bluuebunny/crossref_metadata_2025 huggingface dataset:
Indwelling double pigtail ureteral stent combined or not with surgery for feline ureterolithiasis: complications and outcome in 15 cases
Authors: Manassero Mathieu , Decambron Adeline , Viateau Véronique , Bedu Anne-Sophie , Vallefuoco Rosario , Benchekroun Ghita , Moissonnier Pierre , Maurey Christelle
Published: December 2013

Ureteral obstruction secondary to ureterolithiasis in cats is a challenging situation. Ureteral stenting has recently been introduced to prevent complications that often occurred after ureterotomy or other invasive surgeries. The purpose of this study is to describe the stenting technique and perioperative difficulties, as well as long-term outcome and complications with ureteral stenting in 12 cats with ureteroliths. Fifteen 2.5 Fr soft double pigtail multi-fenestrated ureteral stents were placed in an anterograde fashion under open surgical approaches and with fluoroscopic guidance in 12 cats. Nine cats received a unilateral stent and three received bilateral stents. Ureterotomy or ureteral resection and end-to-end anastomosis were performed in three and four cases, respectively. In six cats, papillotomy was performed to facilitate dilatator and stent placement. All cats recovered well from the surgical procedure, except one cat, which died during the anaesthesia recovery period. Postoperative complications included dysuria (three cases, diagnosed at 15 days, 1 month and 3 months, respectively), urinary tract infection (one case, 1 month after surgery), stent migration requiring stent replacement (one case, 19 months after surgery) and stent obstruction requiring stent removal (three cases with previously end-to-end anastomosis between 2 and 8 months after surgery). Nine cats (75%) were alive at a mean follow-up of 453 ± 194 (123–720) days. The median survival time was >415 days. Stent placement appeared to be a valuable and safe option for treating ureteral obstruction in cats. However, periodic and long-term monitoring of stents is warranted.
An analysis of blogs from medical students on “English Parallel” courses in Central and Eastern Europe
Authors: Mayberry John F
Published: December 2013

During the last 20 years, there has been a significant growth in the training of overseas students especially within the European Union. Informal discussions with past and present students revealed a marked reluctance to take part in interviews about the nature of “English Parallel” courses. Alternative sources of information include blogs and commentaries written on the internet by present and former students at these schools. Such blogs are relatively limited in number and of variable length. They have been written for a variety of reasons and range in content from commentaries on training to wider discussion of life in Central and Eastern Europe. Six blogs were identified from an internet search, and a qualitative approach was adopted for the analysis of text content. Their experience is assessed, and potential approaches to greater integration of training across Europe are considered.
The anatomy and function of Cleland’s ligaments
Authors: Zwanenburg R. L. , Werker P. M. N. , McGrouther D. A.
Published: December 2013

The cutaneous ligaments of the digits have been recognized by anatomists for several centuries, but the best known description is that of John Cleland. Subsequent varying descriptions of their morphology have resulted in the surgical community having an imprecise view of their structure and dynamic function. We micro-dissected 24 fresh frozen fingers to analyze the individual components of Cleland’s ligamentous system. Arising from the proximal interphalangeal (PIP) joint, proximal, and sometimes middle phalanx, we found strong ligaments that ran proximally (PIP-P) and distally (PIP-D). On each side of each finger there was a PIP-P ligament present, which passed obliquely from the lateral side of the proximal and sometimes middle phalanx towards its insertion into the skin at the level of the proximal phalanx. The distal (PIP-D) ligaments were found to pass obliquely distally on the radial and ulnar aspects of the digit towards cutaneous insertions around the middle phalanx. A similar arrangement exists more distally with fibres originating from the DIP joint and middle phalanx (the DIP-P pass obliquely proximally, and the DIP-D, distally). Each individual PIP ligament consisted of three different layers originating from fibres overlying the flexor tendon sheath, periosteum or joint capsule, and extensor expansion. Ligaments arising at the DIP joint had two layers equivalent to the anterior two layers of the proximal ligaments. Cleland’s ligaments act as skin anchors maintaining the skin in a fixed relationship to the underlying skeleton during motion and functional tasks. They also prevent the skin from ‘bagging’, protect the neurovascular bundle, and create a gliding path for the lateral slips of the extensor tendon.
Genetic architecture of resistance to Septoria tritici blotch in European wheat
Authors: Miedaner Thomas , Zhao Yusheng , Gowda Manje , Longin C Friedrich H , Korzun Viktor , Ebmeyer Erhard , Kazman Ebrahim , Reif Jochen C
Published: December 2013

Background

Septoria tritici blotch is an important leaf disease of European winter wheat. In our survey, we analyzed Septoria tritici blotch resistance in field trials with a large population of 1,055 elite hybrids and their 87 parental lines. Entries were fingerprinted with the 9 k SNP array. The accuracy of prediction of Septoria tritici blotch resistance achieved with different genome-wide mapping approaches was evaluated based on robust cross validation scenarios.

Results

Septoria tritici blotch disease severities were normally distributed, with genotypic variation being significantly (P < 0.01) larger than zero. The cross validation study revealed an absence of large effect QTL for additive and dominance effects. Application of genomic selection approaches particularly designed to tackle complex agronomic traits allowed to double the accuracy of prediction of Septoria tritici blotch resistance compared to calculation methods suited to detect QTL with large effects.

Conclusions

Our study revealed that Septoria tritici blotch resistance in European winter wheat is controlled by multiple loci with small effect size. This suggests that the currently achieved level of resistance in this collection is likely to be durable, as involvement of a high number of genes in a resistance trait reduces the risk of the resistance to be overcome by specific pathogen isolates or races.
Identification of new developmentally regulated genes involved in Streptomyces coelicolorsporulation
Authors: Salerno Paola , Persson Jessica , Bucca Giselda , Laing Emma , Ausmees Nora , Smith Colin P , Flärdh Klas
Published: December 2013

Background

The sporulation of aerial hyphae ofStreptomyces coelicoloris a complex developmental process. Only a limited number of the genes involved in this intriguing morphological differentiation programme are known, including some key regulatory genes. The aim of this study was to expand our knowledge of the gene repertoire involved inS. coelicolorsporulation.

Results

We report a DNA microarray-based investigation of developmentally controlled gene expression inS. coelicolor. By comparing global transcription patterns of the wild-type parent and two mutants lacking key regulators of aerial hyphal sporulation, we found a total of 114 genes that had significantly different expression in at least one of the two mutants compared to the wild-type during sporulation. AwhiAmutant showed the largest effects on gene expression, while only a few genes were specifically affected bywhiHmutation. Seven new sporulation loci were investigated in more detail with respect to expression patterns and mutant phenotypes. These includedSCO7449-7451that affect spore pigment biogenesis;SCO1773-1774that encode an L-alanine dehydrogenase and a regulator-like protein and are required for maturation of spores;SCO3857that encodes a protein highly similar to a nosiheptide resistance regulator and affects spore maturation; and four additional loci (SCO4421,SCO4157,SCO0934,SCO1195) that show developmental regulation but no overt mutant phenotype. Furthermore, we describe a new promoter-probe vector that takes advantage of the red fluorescent protein mCherry as a reporter of cell type-specific promoter activity.

Conclusion

Aerial hyphal sporulation inS. coelicoloris a technically challenging process for global transcriptomic investigations since it occurs only as a small fraction of the colony biomass and is not highly synchronized. Here we show that by comparing a wild-type to mutants lacking regulators that are specifically affecting processes in aerial hypha, it is possible to identify previously unknown genes with important roles in sporulation. The transcriptomic data reported here should also serve as a basis for identification of further developmentally important genes in future functional studies.
Proanthocyanidin synthesis in Theobroma cacao: genes encoding anthocyanidin synthase, anthocyanidin reductase, and leucoanthocyanidin reductase
Authors: Liu Yi , Shi Zi , Maximova Siela , Payne Mark J , Guiltinan Mark J
Published: December 2013

Background

The proanthocyanidins (PAs), a subgroup of flavonoids, accumulate to levels of approximately 10% total dry weight of cacao seeds. PAs have been associated with human health benefits and also play important roles in pest and disease defense throughout the plant.

Results

To dissect the genetic basis of PA biosynthetic pathway in cacao (Theobroma cacao), we have isolated three genes encoding key PA synthesis enzymes, anthocyanidin synthase (ANS), anthocyanidin reductase (ANR) and leucoanthocyanidin reductase (LAR). We measured the expression levels of TcANR, TcANS and TcLAR and PA content in cacao leaves, flowers, pod exocarp and seeds. In all tissues examined, all three genes were abundantly expressed and well correlated with PA accumulation levels, suggesting their active roles in PA synthesis. Overexpression of TcANR in an Arabidopsis ban mutant complemented the PA deficient phenotype in seeds and resulted in reduced anthocyanidin levels in hypocotyls. Overexpression of TcANS in tobacco resulted in increased content of both anthocyanidins and PAs in flower petals. Overexpression of TcANS in an Arabidopsis ldox mutant complemented its PA deficient phenotype in seeds. Recombinant TcLAR protein converted leucoanthocyanidin to catechin in vitro. Transgenic tobacco overexpressing TcLAR had decreased amounts of anthocyanidins and increased PAs. Overexpressing TcLAR in Arabidopsis ldox mutant also resulted in elevated synthesis of not only catechin but also epicatechin.

Conclusion

Our results confirm the in vivo function of cacao ANS and ANR predicted based on sequence homology to previously characterized enzymes from other species. In addition, our results provide a clear functional analysis of a LAR gene in vivo.
Glomerular tip adhesions predict the progression of IgA nephropathy
Authors: Maeda Kunihiro , Kikuchi Shogo , Miura Naoto , Suzuki Keisuke , Kitagawa Wataru , Morita Hiroyuki , Banno Shogo , Imai Hirokazu
Published: December 2013

Background

Focal segmental glomerulosclerosis-like lesions have been proposed to be predictive factors for IgA nephropathy. This single center, retrospective cohort study was designed to clarify which clinical and pathological factors are predictive of decreased estimated glomerular filtration rate (eGFR) at 5 and 10 years in IgA nephropathy patients.

Methods

Of the 229 patients with IgA nephropathy who were admitted to Aichi Medical University Hospital between 1986 and 2010, 57 were included in this study during the 5 to 10 years after renal biopsy. Clinical, laboratory, and pathological parameters were analyzed by multiple linear regression analysis with backward elimination to determine independent risk factors. After identifying such factors, we compared patients with and without each factor using the Student’s t test, Wilcoxon test, or Mann–Whitney U test.

Results

Four variables were identified as predictive factors for progression of IgA nephropathy: initial eGFR (p = 0.0002), glomerular tip adhesion (p = 0.004), global sclerosis (p = 0.019), and diastolic blood pressure (p = 0.024). The annual decrease in eGFR of patients with (n = 9) or without glomerular tip adhesions (n = 48) was 4.13 ± 3.58 and 1.49 ± 2.89 ml/min/1.73 m2, respectively (p = 0.015). Serum total cholesterol levels were 231 ± 45 mg/dl and 196 ± 42 mg/dl, respectively (two-sided p = 0.064; one-sided p = 0.032).

Conclusions

The presence of glomerular tip adhesions predicts the progression of IgA nephropathy. High levels of serum total cholesterol may affect glomerular tip adhesions.
A qualitative study on the breastfeeding experiences of first-time mothers in Vientiane, Lao PDR
Authors: Lee Hope Mei Hong , Durham Jo , Booth Jenny , Sychareun Vanphanom
Published: December 2013

Background

The benefits of breastfeeding are well-recognised. The majority of first-time mothers in the Lao People's Democratic Republic however do not follow WHO guidelines of exclusively breastfeeding for the first six months, and less than half breastfeed for two years. UNICEF identified lack of exclusive breastfeeding as the second highest risk factor for under 5 mortality in Lao PDR, closely following lack of skilled delivery care. This study explored the reasons and influences behind first-time mothers' breastfeeding practices, as well as the role of attitudes, beliefs and experiences in influencing those practices.

Methods

A qualitative research design was chosen for this exploratory study. Two districts in Vientiane were selected, and in each district four focus group discussions, two with six first-time mothers and two with health staff were undertaken. In addition, sixteen in-depth interviews with first-time mothers and seven individual key informants were conducted.

Results

Participants demonstrated positive attitudes towards breastfeeding and recognised its importance. Despite this, breastfeeding practices were suboptimal. Few exclusively breastfed for the first six months of the baby’s life and most of the first-time mothers included in the sample had stopped or planned to stop breastfeeding by the time the infant was 18 months of age. Work was named as one of the main reasons for less than ideal breastfeeding practices. Traditional beliefs and advice from health staff and the first-time mothers' own mothers, were important influences on breastfeeding practices. First-time mothers also cited experiencing tension when there were differences in advice they received from different people.

Conclusion

Overall, the mothers were well-informed on the benefits of breastfeeding, and displayed positive attitudes towards it. Nevertheless, few maintained optimal breastfeeding practices in the first two years of the infant’s life. Further effort needs to be directed at addressing knowledge and non-knowledge barriers to optimal breastfeeding practices. Of particular importance is working with employers, developing supportive employment policies, providing postnatal support and working with lay people and health professionals. Research is also needed to identify the optimal combination of interventions to promote good breastfeeding practices.
NCOA3 is a selective co-activator of estrogen receptor α-mediated transactivation of PLAC1 in MCF-7 breast cancer cells
Authors: Wagner Meike , Koslowski Michael , Paret Claudia , Schmidt Marcus , Türeci Özlem , Sahin Ugur
Published: December 2013

Background

Theplacenta-specific 1(PLAC1)gene encodes a membrane-associated protein which is selectively expressed in the placental syncytiotrophoblast and in murine fetal tissues during embryonic development. In contrast to its transcriptional repression in all other adult normal tissues, PLAC1 is frequently activated and highly expressed in a variety of human cancers, in particular breast cancer, where it associates with estrogen receptor α (ERα) positivity. In a previous study, we showed that ERα-signaling in breast cancer cells transactivatesPLAC1expression in a non-classical pathway. As the members of the p160/nuclear receptor co-activator (NCOA) family, NCOA1, NCOA2 and NCOA3 are known to be overexpressed in breast cancer and essentially involved in estrogen-mediated cancer cell proliferation we asked if these proteins are involved in the ERα-mediated transactivation ofPLAC1in breast cancer cells.

Methods

Applying quantitative real-time RT-PCR (qRT-PCR), Western Blot analysis and chromatin immunoprecipitation, we analyzed the involvement of NCOA1, NCOA2, NCOA3 in the ERα-mediated transactivation ofPLAC1in the breast cancer cell lines MCF-7 and SK-BR-3. RNAi-mediated silencing of NCOA3, qRT-PCR, Western blot analysis and ERα activation assays were used to examine the role of NCOA3 in the ERα-mediated regulation of PLAC1 in further detail. Transcript expression ofNCOA3andPLAC1in 48 human breast cancer samples was examined by qRT-PCR and statistical analysis was performed using Student’st-test.

Results

We detected selective recruitment of NCOA3 but not NCOA1 or NCOA2 to thePLAC1promoter only in ERα-positive MCF-7 cells but not in ERα-negative SK-BR-3 breast cancer cells. In addition, we demonstrate that silencing of NCOA3 results in a remarkable decrease of PLAC1 expression levels in MCF-7 cells which cannot be restored by treatment with estradiol (E2). Moreover, significant higher transcript levels ofPLAC1were found only in ERα-positive human breast cancer samples which also show aNCOA3overexpression.

Conclusions

In this study, we identified NCOA3 as a selective co-activator of ERα-mediated transactivation ofPLAC1in MCF-7 breast cancer cells. Our data introducePLAC1as novel target gene of NCOA3 in breast cancer, supporting the important role of both factors in breast cancer biology.
Clinical implication of ZEB-1 and E-cadherin expression in hepatocellular carcinoma (HCC)
Authors: Hashiguchi Motoyuki , Ueno Shinichi , Sakoda Masahiko , Iino Satoshi , Hiwatashi Kiyokazu , Minami Koji , Ando Kei , Mataki Yuko , Maemura Kosei , Shinchi Hiroyuki , Ishigami Sumiya , Natsugoe Shoji
Published: December 2013

Background

While recent research has shown that expression of ZEB-1 in a variety of tumors has a crucial impact on patient survival, there is little information regarding ZEB-1 expression in hepatocellular carcinoma (HCC). This study investigated the co-expression of ZEB-1 and E-cadherin in HCC by immunohistochemistry and evaluated its association with clinical factors, including patient prognosis.

Methods

A total of 108 patients with primary HCC treated by curative hepatectomy were enrolled. ZEB-1 expression was immunohistochemically categorized as positive if at least 1% cancer cells exhibited nuclear staining. E-cadherin expression was divided into preserved and reduced expression groups and correlations between ZEB-1 and E-cadherin expression and clinical factors were then evaluated.

Results

With respect to ZEB-1 expression, 23 patients were classified into the positive group and 85 into the negative group. Reduced E-cadherin expression was seen in 44 patients and preserved expression in the remaining 64 patients. ZEB-1 positivity was significantly associated with reduced expression of E-cadherin (p = 0.027). Moreover, significant associations were found between ZEB-1 expression and venous invasion and TNM stage. ZEB-1 positivity was associated with poorer prognosis (p = 0.025). Reduced E-cadherin expression was significantly associated with intrahepatic metastasis and poorer prognosis (p = 0.047). In particular, patients with both ZEB-1 positivity and reduced E-cadherin expression had a poorer prognosis (p = 0.005). Regardless of E-cadherin status, ZEB-1 was not a significant prognostic factor by multivariate analysis. There was no statistical difference in overall survival when E-cadherin expression was reduced in the ZEB-1 positive group (p = 0.24).

Conclusions

Positive ZEB-1 expression and loss of E-cadherin expression are correlated with poor prognosis in HCC patients and malignancy of ZEB-1 positive tumors involves EMT.
Trends and determinants of mortality in women of reproductive age in rural Guinea-Bissau, West Africa – a cohort study
Authors: Mane Maram , Fisker Ane B , Ravn Henrik , Aaby Peter , Rodrigues Amabelia
Published: December 2013

Background

There are few studies reporting mortality of women of reproductive age (WRA) in developing countries. The trend and patterns of their mortality may be important for documenting the health status of the population in general.

Methods

We used a prospective open cohort of women aged 12 to 49 years living in the Bandim Health Project’s rural Health and Demographic Surveillance System (HDSS) in 5 regions of Guinea-Bissau from 1996 to 2007. Information on in- and out-migration and deaths were collected through the HDSS routine procedures. We assessed the trends in mortality and the associated determinants using Cox regression models.

Results

We followed 27,185 WRA for 141,693 person-years-at-risk (PYO) among whom 9,093 moved out and 1,006 died. Overall standardized mortality rate was 759 per 100,000 PYO. WRA mortality did not decline, but three periods could be distinguished: a stable mortality between 1996–2000 followed by 14% increase in mortality [Hazard rate ratio (HRR) = 1.14; 95% confidence interval (CI): 0.98-1.32; p = 0.08] between 2001–2003, and then in the last period from 2004–2007 a 25% decline (HRR = 0.75; 95% CI: 0.64-0.87; p < 0.001) in relation to the first period. Compared with the years 1990–1996 mortality increased in the first two periods until 2003; only in the last period did mortality reach the same level as in 1990–1996 (HRR = 0.96; 95% CI: 0.82-1.13; p = 0.62). The level of mortality differed between regions. In the adjusted analysis the eastern regions Bafata (HRR = 1.79; 95% CI: 1.38-2.32; p < 0.001) and Gabu (HRR = 1.70; 95% CI: 1.28-2.26; p < 0.001) had significantly higher mortality, but the hazard rate did not differ by ethnic group. As expected the rate increased with increasing age.

Conclusions

Over the twelve-year period mortality of WRA did not decline. A stable mortality in the beginning was followed by an increase and then a return to the previous levels. Further monitoring of mortality is needed to identify the risk factors for the striking regional differences. Advantage should be taken of the HDSS to monitor progress towards the MDGs and beyond.
Household catastrophic medical expenses in eastern China: determinants and policy implications
Authors: Li Xiaohong , Shen Jay J , Lu Jun , Wang Ying , Sun Mei , Li Chengyue , Chang Fengshui , Hao Mo
Published: December 2013

Background

Much of research on household catastrophic medical expenses in China has focused on less developed areas and little is known about this problem in more developed areas. This study aimed to analyse the incidence and determinants of catastrophic medical expenses in eastern China.

Methods

Data were obtained from a health care utilization and expense survey of 11,577 households conducted in eastern China in 2008. The incidence of household catastrophic medical expenses was calculated using the method introduced by the World Health Organization. A multi-level logistic regression model was used to identify the determinants.

Results

The incidence of household catastrophic medical expenses in eastern China ranged from 9.24% to 24.79%. Incidence of household catastrophic medical expenses was lower if the head of household had a higher level of education, labor insurance coverage, while the incidence was higher if they lived in rural areas, had a family member with chronic diseases, had a child younger than 5 years old, had a person at home who was at least 65 years old, and had a household member who was hospitalized. Moreover, the impact of the economic level on catastrophic medical expenses was non-linear. The poorest group had a lower incidence than that of the second lowest income group and the group with the highest income had a higher incidence than that of the second highest income group. In addition, region was a significant determinant.

Conclusions

Reducing the incidence of household catastrophic medical expenses should be one of the priorities of health policy. It can be achieved by improving residents’ health status to reduce avoidable health services such as hospitalization. It is also important to design more targeted health insurance in order to increase financial support for such vulnerable groups as the poor, chronically ill, children, and senior populations.
Health examination utilization in the visually disabled population in Taiwan: a nationwide population-based study
Authors: Hsu Yueh-Han , Tsai Wen-Chen , Kung Pei-Tseng
Published: December 2013

Background

People with visual disabilities have increased health needs but face worse inequity to preventive health examinations. To date, only a few nationwide studies have analyzed the utilization of preventive adult health examinations by the visually disabled population. The aim of this study was to investigate the utilization of health examinations by the visually disabled population, and analyze the factors associated with the utilization.

Methods

Visual disability was certified by ophthalmologists and authenticated by the Ministry of the Interior (MOI), Taiwan. We linked data from three different nationwide datasets (from the MOI, Bureau of Health Promotion, and National Health Research Institutes) between 2006 and 2008 as the data sources. Independent variables included demographic characteristics, income status, health status, and severity of disability; health examination utilization status was the dependent variable. The chi-square test was used to check statistical differences between variables, and a multivariate logistic regression model was used to examine the associated factors with health examination utilization.

Results

In total, 47,812 visually disabled subjects aged 40 years and over were included in this study, only 16.6% of whom received a health examination. Lower utilization was more likely in male subjects, in those aged 65 years and above, insured dependents and those with a top-ranked premium-based salary, catastrophic illness/injury, chronic diseases of the genitourinary system, and severe or very severe disabilities.

Conclusion

The overall health examination utilization in the visually disabled population was very low. Lower utilization occurred mainly in males, the elderly, and those with severe disabilities.
Combination of SLC administration and Tregs depletion is an attractive strategy for targeting hepatocellular carcinoma
Authors: Chen Long , Zhou Shuang , Qin Jie , Hu Heng , Ma Huiying , Liu Binbin , Wang Xuan , Ma Jiaqi , Ye Shenglong , Zhong Cuiping , Zhou Guomin , Liang Chunmin
Published: December 2013

Background

Secondary lymphoid tissue chemokine (SLC) is a key CC chemokine for chemotaxis of immune cells and has been an attractive candidate for anti-tumor treatments. However, among the immune cells recruited by SLC to tumors, the CD25+ Foxp3+ regulatory T cells (Tregs) compromise the anti-tumor effects. In this study, we proposed the combination therapy of intratumoral co-administration of SLC and anti-CD25 monoclonal antibodies (mAbs). We hypothesized that the intratumoral injections of SLC and depletion of Tregs would have stronger inhibition effects on the progression of hepatocellular carcinoma (HCC) in mice.

Methods

C57BL/6 mice were inoculated subcutaneously with the murine HCC cell line, and mice with visible tumors were treated intratumorally with SLC, SLC plus anti-CD25 mAbs or the control antibodies. The percentages of Tregs, effector CD8+ T cells and CD4+ T cells were checked in the tumors, lymph nodes, spleen and liver at regular intervals. The levels of intratumoral IL-12, IFN-γ, IL-10 and TGF-β1 were evaluated. The final anti-tumor effects were measured by the tumor volume and weight as well as the intratumoral activity of MMP2 and MMP9. Bone-marrow-derived dendritic cells were used to explore the mechanisms of maturation induced by SLC in vitro.

Results

Our experiments showed the combination therapy significantly decreased the frequency of Tregs, and increased CD8+ T cells and CD4+ T cells at tumor sites. These alterations were accompanied by an increased level of IL-12 and IFN-γ, and decreased level of IL-10 and TGF-β1. Unexpectedly, we observed a significantly decreased percentage of Tregs, and increased CD8+ T cells and CD4+ T cells in the lymph nodes, spleen and liver after the combination therapy. The growth and invasiveness of HCC was also maximally inhibited in the combination therapy compared with the SLC alone. Furthermore, we confirmed SLC induced the maturation of DCs via NF-κB p65 and this maturation would benefit the combination therapy.

Conclusions

Our data demonstrated that intratumoral co-administration of SLC and anti-CD25 mAbs was an effective treatment for HCC, which was correlated with the altered tumor microenvironment and systemically optimized percentages of Tregs, CD8+ T cells and CD4+ T cells in peripheral immune organs.
Efficient piezoelectric ZnO nanogenerators based on Au-coated silica sphere array electrode
Authors: Ko Yeong Hwan , Nagaraju Goli , Yu Jae Su
Published: December 2013

We reported ZnO nanorod-based piezoelectric nanogenerators (NGs) with Au-coated silica sphere array as an efficient top electrode. This electrode can readily bend the ZnO nanorods due to its enhanced surface roughness, thus resulting in more increased and regular piezoelectric charge output. Under a low external pushing force of 0.3 kgf, the output current and voltage were increased by approximately 2.01 and 1.51 times, respectively, in comparison with a conventional Au top electrode without silica spheres. Also, the effect of Au-coated silica spheres on the bending radius of ZnO nanorods was theoretically investigated.
One-step colloidal synthesis of biocompatible water-soluble ZnS quantum dot/chitosan nanoconjugates
Authors: Ramanery Fábio P , Mansur Alexandra AP , Mansur Herman S
Published: December 2013

Quantum dots (QDs) are luminescent semiconductor nanocrystals with great prospective for use in biomedical and environmental applications. Nonetheless, eliminating the potential cytotoxicity of the QDs made with heavy metals is still a challenge facing the research community. Thus, the aim of this work was to develop a novel facile route for synthesising biocompatible QDs employing carbohydrate ligands in aqueous colloidal chemistry with optical properties tuned by pH. The synthesis of ZnS QDs capped by chitosan was performed using a single-step aqueous colloidal process at room temperature. The nanobioconjugates were extensively characterised by several techniques, and the results demonstrated that the average size of ZnS nanocrystals and their fluorescent properties were influenced by the pH during the synthesis. Hence, novel 'cadmium-free’ biofunctionalised systems based on ZnS QDs capped by chitosan were successfully developed exhibiting luminescent activity that may be used in a large number of possible applications, such as probes in biology, medicine and pharmacy.
Allosteric induction of the CD4-bound conformation of HIV-1 Gp120
Authors: Roitburd-Berman Anna , Dela Gal , Kaplan Gilad , Lewis George K , Gershoni Jonathan M
Published: December 2013

Background

HIV-1 infection of target cells is mediated via the binding of the viral envelope protein, gp120, to the cell surface receptor CD4. This interaction leads to conformational rearrangements in gp120 forming or revealing CD4 induced (CD4i) epitopes which are critical for the subsequent recognition of the co-receptor required for viral entry. The CD4-bound state of gp120 has been considered a potential immunogen for HIV-1 vaccine development. Here we report on an alternative means to induce gp120 into the CD4i conformation.

Results

Combinatorial phage display peptide libraries were screened against HIV-1 gp120 and short (14aa) peptides were selected that bind the viral envelope and allosterically induce the CD4i conformation. The lead peptide was subsequently systematically optimized for higher affinity as well as more efficient inductive activity. The peptide:gp120 complex was scrutinized with a panel of neutralizing anti-gp120 monoclonal antibodies and CD4 itself, illustrating that peptide binding does not interfere with or obscure the CD4 binding site.

Conclusions

Two surfaces of gp120 are considered targets for the development of cross neutralizing antibodies against HIV-1; the CD4 binding site and CD4i epitopes. By implementing novel peptides that allosterically induce the CD4i epitopes we have generated a viral envelope that presents both of these surfaces simultaneously.
Analgesic Tolerance of Opioid Agonists in Mutant Mu-Opioid Receptors Expressed in Sensory Neurons following Intrathecal Plasmid Gene Delivery
Authors: Li Guangwen , Ma Fei , Gu Yanping , Huang Li-Yen Mae
Published: December 2013

Background

Phosphorylation sites in the C-terminus of mu-opioid receptors (MORs) are known to play critical roles in the receptor functions. Our understanding of their participation in opioid analgesia is mostly based on studies of opioid effects on mutant receptors expressed in in vitro preparations, including cell lines, isolated neurons and brain slices. The behavioral consequences of the mutation have not been fully explored due to the complexity in studies of mutant receptors in vivo. To facilitate the determination of the contribution of phosphorylation sites in MOR to opioid-induced analgesic behaviors, we expressed mutant and wild-type human MORs (hMORs) in sensory dorsal root ganglion (DRG) neurons, a major site for nociceptive (pain) signaling and determined morphine- and the full MOR agonist, DAMGO,-induced effects on heat-induced hyperalgesic behaviors and potassium current (IK) desensitization in these rats.

Findings

A mutant hMOR DNA with the putative phosphorylation threonine site at position 394 replaced by an alanine (T394A), i.e., hMOR-T, or a plasmid containing wild type hMOR (as a positive control) was intrathecally delivered. The plasmid containing GFP or saline was used as the negative control. To limit the expression of exogenous DNA to neurons of DRGs, a neuron-specific promoter was included in the plasmid. Following a plasmid injection, hMOR-T or hMOR receptors were expressed in small and medium DRG neurons. Compared with saline or GFP rats, the analgesic potency of morphine was increased to a similar extent in hMOR-T and hMOR rats. Morphine induced minimum IK desensitization in both rat groups. In contrast, DAMGO increased analgesic potency and elicited IK desensitization to a significantly less extent in hMOR-T than in hMOR rats. The development and extent of acute and chronic tolerance induced by repeated morphine or DAMGO applications were not altered by the T394A mutation.

Conclusions

These results indicate that phosphorylation of T394 plays a critical role in determining the potency of DAMGO-induced analgesia and IK desensitization, but has limited effect on morphine-induced responses. On the other hand, the mutation contributes minimally to both DAMGO- and morphine-induced behavioral tolerance. Furthermore, the study shows that plasmid gene delivery of mutant receptors to DRG neurons is a useful strategy to explore nociceptive behavioral consequences of the mutation.
Synthesis and biological evaluation of Combretastatin A-4 derivatives containing a 3’-O-substituted carbonic ether moiety as potential antitumor agents
Authors: Ma Mingyi , Sun Longru , Lou Hongxiang , Ji Mei
Published: December 2013

Background

Combretastatin A-4 (CA-4), which is an excellent antineoplastic agent, was isolated from Combretum caffrum. To date, structural modification studies of CA-4 have focused predominantly on the construction of new therapeutic agents for drug discovery. As a part of our ongoing work towards the modification of natural products, we have focused on the 3’-O-substituent groups in the B-ring of CA-4 under the hypothesis that these novel derivatives will possess good bioactivities and behave as effective antiproliferative pro-drugs.

Results

A series of novel CA-4 derivatives, which contained a 3’-O-substituted carbonic ether moiety, were synthesized and evaluated for their antitumor activities against four tumor cell lines, including MDA-MB-231, MCF-7, K562 and A549 cells. These derivatives exhibited clear antitumor activities, and CA-4E, in particular, showed the highest bioactivity of all of the derivatives tested against all four tumor cell lines, with IC50 values in the range of 1 to 180 nM. Based on its high bioactivity, CA-4E was subsequently selected to investigate the antitumor mechanism of these synthetic compounds. The cell cycle results demonstrated that CA-4E induced time- and dose-dependent G2/M arrest in a similar manner to CA-4, although its effect was more powerful than that of CA-4, and the apoptosis data showed that CA-4E induced cellular apoptosis in a dose-dependent manner.

Conclusions

The newly synthesized CA-4 derivatives exhibited good antitumor activities in vitro, with CA-4E, in particular, showing the highest bioactivity of all of the compounds tested. Furthermore, CA-4E induced time- and dose-dependent G2/M arrest and cellular apoptosis in a dose-dependent manner. Taken together, these results suggest that CA-4E should be subjected to further investigation as a potential anticancer drug candidate.
Chemical characterisation of museum-curated ethnographic resins from Australia and New Guinea used as adhesives, medicines and narcotics
Authors: Bradshaw Fiona
Published: December 2013

Background

Six ethnographic museum resins with documented adhesive, medicinal and narcotic uses have been analysed by gas chromatography–mass spectrometry (GC-MS) as a step towards understanding the role of specific resins in 20th century Australia and New Guinea. Curated in the Pitt Rivers Museum for over a hundred years, these specimens are examples of resin used for three different purposes, some accompanied by ethnographic accounts from the collectors themselves.

Results

The six ethnographic resins have been chemically characterised and identified to species where possible: an adhesive resin from New South Wales is identified as Xanthorrhoea resinosa Pers.; adhesives from New Guinea are tentatively identified as Canarium luzonicum Miq. and beeswax mixed with Canarium spp.; a narcotic resin from New Guinea is identified as Canarium salomonense B.L.Burtt; and the characterisation of spinifex resin from West Australian ‘medicine shells’ hypothesised to be Triodia irritans R.Br is presented.

Conclusions

This study concludes that molecular differentiation between resins from different species is still possible after a hundred years of aging in a museum environment and demonstrates the potential of resin analysis on such aged museum items. These data alongside re-visited ethnographic accounts can confirm, correct, or provide new information to museum records. Furthermore, they can shed new light on the study of the role of these particular resins and mixtures that were used in Indigenous Sahul and contribute towards a framework of analysis and understanding of archaeological resins from this region.
Inhibition of synovitis and joint destruction by a new single domain antibody specific for cyclophilin A in two different mouse models of rheumatoid arthritis
Authors: Wang Li , Jia Junfeng , Wang Conghua , Ma Xiaokui , Liao Chenggong , Fu Zhiguang , Wang Bin , Yang Xiangmin , Zhu Ping , Li Yu , Chen Zhinan
Published: December 2013

Introduction

Cyclophilin A (CypA) is implicated in rheumatoid arthritis (RA) pathogenesis. We studied whether a novel anti-CypA single domain antibody (sdAb) treatment would modulate the severity of the disease in two different animal models of RA.

Methods

A novel sdAb, named sdAbA1, was screened from an immunized camel sdAb library and found to have a high binding affinity (KD = 6.9 × 10-9 M) for CypA. The SCID-HuRAg model and the collagen-induced arthritis (CIA) in mice were used to evaluate the effects of sdAbA1 treatment on inflammation and joint destruction. For in vitro analysis, monocytes/macrophages were purified from synovial fluid and peripheral blood of patients with RA and were tested for the effect of anti-CypA sdAb on metalloproteinase (MMP) production. Human monocyte cell line THP-1 cells were selected and western blot analyses were performed to examine the potential signaling pathways.

Results

In the CIA model of RA, the sdAbA1 treatment resulted in a significant decrease in clinical symptoms as well as of joint damage (P <0.05). In the SCID-HuRAg model, treatment with anti-CypA antibody sdAbA1 significantly reduced cartilage erosion, inflammatory cell numbers and MMP-9 production in the implanted tissues (P <0.05). It also significantly reduced the levels of human inflammatory cytokines IL-6 and IL-8 in mouse serum (P <0.05). No toxic effects were observed in the two animal models. In vitro results showed that sdAbA1 could counteract CypA-dependent MMP-9 secretion and IL-8 production by interfering with the ERK-NF-κB pathway.

Conclusions

Blockade of CypA significantly inhibited synovitis and cartilage/bone erosion in the two tested animal models of RA. Our findings provide evidence that sdAbA1 may be a potential therapeutic agent for RA.
Once You Know, You Are Responsible: The Road from Scholar to Activist
Authors: Siplon Patricia D.
Published: December 2013

Conventional wisdom usually argues that academic research should be conducted with the highest level of objectivity possible. I seek to turn that argument on its head and suggest that taking sides, even pursuing activist tactics, in support of our subjects' goals may be not only desirable but also the most ethical option. Drawing on my own experiences with research and activism in HIV/AIDS, first in the United States and later in East Africa, I present the case for the mutually beneficial relationship between scholarship and activism.
Drosophila intermediate neural progenitors produce lineage-dependent related series of diverse neurons
Authors: Wang Yu-Chun , Yang Jacob S. , Johnston Rebecca , Ren Qingzhong , Lee Ying-Jou , Luan Haojiang , Brody Thomas , Odenwald Ward F. , Lee Tzumin
Published: December 2013

Drosophila type II neuroblasts (NBs), like mammalian neural stem cells, deposit neurons through intermediate neural progenitors (INPs) that can each produce a series of neurons. Both type II NBs and INPs exhibit age-dependent expression of various transcription factors, potentially specifying an array of diverse neurons by combinatorial temporal patterning. Not knowing which mature neurons are made by specific INPs, however, conceals the actual variety of neuron types and limits further molecular studies. Here we mapped neurons derived from specific type II NB lineages and found that sibling INPs produced a morphologically similar but temporally regulated series of distinct neuron types. This suggests a common fate diversification program operating within each INP that is modulated by NB age to generate slightly different sets of diverse neurons based on the INP birth order. Analogous mechanisms might underlie the expansion of neuron diversity via INPs in mammalian brain.
Seeds ofWeigela(Caprifoliaceae) from the Early Miocene of Weichang, China and the biogeographical history of the genus
Authors: Liang Xiao-Qing , Li Ya , Kvaček Zlatko , Wilde Volker , Li Cheng-Sen
Published: December 2013

Seeds of the genusWeigela(Caprifoliaceae) are described from the Early Miocene Hannuoba Formation of Weichang County, Hebei Province, China. They are flat, elliptic, with translucent membranous wings on three sides. Comparison with extant and fossil species ofWeigelaindicates that these seeds are different which therefore were assigned to a new species,Weigela weichangensis. On the basis of the fossil record, the distribution ofWeigelathrough geologic ages is shown on a series of palaeogeographic maps of the Northern Hemisphere. The oldest fossils ofWeigelaare seeds from the Oligocene of West Siberia, Asia. The genus later expanded into East Asia and Europe as well as into Arctic/Subarctic areas of North America via the North Atlantic Land Bridge and/or Bering Land Bridge in the Miocene.Weigeladisappeared from Europe and North America probably during the Pleistocene glaciations, but survived in Asia until now.
Mass Transfer Coefficients and Correlation of Supercritical Carbon Dioxide Extraction of Sarawak Black Pepper
Authors: May Lin Ting , Siew Ping Then , Saptoro Agus , Freddie Panau
Published: December 2013

Bioactive compound, namely piperine, was extracted from Sarawak black pepper using supercritical carbon dioxide extraction. Experiments were carried outin the range of 3,000–5,000 psi (20.7–34.4 MPa) pressures, 318–328 K temperatures, 0.4–1 mm mean particle sizes and5–10 ml/min carbon dioxide flow rates. Experimental data analysis shows that extraction yield ismainly influenced by pressure, particle size and coupled-interactions between these two variables. Extraction process was modeled accounting for intraparticle diffusion and external mass transfer. The kinetics parameters for the internal and external mass transfers were evaluated and estimated. Mass transfer correlation was also developed. From simulation results, good agreement between experimental and simulated data has been found.
Preparation of graphene and inclusion in composites with poly(styrene-b-butadiene-b-styrene)
Authors: Czajka Michael , Shanks Robert A. , Kong Ing
Published: December 2013

The aim of this work was to prepare and characterize nanocomposites containing graphene from intercalated graphite. The graphene was produced by rapid thermal expansion using expandable graphite oxide or obtained commercially. The polymer used was poly(styrene-b-butadiene-b-styrene) (SBS). The SBS was dissolved in p-xylene and the graphene was ultrasonically suspended in the xylene solution. The morphology, dynamic mechanical, electrical, and thermal properties of composites were characterized. Graphene at 1% (w/w) (hydrogen atmosphere) was found to increase the storage modulus (68%) and loss modulus (147%) of the glassy state of polybutadiene in SBS. The damping factor of SBS was enhanced by 74% corresponding to the polystyrene phase of SBS using Cheap Tubes graphene. The composites were insulators at 1% (w/w). The styrene groups in SBS strongly adsorb onto the graphenes, preventing a percolation network that would enhance electrical permittivity. Graphene enhanced physical crosslinks of the polystyrene phase to increase the modulus at low concentration. Graphene dispersion using ultrasonic shear depended on π-π interactions between the aromatic rings of the solvent, graphene, and polystyrene. This is a simple, fast, cheap, and scalable way of making high-quality graphene and a new way of graphene dispersal in polymers.
Wenn Mülleimer sprechen können. Eine sprach- undmedienwissenschaftliche Analyse derWerbekampagne der Stadtreinigung Hamburg
Authors: Eggs Frederike
Published: December 2013

This paper analyses the clean-up campaign organised by Hamburg’s citycleaning service, SRH. Starting in May 2005, the SRH changed the colourof the city’s litter bins from mousey grey to signal red; they also used thelitter bins to advertise their own services using a variety of speech bubbleswhich were not immediately comprehensible, such as for example “Ihr Müllsieht rot.” (“Your rubbish sees red.”) oder “Ich steh’ frei.” (“I am free.”)These speech bubbles can be referred to as cryptic (litter-bin) utterances.The aim of this paper is to analyse the embedding of these cryptic utterancesin a specific space which is characterised by the presence of the redlitter bin. The analysis is intended to show that the two co-present elementsthat are communicatively relevant in this setting – the red litter bin on theone hand and the adhesive label bearing the cryptic utterance on theother – form a single entity in terms of their spatial-visual arrangement,but not in terms of their semiosis. On the contrary, the cryptic nature ofthese utterances – their ‘wittiness’ – is based on their linguistic “doublemeaning” (Freud 1905), which it is up to the recipient to decipher.