bluuebunny/crossref_metadata_2025 huggingface dataset:
Spore development and nuclear inheritance in arbuscular mycorrhizal fungi
Authors: Marleau Julie , Dalpé Yolande , St-Arnaud Marc , Hijri Mohamed
Published: February 2011

Background

A conventional tenet of classical genetics is that progeny inherit half their genome from each parent in sexual reproduction instead of the complete genome transferred to each daughter during asexual reproduction. The transmission of hereditary characteristics from parents to their offspring is therefore predictable, although several exceptions are known. Heredity in microorganisms, however, can be very complex, and even unknown as is the case for coenocytic organisms such as Arbuscular Mycorrhizal Fungi (AMF). This group of fungi are plant-root symbionts, ubiquitous in most ecosystems, which reproduce asexually via multinucleate spores for which sexuality has not yet been observed.

Results

We examined the number of nuclei per spore of four AMF taxa using high Z-resolution live confocal microscopy and found that the number of nuclei was correlated with spore diameter. We show that AMF have the ability, through the establishment of new symbioses, to pass hundreds of nuclei to subsequent generations of multinucleated spores. More importantly, we observed surprising heterogeneity in the number of nuclei among sister spores and show that massive nuclear migration and mitosis are the mechanisms by which AMF spores are formed. We followed spore development of Glomus irregulare from hyphal swelling to spore maturity and found that the spores reached mature size within 30 to 60 days, and that the number of nuclei per spores increased over time.

Conclusions

We conclude that the spores used for dispersal of AMF contain nuclei with two origins, those that migrate into the spore and those that arise by mitosis in the spore. Therefore, these spores do not represent a stage in the life cycle with a single nucleus, raising the possibility that AMF, unlike all other known eukaryotic organisms, lack the genetic bottleneck of a single-nucleus stage.
Genomic characteristics of cattle copy number variations
Authors: Hou Yali , Liu George E , Bickhart Derek M , Cardone Maria Francesca , Wang Kai , Kim Eui-soo , Matukumalli Lakshmi K , Ventura Mario , Song Jiuzhou , VanRaden Paul M , Sonstegard Tad S , Van Tassell Curt P
Published: February 2011

Background

Copy number variation (CNV) represents another important source of genetic variation complementary to single nucleotide polymorphism (SNP). High-density SNP array data have been routinely used to detect human CNVs, many of which have significant functional effects on gene expression and human diseases. In the dairy industry, a large quantity of SNP genotyping results are becoming available and can be used for CNV discovery to understand and accelerate genetic improvement for complex traits.

Results

We performed a systematic analysis of CNV using the Bovine HapMap SNP genotyping data, including 539 animals of 21 modern cattle breeds and 6 outgroups. After correcting genomic waves and considering the pedigree information, we identified 682 candidate CNV regions, which represent 139.8 megabases (~4.60%) of the genome. Selected CNVs were further experimentally validated and we found that copy number "gain" CNVs were predominantly clustered in tandem rather than existing as interspersed duplications. Many CNV regions (~56%) overlap with cattle genes (1,263), which are significantly enriched for immunity, lactation, reproduction and rumination. The overlap of this new dataset and other published CNV studies was less than 40%; however, our discovery of large, high frequency (> 5% of animals surveyed) CNV regions showed 90% agreement with other studies. These results highlight the differences and commonalities between technical platforms.

Conclusions

We present a comprehensive genomic analysis of cattle CNVs derived from SNP data which will be a valuable genomic variation resource. Combined with SNP detection assays, gene-containing CNV regions may help identify genes undergoing artificial selection in domesticated animals.
Phenotypic and transcriptional analysis of the osmotic regulator OmpR in Yersinia pestis
Authors: Gao He , Zhang Yiquan , Han Yanping , Yang Lin , Liu Xia , Guo Zhaobiao , Tan Yafang , Huang Xinxiang , Zhou Dongsheng , Yang Ruifu
Published: February 2011

Background

The osmotic regulator OmpR in Escherichia coli regulates differentially the expression of major porin proteins OmpF and OmpC. In Yersinia enterocolitica and Y. pseudotuberculosis, OmpR is required for both virulence and survival within macrophages. However, the phenotypic and regulatory roles of OmpR in Y. pestis are not yet fully understood.

Results

Y. pestis OmpR is involved in building resistance against phagocytosis and controls the adaptation to various stressful conditions met in macrophages. The ompR mutation likely did not affect the virulence of Y. pestis strain 201 that was a human-avirulent enzootic strain. The microarray-based comparative transcriptome analysis disclosed a set of 224 genes whose expressions were affected by the ompR mutation, indicating the global regulatory role of OmpR in Y. pestis. Real-time RT-PCR or lacZ fusion reporter assay further validated 16 OmpR-dependent genes, for which OmpR consensus-like sequences were found within their upstream DNA regions. ompC, F, X, and R were up-regulated dramatically with the increase of medium osmolarity, which was mediated by OmpR occupying the target promoter regions in a tandem manner.

Conclusion

OmpR contributes to the resistance against phagocytosis or survival within macrophages, which is conserved in the pathogenic yersiniae. Y. pestis OmpR regulates ompC, F, X, and R directly through OmpR-promoter DNA association. There is an inducible expressions of the pore-forming proteins OmpF, C, and × at high osmolarity in Y. pestis, in contrast to the reciprocal regulation of them in E. coli. The main difference is that ompF expression is not repressed at high osmolarity in Y. pestis, which is likely due to the absence of a promoter-distal OmpR-binding site for ompF.
Regulatory effects of cAMP receptor protein (CRP) on porin genes and its own gene in Yersinia pestis
Authors: Gao He , Zhang Yiquan , Yang Lin , Liu Xia , Guo Zhaobiao , Tan Yafang , Han Yanping , Huang Xinxiang , Zhou Dongsheng , Yang Ruifu
Published: February 2011

Background

The cAMP receptor protein (CRP) is a global bacterial regulator that controls many target genes. The CRP-cAMP complex regulates the ompR-envZ operon in E. coli directly, involving both positive and negative regulations of multiple target promoters; further, it controls the production of porins indirectly through its direct action on ompR-envZ. Auto-regulation of CRP has also been established in E. coli. However, the regulation of porin genes and its own gene by CRP remains unclear in Y. pestis.

Results

Y. pestis employs a distinct mechanism indicating that CRP has no regulatory effect on the ompR-envZ operon; however, it stimulates ompC and ompF directly, while repressing ompX. No transcriptional regulatory association between CRP and its own gene can be detected in Y. pestis, which is also in contrast to the fact that CRP acts as both repressor and activator for its own gene in E. coli. It is likely that Y. pestis OmpR and CRP respectively sense different signals (medium osmolarity, and cellular cAMP levels) to regulate porin genes independently.

Conclusion

Although the CRP of Y. pestis shows a very high homology to that of E. coli, and the consensus DNA sequence recognized by CRP is shared by the two bacteria, the Y. pestis CRP can recognize the promoters of ompC, F, and X directly rather than that of its own gene, which is different from the relevant regulatory circuit of E. coli. Data presented here indicate a remarkable remodeling of the CRP-mediated regulation of porin genes and of its own one between these two bacteria.
Hyperbaric oxygen upregulates cochlear constitutive nitric oxide synthase
Authors: Lin Chia-Der , Wei I-Hua , Lai Chih-Ho , Hsia Te-Chun , Kao Ming-Ching , Tsai Ming-Hsui , Wu Ching-Hsiang , Tsai Mang-Hung
Published: February 2011

Background

Hyperbaric oxygen therapy (HBOT) is a known adjuvant for treating ischemia-related inner ear diseases. Controversies still exist in the role of HBOT in cochlear diseases. Few studies to date have investigated the cellular changes that occur in inner ears after HBOT. Nitric oxide, which is synthesized by nitric oxide synthase (NOS), is an important signaling molecule in cochlear physiology and pathology. Here we investigated the effects of hyperbaric oxygen on eardrum morphology, cochlear function and expression of NOS isoforms in cochlear substructures after repetitive HBOT in guinea pigs.

Results

Minor changes in the eardrum were observed after repetitive HBOT, which did not result in a significant hearing threshold shift by tone burst auditory brainstem responses. A differential effect of HBOT on the expression of NOS isoforms was identified. Upregulation of constitutive NOS (nNOS and eNOS) was found in the substructures of the cochlea after HBOT, but inducible NOS was not found in normal or HBOT animals, as shown by immunohistochemistry. There was no obvious DNA fragmentation present in this HBOT animal model.

Conclusions

The present evidence indicates that the customary HBOT protocol may increase constitutive NOS expression but such upregulation did not cause cell death in the treated cochlea. The cochlear morphology and auditory function are consequently not changed through the protocol.
Macromolecular composition of phloem exudate from white lupin (Lupinus albusL.)
Authors: Rodriguez-Medina Caren , Atkins Craig A , Mann Anthea J , Jordan Megan E , Smith Penelope MC
Published: February 2011

Background

Members of the legume genusLupinusexude phloem 'spontaneously' from incisions made to the vasculature. This feature was exploited to document macromolecules present in exudate of white lupin (Lupinus albus[L.]cvKiev mutant), in particular to identify proteins and RNA molecules, including microRNA (miRNA).

Results

Proteomic analysis tentatively identified 86 proteins from 130 spots collected from 2D gels analysed by partial amino acid sequence determination using MS/MS. Analysis of a cDNA library constructed from exudate identified 609 unique transcripts. Both proteins and transcripts were classified into functional groups. The largest group of proteins comprised those involved in metabolism (24%), followed by protein modification/turnover (9%), redox regulation (8%), cell structural components (6%), stress and defence response (6%) with fewer in other groups. More prominent proteins were cyclophilin, ubiquitin, a glycine-rich RNA-binding protein, a group of proteins that comprise a glutathione/ascorbate-based mechanism to scavenge oxygen radicals, enzymes of glycolysis and other metabolism including methionine and ethylene synthesis. Potential signalling macromolecules such as transcripts encoding proteins mediating calcium level and the Flowering locus T (FT) protein were also identified. From around 330 small RNA clones (18-25 nt) 12 were identified as probable miRNAs by homology with those from other species. miRNA composition of exudate varied with site of collection (e.g. upward versus downward translocation streams) and nutrition (e.g. phosphorus level).

Conclusions

This is the first inventory of macromolecule composition of phloem exudate from a species in the Fabaceae, providing a basis to identify systemic signalling macromolecules with potential roles in regulating development, growth and stress response of legumes.
TCF7L2 and therapeutic response to sulfonylureas in patients with type 2 diabetes
Authors: Holstein Andreas , Hahn Michael , Körner Antje , Stumvoll Michael , Kovacs Peter
Published: February 2011

Background

Variants in the TCF7L2 have been shown to be associated with an increased risk for type 2 diabetes (T2D). Since the association with diabetes could be explained by effects on insulin secretion, we investigated whether patients with diabetes risk alleles at rs7903146 might have an altered hypoglycaemic response to sulfonylureas (SUs).

Methods

We recruited 189 patients with T2D being treated with SUs and determined the rs7903146 diabetes risk genotype. We used a logistic regression with secondary SU failure defined as an A1C ≥7.0% after 6 months of SU treatment.

Results

In univariate regression analyses, TCF7L2 genotype was the only predictor of SU treatment failure. The rs7903146 T allele was significantly more frequent in the group of patients who failed to respond to SU (36%) than in the control group (26%) [P = 0.046; odds ratio (OR): 1.57 (1.01-2.45) in an additive mode of inheritance].

Conclusions

Our data suggest that patients with diabetes risk alleles in TCF7L2 have an altered hypoglycaemic response to SUs resulting in earlier secondary failure.
Clinical presentation, histology, and prognoses of malignant melanoma in ethnic Chinese: A study of 522 consecutive cases
Authors: Chi Zhihong , Li Siming , Sheng Xinan , Si Lu , Cui Chuanliang , Han Mei , Guo Jun
Published: February 2011

Background

Malignant melanoma is a rare disease in Asia, and knowledge on its characteristics and clinical outcome in Asian patients is limited. The purpose of this observational study was to determine the clinical presentation and outcome of patients with melanoma in China.

Methods

A database was prospectively established for the purpose of this analysis. The elements of the database included basic demographic data of patients and prognosticators previously reported in literature, as well as follow-up data including clinical outcome after treatment. Medical record of all patients with pathologically diagnosed malignant melanoma consulted in our center since 2006 were retrieved and reviewed. No patient was excluded in this study. Statistical analyses including survival and multivariate analyses of factors associated with survival were respectively performed by Kaplan-Meier method and Cox proportional hazard model.

Results

A total of 522 consecutive and nonselected cases were evaluated. There were 218 cases (41.8%) of acral lentiginous melanoma (ALM), 118 (22.6%) of mucosal melanoma (MCM), 103 (19.7%) of nodular melanoma (NM), 33 (6.3%) of superficial spreading melanoma (SSM), and others were Lentigo maligna melanoma or unclassifiable disease. The proportion of patients with clinical stage I, II, III, and IV diseases were 6.1%, 55.9%, 25.1%, and 12.8%, respectively. Among the 357 cases of cutaneous melanoma, 234 patients (65.5%) had ulceration.

The 5-year overall survival rate of all 522 patients was 41.6%, and the median survival time was 3.92 years (95% CI, 3.282 to 4.558). Five-year survival rates of patients with stage I, II, III, and IV diseases were 94.1%, 44.0%, 38.4% and 4.6% respectively (P < 0.001). Multivariate analysis revealed that clinical stage and the ulceration were two significant prognosticators for OS. In addition, extent of surgery and use of adjuvant therapy were significant prognosticators for DFS in patients with non-metastatic disease after definitive treatment. Pathological subtype was not a significant prognostic factor to predict wither OS or DFS.

Conclusions

Prognoses of patients with malignant melanoma diagnosed in China were suboptimal, and most patients were diagnosed with locally advanced disease (i.e., stage II or above). ALM and MCM are the two most commonly diagnosed pathological subtypes. Clinical staging and presence of ulceration was significantly associated with clinical outcome in terms of OS, while treatment strategy including extent of surgery and use of adjuvant therapy were significant predictors of DFS.
Overexpression of GPR39 contributes to malignant development of human esophageal squamous cell carcinoma
Authors: Xie Fajun , Liu Haibo , Zhu Ying-Hui , Qin Yan-Ru , Dai Yongdong , Zeng Tingting , Chen Leilei , Nie Changjun , Tang Hong , Li Yan , Fu Li , Guan Xin-Yuan
Published: February 2011

Background

By using cDNA microarray analysis, we identified a G protein-coupled receptor, GPR39, that is significantly up-regulated in ESCC. The aim of this study is to investigate the role of GPR39 in human esophageal cancer development, and to examine the prevalence and clinical significance of GPR39 overexpression in ESCC.

Methods

The mRNA expression level of GPR39 was analyzed in 9 ESCC cell lines and 50 primary ESCC tumors using semi-quantitative RT-PCR. Immunohistochemistry was used to assess GPR39 protein expression in tissue arrays containing 300 primary ESCC cases. In vitro and in vivo studies were done to elucidate the tumorigenic role of GPR39 in ESCC cells.

Results

We found that GPR39 was frequently overexpressed in primary ESCCs in both mRNA level (27/50, 54%) and protein level (121/207, 58.5%), which was significantly associated with the lymph node metastasis and advanced TNM stage (P < 0.01). Functional studies showed that GPR39 has a strong tumorigenic ability. Introduction of GPR39 gene into ESCC cell line KYSE30 could promote cell proliferation, increase foci formation, colony formation in soft agar, and tumor formation in nude mice. The mechanism by which amplified GPR39 induces tumorigenesis was associated with its role in promoting G1/S transition via up-regulation of cyclin D1 and CDK6. Further study found GPR39 could enhance cell motility and invasiveness by inducing EMT and remodeling cytoskeleton. Moreover, depletion of endogenous GPR39 by siRNA could effectively decrease the oncogenicity of ESCC cells.

Conclusions

The present study suggests that GPR39 plays an important tumorigenic role in the development and progression of ESCC.
Alexithymia and emotional regulation: A cluster analytical approach
Authors: Chen Jie , Xu Ting , Jing Jin , Chan Raymond CK
Published: February 2011

Background

Alexithymia has been a familiar conception of psychosomatic phenomenon. The aim of this study was to investigate whether there were subtypes of alexithymia associating with different traits of emotional expression and regulation among a group of healthy college students.

Methods

1788 healthy college students were administered with the Chinese version of the 20-item Toronto Alexithymia Scale (TAS-20) and another set of questionnaires assessing emotion status and regulation. A hierarchical cluster analysis was conducted on the three factor scores of the TAS-20. The cluster solution was cross-validated by the corresponding emotional regulation.

Results

The results indicated there were four subtypes of alexithymia, namely extrovert-high alexithymia (EHA), general-high alexithymia (GHA), introvert-high alexithymia (IHA) and non-alexithymia (NA). The GHA was characterized by general high scores on all three factors, the IHA was characterized by high scores on difficulty identifying feelings and difficulty describing feelings but low score on externally oriented cognitive style of thinking, the EHA was characterized by high score on externally oriented cognitive style of thinking but normal score on the others, and the NA got low score on all factors. The GHA and IHA were dominant by suppressive character of emotional regulation and expression with worse emotion status as compared to the EHA and NA.

Conclusions

The current findings suggest there were four subtypes of alexithymia characterized by different emotional regulation manifestations.
Testing the effectiveness of a mindfulness-based intervention to reduce emotional distress in outpatients with diabetes (DiaMind): design of a randomized controlled trial
Authors: van Son Jenny , Nyklíček Ivan , Pop Victor JM , Pouwer François
Published: February 2011

Background

Approximately 20-40% of outpatients with diabetes experience elevated levels of emotional distress, varying from disease-specific distress to general symptoms of anxiety and depression. The patient's emotional well-being is related to other unfavorable outcomes, like reduced quality of life, sub-optimal self-care, impaired glycemic control, higher risk of complications, and increased mortality rates. The purpose of this study is to test the effectiveness of a new diabetes-specific, mindfulness-based psychological intervention. First, with regard to reducing emotional distress; second, with respect to improving quality of life, dispositional mindfulness, and self-esteem of patients with diabetes; third, with regard to self-care and clinical outcomes; finally, a potential effect modification by clinical and personality characteristics will be explored.

Methods/Design

The Diabetes and Mindfulness study (DiaMind) is a randomized controlled trial. Patients with diabetes with low levels of emotional well-being will be recruited from outpatient diabetes clinics. Eligible patients will be randomized to an intervention group or a wait-list control group. The intervention group will receive the mindfulness program immediately, while the control group will receive the program eight months later. The primary outcome is emotional distress (anxiety, stress, depressive symptoms), for which data will be collected at baseline, four weeks, post intervention, and after six months follow-up. In addition, self-report data will be collected on quality of life, dispositional mindfulness, self-esteem, self-care, and personality, while complications and glycemic control will be assessed from medical files and blood pressure will be measured. Group differences will be analyzed with repeated measures analysis of covariance.

The study is supported by grants from the Dutch Diabetes Research Foundation and Tilburg University and has been approved by a medical ethics committee.

Discussion

It is hypothesized that emotional well-being, quality of life, dispositional mindfulness, self-esteem, self-care, and blood pressure will improve significantly more in the mindfulness group compared to the control group. Results of this study can contribute to a better care for patients with diabetes with lowered levels of emotional well-being. It is expected that the first results will become available in 2012.

Trial registration

Dutch Trial Register NTR2145.
Valvular involvement in ANCA-associated systemic vasculitis: a case report and literature review
Authors: Lacoste Chloé , Mansencal Nicolas , m'rad Mona Ben , Goulon-Goeau Catherine , Cohen Pascal , Guillevin Loïc , Hanslik Thomas
Published: February 2011

Background

Antineutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitides have a variety of presentations, but cardiac valvular involvement is rarely diagnosed and its management is not established.

Case presentation

We report the case of a 44 year old man who presented with an ANCA-associated systemic vasculitis and aortic regurgitation of unusual mechanism. Transthoracic and transesophageal echocardiography disclosed septal hypertrophy preventing a complete closure of the aortic valve and thus responsible for a massive aortic regurgitation. After 4 months of immunosuppressive therapy, the valve lesion did not subside and the patient had to undergo aortic valve replacement. This report also reviews the 20 cases of systemic ANCA-associated vasculitis with endocardial valvular involvement previously reported in the English language medical literature.

Conclusions

Valvular involvement in ANCA-associated systemic vasculitides is rarely reported. Most of these lesions are due to Wegener's granulomatosis and half are present when the diagnosis of vasculitis is made. The valvular lesion is usually isolated, aortic regurgitation being the most frequent type, and often requires valve replacement in the months that follow it's discovery.
Evaluation of transduction efficiency in macrophage colony-stimulating factor differentiated human macrophages using HIV-1 based lentiviral vectors
Authors: Leyva Francisco J , Anzinger Joshua J , McCoy J Philip , Kruth Howard S
Published: February 2011

Background

Monocyte-derived macrophages contribute to atherosclerotic plaque formation. Therefore, manipulating macrophage function could have significant therapeutic value. The objective of this study was to determine transduction efficiency of two HIV-based lentiviral vector configurations as delivery systems for the transduction of primary human blood monocyte-derived macrophages.

Results

Human blood monocytes were transduced using two VSV-G pseudotyped HIV-1 based lentiviral vectors containing EGFP expression driven by either native HIV-LTR (VRX494) or EF1α promoters (VRX1090). Lentiviral vectors were added to cultured macrophages at different times and multiplicities of infection (MOI). Transduction efficiency was assessed using fluorescence microscopy and flow cytometry. Macrophages transduced between 2 and 120 hours after culturing showed the highest transduction efficiency at 2-hours transduction time. Subsequently, cells were transduced 2 hours after culturing at various vector concentrations (MOIs of 5, 10, 25 and 50) to determine the amount of lentiviral vector particles required to maximally transduce human monocyte-derived macrophages. On day 7, all transduced cultures showed EGFP-positive cells by microscopy. Flow cytometric analysis showed with all MOIs a peak shift corresponding to the presence of EGFP-positive cells. For VRX494, transduction efficiency was maximal at an MOI of 25 to 50 and ranged between 58 and 67%. For VRX1090, transduction efficiency was maximal at an MOI of 10 and ranged between 80 and 90%. Thus, transductions performed with VRX1090 showed a higher number of EGFP-positive cells than VRX494.

Conclusions

This report shows that VSV-G pseudotyped HIV-based lentiviral vectors can efficiently transduce human blood monocyte-derived macrophages early during differentiation using low particle numbers that do not interfere with differentiation of monocytes into macrophages.
Association of glycemic variability and the presence and severity of coronary artery disease in patients with type 2 diabetes
Authors: Su Gong , Mi Shuhua , Tao Hong , Li Zhao , Yang Hongxia , Zheng Hong , Zhou Yun , Ma Changsheng
Published: February 2011

Background

Glucose variability is one of components of the dysglycemia in diabetes and may play an important role in development of diabetic vascular complications. The objective of this study was to assess the relationship between glycemic variability determined by a continuous glucose monitoring (CGM) system and the presence and severity of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM).

Methods

In 344 T2DM patients with chest pain, coronary angiography revealed CAD (coronary stenosis ≥ 50% luminal diameter narrowing) in 252 patients and 92 patients without CAD. Gensini score was used to assess the severity of CAD. All participants' CGM parameters and biochemical characteristics were measured at baseline.

Results

Diabetic patients with CAD were older, and more were male and cigarette smokers compared with the controls. Levels of the mean amplitude of glycemic excursions (MAGE) (3.7 ± 1.4 mmol/L vs. 3.2 ± 1.2 mmol/L, p < 0.001), postprandial glucose excursion (PPGE) (3.9 ± 1.6 mmol/L vs. 3.6 ± 1.4 mmol/L, p = 0.036), serum high-sensitive C-reactive protein (hs-CRP) (10.7 ± 12.4 mg/L vs. 5.8 ± 6.7 mg/L, p < 0.001) and creatinine (Cr) (87 ± 23 mmol/L vs. 77 ± 14 mmol/L, p < 0.001) were significantly higher in patients with CAD than in patients without CAD. Gensini score closely correlated with age, MAGE, PPGE, hemoglobin A1c(HbA1c), hs-CRP and total cholesterol (TC). Multivariate analysis indicated that age (p < 0.001), MAGE (p < 0.001), serum levels of HbA1c(p = 0.022) and hs-CRP (p = 0.005) were independent determinants for Gensini score. Logistic regression analysis revealed that MAGE ≥ 3.4 mmol/L was an independent predictor for CAD. The area under the receiver-operating characteristic curve for MAGE (0.618, p = 0.001) was superior to that for HbA1c(0.554, p = 0.129).

Conclusions

The intraday glycemic variability is associated with the presence and severity of CAD in patients with T2DM. Effects of glycemic excursions on vascular complications should not be neglected in diabetes.
Citrus flavonoids repress the mRNA for stearoyl-CoA desaturase, a key enzyme in lipid synthesis and obesity control, in rat primary hepatocytes
Authors: Nichols LaNita A , Jackson Daniel E , Manthey John A , Shukla Shivendra D , Holland Lené J
Published: February 2011

Citrus flavonoids have been shown to decrease plasma lipid levels, improve glucose tolerance, and attenuate obesity. One possible mechanism underlying these physiological effects is reduction of hepatic levels of the mRNA for stearoyl-CoA desaturase-1 (SCD1), since repression of this enzyme reduces hyperlipidemia and adiposity. Here, we show that citrus flavonoids of two structural classes reduce SCD1 mRNA concentrations in a dose-dependent manner in rat primary hepatocytes. This is the first demonstration of repression of SCD1 by citrus flavonoids, either in vivo or in cultured cells. Furthermore, it is the first use of freshly-isolated hepatocytes from any animal to examine citrus flavonoid action at the mRNA level. This study demonstrates that regulation of SCD1 gene expression may play a role in control of obesity by citrus flavonoids and that rat primary hepatocytes are a physiologically-relevant model system for analyzing the molecular mechanisms of flavonoid action in the liver.
Spin effects in InAs self-assembled quantum dots
Authors: dos Santos Ednilson C , Gobato Yara Galvão , Brasil Maria JSP , Taylor David A , Henini Mohamed
Published: February 2011

We have studied the polarized resolved photoluminescence in an n-type resonant tunneling diode (RTD) of GaAs/AlGaAs which incorporates a layer of InAs self-assembled quantum dots (QDs) in the center of a GaAs quantum well (QW). We have observed that the QD circular polarization degree depends on applied voltage and light intensity. Our results are explained in terms of the tunneling of minority carriers into the QW, carrier capture by InAs QDs and bias-controlled density of holes in the QW.
Quasi-radial growth of metal tube on si nanowires template
Authors: Huang Zhipeng , Liu Lifeng , Geyer Nadine
Published: February 2011

It is reported in this article that Si nanowires can be employed as a positive template for the controllable electrochemical deposition of noble metal tube. The deposited tube exhibits good crystallinity. Scanning electron microscope and transmission electron microscope characterizations are conducted to reveal the growth process of metal tube, showing that the metal tube grows quasi-radially on the wall of Si nanowire. The quasi-radial growth of metal enables the fabrication of thickness-defined metal tube via changing deposition time. Inner-diameter-defined metal tube is achieved by choosing Si nanowires with desired diameter as a template. Metal tubes with inner diameters ranging from 1 μm to sub-50 nm are fabricated.
Study of the vertical transport in p-doped superlattices based on group III-V semiconductors
Authors: dos Santos Osmar FP , Rodrigues Sara CP , Sipahi Guilherme M , Scolfaro Luísa MR , da Silva Eronides F
Published: February 2011

The electrical conductivity σ has been calculated for p-doped GaAs/Al0.3Ga0.7As and cubic GaN/Al0.3Ga0.7N thin superlattices (SLs). The calculations are done within a self-consistent approach to the

k
→

⋅

p
→

theory by means of a full six-band Luttinger-Kohn Hamiltonian, together with the Poisson equation in a plane wave representation, including exchange correlation effects within the local density approximation. It was also assumed that transport in the SL occurs through extended minibands states for each carrier, and the conductivity is calculated at zero temperature and in low-field ohmic limits by the quasi-chemical Boltzmann kinetic equation. It was shown that the particular minibands structure of the p-doped SLs leads to a plateau-like behavior in the conductivity as a function of the donor concentration and/or the Fermi level energy. In addition, it is shown that the Coulomb and exchange-correlation effects play an important role in these systems, since they determine the bending potential.
Expression and characterization of recombinant VP19c protein and N-terminal from duck enteritis virus
Authors: Xiang Jun , Zhang Shunchuan , Cheng Anchun , Wang Mingshu , Chang Hua , Shen Chanjuan , Zhu Dekang , Jia Renyong , Luo Qihui , Chen Zhengli , Chen Xiaoyue
Published: February 2011

Background

Previous studies have indicated that the VP19c protein and its homology play similar roles in capsid assembly of all Alphaherpesvirus subfamily. However, there is no report on the VP19c protein of duck enteritis virus (DEV). In this study, we expressed the DEV VP19c protein and presented its antigenic properties. Moreover, we developed polyclonal antibody against the VP19c protein and characterized it.

Methods

A recombinant VP19c (rVP19c) and N-terminal were expressed in Escherichia coli (E.coli) and purified by Ni2+-affinity chromatography. The antigenic properties of the recombinant protein were determined by Western blot and indirect enzyme-linked immunosorbent assay (ELISA). Furthermore, the polyclonal antibodies against the purified recombinant proteins were produced and the titer of polyclonal antibody was determined by ELISA analysis. Finally, the antibody was used to recognize the VP19c in the cells infected with DEV in the immunofluorescence assay.

Results

The N-terminally His-tagged rVP19c and rVP19c(N) were produced as inclusion bodies in E. coli strain BL21 (DE3) with molecular weight of about 66 and 46 kDa. Then the proteins were purified to reach the level of homogeneity. Western blot and ELISA analysis that the rVP19c seems to be structurally and antigenically very similar to native VP19c and the N-terminus of VP19c may contain most antigenic linear-epitopes. Furthermore, ELISA analysis demonstrated that the titer of polyclonal antibody was approximately 1:12800, and in the immunofluorescence assay, the antibody was able to recognize the VP19c in the cells infected with DEV.

Conclusions

To our knowledge, this was the first report on basic properties of DEV VP19c protein. In the present study, we obtained a high-level expression of the recombinant VP19c protein as well as high titers of rabbit polyclonal antibody against to VP19c protein. The anti-rVP19c serum was able to detect the VP19c protein in DEV infected cells and the VP19c protein targeted to the nucleus as distinct punctate speckles. This specific polyclonal antibody provides a good tool for further studying structural and functional characterization of DEV VP19c.
Chemical restraint in routine clinical practice: a report from a general hospital psychiatric ward in Greece
Authors: Bilanakis Nikolaos , Papamichael Georgios , Peritogiannis Vaios
Published: February 2011

Background

There is a dearth of studies regarding chemical restraint in routine clinical psychiatric practice. There may be wide variations between different settings and countries.

Methods

A retrospective study on chemical restraint was performed in the 11-bed psychiatric ward of the General Hospital of Arta, in northwestern Greece. All admissions over a 2-year-period (from March 2008 to March 2010) were examined.

Results

Chemical restraint was applied in 33 cases (10.5% of total admissions). From a total of 82 injections, 22 involved a benzodiazepine and/or levomepromazine, whereas 60 injections involved an antipsychotic agent, almost exclusively haloperidol (96.7% of cases), usually in combination with a benzodiazepine (61.7% of cases). In 36.4% of cases the patient was further subjected to restraint or seclusion.

Conclusions

In our unit, clinicians prefer the combined antipsychotic/benzodiazepine regimen for the management of patients' acute agitation and violent behaviour. Conventional antipsychotics are administrated almost exclusively and in a significant proportion of cases further coercive measures are applied. Studies on the practice of chemical restraint should be regularly performed in clinical settings.
Public crack cocaine smoking and willingness to use a supervised inhalation facility: implications for street disorder
Authors: DeBeck Kora , Buxton Jane , Kerr Thomas , Qi Jiezhi , Montaner Julio , Wood Evan
Published: February 2011

Background

The health risks of crack cocaine smoking in public settings have not been well described. We sought to identify factors associated with public crack smoking, and assess the potential for a supervised inhalation facility to reduce engagement in this behavior, in a setting planning to evaluate a medically supervised crack cocaine smoking facility.

Methods

Data for this study were derived from a Canadian prospective cohort of injection drug users. Using multivariate logistic regression we identified factors associated with smoking crack cocaine in public areas. Among public crack smokers we then identified factors associated with willingness to use a supervised inhalation facility.

Results

Among our sample of 623 people who reported crack smoking, 61% reported recently using in public locations. In multivariate analysis, factors independently associated with public crack smoking included: daily crack cocaine smoking; daily heroin injection; having encounters with police; and engaging in drug dealing. In sub analysis, 71% of public crack smokers reported willingness to use a supervised inhalation facility. Factors independently associated with willingness include: female gender, engaging in risky pipe sharing; and having encounters with police.

Conclusion

We found a high prevalence of public crack smoking locally, and this behavior was independently associated with encounters with police. However, a majority of public crack smokers reported being willing to use a supervised inhalation facility, and individuals who had recent encounters with police were more likely to report willingness. These findings suggest that supervised inhalation facilities offer potential to reduce street-disorder and reduce encounters with police.
Sensory and motor neuronopathy in a patient with the A382P TDP-43 mutation
Authors: Camdessanché Jean-Philippe , Belzil Véronique V , Jousserand Guillemette , Rouleau Guy A , Créac'h Christelle , Convers Philippe , Antoine Jean-Christophe
Published: February 2011

Patients with TARDBP mutations have so far been classified as ALS, sometimes with frontal lobe dysfunction. A 66-year-old patient progressively developed a severe sensory disorder, followed by a motor disorder, which evolved over nine years. Symptoms started in the left hand and slowly involved the four limbs. Investigations were consistent with a mixed sensory and motor neuronopathy. A heterozygous change from an alanine to a proline at amino acid 382 was identified in exon 6 of the TARDPB gene (p.A382P). This case expands the phenotypic spectrum associated with mutations in the TARDBP gene and shows that sensory neurons can be severely damaged early in the course of the disease, following a propagating process, with an orderly progression from a focal starting point. A combination of severe sensory and motor neuronopathy is rarely encountered in clinical practice. The possibility of an A382P TDP-43 mutation should be considered in patients with such an association.
Predicting the points of interaction of small molecules in the NF-κB pathway
Authors: Patel Yogendra , Heyward Catherine A , White Michael RH , Kell Douglas B
Published: February 2011

Background

The similarity property principle has been used extensively in drug discovery to identify small compounds that interact with specific drug targets. Here we show it can be applied to identify the interactions of small molecules within the NF-κB signalling pathway.

Results

Clusters that contain compounds with a predominant interaction within the pathway were created, which were then used to predict the interaction of compounds not included in the clustering analysis.

Conclusions

The technique successfully predicted the points of interactions of compounds that are known to interact with the NF-κB pathway. The method was also shown to be successful when compounds for which the interaction points were unknown were included in the clustering analysis.
Integrative analysis of next generation sequencing for small non-coding RNAs and transcriptional regulation in Myelodysplastic Syndromes
Authors: Beck Dominik , Ayers Steve , Wen Jianguo , Brandl Miriam B , Pham Tuan D , Webb Paul , Chang Chung-Che , Zhou Xiaobo
Published: February 2011

Background

Myelodysplastic Syndromes (MDSS) are pre-leukemic disorders with increasing incident rates worldwide, but very limited treatment options. Little is known about small regulatory RNAs and how they contribute to pathogenesis, progression and transcriptome changes in MDS.

Methods

Patients' primary marrow cells were screened for short RNAs (RNA-seq) using next generation sequencing. Exon arrays from the same cells were used to profile gene expression and additional measures on 98 patients obtained. Integrative bioinformatics algorithms were proposed, and pathway and ontology analysis performed.

Results

In low-grade MDS, observations implied extensive post-transcriptional regulation via microRNAs (miRNA) and the recently discovered Piwi interacting RNAs (piRNA). Large expression differences were found for MDS-associated and novel miRNAs, including 48 sequences matching to miRNA star (miRNA*) motifs. The detected species were predicted to regulate disease stage specific molecular functions and pathways, including apoptosis and response to DNA damage. In high-grade MDS, results suggested extensive post-translation editing via transfer RNAs (tRNAs), providing a potential link for reduced apoptosis, a hallmark for this disease stage. Bioinformatics analysis confirmed important regulatory roles for MDS linked miRNAs and TFs, and strengthened the biological significance of miRNA*. The "RNA polymerase II promoters" were identified as the tightest controlled biological function. We suggest their control by a miRNA dominated feedback loop, which might be linked to the dramatically different miRNA amounts seen between low and high-grade MDS.

Discussion

The presented results provide novel findings that build a basis of further investigations of diagnostic biomarkers, targeted therapies and studies on MDS pathogenesis.
Effects of ulinastatin and docataxel on breast tumor growth and expression of IL-6, IL-8, and TNF-α
Authors: Zhao Xiaoliang , Sun Xin , Gao Feng , Luo Jie , Sun Zhijun
Published: February 2011

Objective

This study investigated the effects of Ulinastatin (UTI) and docataxel (Taxotere, TAX) on tumor growth and expression of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) in breast cancer.

Methods

MDA-MB-231 human breast carcinoma cells were cultured in vitro and injected into nude mice to establish breast tumor xenografts in vivo. Cultured cells and mice with tumors were randomly divided into four groups for treatment with TAX, UTI, and TAX+UTI. The effects of these drug treatments on cell proliferation and apoptosis was measured using the MTT assay and the Annexin V/propidium iodide (PI) double-staining method, respectively. IL-6, IL-8, and TNF-α expression levels were determined by measuring mRNA transcripts in cultured cells by RT-PCR and cytokine proteins in solid tumors using immunohistochemistry.

Results

UTI, TAX, and UTI+TAX inhibited the growth of MDA-MB-231 cells in vitro and tumors in vivo. These two drugs, particularly when used in combination, promote tumor cell apoptosis and down-regulate the expression IL-6, IL-8, and TNF-α cytokines.

Conclusion

Both UTI and TAX inhibited the growth of MDA-MB-231 breast carcinoma cells. UTI enhanced the inhibitory effect of TAX by a mechanism consistent with the down-regulated expression of IL-6, IL-8, and TNF-α.
Trends in detectable viral load by calendar year in the Australian HIV observational database
Authors: Law Matthew G , Woolley Ian , Templeton David J , Roth Norm , Chuah John , Mulhall Brian , Canavan Peter , McManus Hamish , Cooper David A , Petoumenos Kathy ,   the Australian HIV Observational Database (AHOD)
Published: February 2011

Background

Recent papers have suggested that expanded combination antiretroviral treatment (cART) through lower viral load may be a strategy to reduce HIV transmission at a population level. We assessed calendar trends in detectable viral load in patients recruited to the Australian HIV Observational Database who were receiving cART.

Methods

Patients were included in analyses if they had started cART (defined as three or more antiretrovirals) and had at least one viral load assessment after 1 January 1997. We analyzed detectable viral load (>400 copies/ml) in the first and second six months of each calendar year while receiving cART. Repeated measures logistic regression methods were used to account for within and between patient variability. Rates of detectable viral load were predicted allowing for patients lost to follow up.

Results

Analyses were based on 2439 patients and 31,339 viral load assessments between 1 January 1997 and 31 March 2009. Observed detectable viral load in patients receiving cART declined to 5.3% in the first half of 2009. Predicted detectable viral load based on multivariate models, allowing for patient loss to follow up, also declined over time, but at higher levels, to 13.8% in 2009.

Conclusions

Predicted detectable viral load in Australian HIV Observational Database patients receiving cART declined over calendar time, albeit at higher levels than observed. However, over this period, HIV diagnoses and estimated HIV incidence increased in Australia.
Validation of rheumatoid arthritis diagnoses in health care utilization data
Authors: Kim Seo Young , Servi Amber , Polinski Jennifer M , Mogun Helen , Weinblatt Michael E , Katz Jeffrey N , Solomon Daniel H
Published: February 2011

Introduction

Health care utilization databases have been increasingly used for studies of rheumatoid arthritis (RA). However, the accuracy of RA diagnoses in these data has been inconsistent.

Methods

Using medical records and a standardized abstraction form, we examined the positive predictive value (PPV) of several algorithms to define RA diagnosis using claims data: A) at least two visits coded for RA (ICD-9, 714); B) at least three visits coded for RA; and C) at least two visits to a rheumatologist for RA. We also calculated the PPVs for the subgroups identified by these algorithms combined with pharmacy claims data for at least one disease-modifying anti-rheumatic drug (DMARD) prescription.

Results

We invited 9,482 Medicare beneficiaries with pharmacy benefits in Pennsylvania to participate; 2% responded and consented for review of their medical records. There was no difference in characteristics between respondents and non-respondents. Using 'RA diagnosis per rheumatologists' as the gold standard, the PPVs were 55.7% for at least two claims coded for RA, 65.5% for at least three claims for RA, and 66.7% for at least two rheumatology claims for RA. The PPVs of these algorithms in patients with at least one DMARD prescription increased to 86.2%-88.9%. When fulfillment of 4 or more of the ACR RA criteria was used as the gold standard, the PPVs of the algorithms combined with at least one DMARD prescriptions were 55.6%-60.7%.

Conclusions

To accurately identify RA patients in health care utilization databases, algorithms that include both diagnosis codes and DMARD prescriptions are recommended.