bluuebunny/crossref_metadata_2025 huggingface dataset:
Would You Like Fries (380 Calories) With That? Menu Labeling Mitigates the Impact of Weight-Based Stereotype Threat on Food Choice
Authors: Brochu Paula M. , Dovidio John F.
Published: August 2013

Policies that focus on self-regulation are being implemented to reduce obesity. One policy is menu labeling, the provision of calorie information on restaurant menus, which has evidenced mixed results. To illuminate the role of psychological processes, we examined the effect of weight-based stereotype threat on food choice as a function of body mass index (BMI). In Study 1, participants under stereotype threat ordered food containing more calories from a conventional menu that did not present calorie information as BMI increased, whereas no association between BMI and calories was found in the control (no threat) condition. In Study 2, participants under stereotype threat ordered more calories from a conventional menu as BMI increased, whereas no association between BMI and calories was found among participants who ordered from a calorie menu, demonstrating that menu labeling eliminated the stereotype threat effect. Theoretical and practical implications for stereotype threat and policy interventions are discussed.
Outcomes After Fixation of Proximal Humerus (OTA Type 11) Fractures in the Elderly Patients Using Modern Techniques
Authors: Shulman Brandon S. , Ong Crispin C. , Lee James H. , Karia Raj , Zuckerman Joseph D. , Egol Kenneth A.
Published: August 2013

Purpose

To investigate the effects of age on the clinical, functional, and radiographic outcomes of patients with proximal humerus fractures treated operatively with locking plates.

Methods

Between February 2003 and July 2012, all patients who sustained a proximal humerus fracture who presented to our institution were enrolled into a database. Patients were followed up at 1, 6, 12, 26, and 52 weeks postoperatively with physical examination and radiographs. Validated functional outcomes scores were collected at 6 and 12 months. Complications were recorded as they occurred. Statistical analysis was conducted to assess for functional, physical, or radiographic differences between patients age younger than 65 and patients age 65 or older.

Results

Of the 147 consecutive patients treated operatively for a proximal humerus fracture, 115 (78%) patients with an average follow-up of 16 months met the inclusion criteria for this study. The young cohort (patients < 65) included 70 patients with an average age of 53, whereas the elderly cohort (patients ≥ 65) included 45 patients with an average age of 73. The older cohort had significantly more women ( P = .04), but there was no statistical difference in fracture type between the age groups. There were no differences in the radiographic measures of screw penetration, humeral head height, and neck-shaft angle between the age groups. There were no differences in physical examination scores between the age groups. There were no significant differences in functional outcomes or complication rates between the age groups.

Conclusion

Treating proximal humerus fractures operatively with locked plates can overcome the challenges of poor bone quality that often occur with increasing age. Age should not play a significant role in the decision-making process for treating proximal humerus fractures that would otherwise be indicated for surgical fixation.
DOCK8 is critical for the survival and function of NKT cells
Authors: Crawford Greg , Enders Anselm , Gileadi Uzi , Stankovic Sanda , Zhang Qian , Lambe Teresa , Crockford Tanya L. , Lockstone Helen E. , Freeman Alexandra , Arkwright Peter D. , Smart Joanne M. , Ma Cindy S. , Tangye Stuart G. , Goodnow Christopher C. , Cerundolo Vincenzo , Godfrey Dale I. , Su Helen C. , Randall Katrina L. , Cornall Richard J.
Published: August 2013

Key Points

The development and survival of mature NKT cells are impaired in DOCK8-deficient mice. DOCK8 is required for antigen-induced NKT cell proliferation and cytokine production.
A preliminary study on the relationship between central auditory processing and childhood primary headaches in the intercritical phase
Authors: Ciriaco Antonella , Russo Angelo , Monzani Daniele , Genovese Elisabetta , Benincasa Paola , Caffo Ernesto , Pini Luigi Alberto
Published: August 2013

Background

Recently, an increasing number of articles have appeared on central auditory processing disorders, but in the literature there is only one study that evaluated the possible correlation between migraine in the critical phase and central auditory processing. The aim of our study was to assess the correlation between auditory processing information and childhood primary headaches in the intercritical phase.

Methods

This is an observational study. We enrolled 54 patients, 30 with primary headache (migraine and tension headache) and 24 normal controls, matched for sex and age. The mean age at first observation was 9 years 10 months; the duration of observational follow-up was 2 years. Both groups had normal audiological and neurological profiles, normal peripheral hearing acuity and normal cognitive and behavioral skills. We excluded patients who had undergone pharmacological prophylactic treatment for headaches in the 6 months preceding the study and subjects with a frequency of headache lower than one every two months. After enrolment, both groups were analyzed with a computerized test battery for Speech Perception Tests in silence and in noise background to assess speech perception disabilities. In addition, with a test battery of Speech Perception Tests, we compared patients with migraines and tension-type headaches. The non-parametric χ2 test, the Mann–Whitney U-test and the Wilcoxon signed ranks test were used for statistical analysis. P-values <0.05 were considered significant and STATA 10 software was used for statistical analyses.

Results

Our results showed that patients with primary headache (migraine and tension-type headache), had a deficit of auditory processing in noisy background compared to control cases, but we found no significant differences when we compared patients with migraine and tension-type headache.

Conclusions

This is a work in progress and further studies are needed to assess the relationship between the impairment of auditory processing and primary headache, not only to improve the diagnostic approach to primary headache, but also to improve therapeutic intervention.
Tracking the evolution of sex chromosome systems in Melanoplinae grasshoppers through chromosomal mapping of repetitive DNA sequences
Authors: Palacios-Gimenez Octavio M , Castillo Elio R , Martí Dardo A , Cabral-de-Mello Diogo C
Published: August 2013

Background

The accumulation of repetitive DNA during sex chromosome differentiation is a common feature of many eukaryotes and becomes more evident after recombination has been restricted or abolished. The accumulated repetitive sequences include multigene families, microsatellites, satellite DNAs and mobile elements, all of which are important for the structural remodeling of heterochromatin. In grasshoppers, derived sex chromosome systems, such as neo-XY♂/XX♀ and neo-X1X2Y♂/X1X1X2X2♀, are frequently observed in the Melanoplinae subfamily. However, no studies concerning the evolution of sex chromosomes in Melanoplinae have addressed the role of the repetitive DNA sequences. To further investigate the evolution of sex chromosomes in grasshoppers, we used classical cytogenetic and FISH analyses to examine the repetitive DNA sequences in six phylogenetically related Melanoplinae species with X0♂/XX♀, neo-XY♂/XX♀ and neo-X1X2Y♂/X1X1X2X2♀ sex chromosome systems.

Results

Our data indicate a non-spreading of heterochromatic blocks and pool of repetitive DNAs (C0t-1 DNA) in the sex chromosomes; however, the spreading of multigene families among the neo-sex chromosomes ofEurotettixandDichromatoswas remarkable, particularly for 5S rDNA. In autosomes, FISH mapping of multigene families revealed distinct patterns of chromosomal organization at the intra- and intergenomic levels.

Conclusions

These results suggest a common origin and subsequent differential accumulation of repetitive DNAs in the sex chromosomes ofDichromatosand an independent origin of the sex chromosomes of the neo-XY and neo-X1X2Y systems. Our data indicate a possible role for repetitive DNAs in the diversification of sex chromosome systems in grasshoppers.
Solanum torvum responses to the root-knot nematode Meloidogyne incognita
Authors: Bagnaresi Paolo , Sala Tea , Irdani Tiziana , Scotto Cristina , Lamontanara Antonella , Beretta Massimiliano , Rotino Giuseppe Leonardo , Sestili Sara , Cattivelli Luigi , Sabatini Emidio
Published: August 2013

Background

Solanum torvum Sw is worldwide employed as rootstock for eggplant cultivation because of its vigour and resistance/tolerance to the most serious soil-borne diseases as bacterial, fungal wilts and root-knot nematodes. The little information on Solanum torvum (hereafter Torvum) resistance mechanisms, is mostly attributable to the lack of genomic tools (e.g. dedicated microarray) as well as to the paucity of database information limiting high-throughput expression studies in Torvum.

Results

As a first step towards transcriptome profiling of Torvum inoculated with the nematode M. incognita, we built a Torvum 3’ transcript catalogue. One-quarter of a 454 full run resulted in 205,591 quality-filtered reads. De novo assembly yielded 24,922 contigs and 11,875 singletons. Similarity searches of the S. torvum transcript tags catalogue produced 12,344 annotations. A 30,0000 features custom combimatrix chip was then designed and microarray hybridizations were conducted for both control and 14 dpi (day post inoculation) with Meloidogyne incognita- infected roots samples resulting in 390 differentially expressed genes (DEG). We also tested the chip with samples from the phylogenetically-related nematode-susceptible eggplant species Solanum melongena. An in-silico validation strategy was developed based on assessment of sequence similarity among Torvum probes and eggplant expressed sequences available in public repositories. GO term enrichment analyses with the 390 Torvum DEG revealed enhancement of several processes as chitin catabolism and sesquiterpenoids biosynthesis, while no GO term enrichment was found with eggplant DEG.

The genes identified from S. torvum catalogue, bearing high similarity to known nematode resistance genes, were further investigated in view of their potential role in the nematode resistance mechanism.

Conclusions

By combining 454 pyrosequencing and microarray technology we were able to conduct a cost-effective global transcriptome profiling in a non-model species. In addition, the development of an in silico validation strategy allowed to further extend the use of the custom chip to a related species and to assess by comparison the expression of selected genes without major concerns of artifacts. The expression profiling of S. torvum responses to nematode infection points to sesquiterpenoids and chitinases as major effectors of nematode resistance. The availability of the long sequence tags in S. torvum catalogue will allow precise identification of active nematocide/nematostatic compounds and associated enzymes posing the basis for exploitation of these resistance mechanisms in other species.
The auriculo-vagal afferent pathway and its role in seizure suppression in rats
Authors: He Wei , Jing Xiang-Hong , Zhu Bing , Zhu Xin-Long , Li Liang , Bai Wan-Zhu , Ben Hui
Published: August 2013

Background

The afferent projections from the auricular branch of the vagus nerve (ABVN) to the nucleus tractus solitaries (NTS) have been proposed as the anatomical basis for the increased parasympathetic tone seen in auriculo-vagal reflexes. As the afferent center of the vagus nerve, the NTS has been considered to play roles in the anticonvulsant effect of cervical vagus nerve stimulation (VNS). Here we proposed an “auriculo-vagal afferent pathway” (AVAP), by which transcutaneous auricular vagus nerve stimulation (ta-VNS) suppresses pentylenetetrazol (PTZ)-induced epileptic seizures by activating the NTS neurons in rats.

Results

The afferent projections from the ABVN to the NTS were firstly observed in rats. ta-VNS increased the first grand mal latency of the epileptic seizure and decreased the seizure scores in awake rats. Furthermore, when the firing rates of the NTS neurons decreased, epileptiform activity manifested as electroencephalogram (EEG) synchronization increased with 0.37±0.12 s delay in anaesthetized rats. The change of instantaneous frequency, mean frequency of the NTS neurons was negative correlated with the amplitude of the epileptic activity in EEG traces. ta-VNS significantly suppressed epileptiform activity in EEG traces via increasing the firing rates of the neurons of the NTS. In comparison with tan-VNS, the anticonvulsant durations of VNS and ta-VNS were significantly longer (P<0.01). There was no significant difference between the anticonvulsant durations of VNS and ta-VNS (P>0.05). The anticonvulsant effect of ta-VNS was weakened by reversible cold block of the NTS.

Conclusions

There existed an anatomical relationship between the ABVN and the NTS, which strongly supports the concept that ta-VNS has the potential for suppressing epileptiform activity via the AVAP in rats. ta-VNS will provide alternative treatments for neurological disorders, which can avoid the disadvantage of VNS.
Interventionally implanted port catheter systems for hepatic arterial infusion of chemotherapy in patients with primary liver cancer: A phase II-study (NCT00356161)
Authors: Sinn Marianne , Nicolaou Annett , Ricke Jens , Podrabsky Pjotr , Seehofer Daniel , Gebauer Bernhard , Pech Maciej , Neuhaus Peter , Dörken Bernd , Riess Hanno , Hildebrandt Bert
Published: August 2013

Background

Hepatic arterial infusion (HAI) of chemotherapy requires the implantation of a transcatheter application system which is traditionally performed by surgery. This procedure, but particularly the adjacent drug application via pump or port is often hampered by specific complications and device failure. Interventionally implanted port catheter systems (IIPCS) facilitate the commencement of HAI without need for laparatomy, and are associated with favorable complication rates. We here present an evaluation of the most important technical endpoints associated with the use of IIPCS for HAI in patients with primary liver cancers.

Methods

70 patients (pts) with hepatocellular (HCC, n=33) and biliary tract cancer (BTC, n=37) were enrolled into a phase II –study. Of those, n=43 had recurrent disease and n=31 suffered from liver-predominant UICC-stage IVb. All pts were provided with IIPCSs before being treated with biweekly, intraarterial chemotherapy (oxaliplatin, 5-Flourouracil, folinic acid). The primary objective of the trial was defined as evaluation of device-related complications and port duration.

Results

Implantation of port catheters was successful in all patients. Mean treatment duration was 5.8 months, and median duration of port patency was not reached. Disease-progression was the most common reason for treatment discontinuation (44 pts., 63%), followed by chemotherapy-related toxicity (12 pts., 17%), and irreversible device failure (5 pts., 7%). A total of 28 port complications occurred in 21 pts (30%). No unexpected complications were observed.

Conclusions

HAI via interventionally implanted port catheters can be safely applied to patients with primary liver tumors far advanced or/and pretreated.
RETRACTED ARTICLE: High expression level and nuclear localization of Sam68 are associated with progression and poor prognosis in colorectal cancer
Authors: Liao Wen-Ting , Liu Jun-Ling , Wang Zheng-Gen , Cui Yan-Mei , Shi Ling , Li Ting-Ting , Zhao Xiao-Hui , Chen Xiu-Ting , Ding Yan-Qing , Song Li-Bing
Published: August 2013

Background

Src-associated in mitosis (Sam68; 68 kDa) has been implicated in the oncogenesis and progression of several human cancers. The aim of this study was to investigate the clinicopathologic significance of Sam68 expression and its subcellular localization in colorectal cancer (CRC).

Methods

Sam68 expression was examined in CRC cell lines, nine matched CRC tissues and adjacent noncancerous tissues using reverse transcription (RT)-PCR, quantitative RT-PCR and Western blotting. Sam68 protein expression and localization were determined in 224 paraffin-embedded archived CRC samples using immunohistochemistry. Statistical analyses were applied to evaluate the clinicopathologic significance.

Results

Sam68 was upregulated in CRC cell lines and CRC, as compared with normal tissues; high Sam68 expression was detected in 120/224 (53.6%) of the CRC tissues. High Sam68 expression correlated significantly with poor differentiation (P = 0.033), advanced T stage (P < 0.001), N stage (P = 0.023) and distant metastasis (P = 0.033). Sam68 nuclear localization correlated significantly with poor differentiation (P = 0.002) and T stage (P =0.021). Patients with high Sam68 expression or Sam68 nuclear localization had poorer overall survival than patients with low Sam68 expression or Sam68 cytoplasmic localization. Patients with high Sam68 expression had a higher risk of recurrence than those with low Sam68 expression.

Conclusions

Overexpression of Sam68 correlated highly with cancer progression and poor differentiation in CRC. High Sam68 expression and Sam68 nuclear localization were associated with poorer overall survival.
CT of the chest with model-based, fully iterative reconstruction: comparison with adaptive statistical iterative reconstruction
Authors: Ichikawa Yasutaka , Kitagawa Kakuya , Nagasawa Naoki , Murashima Shuichi , Sakuma Hajime
Published: August 2013

Background

The recently developed model-based iterative reconstruction (MBIR) enables significant reduction of image noise and artifacts, compared with adaptive statistical iterative reconstruction (ASIR) and filtered back projection (FBP). The purpose of this study was to evaluate lesion detectability of low-dose chest computed tomography (CT) with MBIR in comparison with ASIR and FBP.

Methods

Chest CT was acquired with 64-slice CT (Discovery CT750HD) with standard-dose (5.7 ± 2.3 mSv) and low-dose (1.6 ± 0.8 mSv) conditions in 55 patients (aged 72 ± 7 years) who were suspected of lung disease on chest radiograms. Low-dose CT images were reconstructed with MBIR, ASIR 50% and FBP, and standard-dose CT images were reconstructed with FBP, using a reconstructed slice thickness of 0.625 mm. Two observers evaluated the image quality of abnormal lung and mediastinal structures on a 5-point scale (Score 5 = excellent and score 1 = non-diagnostic). The objective image noise was also measured as the standard deviation of CT intensity in the descending aorta.

Results

The image quality score of enlarged mediastinal lymph nodes on low-dose MBIR CT (4.7 ± 0.5) was significantly improved in comparison with low-dose FBP and ASIR CT (3.0 ± 0.5, p = 0.004; 4.0 ± 0.5, p = 0.02, respectively), and was nearly identical to the score of standard-dose FBP image (4.8 ± 0.4, p = 0.66). Concerning decreased lung attenuation (bulla, emphysema, or cyst), the image quality score on low-dose MBIR CT (4.9 ± 0.2) was slightly better compared to low-dose FBP and ASIR CT (4.5 ± 0.6, p = 0.01; 4.6 ± 0.5, p = 0.01, respectively). There were no significant differences in image quality scores of visualization of consolidation or mass, ground-glass attenuation, or reticular opacity among low- and standard-dose CT series. Image noise with low-dose MBIR CT (11.6 ± 1.0 Hounsfield units (HU)) were significantly lower than with low-dose ASIR (21.1 ± 2.6 HU, p < 0.0005), low-dose FBP CT (30.9 ± 3.9 HU, p < 0.0005), and standard-dose FBP CT (16.6 ± 2.3 HU, p < 0.0005).

Conclusion

MBIR shows greater potential than ASIR for providing diagnostically acceptable low-dose CT without compromising image quality. With radiation dose reduction of >70%, MBIR can provide equivalent lesion detectability of standard-dose FBP CT.
Development of a quantitative food frequency questionnaire for Brazilian patients with type 2 diabetes
Authors: Sarmento Roberta Aguiar , Riboldi Bárbara Pelicioli , da Costa Rodrigues Ticiana , de Azevedo Mirela Jobim , de Almeida Jussara Carnevale
Published: August 2013

Background

To investigate the association between dietary components and development of chronic diabetic complications, the dietary evaluation should include a long period, months or years. The present manuscript aims to develop a quantitative food frequency questionnaire (FFQ) and a portfolio with food photos to assess the usual intake pattern of Brazilian patients with type 2 diabetes to be used in future studies.

Methods

Dietary data using 3-day weighed diet records (WDR) from 188 outpatients with type 2 diabetes were used to construct the list of usually consumed foods. Foods were initially clustered into eight groups: “cereals, tubers, roots, and derivatives”; “vegetables and legumes”; “fruits”; “beans”; “meat and eggs”; “milk and dairy products”; “oils and fats”, and “sugars and sweets”. The frequency of food intake and the relative contribution of each food item to the total energy and nutrient intakes were calculated. Portion sizes were determined according to the 25th, 50th, 75th, and 95th percentiles of intake for each food item.

Results

A total of 62 food items were selected based on the 3-day WDR and another 27 foods or how they are prepared and nine beverages were included after the expert examination. Also, a portfolio with food photos of each included food item and portion sizes was made to assist the patients in identifying the consumed portion.

Conclusions

We developed a practical quantitative FFQ and portfolio with photos of 98 food items covering those most commonly consumed in the past 12 months, to assess the usual diet pattern of patients with type 2 diabetes in Southern Brazil.
The co-expression of functional gastric proteins in dynamic gastric diseases and its clinical significance
Authors: Xu Qian , Sun Li-ping , Wang Ben-gang , Liu Jing-wei , Li Ping , He Cai-yun , Yuan Yuan
Published: August 2013

Background

Pepsinogen C (PGC) and mucin1 (MUC1) are important physiologically functional gastric proteins; Mucin2 (MUC2) is an “ectopic” functional protein in intestinal metaplasia of gastric mucosa. We analyzed the co-expression of the above-mentioned three proteins in dynamic gastric diseases {superficial gastritis (SG)-atrophic gastritis (AG)--gastric cancer (GC)} as well as different histological types of gastric cancer in order to find molecular phenotypes of gastric cancer and precancerous disease and further explore the potential co-function of PGC, MUC1 and MUC2 in the occurrence and development of gastric cancer.

Methods

The SG-AG-GC sequence was 57-57-70 cases in this case–control study, respectively. Different histological types of GC were 28 cases of highly and moderately differentiated aden ocarcinoma (HMDA)、30 of poorly differentiated adenocarcinoma (PDA) and 12 of mucinous adenocarcinoma (MA) or signet ring cell carcinoma (SRCC). PGC, MUC1 and MUC2 expression in situ were detected in all 184 cases using immunohistochemistry.

Results

Both PGC and MUC1 had a significantly decreased expression in GC than in SG and AG (P < 0.0001 and P < 0.01, respectively); While MUC2 had a significant increased expression in AG than in SG and GC (P < 0.0001). Seven phenotypes of PGC, MUC1 and MUC2 co-expression were found in which PGC+/MUC1+/MUC2- phenotype took 94.7%(54/57) in SG group; PGC+/MUC1+/MUC2+ and PGC-/MUC1+/MUC2+ phenotype took 43.9% (25/57) and 52.6% (30/57) in AG; the phenotypes in GC group appeared variable; extraordinarily, PGC-/MUC1-/MUC2+ phenotype took 100% (6/6) in MA or SRCC group and had a statistical significance compared with others (P < 0.05).

Conclusions

Phenotypes of PGC, MUC1 and MUC2 co-expression in dynamic gastric diseases are variable. In SG group it always showed PGC+/MUC1+/MUC2- phenotype and AG group showed two phenotypes (PGC+/MUC1+/MUC2+ and PGC-/MUC1+/MUC2+); the phenotypes in GC group appeared variable but the phenotype of PGC-/MUC1-/MUC2+ may be a predictive biomarker for diagnosing MA or SRCC, or distinguishing histological MA or SRCC from tubular adenocarcinoma accompanied by mucinous secretion or signet ring cell scattered distribution.
Pronounced cancer resistance in a subterranean rodent, the blind mole-rat, Spalax: in vivo and in vitroevidence
Authors: Manov Irena , Hirsh Mark , Iancu Theodore C , Malik Assaf , Sotnichenko Nick , Band Mark , Avivi Aaron , Shams Imad
Published: August 2013

Background

Subterranean blind mole rats(Spalax)are hypoxia tolerant (down to 3% O2), long lived (>20 years) rodents showing no clear signs of aging or aging related disorders. In 50 years ofSpalaxresearch, spontaneous tumors have never been recorded among thousands of individuals.Here we addressed the questions of (1) whetherSpalaxis resistant to chemically-induced tumorigenesis, and (2) whether normal fibroblasts isolated fromSpalaxpossess tumor-suppressive activity.

Results

Treating animals with 3-Methylcholantrene (3MCA) and 7,12-Dimethylbenz(a) anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA), two potent carcinogens, confirmedSpalaxhigh resistance to chemically induced cancers. While all mice and rats developed the expected tumors following treatment with both carcinogens, amongSpalaxno tumors were observed after DMBA/TPA treatment, while 3MCA induced benign fibroblastic proliferation in 2Spalaxindividuals out of12, and only a single animal from the advanced age group developed malignancy 18 months post-treatment. The remaining animals are still healthy 30 months post-treatment.In vitroexperiments showed an extraordinary ability of normalSpalaxcultured fibroblasts to restrict malignant behavior in a broad spectrum of human-derived and in newly isolatedSpalax3MCA-induced cancer cell lines. Growth of cancer cells was inhibited by either direct interaction withSpalaxfibroblasts or with soluble factors released into culture media and soft agar. This was accompanied by decreased cancer cell viability, reduced colony formation in soft agar, disturbed cell cycle progression, chromatin condensation and mitochondrial fragmentation. Cells from another cancer resistant subterranean mammal, the naked mole rat, were also tested for direct effect on cancer cells and, similar toSpalax, demonstrated anti-cancer activity. No effect on cancer cells was observed using fibroblasts from mouse, rat orAcomys.Spalaxfibroblast conditioned media had no effect on proliferation of noncancerous cells.

Conclusions

This report provides pioneering evidence thatSpalaxis not only resistant to spontaneous cancer but also to experimentally induced cancer, and shows the unique ability ofSpalaxnormal fibroblasts to inhibit growth and kill cancer cells, but not normal cells, either through direct fibroblast-cancer cell interaction or via soluble factors. Obviously, along with adaptation to hypoxia,Spalaxhas evolved efficient anti-cancer mechanisms yet to be elucidated. Exploring the molecular mechanisms allowingSpalaxto survive in extreme environments and to escape cancer as well as to kill homologous and heterologous cancer cells may hold the key for understanding the molecular nature of host resistance to cancer and identify new anti-cancer strategies for treating humans.
In vitro prion protein conversion suggests risk of bighorn sheep (Ovis canadensis) to transmissible spongiform encephalopathies
Authors: Morawski Aaron R , Carlson Christina M , Chang Haeyoon , Johnson Christopher J
Published: August 2013

Background

Transmissible spongiform encephalopathies (TSEs) affect both domestic sheep (scrapie) and captive and free-ranging cervids (chronic wasting disease; CWD). The geographical range of bighorn sheep (Ovis canadensis; BHS) overlaps with states or provinces that have contained scrapie-positive sheep or goats and areas with present epizootics of CWD in cervids. No TSEs have been documented in BHS, but the susceptibility of this species to TSEs remains unknown.

Results

We acquired a library of BHS tissues and found no evidence of preexisting TSEs in these animals. The prion protein gene (Prnp) in all BHS in our library was identical to scrapie-susceptible domestic sheep (A136R154Q171 genotype). Using an in vitro prion protein conversion assay, which has been previously used to assess TSE species barriers and, in our study appears to recollect known species barriers in mice, we assessed the potential transmissibility of TSEs to BHS. As expected based upon Prnp genotype, we observed BHS prion protein conversion by classical scrapie agent and evidence for a species barrier between transmissible mink encephalopathy (TME) and BHS. Interestingly, our data suggest that the species barrier of BHS to white-tailed deer or wapiti CWD agents is likely low. We also used protein misfolding cyclic amplification to confirm that CWD, but not TME, can template prion protein misfolding in A136R154Q171 genotype sheep.

Conclusions

Our results indicate the in vitro conversion assay used in our study does mimic the species barrier of mice to the TSE agents that we tested. Based on Prnp genotype and results from conversion assays, BHS are likely to be susceptible to infection by classical scrapie. Despite mismatches in amino acids thought to modulate prion protein conversion, our data indicate that A136R154Q171 genotype sheep prion protein is misfolded by CWD agent, suggesting that these animals could be susceptible to CWD. Further investigation of TSE transmissibility to BHS, including animal studies, is warranted. The lack of reported TSEs in BHS may be attributable to other host factors or a lack of TSE surveillance in this species.
Rectal endoscopy findings following stereotactic body radiation therapy for clinically localized prostate cancer
Authors: Sood Sumit , Ju Andrew W , Wang Honkung , Lei Siyuan , Uhm Sunghae , Zhang Guowei , Suy Simeng , Carroll John , Lynch John , Dritschilo Anatoly , Collins Sean P
Published: August 2013

Background

Treating prostate cancer with SBRT could potentially minimize radiation proctitis by reducing high-dose rectal irradiation. In addition, it offers the potential radiobiologic benefits of hypofractionation. This study reports the endoscopic changes and the associated clinical rectal toxicity in these patients.

Methods

We reviewed the records of patients treated from 2008–2011 for localized prostate cancer who had rectal endoscopy following SBRT. SBRT was delivered either as primary treatment in 5 fractions of 7–7.25 Gy, or as an initial boost in 3 fractions of 6.5 Gy followed by conventionally fractionated radiotherapy to 45–50.4 Gy. Endoscopic changes were graded using the Vienna Rectoscopy Score (VRS). Rectal toxicity was graded via CTCAEv.4. Rectal quality of life (QOL) was assessed via the bowel domain of the EPIC-26 questionnaire.

Results

Fifty-one patients with a median 23 months follow-up were analyzed. Thirty-five patients completed SBRT monotherapy and 16 patients received SBRT as a boost to conventionally fractionated IMRT. The median interval from SBRT to rectal endoscopy was 13 months. Endoscopy revealed VRS Grade 1–2 telangiectasias for 10 patients and VRS Grade 1–2 mucosal edema for 12 patients. No rectal ulcerations, strictures or necrosis were observed. Grade 1–2 late rectal bleeding occurred in 10 patients. There were no CTCAEv.4 Grade ≥3 toxicities. Mean EPIC bowel scores decreased from a baseline value of 96.9 to 82.3 at 1-month, but subsequently increased to 91.0 at 24 months.

Conclusions

In this cohort that is skewed towards patients with rectal complaints, the rate and severity of endoscopic changes following SBRT is low. Rectal toxicity and QOL were comparable to patients treated with other radiation modalities. Prospective trials examining the endoscopic outcomes following SBRT for prostate cancer are needed for confirmation of the findings of this study.

Trial registration

The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009–510).
Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile
Authors: White Katie M , Alba Raul , Parker Alan L , Wright Audrey F , Bradshaw Angela C , Delles Christian , McDonald Robert A , Baker Andrew H
Published: August 2013

Background

Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.

Methods

Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3).

Results

Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T*F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T*F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T*F35++ were less prevalent than Ad5 neutralising antibodies.

Conclusions

We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer.
Performance evaluation of data aggregation for cluster-based wireless sensor network
Authors: Sinha Adwitiya , Lobiyal Daya Krishan
Published: August 2013

In wireless sensor network, data fusion is considered an essential process for preserving sensor energy. Periodic data sampling leads to enormous collection of raw facts, the transmission of which would rapidly deplete the sensor power. In this paper, we have performed data aggregation on the basis of entropy of the sensors. The entropy is computed from the proposed local and global probability models. The models provide assistance in extracting high precision data from the sensor nodes. We have also proposed an energy efficient method for clustering the nodes in the network. Initially, sensors sensing the same category of data are placed within a distinct cluster. The remaining unclustered sensors estimate their divergence with respect to the clustered neighbors and ultimately join the least-divergent cluster. The overall performance of our proposed methods is evaluated using NS-2 simulator in terms of convergence rate, aggregation cycles, average packet drops, transmission cost and network lifetime. Finally, the simulation results establish the validity and efficiency of our approach.
The effects of active labour market policies for immigrants receiving social assistance in Denmark
Authors: Heinesen Eskil , Husted Leif , Rosholm Michael
Published: August 2013

We estimate the effect of active labour-market programmes on the exit rate to regular employment for non-western immigrants in Denmark who receive social assistance. We use the timing-of-events duration model and rich administrative data. We find large positive post-programme effects, and, surprisingly, even most in-programme effects are positive. The effects are largest for subsidized employment programmes, but effects are also large and significant for direct employment programmes and other programmes. Effects are larger if programmes begin after six months of unemployment. Implications of our estimates are illustrated by calculating effects on the duration to regular employment over a five-year period.

JEL classification codes

J64, J24, J68, J61, C41
Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors
Authors: Lechner Matthias , Frampton Garrett M , Fenton Tim , Feber Andrew , Palmer Gary , Jay Amrita , Pillay Nischalan , Forster Martin , Cronin Maureen T , Lipson Doron , Miller Vincent A , Brennan Timothy A , Henderson Stephen , Vaz Francis , O'Flynn Paul , Kalavrezos Nicholas , Yelensky Roman , Beck Stephan , Stephens Philip J , Boshoff Chris
Published: August 2013

Background

Human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) is an emerging disease, representing a distinct clinical and epidemiological entity. Understanding the genetic basis of this specific subtype of cancer could allow therapeutic targeting of affected pathways for a stratified medicine approach.

Methods

Twenty HPV+ and 20 HPV- laser-capture microdissected oropharyngeal carcinomas were used for paired-end sequencing of hybrid-captured DNA, targeting 3,230 exons in 182 genes often mutated in cancer. Copy number alteration (CNA) profiling, Sequenom MassArray sequencing and immunohistochemistry were used to further validate findings.

Results

HPV+ and HPV- oropharyngeal carcinomas cluster into two distinct subgroups. TP53 mutations are detected in 100% of HPV negative cases and abrogation of the G1/S checkpoint by CDKN2A/B deletion and/or CCND1 amplification occurs in the majority of HPV- tumors.

Conclusion

These findings strongly support a causal role for HPV, acting via p53 and RB pathway inhibition, in the pathogenesis of a subset of oropharyngeal cancers and suggest that studies of CDK inhibitors in HPV- disease may be warranted. Mutation and copy number alteration of PI3 kinase (PI3K) pathway components appears particularly prevalent in HPV+ tumors and assessment of these alterations may aid in the interpretation of current clinical trials of PI3K, AKT, and mTOR inhibitors in HNSCC.
Increased expression of intrinsic antiviral genes in HLA-B*57-positive individuals
Authors: Raposo Rui André Saraiva , Abdel-Mohsen Mohamed , Holditch Sara J , Kuebler Peter J , Cheng Rex G , Eriksson Emily M , Liao Wilson , Pillai Satish K , Nixon Douglas F
Published: August 2013

The genetic background of HIV-1-infected subjects, particularly the HLA class I haplotype, appears to be critical in determining disease progression rates, thought to be a result of the role of HIV-1-specific CD8+ T cell responses. The HLA-B*57 allele is strongly associated with viremic suppression and slower disease progression. However, there is considerable heterogeneity in HIV-1 disease progression rates among HLA-B*57-positive subjects, suggesting that additional factors may help to contain viral replication. In this report, we investigated the association between host restriction factors, other established immunological parameters, and HLA type in HIV-1-seronegative individuals. Our results demonstrate that healthy, uninfected HLA-B*57-positive individuals exhibit significantly higher gene-expression levels of host restriction factors, such as APOBEC3A, APOBEC3B, BST-2/tetherin, and ISG15. Interestingly, HLA-B*57 individuals have significantly lower CD4+ T cell frequencies but harbor slightly more activated CD4+ T cells compared with their HLA-B*35 counterparts. We detected significant correlations between CD4+ T cell activation and expression of several APOBEC3 family members, BST-2/tetherin, SAMHD1, and TRIM5α in HLA-B*57-positive individuals. To our knowledge, this is the first report showing distinct associations between host restriction factors and HLA class I genotype. Our results provide insights into natural protection mechanisms and immunity against HIV-1 that fall outside of classical HLA-mediated effects.
The Krüppel-Like Protein Gli-Similar 3 (Glis3) Functions as a Key Regulator of Insulin Transcription
Authors: ZeRuth Gary T. , Takeda Yukimasa , Jetten Anton M.
Published: August 2013

Transcriptional regulation of insulin in pancreatic β-cells is mediated primarily through enhancer elements located within the 5′ upstream regulatory region of the preproinsulin gene. Recently, the Krüppel-like transcription factor, Gli-similar 3 (Glis3), was shown to bind the insulin (INS) promoter and positively influence insulin transcription. In this report, we examined in detail the synergistic activation of insulin transcription by Glis3 with coregulators, CREB-binding protein (CBP)/p300, pancreatic and duodenal homeobox 1 (Pdx1), neuronal differentiation 1 (NeuroD1), and v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA). Our data show that Glis3 expression, the binding of Glis3 to GlisBS, and its recruitment of CBP are required for optimal activation of the insulin promoter in pancreatic β-cells not only by Glis3, but also by Pdx1, MafA, and NeuroD1. Mutations in the GlisBS or small interfering RNA−directed knockdown of GLIS3 diminished insulin promoter activation by Pdx1, NeuroD1, and MafA, and neither Pdx1 nor MafA was able to stably associate with the insulin promoter when the GlisBS were mutated. In addition, a GlisBS mutation in the INS promoter implicated in the development of neonatal diabetes similarly abated activation by Pdx1, NeuroD1, and MafA that could be reversed by increased expression of exogenous Glis3. We therefore propose that recruitment of CBP/p300 by Glis3 provides a scaffold for the formation of a larger transcriptional regulatory complex that stabilizes the binding of Pdx1, NeuroD1, and MafA complexes to their respective binding sites within the insulin promoter. Taken together, these results indicate that Glis3 plays a pivotal role in the transcriptional regulation of insulin and may serve as an important therapeutic target for the treatment of diabetes.
Quantum Chemical Studies on Dioxygen Activation and Methane Hydroxylation by Diiron and Dicopper Species as well as Related Metal–Oxo Species
Authors: Yoshizawa Kazunari
Published: August 2013

Quantum chemical studies by the author and co-workers on dioxygen activation and methane hydroxylation by diiron and dicopper enzyme species as well as related metal–oxo species are reviewed. The activation of the O–O bond of dioxygen at the mono- and dimetal sites of metalloenzymes is an essential process in the initial catalytic stages of naturally occurring oxygenation reactions. A way of orbital thinking about dioxygen activation at diiron and dicopper enzymes is developed at the extended Hückel level of theory. Two different reaction pathways that lead from dimetal peroxo complexes with µ-η1:η1-O2 and µ-η2:η2-O2 modes to the corresponding dioxo complexes are discussed in detail. In considering the mechanism of methane hydroxylation, special attention to FeO+-mediated methane hydroxylation that occurs under ion cyclotron resonance (ICR) conditions is given. Mechanistic aspects about methane hydroxylation by the bare transition-metal oxide ions ScO+, TiO+, VO+, CrO+, MnO+, FeO+, CoO+, NiO+, and CuO+ are systematically analyzed on the basis of density functional theory (DFT) calculations. An important feature in the reaction is the spin crossover between the high-spin and low-spin potential energy surfaces in particular in the C–H activation process. The spin inversion from the high-spin state to the low-spin state effectively decreases the barrier height of C–H activation. Another feature in the reaction is that no radical species is involved in the course of the hydroxylation because the methyl species formed as a result of the C–H bond cleavage can directly coordinate to the metal active site. The coupling of the OH and CH3 ligands occurs to produce methanol at the metal active center. The reaction profiles obtained from DFT calculations are similar to those of the Gif chemistry proposed by D. H. R. Barton, in particular the involvement of the HO–M–CH3 species as an intermediate in the hydroxylation of methane. The nonradical mechanism is extended to methane hydroxylation by the diiron and dicopper species of methane monooxygenase (MMO). This mechanism is possible when the metal active center is coordinatively unsaturated to have a space for the coordination of the OH and CH3 groups as ligands. Although compelling discussion to support the involvement of oxygen- and carbon-centered radicals is provided, the nonradical mechanism still seems to be applicable for methane hydroxylation from the viewpoint of reaction selectivity. Kinetic isotope effects (KIEs) in the C–H activation process by the bare FeO+ complex and diiron and dicopper enzyme models are compared with respect to the radical and nonradical mechanisms by using transition state theory.
Syntheses and Photochromic Properties of Thiophenophan-1-ene-S,S,S′,S′-tetraoxides
Authors: Takeshita Michinori , Kodama Tomohiro , Wada Yuta , Hatcho Natsumi
Published: August 2013

Photochromic thiophenophan-1-ene-S,S,S′,S′-tetraoxides have been synthesized by oxidation of sulfur atoms of thiophenophan-1-enes, and their photochromic properties were studied. The tetraoxides indicated photochromism and the quantum yields for photocyclization reactions became higher than that of nonbridged dithienylethene-S,S,S′,S′-tetraoxide due to fixation of conformations.
Highly Regioselective Palladium-catalyzed Double Hydroselenation of Terminal Alkynes with Benzeneselenol in the Presence of Acetic Acid
Authors: Ikeda Takuma , Tamai Taichi , Daitou Masayuki , Minamida Yoshiaki , Mitamura Takenori , Kusano Hiroki , Nomoto Akihiro , Ogawa Akiya
Published: August 2013

Palladium diacetate (Pd(OAc)2), in the presence of acetic acid, is found to exhibit excellent catalytic activity for the double hydroselenation of terminal alkynes with benzeneselenol to yield the corresponding diselenoketals regioselectively.
Palladium-catalyzed Oxidation of Benzyl Ketones to Synthesis of α-Acetoxy Ketones Using Molecular Oxygen
Authors: Chen Zheng-Wang , Ye Dong-Nai , Ye Min , Liu Liang-Xian
Published: August 2013

An efficient procedure for the preparation of α-acetoxy ketone derivatives by palladium-catalyzed oxidation reactions employing molecular oxygen as the sole oxidant has been reported. A variety of benzyl ketones were used to investigate the scope of the reactions.
Observational articles: a tool to reconstruct ecological history based on chronicling unusual events
Authors: Boero Ferdinando
Published: August 2013

Natural history is based on observations, whereas modern ecology is mostly based on experiments aimed at testing hypotheses, either in the field or in a computer. Furthermore, experiments often reveal generalities that are taken as norms. Ecology, however, is a historical discipline and history is driven by both regularities (deriving from norms) and irregularities, or contingencies, which occur when norms are broken. If only norms occured, there would be no history. The current disregard for the importance of contingencies and anecdotes is preventing us from understanding ecological history. We need rules and norms, but we also need records about apparently irrelevant things that, in non-linear systems like ecological ones, might become the drivers of change and, thus, the determinants of history. The same arguments also hold in the field of evolutionary biology, with natural selection being the ecological driver of evolutionary change. It is important that scientists are able to publish potentially important observations, particularly those that are unrelated to their current projects that have no sufficient grounds to be framed into a classical eco-evolutionary paper, and could feasibly impact on the history of the systems in which they occurred. A report on any deviation from the norm would be welcome, from the disappearance of species to their sudden appearance in great quantities. Any event that an “expert eye” (i.e. the eye of a naturalist) might judge as potentially important is worth being reported.