bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China
Authors: Wei Xiaolin , Zhang Xiulei , Yin Jia , Walley John , Beanland Rachel , Zou Guanyang , Zhang Hongmei , Li Fang , Liu Zhimin , Zee Benny CY , Griffiths Sian M
Published: January 2014

Background

This paper reports findings from the prevalence survey conducted in Shandong China in 2010, a province with a population of 94 million. This study aimed to estimate TB prevalence of the province in 2010 in comparison with the 2000 survey; and to compare yields of TB cases from different case finding approaches.

Methods

A population based, cross-sectional survey was conducted using multi-stage random cluster sampling. 54,279 adults participated in the survey with a response rate of 96%. Doctors interviewed and classified participants as suspected TB cases if they presented with persistent cough, abnormal chest X-ray (CXRAY), or both. Three sputum specimens of all suspected cases were collected and sent for smear microscopy and culture.

Results

Adjusted prevalence rate of bacteriologically confirmed cases was 34 per 100,000 for adults in Shandong in 2010. Compared to the 2000 survey, TB prevalence has declined by 80%. 53% of bacteriologically confirmed cases did not present persistent cough. The yield of bacteriologically confirmed cases was 47% by symptom screening and 95% by CXRAY. Over 50% of TB cases were among over 65’s.

Conclusions

The prevalence rate of bacteriologically confirmed cases was significantly reduced compared with 2000. The survey raised challenges to identify TB cases without clear symptoms.
Experience of physical violence and mental health among young men and women: a population-based study in Sweden
Authors: Fridh Maria , Lindström Martin , Rosvall Maria
Published: January 2014

Background

In Sweden mental ill-health has increased among the young, especially among young women. Our aim was to investigate the association between experience of physical violence during the past year and self rated psychological health among young men and women.

Methods

The study population consisted of men (n = 2,624) and women (n = 3,569) aged 18–34 years who participated in the 2008 public health survey study in Skåne. The survey was a cross-sectional stratified random sample postal questionnaire study with a 54.1% participation rate. Associations were investigated by logistic regression models.

Results

The prevalence of poor psychological health was 18.9% among men and 27.7% among women. One in ten men and one in twenty women had experienced physical violence during the past year. Most men were violated in public places, while women were most often violated at home. Women who had experienced violence during the past year showed more than doubled odds of poor psychological health, odds ratio (OR): 2.66 (95% confidence interval (CI): 2.00, 3.53). Such an association could not be seen in men OR: 1.12 (95% CI: 0.85, 1.47). Adjustment for covariates (i.e. age, country of birth, socioeconomic status, economic stress, alcohol risk consumption, emotional support, instrumental support and generalized trust in other people) did not change the association found among women.

Conclusion

Violated women, but not men, showed nearly doubled odds of poor psychological health after multiple adjustments. There was also a gender difference regarding location of violence. Awareness of gender differences regarding context and mental impact of violence may assist public health workers in reducing the consequences of violence and to design preventive strategies.
Electronic immunization data collection systems: application of an evaluation framework
Authors: Heidebrecht Christine L , Kwong Jeffrey C , Finkelstein Michael , Quan Sherman D , Pereira Jennifer A , Quach Susan , Deeks Shelley L
Published: January 2014

Background

Evaluating the features and performance of health information systems can serve to strengthen the systems themselves as well as to guide other organizations in the process of designing and implementing surveillance tools. We adapted an evaluation framework in order to assess electronic immunization data collection systems, and applied it in two Ontario public health units.

Methods

The Centers for Disease Control and Prevention’s Guidelines for Evaluating Public Health Surveillance Systems are broad in nature and serve as an organizational tool to guide the development of comprehensive evaluation materials. Based on these Guidelines, and informed by other evaluation resources and input from stakeholders in the public health community, we applied an evaluation framework to two examples of immunization data collection and examined several system attributes: simplicity, flexibility, data quality, timeliness, and acceptability. Data collection approaches included key informant interviews, logic and completeness assessments, client surveys, and on-site observations.

Results

Both evaluated systems allow high-quality immunization data to be collected, analyzed, and applied in a rapid fashion. However, neither system is currently able to link to other providers’ immunization data or provincial data sources, limiting the comprehensiveness of coverage assessments. We recommended that both organizations explore possibilities for external data linkage and collaborate with other jurisdictions to promote a provincial immunization repository or data sharing platform.

Conclusions

Electronic systems such as the ones described in this paper allow immunization data to be collected, analyzed, and applied in a rapid fashion, and represent the infostructure required to establish a population-based immunization registry, critical for comprehensively assessing vaccine coverage.
Process inhomogeneity leads to rapid side product turnover in cultivation of Corynebacterium glutamicum
Authors: Käß Friedrich , Junne Stefan , Neubauer Peter , Wiechert Wolfgang , Oldiges Marco
Published: January 2014

Background

Corynebacterium glutamicumhas large scale industrial applications in the production of amino acids and the potential to serve as a platform organism for new products. This means the demand for industrial process development is likely to increase. However, large scale cultivation conditions differ from laboratory bioreactors, mostly due to the formation of concentration gradients at the industrial scale. This leads to an oscillating supply of oxygen and nutrients for microorganisms with uncertain impact on metabolism. Scale-down bioreactors can be applied to study robustness and physiological reactions to oscillating conditions at a laboratory scale.

Results

In this study,C. glutamicumATCC13032 was cultivated by glucose limited fed-batch cultivation in a two-compartment bioreactor consisting of an aerobic stirred tank and a connected non-aerated plug flow reactor with optional feeding. Continuous flow through both compartments generated oscillating profiles with estimated residence times of 45 and 87 seconds in the non-aerated plug flow compartment. Oscillation of oxygen supply conditions at substrate excess and oscillation of both substrate and dissolved oxygen concentration were compared to homogeneous reference cultivations. The dynamic metabolic response of cells within the anaerobic plug flow compartment was monitored throughout the processes, detecting high turnover of substrate into metabolic side products and acidification within oxygen depleted zones. It was shown that anaerobic secretion of lactate into the extracellular culture broth, with subsequent reabsorption in the aerobic glucose-limited environment, leads to mixed-substrate growth in fed-batch processes. Apart from this, the oscillations had only a minor impact on growth and intracellular metabolite characteristics.

Conclusions

Carbon metabolism ofC. glutamicumchanges at oscillating oxygen supply conditions, leading to a futile cycle over extracellular side products and back into oxidative pathways. This phenomenon facilitates a dynamic and flexible shift of oxygen uptake at inhomogeneous process conditions. There is no loss of process characteristics at oscillation times in the minute range, which emphasizes the robustness ofC. glutamicumin comparison to other industrial microorganisms. Therefore, the metabolic phenotype ofC. glutamicumseems to be particularly well-suited for cultivation at inhomogeneous process conditions for large-scale fed-batch application, which is in good accordance with the respective industrial experiences.
Quality of life impact of mental health conditions in England: results from the adult psychiatric morbidity surveys
Authors: Roberts Jennifer , Lenton Pamela , Keetharuth Anju D , Brazier John
Published: January 2014

Background

The main objective is to present health state utility estimates for a broad range of mental health conditions including anxiety, depression, long-term depression, obsessive compulsive disorder, phobia, panic disorder, psychosis, alcohol and drug dependency that can be used in economic models.

Methods

This study uses pooled data from the Adult Psychiatric Morbidity Surveys carried out in 2000 and 2007 of a representative sample of the general population in England. Health state utility values measured by the SF-6D and EQ-5D indices are the dependent variables. Independent variables include background characteristics, mental health and physical health conditions. Regression models were estimated using OLS for the SF-6D and tobit for EQ-5D. Further regressions were carried out to consider the impact of mental health and physical health morbidities and the impact of severity of conditions on utility values.

Results

Mental health conditions tend to have a larger impact on health state utility values than physical health conditions. The mental health conditions associated with the highest decrements in utility are: depression, mixed anxiety and depressive disorders and long-term depression. Interaction terms used to model the effect of co-morbidities are generally found to be positive implying that simply adding the utility decrements for two mental health conditions overestimates the burden of the disease.

Conclusions

This paper presents reliable and representative community based mean SF-6D and EQ-5D estimates with standard errors for health state utility values across a broad range of mental health conditions that can be used in cost effectiveness modelling.
Acute pancreatitis and obstructive jaundice as initial complaints of hepatocellular carcinoma: case report
Authors: Jiang Guo-Qing , Qian Jian-Jun , Yao Jie , Jin Sheng-Jie , Bai Dou-Sheng
Published: January 2014

Background

Patients with cirrhosis-associated hepatocellular carcinoma (HCC) rarely present with acute pancreatitis (AP) and obstructive jaundice as the main clinical features. AP with obstructive jaundice caused by common bile duct embolism (CBDE) is very rare.

Case presentation

A 54-year-old man with CBDE was misdiagnosed with common bile duct stones three times over a 7-month period. Investigations during this time did not identify CBDE. Surgical exploration was performed because of AP, obstructive jaundice, and a tumor in the left lobe of the liver. CBDE from the hepatic tumor was diagnosed by intraoperative biopsy and frozen section examination. The patient underwent left hemihepatectomy, cholecystectomy, and bile duct exploration.

Conclusion

Preoperative diagnosis of CBDE is difficult because of the rarity of the condition, lack of physician awareness, and easy misdiagnosis on imaging examinations. Early and accurate diagnosis of this condition is important.
In lumbosacral plexus injuries can we identify indicators that predict spontaneous recovery or the need for surgical treatment? Results from a clinical study on 72 patients
Authors: Zollino Gianluca , Ferraresi Stefano , Garozzo Debora
Published: January 2014

Background Post-traumatic lumbosacral plexus injuries seem to be rare events, spontaneously recovering in high percentage: as surgery is often challenging and results in poor outcome, many Authors have advocated conservative treatment only. Nevertheless surgery should not be ruled out: in invalidating injuries, it can restore basic function in the lower extremities.

Therefore, it might be necessary to establish guidelines for the management and the indication to surgery in such cases.

This study aims to identify indicators predicting spontaneous recovery or the need for surgery.

Method The clinical and radiological data of 72 patients with a post-traumatic lumbosacral plexus injury were reviewed. A follow up equal or superior to 3 years is available in 42 cases.

Results Lumbosacral plexus injuries mostly occurred during road accidents. The incidence of associated lesions was relevant: bone injuries were found in 85% of patients, internal lesions in 30% and vascular injuries in 8%.

Lumbosacral trunk and sacral plexus palsies were the most frequent injury patterns.

Root avulsions were revealed in 23% of cases and only in sacral plexus and complete lumbosacral plexus injuries: L5 and S1 were the roots more prone to avulsions.

About 70% of cases recovered spontaneously, mostly in 18 months. Spontaneous recovery was the rule in lumbar plexus and lumbosacral trunk injuries (where root avulsions never occurred) or in sacral and complete lumbosacral plexus palsies due to compression injuries.

The causative mechanism correlated with the injury pattern, the associated bone injury being often predictive of the severity of the nerve injury.

Lumbosacral plexus injuries occurred in car crashes were generally associated with fractures causing compression on the nerves, thus resulting in injuries often amenable of spontaneous recovery.

Motorcycle accidents implied high kinetic energy traumas where traction played an important role, as the high percentage of sacroiliac joint separations demonstrated (found in more than 50% of cases and always associated to root avulsions).

Loss of sphincteral control and excruciating leg pain were also invariably associated with avulsions.

Conclusions Clinical and radiological data can help to predict the occurrence of spontaneous recovery or the need for surgery in post-traumatic lumbosacral plexus injuries.
MicroRNA-26a negatively regulates toll-like receptor 3 expression of rat macrophages and ameliorates pristane induced arthritis in rats
Authors: Jiang Congshan , Zhu Wenhua , Xu Jing , Wang Bo , Hou Weikun , Zhang Rui , Zhong Nannan , Ning Qilan , Han Yan , Yu Hongchuan , Sun Jian , Meng Liesu , Lu Shemin
Published: January 2014

Introduction

Abnormal toll-like receptor (TLR)3 signaling plays an indispensable role in pathogenesis of both experimental and human rheumatoid arthritis, and microRNAs (miRNAs) might orchestrate this signaling pathway. This study was performed to determine the relationship between miR-26a and TLR3 in rat macrophages and to observe effects of miR-26a mimic on pristane induced arthritis (PIA) in rats.

Methods

Dual luciferase reporter assay was used to validate the direct interaction between miR-26a (a candidate miRNA to target tlr3 mRNA) and tlr3 3′UTR. MiR-26a regulation on TLR3 gene expression was determined using RT-qPCR and Western blotting after miR-26a mimics and inhibitors were transfected into rat macrophage line NR8383 cells. Poly I:C (TLR3 ligand) was used to trigger TLR3 activation, and mRNA expression of its downstream cytokines interferon (ifn)-β and tumor necrosis factor (tnf)-α was accordingly detected to determine the regulation of TLR3 signaling. Expressions of TLR3 and miR-26a were detected during rat bone marrow derived macrophage (BMDM) induction, in pristane stimulated NR8383 cells and spleens from methotrexate (MTX) treated PIA rats. A miR-26a mimic was administrated intraperitoneally to PIA rats, and arthritis severity was evaluated by macroscopic or microscopic observations.

Results

Direct target relationship between miR-26a and tlr3 mRNA in rats was confirmed. Modifications of miR-26a function by transfection of miR-26a mimics and inhibitors exhibited corresponding repression and augmentation of TLR3 and its signaling downstream cytokine expressions in NR8383 cells. The alteration of miR-26a expression was negatively related with TLR3 expression during BMDM induction, in pristane-primed NR8383 cells and PIA rat spleens. Moreover, both abnormal expressions were rescued in MTX treated arthritis rat spleens. The miR-26a mimic treatment displayed the depression of TLR3 expression and ameliorated the disease severity in the rats with pristane induced arthritis.

Conclusions

MiR-26a negatively regulates TLR3 signaling via targeting of TLR3 itself in rat macrophages, and this finding provides a novel insight into abnormal TLR3 overexpression during experimental arthritis.
Oral delivery of oligomeric procyanidins in Apple Poly® enhances type I IFN responses in vivo
Authors: Snyder Deann T , Robison Amanda , Kemoli Sharon , Kimmel Emily , Holderness Jeff , Jutila Mark A , Hedges Jodi F
Published: January 2014

Type I IFN signaling is a central pathway that provides critical innate protection from viral and bacterial infection and can have regulatory outcomes in inflammatory settings. We determined previously that OPCs contained in the dietary supplement APP enhanced responses to type I IFN in vitro. Here, we confirm that OPCs from two different sources significantly increased pSTAT1, whereas a monomeric form of procyanidin did not. We hypothesized that similar responses could be induced in vivo following ingestion of APP. Ingestion of APP before injection of polyI:C enhanced in vivo responses to type I IFNs in mice. When human subjects ingested APP, enhanced responses to type I IFN and enhanced pSTAT1 ex vivo were detected, whereas ingestion of RES, a monomeric polyphenol, induced minimal such changes. Polyphenols are best known for induction of anti-inflammatory and antioxidant responses; however, our findings suggest a unique, nonantioxidant aspect of OPCs that is broadly applicable to many disease settings. The capacity of oral OPCs to enhance type I IFN signaling in vivo can augment innate protection and may, in part, contribute to the noted anti-inflammatory outcome of ingestion of OPCs from many sources.
Characterizing Ground Motions that Collapse Steel Special Moment-Resisting Frames or Make Them Unrepairable
Authors: Olsen Anna H. , Heaton Thomas H. , Hall John F.
Published: January 2014

This work applies 64,765 simulated seismic ground motions to four models each of 6- or 20-story, steel special moment-resisting frame buildings. We consider two vector intensity measures and categorize the building response as “collapsed,” “unrepairable,” or “repairable.” We then propose regression models to predict the building responses from the intensity measures. The best models for “collapse” or “unrepairable” use peak ground displacement and velocity as intensity measures, and the best models predicting peak interstory drift ratio, given that the frame model is “repairable,” use spectral acceleration and epsilon ( ∊) as intensity measures. The more flexible frame is always more likely than the stiffer frame to “collapse” or be “unrepairable.” A frame with fracture-prone welds is substantially more susceptible to “collapse” or “unrepairable” damage than the equivalent frame with sound welds. The 20-story frames with fracture-prone welds are more vulnerable to P-delta instability and have a much higher probability of collapse than do any of the 6-story frames.
The influence of chromatic background on the photosensitivity of tilapia erythrophores
Authors: Chen Shyh-Chi , Hornsby Mark A. W. , Robertson R. Meldrum , Hawryshyn Craig W.
Published: January 2014

Non-mammalian vertebrates and invertebrates use extraretinal photoreceptors to detect light and perform diverse non-image-forming functions. Compared to well-studied visual systems, the effect of ambient light conditions on photosensory systems of extraretinal photoreceptors is poorly understood. Chromatophores are photosensitive dermal pigment cells that play an important role in the formation of body color patterns to fit the surrounding environment. Here, we used tilapia erythrophores to investigate the relationship between environmental light and chromatophore photoresponses. All erythrophores from three spectral conditions aggregated their pigment granules in UV/short wavelengths and dispersed in middle/long wavelengths. Unlike retinal visual systems, environmental light did not change the usage of the primary opsins responsible for aggregation and dispersion. In addition, short wavelength-rich and red-shifted background conditions led to an inhibitory effect on erythrophore photoresponses. We suggest that, as extraretinal photoreceptors for non-image-forming functions, chromatophores directly adjust their photoresponse sensitivity via changes in opsin expression levels rather than opsin types when environmental light changes.
PI4KIIIα is required for cortical integrity and cell polarity during Drosophila oogenesis
Authors: Tan Julie , Oh Karen , Burgess Jason , Hipfner David R. , Brill Julie A.
Published: January 2014

Phosphoinositides regulate myriad cellular processes, acting as potent signaling molecules in conserved signaling pathways and as organelle gatekeepers that recruit effector proteins to membranes. Phosphoinositide-generating enzymes have been studied extensively in yeast and cultured cells, yet their roles in animal development are not well understood. Here, we analyze Drosophila melanogaster phosphatidylinositol (PI) 4-kinase IIIα (PI4KIIIα) during oogenesis. We demonstrate that PI4KIIIα is required for production of plasma membrane PI4P and PI(4,5)P2 and is crucial for actin organization, membrane trafficking and cell polarity. Female germ cells mutant for PI4KIIIα exhibit defects in cortical integrity associated with failure to recruit the cytoskeletal-membrane crosslinker Moesin and the exocyst subunit Sec5. These effects reflect a unique requirement for PI4KIIIα, as egg chambers from flies mutant for either of the other Drosophila PI4Ks, fwd or PI4KII, show Golgi but not plasma membrane phenotypes. Thus, PI4KIIIα is a critical regulator of a functionally distinct pool of PI4P that is essential for PI(4,5)P2-dependent processes in Drosophila development.
The non-receptor tyrosine kinase Ack1 regulates activated EGFR fate by inducing trafficking to the p62/NBR1 pre-autophagosome
Authors: Jones Sylwia , Cunningham Debbie L. , Rappoport Joshua Z. , Heath John K.
Published: January 2014

Growth factor signalling regulates multiple cellular functions and its misregulation has been linked to cancer development and progression. Ack1 (Activated Cdc42-associated kinase 1, TNK2), a non-receptor tyrosine kinase, has been implicated in trafficking and degradation of epidermal growth factor receptor (EGFR), yet the precise functions remain elusive. In this report we investigate the role of Ack1 in EGFR trafficking and show that Ack1 partially colocalises to Atg16L-positive structures upon EGF stimulation. These are proposed to be the isolation membranes during autophagosome formation. In addition we find that Ack1 colocalises and interacts with sequestosome 1 (p62/SQSTM1), a receptor for selective autophagy, via a ubiquitin associated domain and this interaction decreases upon EGF treatment, thus suggesting that Ack1 moves away from p62/SQSTM1 compartments. Furthermore, Ack1 interacts and colocalises with NBR1, another autophagic receptor, and this colocalisation is enhanced in the presence of ectopically expressed p62/SQSTM1. Finally, Ack1 knock-down results in accelerated lysosomal localisation of EGFR upon EGF treatment. Structure-function analyses of a panel of Ack1 deletion mutants have revealed key mechanistic aspects of these relationships. The Mig6-homology domain and clathrin binding domain both contribute to the colocalisation with EGFR, whereas the UBA domain is critical for the colocalisation with p62/SQSTM1, but not NBR1. Taken together, our studies demonstrate a novel role for Ack1 in diverting activated EGFR into a non-canonical degradative pathway, marked by association with p62/SQSTM1, NBR1 and Atg16L.
The SMN Tudor SIM-like domain is key to SmD1 and coilin interactions and to Cajal body biogenesis
Authors: Tapia Olga , Lafarga Vanesa , Bengoechea Rocio , Palanca Ana , Lafarga Miguel , Berciano María T.
Published: January 2014

Cajal bodies (CBs) are nuclear organelles involved in the maturation of spliceosomal snRNPs. They concentrate coilin, snRNPs and the survival motor neuron protein (SMN). Dysfunction of CB assembly is an essential component of spinal muscular atrophy (SMA). Here we demonstrate that SMN is a SUMO1 target that has a SUMO-like interacting motif (SIM-like) in the Tudor domain. The expression of SIM-like mutant constructs abolishes the interaction of SMN with the spliceosomal SmD1, severely decreases SMN-coilin interaction and prevents CB assembly. Accordingly, the SMN SIM-like-mediated interactions are important for CB biogenesis and their dysfunction can be involved in SMA pathophysiology.
PDE4B mediates local feedback regulation of β1-adrenergic cAMP signaling in a sarcolemmal compartment of cardiac myocytes
Authors: Mika Delphine , Richter Wito , Westenbroek Ruth E. , Catterall William A. , Conti Marco
Published: January 2014

Multiple cAMP phosphodiesterase (PDE) isoforms play divergent roles in cardiac homeostasis, but the molecular basis for their non-redundant function remains poorly understood. Here we report a novel role for the PDE4B isoform in β-adrenergic (βAR) signaling in the heart. Genetic ablation of PDE4B disrupts βAR-induced cAMP transients measured by FRET-sensors only at the sarcolemma but not in the bulk cytosol of cardiomyocytes. This effect is further restricted to a subsarcolemmal compartment since PDE4B regulates β1AR-, but not β2AR- or PGE2-induced responses. The spatially restricted function of PDE4B is confirmed by its selective effects on PKA-phosphorylation patterns. PDE4B limits PKA-phosphorylation of key players in excitation-contraction coupling that reside in the sarcolemmal compartment, including L-type Ca2+ channels and ryanodine receptors, but not phosphorylation of distal/cytosolic proteins. β1AR- but not β2AR-ligation induces PKA-dependent activation of PDE4B and interruption of this negative feedback with PKA inhibitors increases sarcolemmal cAMP. Thus, PDE4B mediates a critical PKA-dependent feedback that controls β1AR-dependent cAMP signals in a restricted subsarcolemmal domain. Disruption of this feedback augments local cAMP/PKA signals leading to increased intracellular Ca2+ levels and contraction rate.
The Mon1-Ccz1 GEF activates the Rab7 GTPase Ypt7 via a longin fold-Rab interface and association with PI-3-P-positive membranes
Authors: Cabrera Margarita , Nordmann Mirjana , Perz Angela , Schmedt David , Gerondopoulos Andreas , Barr Francis , Piehler Jacob , Engelbrecht-Vandré Siegfried , Ungermann Christian
Published: January 2014

For their function in fusion and signaling, Rab GTPases need to be converted into their active GTP form. We previously identified the conserved Mon1-Ccz1 complex as the guanine nucleotide exchange factor (GEF) of the yeast Rab7 GTPase Ypt7. To address the possible GEF mechanism, we generated a homology model of the predicted longin domains of Mon1 and Ccz1 using as template the Rab-binding surface of the TRAPP complex. Based on this, we identified mutations in both yeast Mon1 and Ccz1 that block Ypt7 activation, without affecting heterodimer formation and intracellular localization of Mon1 and Ccz1 at endosomes. Strikingly, the activity of the isolated Mon1-Ccz1 complex for Ypt7 is highly stimulated on membranes, and is promoted by the same anionic phospholipids such as phosphatidylinositol-3-phosphate (PI-3-P) that also support membrane-association of the GEF complex. Our data imply that the GEF activity of the Mon1-Ccz1 complex towards Rab7/Ypt7 requires the interface formed by their longin domains and profits strongly from its association with the organelle surface.
A role for the CB-associated SUMO isopeptidase USPL1 in RNAPII-mediated snRNA transcription
Authors: Hutten Saskia , Chachami Georgia , Winter Ulrike , Melchior Frauke , Lamond Angus I.
Published: January 2014

Cajal bodies are nuclear structures involved in snRNP and snoRNP biogenesis, telomere maintenance and histone mRNA processing. Recently, the SUMO isopeptidase USPL1 was identified as a Cajal body component essential for cellular growth and Cajal body integrity. However, a cellular function for USPL1 is so far unknown. Here, we use RNAi mediated knockdown in human cells in combination with biochemical and fluorescence microscopy approaches to investigate the function of USPL1 and its relation to Cajal bodies. We demonstrate that the levels of RNAPII-transcribed snRNAs are reduced upon knockdown of USPL1 and that downstream processes such as snRNP assembly and pre-mRNA splicing are compromised. Importantly, we find that USPL1 associates directly with U snRNA loci and that it interacts and colocalizes with components of the Little Elongation Complex, which is involved in RNAPII-mediated snRNA transcription. Thus our data indicate that USPL1 plays a key role in the process of RNAPII-mediated snRNA transcription.
Cdk1-dependent phosphorylation of Iqg1 governs actomyosin ring assembly prior to cytokinesis
Authors: Naylor Stephen G. , Morgan David O.
Published: January 2014

Contraction of the actomyosin ring (AMR) provides the centripetal force that drives cytokinesis. In budding yeast, assembly and contraction of the AMR is coordinated with membrane deposition and septum formation at the bud neck. A central player in this process is Iqg1, which promotes recruitment of actin to the myosin ring and links AMR assembly with that of septum-forming components. We observed early actin recruitment in response to inhibition of cyclin-dependent kinase 1 (Cdk1) activity, and we find that the Cdk1-dependent phosphorylation state of Iqg1 is a determining factor in the timing of bud neck localization of both Iqg1 and actin, with both proteins accumulating prematurely in cells expressing nonphosphorylatable Iqg1 mutants. We also identified the primary septum regulator Hof1 as a binding partner of Iqg1, providing a regulatory link between the septation and contractile pathways that cooperate to complete cytokinesis.
Facile Preparation of Ionic Liquid Containing Silsesquioxane Framework
Authors: Ishii Takuhiro , Mizumo Tomonobu , Kaneko Yoshiro
Published: January 2014

An ionic liquid containing silsesquioxane framework (SQ-IL) was successfully prepared by the hydrolytic condensation of trimethyl[3-(triethoxysilyl)propyl]ammonium chloride in aqueous solution of bis(trifluoromethanesulfonyl)imide (TFSI). The energy-dispersive X-ray analysis of SQ-IL indicated that the molar ratio of quaternary ammonium cation to TFSI anion in SQ-IL was ca. 1:1. The 29Si NMR spectrum of SQ-IL showed two broad peaks in T2 and T3 regions. The weight-average molecular weight estimated by static light-scattering measurement was ca. 1.8 × 103. In addition, the X-ray diffraction pattern of SQ-IL did not show any diffraction peaks. On the basis of these results, it was concluded that SQ-IL was an amorphous oligomeric silsesquioxane compound containing equimolar quaternary ammonium cations and TFSI anions. The differential scanning calorimetry thermogram of SQ-IL exhibited an endotherm peak due to glass transition at 15 °C, and SQ-IL showed fluidity over ca. 35 °C, indicating that SQ-IL was fluid below 100 °C (i.e., an ionic liquid). In the thermogravimetric analyses, the temperatures of thermal decomposition of SQ-IL were higher than those of N,N,N-trimethyl-N-propylammonium bis(trifluoromethanesulfonyl)imide, which is an ionic liquid compound with the same structure as that of the side chains of SQ-IL. This result indicated that the silsesquioxane framework could suppress thermal degradation.
Cellular mRNAs access second ORFs using a novel amino acid sequence-dependent coupled translation termination–reinitiation mechanism
Authors: Gould Phillip S. , Dyer Nigel P. , Croft Wayne , Ott Sascha , Easton Andrew J.
Published: January 2014

Polycistronic transcripts are considered rare in the human genome. Initiation of translation of internal ORFs of eukaryotic genes has been shown to use either leaky scanning or highly structured IRES regions to access initiation codons. Studies on mammalian viruses identified a mechanism of coupled translation termination–reinitiation that allows translation of an additional ORF. Here, the ribosome terminating translation of ORF-1 translocates upstream to reinitiate translation of ORF-2. We have devised an algorithm to identify mRNAs in the human transcriptome in which the major ORF-1 overlaps a second ORF capable of encoding a product of at least 50 aa in length. This identified 4368 transcripts representing 2214 genes. We investigated 24 transcripts, 22 of which were shown to express a protein from ORF-2 highlighting that 3′ UTRs contain protein-coding potential more frequently than previously suspected. Five transcripts accessed ORF-2 using a process of coupled translation termination–reinitiation. Analysis of one transcript, encoding the CASQ2 protein, showed that the mechanism by which the coupling process of the cellular mRNAs was achieved was novel. This process was not directed by the mRNA sequence but required an aspartate-rich repeat region at the carboxyl terminus of the terminating ORF-1 protein. Introduction of wobble mutations for the aspartate codon had no effect, whereas replacing aspartate for glutamate repeats eliminated translational coupling. This is the first description of a coordinated expression of two proteins from cellular mRNAs using a coupled translation termination–reinitiation process and is the first example of such a process being determined at the amino acid level.
Ten years of NovoMix 30 in Russian and international clinical practice
Authors: Surkova Elena Viktorovna
Published: January 2014

Insulin treatment for type 2 diabetes mellitus is challenging in elderly people. Biphasic insulin preparations technically simplify this task, but also increase compliance and facilitate the achievement of therapeutic goals.
Genetic framework of type 2 diabetes mellitus
Authors: Bondar' Irina Arkad'evna , Shabel'nikova Olesya Yur'evna
Published: January 2014

More than 100 genes associated with the risk of type 2 diabetes mellitus (T2DM) are now established. Most of them affect insulin secretion, adipogenesis and insulin resistance, but the exact molecular mechanisms determining their involvement in the pathogenesis of T2DM are not understood completely.
Rs7903146 variant of TCF7L2 gene and rs18012824 variant of PPARG2 gene (Pro12Ala) are associated with type 2 diabetes mellitus in Novosibirsk population
Authors: Bondar' Irina Arkad'evna , Filipenko Maksim Leonidovich , Shabel'nikova Olesya Yur'evna , Sokolova Ekaterina Alexandrovna
Published: January 2014

Aim.  To investigate the association of polymorphisms in TCF7L2 and PPARG2 genes with type 2 diabetes mellitus (T2DM) in Novosibirsk population. Materials and Methods. We examined 391 patients with T2DM and 556 individuals with normal glucose metabolism. Allelic identification was performed with TaqMan technique, implementing allele-specific real-time PCR. Results.  Analysis shows that allelic frequency distribution of rs1801282 variant of PPARG2 gene and rs7903146 variant of TCF7L2 differs significantly between the study and control groups (OR [CI 95%]=1.44 [1.12?1.85], p=0.005 and OR [CI 95%]=1.57 [1.17?2.10], p=0.003, respectively). T2DM patients with T/T genotype of rs7903146 variant of TCF7L2 gene had lower BMI (p=0.02). Observed combination of risk alleles reached 99%. Combined beta-cell dysfunction and insulin resistance genotypes were identified in 56% of tested subjects, isolated insulin resistance ? in 42.2% of subjects, and isolated beta-cell dysfunction ? in 0.8% of subjects. Conclusion.  Our data shows that carrier state of 12Pro rs1801284 variant of PPARG2 gene and T-allele rs7903146 variant of TCF7L2 gene are associated with T2DM in Novosibirsk population, increasing its risk 1.44 and 1.57 times, respectively. Combination of these polymorphisms was observed in 99% of patients with T2DM.
Markers for gastrointestinal autoimmune disorders in patients with type 1 diabetes mellitus
Authors: Derevyanko Olga Sergeevna , Dalantaeva Nadezhda Sergeevna , Pekareva Elena Vladimirovna , Ivanova Olga Nikolaevna , Goncharov Nikolay Petrovich , Nikonova Tatiana Vasil'evna , Smirnova Olga Mikhailovna
Published: January 2014

Aim.  to assess the occurrence of autoantibodies characteristic of autoimmune pancreatitis and gastritis in patients with type 1 diabetes mellitus (T1DM), and to analyze clinical features of positive subjects. Materials and Methods.  84 patients (39 male, 45 female) with T1DM were subdivided into two groups and underwent biochemical, immunologic and instrumental examination. Results.  Markers for gastrointestinal autoimmune disorders were found to be highly prevalent in patients with T1DM, even in those asymptomatic according to instrumental diagnostic methods. Conclusion. Our data suggests that T1DM patients are at higher risk of corresponding, possibly asymptomatic autoimmune disorders.
Message from Editor-in-Cheif
Authors: Dedov Ivan Ivanovich
Published: January 2014

We are happy to congratulate our readers with the 15th anniversary of this title. The journal enters 2014 with almost one thousand published papers - a remarkable path that inspires confidence in future progress. .
Morphology of bronchial epithelium in rodent streptozotocin-induced diabetes mellitus
Authors: Pivovarova Oksana Anatolyevna , Mankovsky Boris Nikitich
Published: January 2014

Aim.  To study the morphology of bronchial epithelium in a rodent streptozotocin-induced (STZ) diabetes mellitus. Materials and Methods. . Diabetes mellitus was introduced in 47 white Wistar rats aged 5?6 months (body weight 234.0?2.64 g). 43 white Wistar rats of the same age were used as control subjects (body weight 242.0?2.13). Diabetes was induced by single intraperitoneal injection of STZ (SIGMA, USA) 60 mg/kg in 0.1 M citrate buffer, pH 4.5. Results. A statistically significant decrease in the total epithelial area by 25.9% was observed in the study group, accompanied by a reduction of the supranuclear zone by 22.1% vs. the control group. Conclusion. We found that bronchial mucous membrane in rodents with STZ-induced diabetes mellitus exhibits signs of atrophy and partial loss of mucous production by bronchial secretory cells.
The effects of structured self-monitoring of blood glucose on therapeutic effectiveness and adherence in patients with type 2 diabetes mellitus initiating insulin treatment
Authors: Suvorova Lyudmila Alexandrovna , Petrov Alexander Vladimirovich , Strongin Leonid Grigor'evich
Published: January 2014

Aim.  To compare the efficiency of standard and structured approaches to self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes mellitus (T2DM) initiating insulin treatment. Materials and Methods. This open prospective randomized clinical trial included 51 T2DM patients who initiated insulin therapy in either outpatient or inpatient setting. Subjects were randomized in standard and structured SMBG groups, the structured group used an advanced Accu-Chek 360 View protocol. Evaluation included clinical examination and laboratory testing of HbA1c levels at the beginning of the treatment and after 3 months of the follow-up period. Results. 70% of the structured self-monitoring group and 32% of the control group achieved therapeutic goals (p=0.008). Higher adherence was associated with better glycemic control in both groups ? and vice versa. However, among patients with low adherence, 73% of advanced SMBG group managed to achieve therapeutic goals vs. 19% in the control group (p=0.005). In addition, patients in the structured monitoring group gained less weight as compared to the control (1.0?2.88 kg vs. 3.2?2.56 kg; p=0.005). Conclusion. Structured SMBG commenced at the initiation of insulin therapy improves glycemic control in a greater fraction of patients, especially in those with low adherence to treatment. Structured SMBG also partially alleviates weight gain as side effect of insulin treatment.
Evaluation of glycemic control, quality of life and psychological characteristics in patients with type 1 diabetes mellitus
Authors: Shishkova Yuliya Andreevna , Motovilin Oleg Gennad'evich , Surkova Elena Viktorovna , Mayorov Alexander Yur'evich
Published: January 2014

Aim. To identify psychological characteristics associated with better glycemic control and higher quality of life (QoL) in patients with type 1 diabetes mellitus (T1DM). Materials and Methods.  The study included 140 T1DM patients (47 males) aged 18 to 28 years. Assessment of the QoL and associated emotional state (ES) was performed by validated localized questionnaires, supplemented with the inventories for evaluation of psychological characteristics. Based on the acquired data we performed a trilateral analysis of glycemic control, QoL and ES, followed by testing of these parameters for correlation with certain psychological characteristics, including disease attitude, mindfulness, self-attitude and self-assessment, coping strategies, autoregulation parameters and the locus of control. Results.  In the studied sample, better glycemic control was associated with higher QoL and more favourable ES. We also identified several psychological characteristics associated with an improvement in all three primary parameters, namely: higher level of mindfulness, internal locus of control and ergopathic attitude. Conclusion.  The diagnostic inventory for QoL and ES evaluation used in the present study may be helpful for psychological testing in patients with T1DM.
Prevalence of type 2 diabetes mellitus and its complications among the population of Moscow Region ? a cross-sectional epidemiological study
Authors: Suntsov Yury Ivanovich , Bolotskaya Lyubov' Leonidovna , Rudakova Olga Gennad'evna , Andrianova Ekaterina Andreevna , Tolkacheva Anna Anatol'evna , Kon Irina L'vovna
Published: January 2014

Aim.  To estimate the prevalence of type 2 diabetes mellitus (T2DM) among the population of Moscow Region, as well as the actual prevalence of diabetes complications in individuals already diagnosed with DM. Materials and Methods. 2403 inhabitants of Stupinksy and Domodedovsky areas aged 30 to 70 years were selected by means of random sampling for the estimation of T2DM prevalence. Another 600 individuals inhabiting Pushkinsky and Serpukhovsky areas were randomly selected for the estimation of the prevalence of DM complications (including patients with T2DM). Clinical screening was performed by the mobile diagnostic team. Results. HbA1c level was tested in all participants. The cut-off point for the diagnosis of DM was set for . HbA1c>6.5% according to the WHO guidelines (2011). 204 individuals (8.49%) met this criterion and were selected for further evaluation by OGTT with the following Results. 28.04% were positive for glycemic disorders, including T2DM (8.53%), IGT (17.07%), IFG (2.44%). The highest prevalence of T2DM was found in the elder group (60?70 years old). The prevalence of diabetic retinopathy was estimated at 26.06%, being 2 times higher among T2DM patients than previously calculated for Moscow Region by the Russian State Diabetes Register (13.2%). The microalbuminuria stage of diabetic nephropathy was diagnosed in 46.1% of diabetes patients, being 5 times more prevalent than previously estimated for Moscow Region by the Russian State Diabetes Register (5.84%). Conclusion. The actual prevalence of T2DM in Moscow Region is markedly higher than the registered. The prevalence of diabetes complications is also significantly underestimated. Most patients do not achieve . HbA1c targets (
Anti-VEGF agents in the treatment of diabetic macular edema
Authors: Konenkov Vladimir Iosifovich , Klimontov Vadim Valerievich , Chernykh Valeriy Vyacheslavovich , Tjan Nadezhda Viktorovna
Published: January 2014

Diabetic macular edema (DME) is a common complication associated with the loss of visual acuity in diabetic patients. Intravitreal injections of vascular endothelium growth factor (VEGF) inhibitors (anti-VEGF therapy) have been proposed recently as a new treatment option for patients with DME. In this review we summarized results of randomized clinical trials of VEGF inhibitors in DME patients. The results indicate that all studied inhibitors (ranibizumab, bevacizumab, pegaptanib and aflibersept) reduce the retinal thickness and improve of visual acuity in DME when are used as a monotherapy or in combination with the laser treatment. Optimal course duration and effectiveness predictors of anti-VEGF therapy in DME should be elucidate in the future studies.
Because I (Don't) Deserve It: How Relationship Reminders and Deservingness Influence Consumer Indulgence
Authors: Cavanaugh Lisa A.
Published: January 2014

Marketers regularly remind consumers of valued social relationships (e.g., close friends, family, romantic couples) to influence choice and consumption. However, the author's research reveals that such relationship reminders can backfire when consumers lack or no longer have these highlighted relationships. The author shows that reminding consumers of relationships they lack reduces their perceptions of deservingness and causes them to restrict indulgent consumption. Five studies establish the effect of relationship reminders on indulgence and provide support for the underlying process by both measuring and manipulating perceptions of deservingness.
Vitamin D levels and liver histological alterations in children with nonalcoholic fatty liver disease
Authors: Nobili Valerio , Giorgio Valentina , Liccardo Daniela , Bedogni Giorgio , Morino Giuseppe , Alisi Anna , Cianfarani Stefano
Published: January 2014

Objective

To investigate the association between plasma vitamin D (VD) levels and histological liver damage in children with nonalcoholic fatty liver disease (NAFLD).

Subjects and methods

In this cross-sectional study, carried out in a tertiary care center for obesity, 73 consecutive overweight and obese children with persistently elevated serum aminotransferase levels and diffusely hyperechogenic liver on ultrasonography were selected for liver biopsy. Nonalcoholic steatohepatitis (NASH) and fibrosis were histologically diagnosed using NAFLD Clinical Research Network (CRN) criteria. The plasma levels of 25-OH-VD were measured by HPLC. Bone mineral density (BMD) of lumbar spine was evaluated by dual-energy X-ray absorptiometry. Multiple linear regression analysis was used to evaluate the association between 25-OH-VD levels and the predictors of interest after correction for age, gender, waist circumference, BMI, and other potential confounders.

Results

The children (64% males) were aged 8–18 years, and their median BMI was 2.45 SDS. Both parathyroid hormone levels and BMD were within the normal range. All cases of fibrosis were detected in children with NASH. On multivariable linear regression with correction for age, gender, and BMI, 25-OH-VD levels were found to be 9 (95% CI 12–6) ng/ml lower in children with NASH than in those without NASH (P<0.001) and 9 (12–6) ng/ml lower in children with stage 1 fibrosis than in those with stage 0 fibrosis and 9 (13–6) ng/ml lower in children with stage 2 than in those with stage 0 fibrosis (P<0.001 for both).

Conclusion

VD levels are inversely associated with NASH and fibrosis in children with NAFLD.