bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emerging roles of Myc in stem cell biology and novel tumor therapies
Authors: Yoshida Go J. 
Published: July 2018

AbstractThe pathophysiological roles and the therapeutic potentials of Myc family are reviewed in this article. The physiological functions and molecular machineries in stem cells, including embryonic stem (ES) cells and induced pluripotent stem (iPS) cells, are clearly described. The c-Myc/Max complex inhibits the ectopic differentiation of both types of artificial stem cells. Whereas c-Myc plays a fundamental role as a “double-edged sword” promoting both iPS cells generation and malignant transformation, L-Myc contributes to the nuclear reprogramming with the significant down-regulation of differentiation-associated genetic expression. Furthermore, given the therapeutic resistance of neuroendocrine tumors such as small-cell lung cancer and neuroblastoma, the roles of N-Myc in difficult-to-treat tumors are discussed. N-Myc-driven neuroendocrine tumors tend to highly express NEUROD1, thereby leading to the enhanced metastatic potential. Importantly enough, accumulating evidence strongly suggests that c-Myc can be a promising therapeutic target molecule among Myc family in terms of the biological characteristics of cancer stem-like cells (CSCs). The presence of CSCs leads to the intra-tumoral heterogeneity, which is mainly responsible for the therapeutic resistance. Mechanistically, it has been shown that Myc-induced epigenetic reprogramming enhances the CSC phenotypes. In this review article, the author describes two major therapeutic strategies of CSCs by targeting c-Myc; Firstly, Myc-dependent metabolic reprogramming is closely related to CD44 variant-dependent redox stress regulation in CSCs. It has been shown that c-Myc increases NADPH production via enhanced glutaminolysis with a finely-regulated mechanism. Secondly, the dormancy of CSCs due to FBW7-depedent c-Myc degradation pathway is also responsible for the therapeutic resistance to the conventional anti-tumor agents, the action points of which are largely dependent on the operation of the cell cycle. That is why the loss-of-functional mutations of FBW7 gene are expected to trigger “awakening” of dormant CSCs in the niche with c-Myc up-regulation. Collectively, although the further research is warranted to develop the effective anti-tumor therapeutic strategy targeting Myc family, we cancer researchers should always catch up with the current advances in the complex functions of Myc family in highly-malignant and heterogeneous tumor cells to realize the precision medicine.
Antibody-mediated oral delivery of therapeutic DNA for type 2 diabetes mellitus
Authors: Cha Seungbin , Lee Sun Hwa , Kang Sung Hun , Hasan Mohammad Nazmul , Kim Young Jun , Cho Sungpil , Lee Yong-Kyu 
Published: July 2018

Abstract

Background
Diabetes mellitus (DM) is a chronic progressive metabolic disease that involves uncontrolled elevation of blood glucose levels. Among various therapeutic approaches, GLP-1 prevents type 2 diabetes mellitus (T2DM) patients from experiencing hyperglycemic episodes. However, the short half-life (< 5 min) and rapid clearance of GLP-1 often limits its therapeutic use. Here, we developed an oral GLP-1 gene delivery system to achieve an extended antidiabetic effect.

Methods

Human IgG1 (hIgG1)-Fc-Arg/pDNA complexes were prepared by an electrostatic complexation of the expression plasmid with various ratios of the positively modified Fc fragments of an antibody (hIgG1-Fc-Arg) having a targeting ability to FcRn receptor. The shape and size of the complexes were examined by atomic force and field emission electron microscope. The stability of the complexes was tested in simulated gastrointestinal pH and physiological serum condition. Cellular uptake, transport, and toxicity of the complexes were tested in the Caco-2 cells. Biodistribution and antidiabetic effect of the complexes were observed in either Balb/c mice or Lep
db/db
mice.

Results

A 50/1 ratio of the hIgG1-Fc-Arg/pDNA produced a complex structure having approximately 40 ~ 60 nm size and also demonstrated protection of pDNA in the complex from the physiological pH and serum conditions. Cellular uptake and transport of the complex were demonstrated in Caco-2 cells having FcRn receptor expression and forming the monolayer-polarized structure. The cellular toxicity of both delivery vehicle and the complex revealed their minimal toxicity comparable with nontoxicity of a commercial transfection reagent. Biodistribution of the complex showed the detectable distribution of the complex in the most parts of gastrointestinal tract due to ubiquitous expression of the FcRn receptors. An in vivo type 2 diabetes treatment study of oral administration of hIgG1-Fc-9Arg/pGLP-1 complexes showed absorption and expression in GI tract of either Balb/c mice or Lep
db/db
mice.

Conclusion
In this study, we developed an oral GLP-1 gene delivery system on the platform of cationic hIgG1-Fc-9Arg. Prolonged t1/2, less immunoactivity, and better bioactivities of hIgG-Fc-9Arg/pGLP-1 complexes appeared to be a promising approach to achieve potent treatment of type 2 diabetes treatment.
Men in eating disorder units: a service evaluation survey regarding mixed gender accommodation rules in an eating disorder setting
Authors: Fukutomi Akira , Connan Frances , Winston Anthony P. , Ghosh Pia 
Published: July 2018

Aims and methodThis service evaluation was conducted to find out: (1) if mixed gender accommodation in eating disorder units is perceived to be helpful or unhelpful for recovery, and (2) if men were being discriminated against by the implementation of the 2010 Department of Health (DoH) guidelines on the elimination of mixed gender wards. All 32 in-patient units accredited on the Quality Network for Eating Disorders were contacted via a survey.ResultsWe received 38 responses from professionals from 26 units and 53 responses from patients (46 female, 7 male) from 7 units. Four units had closed admissions to male patients due to DoH guidelines.Clinical implicationsWe found that it is possible to provide admission for men with eating disorders, while respecting the single gender accommodation rules, and that doing so is likely to be helpful for both genders and prevents discrimination against men.Declaration of interestNone.
Insulin Is Transcribed and Translated in Mammalian Taste Bud Cells
Authors: Doyle Máire E , Fiori Jennifer L , Gonzalez Mariscal Isabel , Liu Qing-Rong , Goodstein Erin , Yang Hyekyung , Shin Yu-Kyong , Santa-Cruz Calvo Sara , Indig Fred E , Egan Josephine M 
Published: July 2018

AbstractWe and others have reported that taste cells in taste buds express many peptides in common with cells in the gut and islets of Langerhans in the pancreas. Islets and taste bud cells express the hormones glucagon and ghrelin, the same ATP-sensitive potassium channel responsible for depolarizing the insulin-secreting β cell during glucose-induced insulin secretion, as well as the propeptide-processing enzymes PC1/3 and PC2. Given the common expression of functionally specific proteins in taste buds and islets, it is surprising that no one has investigated whether insulin is synthesized in taste bud cells. Using immunofluorescence, we demonstrated the presence of insulin in mouse, rat, and human taste bud cells. By detecting the postprocessing insulin molecule C-peptide and green fluorescence protein (GFP) in taste cells of both insulin 1-GFP and insulin 2-GFP mice and the presence of the mouse insulin transcript by in situ hybridization, we further proved that insulin is synthesized in individual taste buds and not taken up from the parenchyma. In addition to our cytology data, we measured the level of insulin transcript by quantitative RT-PCR in the anterior and posterior lingual epithelia. These analyses showed that insulin is translated in the circumvallate and foliate papillae in the posterior, but only insulin transcript was detected in the anterior fungiform papillae of the rodent tongue. Thus, some taste cells are insulin-synthesizing cells generated from a continually replenished source of precursor cells in the adult mammalian lingual epithelium.
Prevalence, Clinical and Biochemical Spectrum, and Treatment Outcome of Acromegaly With Normal Basal GH at Diagnosis
Authors: Espinosa de los Monteros Ana Laura , Sosa-Eroza Ernesto , Gonzalez Baldomero , Mendoza Victoria , Mercado Moises 
Published: July 2018

Abstract

Context
The term micromegaly has been used to describe a subset of patients who have elevated IGF-1 levels but apparently normal basal GH (bGH) concentrations and often a glucose-suppressed GH of &lt;1 ng/mL.

Objective
To evaluate the prevalence, clinical spectrum, and therapeutic outcome of acromegaly with normal bGH at diagnosis.

Design and Methods
Retrospective analysis of a cohort of patients with acromegaly diagnosed and treated at a tertiary care center.

Results
A cohort of 528 patients with acromegaly was stratified according to bGH at diagnosis: group 1, &lt;2 ng/mL, n = 16; group 2, 2 to 9.9 ng/mL, n = 202; group 3, 10 to 99 ng/mL, n = 294; and group 4, ≥100 ng/mL, n = 16. Patients in group 1 (normal bGH) constituted 3% of the total cohort and were significantly older and more likely to be male than patients in the other groups. The frequency of acromegalic symptoms, signs, and comorbidities was similar between the four patient groups. Patients in group 1 more often harbored microadenomas (75%) and had significantly lower median IGF-1 and postglucose GH levels. Surgical success rates were similar between patients from groups 1 (53.8%), 2 (54.1%), and 3 (36.9%), whereas only 13.3% of patients in group 4 achieved remission.

Conclusion
Normal bGH acromegaly is uncommon in real life. These patients have some distinctive features that argue against this being simply acromegaly in its early stages.
Integrin signaling downregulates filopodia during muscle–tendon attachment
Authors: Richier Benjamin , Inoue Yoshiko , Dobramysl Ulrich , Friedlander Jonathan , Brown Nicholas H. , Gallop Jennifer L. 
Published: July 2018

ABSTRACT
Cells need to sense their environment to ensure accurate targeting to specific destinations. This occurs in developing muscles, which need to attach to tendon cells before muscle contractions can begin. Elongating myotube tips form filopodia, which are presumed to have sensory roles, and are later suppressed upon building the attachment site. Here, we use live imaging and quantitative image analysis of lateral transverse (LT) myotubes in Drosophila to show that filopodia suppression occurs as a result of integrin signaling. Loss of the integrin subunits αPS2 and βPS (also known as If and Mys, respectively, in flies) increased filopodia number and length at stages when they are normally suppressed. Conversely, inducing integrin signaling, achieved by the expression of constitutively dimerised βPS cytoplasmic domain (diβ), prematurely suppressed filopodia. We discovered that the integrin signal is transmitted through the protein G protein-coupled receptor kinase interacting ArfGAP (Git) and its downstream kinase p21-activated kinase (Pak). Absence of these proteins causes profuse filopodia and prevents the filopodial inhibition mediated by diβ. Thus, integrin signaling terminates the exploratory behavior of myotubes seeking tendons, enabling the actin machinery to focus on forming a strong attachment and assembling the contractile apparatus.
New ubiquitin-dependent mechanisms regulating the Aurora B–protein phosphatase 1 balance in Saccharomyces cerevisiae
Authors: Ravindran Rini , Polk Paula , Robinson Lucy C. , Tatchell Kelly 
Published: July 2018

ABSTRACT
Protein ubiquitylation regulates many cellular processes, including cell division. We report here a novel mutation altering the Saccharomyces cerevisiae E1 ubiquitin-activating enzyme (uba1-W928R) that suppresses the temperature sensitivity and chromosome loss phenotype of a well-characterized Aurora B mutant (ip1-2). The uba1-W928R mutation increases histone H3-S10 phosphorylation in the ipl1-2 strain, indicating that uba1-W928R acts by increasing Ipl1 activity and/or reducing the opposing protein phosphatase 1 (PP1; Glc7 in S. cerevisiae) phosphatase activity. Consistent with this hypothesis, Ipl1 protein levels and stability are elevated in the uba1-W928R mutant, likely mediated via the E2 enzymes Ubc4 and Cdc34. In contrast, the uba1-W928R mutation does not affect Glc7 stability, but exhibits synthetic lethality with several glc7 mutations. Moreover, uba1-W928R cells have an altered subcellular distribution of Glc7 and form nuclear Glc7 foci. These effects are likely mediated via the E2 enzymes Rad6 and Cdc34. Our new UBA1 allele reveals new roles for ubiquitylation in regulating the Ipl1–Glc7 balance in budding yeast. While ubiquitylation likely regulates Ipl1 protein stability via the canonical proteasomal degradation pathway, a non-canonical ubiquitin-dependent pathway maintains normal Glc7 localization and activity.
This article has an associated First Person interview with the first author of the paper.
Functional analyses of Pericentrin and Syne-2 interaction in ciliogenesis
Authors: Falk Nathalie , Kessler Kristin , Schramm Sinja-Fee , Boldt Karsten , Becirovic Elvir , Michalakis Stylianos , Regus-Leidig Hanna , Noegel Angelika A. , Ueffing Marius , Thiel Christian T. , Roepman Ronald , Brandstätter Johann Helmut , Gießl Andreas 
Published: July 2018

ABSTRACT
Pericentrin (Pcnt) is a multifunctional scaffold protein and mutations in the human PCNT gene are associated with several diseases, including ciliopathies. Pcnt plays a crucial role in ciliary development in olfactory receptor neurons, but its function in the photoreceptor-connecting cilium is unknown. We downregulated Pcnt in the retina ex vivo and in vivo via a virus-based RNA interference approach to study Pcnt function in photoreceptors. ShRNA-mediated knockdown of Pcnt impaired the development of the connecting cilium and the outer segment of photoreceptors, and caused a nuclear migration defect. In protein interaction screens, we found that the outer nuclear membrane protein Syne-2 (also known as Nesprin-2) is an interaction partner of Pcnt in photoreceptors. Syne-2 is important for positioning murine photoreceptor cell nuclei and for centrosomal migration during early ciliogenesis. CRISPR/Cas9-mediated knockout of Syne-2 in cell culture led to an overexpression and mislocalization of Pcnt and to ciliogenesis defects. Our findings suggest that the Pcnt–Syne-2 complex is important for ciliogenesis and outer segment formation during retinal development and plays a role in nuclear migration.
Assessment of cold sink effect in postulated renal cryoablation by analyzing radiographic ice ball on computed tomography
Authors: Park Sung Yoon , Won Jong Yun , Oh Young Taik , Jung Dae Chul , Kim Gyoung Min , Kim Man Deuk 
Published: July 2018

Objective:
We analyzed CT characteristics of radiographic ice ball according to anatomical location and freezing number in renal cryoablation.

Methods:
30 patients who underwent percutaneous cryoablation for renal lesions. Computed tomography (CT) was conducted at 9 min during every freezing in order to evaluate a radiographic ice ball. Software was used to reconstruct CT images of the radiographic ice ball perpendicular to cryoprobes. For each radiographic ice ball, two types of radius were measured: (a) lateral radius from epicenter to perirenal direction and (b) medial radius from epicenter to renal sinus direction. Lateral and medial radius or diameters (lateral radius plus medial radius) during the first and second freezing were compared using paired t-test, respectively.

Results:
Medial radius of radiographic ice ball was significantly shorter than lateral radius (first freezing, 13.8 vs 17.0 mm, p &lt; 0.001; second freezing, 16.0 vs 19.3 mm, p &lt; 0.001). The diameter during the second freezing was significantly longer than that during the first freezing (35.3 vs 30.8 mm, p &lt; 0.001).

Conclusion:
In renal cryoablation, evaluating radiographic ice ball helps identify potential postulated cold sink effect in the central portion of kidney.

Advances in knowledge:
Radiologic information of postulated cold sink effect in the kidney may help secure sufficient safety margins.
Evaluation of altered pyroclastics from Rhodope prefecture, Thrace, Greece as constituents of pozzolanic cements
Authors: ΜΑΡΑΝΤΟΣ Ι. , ΚΟΣΙΑΡΗΣ Γ. , ΠΕΡΔΙΚΑΤΣΗΣ Β. , ΚΑΡΑΝΤΑΣΗ Σ. , ΚΑΛΟΕΙΔΑΣ Β. , ΜΑΛΑΜΗ Χ. 
Published: July 2018

In the Komotini Tertiary basin, tuffs of various types are alternated with tuffites, siltostones, sandstones and marls forming a thick volcanosedimentary sequence. The tuffs are characterised as ash-, fine ash- and in some cases as welded ash tuffs. Crystal-,lappili- and breccia tuffs also occur. The tuffs are built up of glass shards, pumice shards and crystal fragments which are cemented by glassy material. Crystal fragments are represented by quartz crystals. Plagioclase, albite, sanidine and biotite exist as well. Essentially, the vitric parts of the tuffs are altered to zeolites (heulandite 2 and/or mordenite, analcime, laumontite / scolecite), clay minerals (smectite, kaolinite +/or mixed layer I/S of regular type), Si02 minerals (quartz, cristobalite) and K-feldspar. For the purposes of this study, firstly, standard portland cement concrete specimens and concrete specimens with pyroclastic material from three different places, replacing portland cement by 20%, were prepared. The mineralogical composition of the samples under study and the area where they come from, is as follows: a. Iampolis: analcime + quartz + K-feldspar + albite + Illite/Smectite b. Darmeni : analcime + quartz + K-feldspar + albite + calcite c. Skaloma : smectite + cristobalite + heulandite-2 + mordenite + K-feldspar + quartz The compressive strength of the prepared specimens after periods of 7 and 28 days was measured and the pozzolanic activity of the samples was calculated according to ASTM Standard C618. Following the first test, the pozzolanic activity of a second sample from Iampolis area was more extensively studied. The compressive strength of concrete specimens made of 100% Portland cement of 145 type, and concrete specimens that were prepared by replacing Portland cement in proportions of 10, 20, 30 and 40% was determined. From the results of this study it is concluded that the analcimic tuffs could be a potential source for pozzolanic cement. More extensive study is needed for the estimation of the percentage of the altered pyroclastics that gives the optimum results concerning the cement pozzolanic activity. The optimization of the pozzolanic properties of the altered pyroclastics by calcination may be investigated as well.
The effect of aerobic exercise on relative leukocyte telomere length in male Sprague-Dawley rats given a high fat-diet
Authors: Santoso Dewi Irawati Soeria , Paramita Nurul , Prijanti Ani Retno , Hendrawan Thressia , Wicaksono Swandito 
Published: July 2018

Background: There is an increasing number of studies showing that physical activity and aerobic exercise have a positive effect on telomere length. Some studies also show that dynamics of telomere length is influenced by various environmental factors such as lifestyle and diet. However, the association between exercise and diet with telomere length is still questionable. The aim of this study was to examine the effects of aerobic physical exercise on relative telomere length changes in high fat-diet condition in rat animal models. Methods: This study was an in vivo experimental study using twelve Sprague-Dawley male white rats (12-month-old). Subjects were evenly and randomly divided into two groups (n=6): (1) high fat-diet fed control group; (2) high fat-diet fed and aerobic exercise treatment group. Aerobic exercise was conducted using animal treadmill with intensity of 20 m/min, 5 days/week. At weeks 4 and 8, relative telomere length was compared with week 0 control group, using q-RT-PCR. Results: Lengthening of relative telomere length was observed in both control and treatment groups at weeks 4 and 8, when compared to week 0 control group. The lengthening in the control group was much greater than the treatment group. Conclusions: Excessive increase of relative telomere length was seen in high fat-diet conditions. Aerobic exercise for 8 weeks suppresses excessive increase of relative telomere length in high fat-diet conditions.
Revealing HIV viral load patterns using unsupervised machine learning and cluster summarization
Authors: Farooq Samir A. , Weisenthal Samuel J. , Trayhan Melissa , White Robert J. , Bush Kristen , Mariuz Peter R. , Zand Martin S. 
Published: July 2018

HIV RNA viral load (VL) is an important outcome variable in studies of HIV infected persons. There exists only a handful of methods which classify patients by VL patterns. Most methods place limits on the use of viral load measurements, are often specific to a particular study design, and do not account for complex, temporal variation. To address this issue, we propose a set of four unambiguous computable characteristics (features) of time-varying HIV viral load patterns, along with a novel centroid-based classification algorithm, which we use to classify a population of 1,576 HIV positive clinic patients into one of five different viral load patterns (clusters) often found in the literature: durably suppressed viral load (DSVL), sustained low viral load (SLVL), sustained high viral load (SHVL), high viral load suppression (HVLS), and rebounding viral load (RVL). The centroid algorithm summarizes these clusters in terms of their centroids and radii. We show that this allows new VL patterns to be assigned pattern membership based on the distance from the centroid relative to its radius, which we term radial normalization classification. This method has the benefit of providing an objective and quantitative method to assign VL pattern membership with a concise and interpretable model that aids clinical decision making. This method also facilitates meta-analyses by providing computably distinct HIV categories. Finally we propose that this novel centroid algorithm could also be useful in the areas of cluster comparison for outcomes research and data reduction in machine learning.
Non-flushing of IV administration sets: an under-recognised under-dosing risk
Authors: Cooper Dawn Michelle , Rassam Thomas , Mellor Adrian 
Published: July 2018

Background: intravenous (IV) drugs are administered widely and under-dosing can result in therapy failure. The aim of this study was to quantify frequency, volume and dose of drug discarded within administration sets in the clinical setting. Methods: residual volume for 24 different administration sets was measured under controlled conditions in a laboratory. Clinical assessment of current practice regarding post-infusion flushing occurred in 6 departments of one teaching hospital in the UK over 7 days. Details of drug last infused, (concentration, diluent and volume) and type and brand of administration set were collected. Results: 74% of administration sets were not flushed. Non-flushing exceeded 90% and 61% for gravity and pump infusions respectively (p<0.001) in all areas excluding oncology. Oncology was the only area where flushing was standard practice for all infusions (p<0.001). Mean residual volume of the administration sets was 13.1 ml and 16.7 ml for gravity and pump sets respectively. Antibiotics were commonly infused and up to 21% of antibiotic dose was frequently discarded. Conclusions: the findings suggest disposal of substantial volumes of drugs occurs frequently in general hospital areas. Without clear national and local policies this unrecognised under-dosing will continue.