irregular pattern of growth hormone secretion. Disorders of the hormone secretion of the neurosecretory dysfunction type with a partial deficit of growth hormone were revealed in the majority (20 out of 32) patients, which may be the cause of growth retardation. In twelve patients the levels of both stimulated and spontaneous secretion were normal.
ETIKA BERMEDIA SOSIAL DALAM MENYIKAPI PEMBERITAAN BOHONG (HOAX) PERSPEKTIF HADIS
Authors: Al-Ayyubi M. Zia
Published: October 2019

This paper will discusses about the troubling phenomenathat occur in cyberspace, precisely on social media. The negative contents are found, both attacking groups, and individuals.The attack usually uses content in the form of provocation, slander, hate speech, hoaxes, appealing opinions that lead to defamation, etc. The problem above, if we examine its historicity in Islamic history, it turns out that this phenomena has been happening since the early days of Islam. Precisely, one of the prophet's wives, Siti Aisyah, who was accused of committing adultery with one of the war soldiers. Then the incident became the cause of the revelation bara’ah’s letter. Back then, the kind of news mentioned above was disseminated by transmission media. In the present, it is disseminated with social media which is even faster in its flow of transmission. So the term viral appears. The offer submitted in this paper is the attitude and ethics of every netizens in social media with a hadith approach. So that it can be finally in accordance with the with the portion and proportion in utilizing a social media. Keyword: Hermeneutics Hadis, Etics, Social Media, Hoax.
PENAFSIRAN SUFISTIK KH. SHALIH DARAT TERHADAP Q.S. AL-BAQARAH: 183
Authors: Abshor M. Ulil
Published: October 2019

Sufi interpretation is an important part in expressing the meaning contained in the Qur’an, there is the meaning of outer and inner meaning. The meaning of outer is the outside of textual meaning that is the spiritual area. Sufi interpretation does not mean leaving the aspect of outer or aspects of language, but at the same time combing the inner aspect, this also happens in the book of Tafsir Fayd al-Rahman by KH. Shalih Darat. The intended orientation in Sufiinterpretation is more about overcoming mental problems that often forget the essence of essential life. The inner meaning will provide added value in matters of worship, especially in the interpretation of the letter (Q.S. al-Baqarah: 183). In interpreting the verse KH. Shalih Darat interprets the Isyari, so that the essential inner meaning is obtained to express the social dimensions that encourage the birth of empathy in the family, social, and among humans. So that the container in realizing superior social dimensions in the community needs to increase fasting both in terms of dhohir and in terms of the heart. The approach taken in this study uses a sufistic approach to the theory of Sufi Ishari and Isharah method (Devine Method). The results obtained from the interpretation of the verse parse about fasting there are four things, taqwa which manifests on the dimension of divinity and the human dimension of basyariah, manifests itself in the form of love between humans, disciplined life and tazqiyah al-Nafs.Keywords: Fasting, Tafsir Faidh al-Rahman, Sufistik Logic
Medicinal plants with preventive and therapeutic effect on diarrhoea: A cross-sectional epidemiologic and ethnobotanical study in traditional therapists of Shahrekord, south-west of Iran
Authors: Anbari Khatereh , Abbaszadeh Saber , Basati Gholam
Published: October 2019

Chemical treatments for diarrhoea usually lead to side effects, so humans are seeking out a safe pharmaceutical source to cure them. From ancient times, medicinal plants have served as an important pharmaceutical source for the treatment of various acute and chronic diseases and infectious and non-infectious diseases. This study was carried out from April 2017 to February 2018 by interviewing with and administering a questionnaires to 29 traditional therapists. The questionnaire also included demographic items. The interviewers referred to the participants in person and asked them certain questions to elicit their beliefs about herbal medicine. Data were finally analyzed by the Excel software. In this study, the frequency of plant use was calculated by using a formula. According to the ethnobotanical knowledge of the region under study, Astragalus hamosus L., Ziziphora taurica M.Bieb., Anthemis hyalina DC., Plantago major L., Quercus brantii Lindl., Myrtus communis L., Satureja bachtiarica Bung., Glycyrrhiza glabra L., Peganum harmala L., Rheum ribes L., Rumex pulcher L., Artemisia absinthium, Descurainia sophia (L.) Prantle., Plantago major L. and some others medicinal plants are used as antidiarrhoeal medicinal plants. Most plant species reported belong to the Asteraceae family and the aerial part (36%) is the most frequently used plant organ for cases of diarrhoea in Shahrekord. The scientific registration and review of the written and non-written knowledge of different ethnicities in Iran regarding traditional medicine will help preserve the valuable treasure of thousands of years of Iranians’ medical knowledge and experience and will provide the basis for the discovery of new drugs and the progress of the pharmaceutical industry.
Hypothetical bias and framing effect in the valuation of private consumer goods
Authors: Brzozowicz Magdalena
Published: October 2019

In a laboratory experiment, I examined two behavioural effects: hypothetical bias and the framing effect. I elicited willingness to pay (WTP) for a cosmetic product, and manipulated framing conditions (positive vs. negative attribute framing) and incentives to reveal the actual valuation (hypothetical vs. real). I demonstrated that hypothetical bias has a significant impact on WTP values; however, the framing effect has no effect on the valuation of the product. Similarly, I found no interaction between the two effects. This observation contributes to claims that hypothetical research methods lead to equally reliable data as those based on consequential choices.
Thermodynamics and Industrial Trial on Increasing the Carbon Content at the BOF Endpoint to Produce Ultra-Low Carbon IF Steel by BOF-RH-CSP Process
Authors: Jing Guo , Shu-Sen Cheng , Hanjie Guo
Published: October 2019

Thermodynamic analysis was performed to obtain the relation between the carbon content at the BOF endpoint and the dissolved oxygen content in liquid steel and the (FeO + MnO) content in the slag with the help of thermodynamic calculation software FactSage. It finds that both the [O] and (FeO + MnO) content increase with decreasing the carbon content at the BOF endpoint and the increasing rate is larger when the carbon content is lower. In addition, in the case of the higher temperature at the BOF endpoint the [O] in liquid steel increase and the (FeO + MnO) in the slag increase as well. The consumption of O2 for decarbonization at the BOF endpoint is much more than that in RH degasser since the majority of the blowing O2 at the BOF endpoint will produce FeO into the slag, thus it increase the metal loss and deteriorate the steel cleanness during the consequent refining process. As a result, the carbon content at the BOF endpoint should be properly increased within the RH decarbonization ability. At last, industrial trials were carried out and confirmed that total oxygen consumption decrease obviously and the (FeO + MnO) of final BOF slag decline as well with increasing carbon content at BOF endpoint from 0.042% to 0.081%. In addition, it almost does not slow down the RH process and the carbon content in final steel all met the demand of the ultra-low carbon steel. In addition, mechanical properties of IF steel with higher carbon content at the endpoint of BOF are almost all more superior to those of heat with lower carbon content at BOF endpoint.
Numerical Analysis of TB32 Crash Tests for 4-cable Guardrail Barrier System Installed on the Horizontal Convex Curves of Road
Authors: Wilde Krzysztof , Bruski Dawid , Budzyński Marcin , Burzyński Stanisław , Chróścielewski Jacek , Jamroz Kazimierz , Pachocki Łukasz , Witkowski Wojciech
Published: October 2019

Horizontal curves are one of the elements of road infrastructure where statistically a relatively high number of accidents have been reported. In the last 10 years in Poland, approximately 10% of all road accidents happened on horizontal curves of roads and was responsible for approximately 14% of all fatalities on Polish roads. Thus, this issue is important and requires extensive research and proper road safety treatments. One possible measure that may contribute to improvement of safety on road curves may be barriers. The purpose of this work is to assess, with use of numerical simulations, the performance of the 4-cable barrier systems installed on horizontal road convex curves. The most important parameters for road safety barriers are presented including the effect of various impact velocities and the radiuses of the road curves.
Nonlinear Vibration of Truncated Conical Shells: Donnell, Sanders and Nemeth Theories
Authors: Bakhtiari Mehrdad , Lakis Aouni A. , Kerboua Youcef
Published: October 2019

Nonlinear free vibration of truncated conical shells has been investigated for three different shell theories; Donnell, Sanders and Nemeth to investigate the effect of their simplifying assumptions. The displacement field of a finite element model that was obtained from the exact solution of equilibrium equations of Sander’s improved first-approximation theory is used to define the nonlinear strain energy of conical shells. Employing generalized coordinates method the equations of motion are derived and subsequently the amplitude equation of nonlinear vibration of conical shells was developed. The amplitude equation is solved for multiple cases of isotropic materials. Linear and nonlinear free vibration results are validated against the existing studies in scientific literature and demonstrate good accordance. The validated model is used to investigate effects of different parameters including circumferential mode number, cone-half angle, length to radius ratio, thickness to radius ratio and boundary conditions for the nonlinear vibration of conical shells.
The crystal structure of 3-benzyl-1-((8-(benzyloxy)quinolin-2-yl)methyl)-1H-imidazol-3-ium hexafluorophosphate, C27H24N3OF6P
Authors: Jiewei Luo , Shilu Zhang , Yiming Liu , Bo Zhao
Published: October 2019

C27H24N3OF6P, monoclinic, Cc (no. 9), a = 18.0589(18) Å, b = 12.5100(9) Å, c = 13.3659(12) Å, β = 124.522(7)°, V = 2487.9(4) Å3, Z = 4, R
gt(F) = 0.0437, wR
ref(F
2) = 0.1141, T = 113(2) K.
Crystal structure of N′2
,N′6
-bis((E)-1-(pyrazin-2-yl)ethylidene)pyridine-2,6-dicarbohydrazide — methanol (1/2), C21H25N9O4
Authors: Xiangqing Fang , Ren Wang , Kai Du , Jia Gu , Liguo Yang
Published: October 2019

C21H25N9O4, monoclinic, P2/n (no. 13), a = 10.277(3) Å, b = 10.081(3) Å, c = 11.264(4) Å, β = 104.582(4)°, V = 1129.4(6) Å3, Z = 2, R
gt(F) = 0.0452, wR
ref(F
2) = 0.1278, T = 296(2) K [1], [2], [3].
The search for the imperfect language
Authors: Leone Massimo
Published: October 2019

The meta-semiotic ideology that underpins most contemporary semiotics seems at odds with the one that underlies the attempt at planning and creating a new language. Semiotics, as well as modern linguistics, has increasingly evolved into a substantially descriptive endeavor, excluding any consistent normative purpose. Faithful to the epistemology of Ferdinand de Saussure, semiotics does not primarily aim at either pointing at some supposed flaws of such or such language or at proposing some new linguistic forms meant to fix them. The article analyses linguistic utopias from the perspective of present-day semiotics.
What is political semiotics and why does it matter? A reply to Janar Mihkelsaar
Authors: Selg Peeter , Ventsel Andreas
Published: October 2019

In view of the recent criticisms of Janar Mihkelsaar the authors explicate their position on what political semiotics is and why it is important for both semiotics and the social sciences. Some further research trajectories are also discussed in moving from semiotic theory of hegemony to fully developed subdiscipline of political semiotics that would be part of the “relational turn” in political analysis more generally.
Zur Gründung von gemeinwesenorientierten Genossenschaften
Authors: Thürling Marleen
Published: October 2019

Seit Beginn der 2000er Jahre gründen sich vermehrt gemeinwesenorientierte Genossenschaften in den Bereichen Infrastruktur, Daseinsvorsorge und Soziales. Vor dem Hintergrund bestehender Versorgungsprobleme vor allem im ländlichen Raum, werden diese Gründungen zunehmend als mögliche Lösungen zur Erbringung von Angeboten und Dienstleistungen der Daseinsvorsorge diskutiert. Gleichzeitig gibt es bislang nur wenig empirisch gesicherte Erkenntnisse zu diesem Phänomen. Auf der Grundlage der Neugründungsstatistik der DZ Bank wurden im Rahmen eines Forschungsprojekts am Institut für Genossenschaftswesen der Humboldt-Universität zu Berlin die Gründung von Genossenschaften in den Bereichen der Daseinsvorsorge, Infrastruktur und Soziales in den Jahren 2006 und 2018 erhoben. Untersucht wurde, wo diese Genossenschaften gegründet wurden; dabei zeigen sich deutliche regionale Unterschiede, die Hinweise auf folgende Fragen liefern: sind diese Genossenschaften eine Reaktion auf besondere Strukturschwäche und Problemlagen, oder entstehen sie dort, wo Gründer*innen besonders gute Rahmenbedingungen und entsprechende Ressourcen für die Gründung vorfinden.
It Will Take a Global Movement to Curb Corruption in Health Systems Comment on "We Need to Talk About Corruption in Health Systems"
Authors: Witvliet Margot I.
Published: October 2019

Corruption in health systems is a problem around the world. Prior research consistently shows that corruption is detrimental to population health. Yet public health professionals are slow to address this complicated issue on a global scale. In the editorial entitled "We Need to Talk About Corruption in Health Systems" concern with the general lack of discourse on this topic amongst health professionals is highlighted. In this invited commentary three contributing factors that hamper public dialogue on corruption are discussed. These include (i) corrupt acts are often not illegal, (ii) government and medical professionals continued acceptance of corruption in the health systems, and (iii) lack of awareness within the general public on the extent of the problem. It is advocated that a global movement that is fully inclusive needs to occur to eradicate corruption.
The Co-Constitution of Health Systems and Innovation Comment on "What Health System Challenges Should Responsible Innovation in Health Address? Insights From an International Scoping Review"
Authors: Peine Alexander
Published: October 2019

Lehoux et al provide a timely and relevant turn on the broad and ongoing discussion around the introduction of health technology and innovation. More specifically, the authors suggest a demand-driven approach to health innovation that starts from identifying challenges and demands at the health system level. In this commentary, I review a number of underlying implications of their study in relation to positions of technology push and techno-optimism, and to the narrow focus on health technology assessment on economic and clinical values. While Lehoux et al’s scoping review provides very relevant insights with the potential to drive further empirical research, it is less clear about its conceptual basis. In particular, the somewhat artificial distinction between health innovations and health systems is worth further scrutiny. I discuss some potential risks of this separation, and propose to more openly address the co-constitution of health, health systems and technology in future research along the lines suggested by Lehoux et al.