bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychographic Segments of College Females and Males in Relation to Substance Use Behaviors
Authors: Suragh Tiffany Ashley , Berg Carla J. , Nehl Eric J.
Published: July 2013

Objectives

A common commercial marketing segmentation technique is to divide a population into groups based on psychographic characteristics (i.e., attitudes and interests). We used this approach to define segments of female and male college students and examine substance use differences.

Method

We administered an online survey to 24,055 students at six colleges in the Southeastern United States (response rate 20.1%, n = 4,840), obtaining complete data from 3,469 participants. We assessed sociodemographics, psychographic factors such as those used by the tobacco industry to define market segments, and substance use (cigarettes, other tobacco products, alcohol, and marijuana). Cluster analysis was conducted among females and males using 15 psychographic measures (sensation seeking, Big Five personality traits, and nine measures adapted from tobacco industry documents), identifying three segments per sex.

Results

Safe responsibles were characterized by high levels of agreeableness, conscientiousness, emotional stability, academic achievement, and religious service attendance. Stoic individualists were characterized by low extraversion, sensation seeking, and openness. Thrill-seeking socializers were characterized by high levels of sensation seeking and extraversion. Among females, thrill-seeking socializers were significantly more likely than safe responsibles to have used any substance in the prior 30 days (odds ratio [OR] = 2.04, 95% confidence interval [CI] [1.65, 2.52]; Nagelkerke R2 = .084). Among males, stoic individualists (OR = 1.50, CI [1.08, 2.08]) and thrill-seeking socializers (OR = 1.53, CI [1.09, 2.13]) were more likely than safe responsibles to have used substances in the past 30 days (Nagelkerke R2: .109).

Conclusion

Psychographic segmentation can identify young adult subgroups with differing psychographic and substance use profiles and inform health campaigns and messaging targeting youth.
l-DOPA and graft-induced dyskinesia: Different treatment, same story?
Authors: Breger Ludivine S , Lane Emma L
Published: July 2013

One of the well-recognized problems of long-term l-3,4-dihydroxyphenylalanine (l-DOPA) therapy in the treatment of Parkinson’s disease is the development of l-DOPA induced dyskinesia. These abnormal movements cause significant disability and narrow the therapeutic window of l-DOPA. Cell transplantation is one of the most promising upcoming therapies for the treatment of Parkinson’s disease, and may help alleviate or avoid l-DOPA-induced dyskinesia. However, the more recently acknowledged phenomenon of graft-induced dyskinesia is posing a major obstacle to the success of this treatment. This motor side-effect closely resembles abnormal movements induced by chronic l-DOPA treatment, yet they remain after withdrawal of the medication indicating their origins lie in the transplant. In this review, we compare these two therapy-induced adverse effects, from the way they manifest in patients to the possible mechanisms underlying their development.
Extent of load-independence of pressure-normalized stress in swine
Authors: Jia Xinwei , Choy Jenny S , Zhang Zhen-Du , Svendsen Mark , Zhong Liang , Tan Ru S , Kassab Ghassan S
Published: July 2013

A load-independent index of myocardial contractility provides a measure of cardiac function. Previous contractility indices have been shown to be either load-dependent or invasive. We sought to determine the extent of load (preload and afterload)-independence of d σ*/d tmax( σ* is pressure-normalized stress) in comparison with other well-established indices. Six anaesthetized pigs underwent left ventricular pressure–volume measurements under various load conditions. The average preload was decreased by 70.0 ± 15.0% (from 39.2 ± 6.4 mL to 11.7 ± 7.7 mL) and increased by 49.3 ± 5.9% (from 35.1 ± 7.4 mL to 51.7 ± 8.9 mL). The average afterload was increased by 74.3 ± 43.5% (from 3.3 ± 0.6 mmHg/mL to 5.7 ± 1.7 mmHg/mL). When preload was reduced within an average of 21.7% (39.2 ± 6.4 mL to 30.7 ± 6.2 mL) using occlusion of the inferior vena cava, d σ*/d tmaxdid not change significantly (6.50 ± 1.10 s−1vs 6.60 ± 0.90 s−1, P = non-significant [NS]). When preload was increased within an average of 29.3% (35.1 ± 7.4 mL to 45.4 ± 7.3 mL) from infusion of normal saline, d σ*/d tmaxdid not change significantly (7.04 ± 1.00 s−1vs 7.29 ± 1.10 s−1, P = NS). When afterload was increased within an average of 42.4% (3.3 ± 0.6 mmHg/mL to 4.7 ± 1.0 mmHg/mL) using intra-aortic balloon occlusion, d σ*/d tmaxdid not change significantly (6.72 ± 1.18 s−1vs 6.89 ± 1.28 s−1, P = NS). As expected, d σ*/d tmaxwas significantly increased with dobutamine. A linear regression showed no correlation between d σ*/d tmaxand preload ( r2 = 0.02, P = 0.17) within a maximum range of −30% to +50% of preload change, or between d σ*/d tmaxand afterload ( r2 = 0.03, P = 0.36) within maximum range of 0–100% of afterload increase, respectively. In conclusion, d σ*/d tmaxis independent of loading conditions within an average of 21.7% of preload decrease, 29.3% of preload increase, 42.4% of afterload increase, and sensitive to dobutamine infusion.
Pronounced hypoxia in the subventricular zone following traumatic brain injury and the neural stem/progenitor cell response
Authors: Baumann Gisela , Travieso Lissette , Liebl Daniel J , Theus Michelle H
Published: July 2013

Traumatic brain injury (TBI) elicits identifiable changes within the adult subventricular zone (SVZ). Previously, we demonstrated that EphB3/ephrinB3 interaction inhibits neural stem/progenitor cell (NSPC) proliferation and downregulating this pathway following TBI plays a pivotal role in the expansion of the SVZ neurogenic compartment. It remains unclear, however, what early initiating factors may precede these changes. Using hypoxyprobe-1 (HPb) to identify regions of low oxygen tension or hypoxia (<1%), we found HPb uptake throughout the cortex (CTX), corpus callosum (CC) and SVZ within the first 24 h following controlled cortical impact (CCI) injury. At this early time point, HPb co-localized with EphB3 in the SVZ. NSPC specific markers also co-localized with HPb staining throughout the lateral wall of the ventricle. To determine the cell autonomous effects of hypoxia on EphB3/ephrinB3 signaling in NSPCs, we used an in vitro model of hypoxia to mimic 1% oxygen in the presence and absence of soluble aggregated ephrinB3 (eB3). As expected, hypoxia stimulated the uptake of 5-bromo-2′-deoxyuridine (BrdU) and reduced cell death. Coincident with these proliferative changes, both Hif1-α and phospho (p)-AKT were increased while EphB3 expression was decreased. Stimulation of EphB3 attenuated hypoxia-induced proliferation and prevented phosphorylation of AKT. Hif1-α accumulation, on the other hand, was not affected by EphB3/ephrinB3 signaling. These findings indicate that this pathway limits the NSPC response to hypoxic stimuli. These studies also suggest that early transient changes in oxygen tension following localized cortical injury may initiate a growth-promoting response in the SVZ.
HDAC9 gene is associated with stroke risk in a Chinese population
Authors: Han Yan , Sun Wenzhu , Wang Li , Tao Sha , Tian Lu , Hao Yong , Zhang Wei , Wu Shuai , Li Shixu , Lv Huihui , Zheng S Lilly , Sun Jielin , Xu Jianfeng
Published: July 2013

A recent Genome-Wide Association study (GWAS) identified rs11984041 on HDAC9 gene to be significantly associated with stroke in a Caucasian population. However, whether HDAC9 gene also plays a role in other ethnicities is unknown. The current study was conducted to investigate the association of single nucleotide polymorphisms (SNPs) on HDAC9 gene and stroke risk in a Chinese population. Sixteen tagging SNPs for HDAC9 gene were genotyped in a Chinese population of 279 stroke cases and 984 controls from Changhai Hospital in Shanghai, China. The candidate region of HDAC9 investigated was on a haplotype block located between two recombination hotspots in the tail region of HDAC9, the only region harbouring significantly associated SNPs based on the previous GWAS. rs11984041 was not polymorphic in Chinese population. Two other SNPs, rs2389995 and rs2240419 on HDAC9 of chromosome 7q21.1, were significantly associated with large-vessel stroke risk, with P values of 0.035 and 0.042, respectively ( Table 3 ). Individuals with risk allele (A) for rs2389995 and (T) for rs2240419 had increased risk of stroke (odds ratio [OR] = 1.33, 95% confidence interval [CI]: 1.01–1.75; and OR = 1.29, 95% CI: 1.02–1.63), respectively. Multivariate analysis including both SNPs in the logistic regression model revealed independent association effects of each SNP, with a P = 0.013 and 0.010, respectively. The results from our studies indicate HDAC9 gene is significantly associated with large-vessel stroke risk in Chinese population. However, SNPs on HDAC9 gene display heterogeneity effects across different ethnic populations. Additional studies are needed to further evaluate our results.
The value of plasma neurotensin and cytokine measurement for the detection of bowel ischaemia in clinically doubtful cases: A prospective study
Authors: Sgourakis George , Papapanagiotou Aggeliki , Kontovounisios Christos , Karamouzis Michalis V , Lanitis Sophocles , Konstantinou Chloe , Karaliotas Constantine , Papavassiliou Athanasios G
Published: July 2013

The aim of this prospective study was to examine whether serum neurotensin, interleukin (IL)-6, and IL-8 are early predictor of bowel ischaemia especially in clinically equivocal cases. To this end, 56 patients were assigned to the following groups according to their disease: bowel ischaemia (group 1: n = 14), small bowel obstruction (group 2: n = 12), acute inflammation (group 3: n = 6), perforation (group 4: n = 8), and colorectal adenocarcinoma (group 5: n = 16). Fifteen healthy controls were assigned to group 6. Blood samples were obtained at enrollment, all measurements were done blindly, and all patients underwent surgery. Pretreatment doubtful diagnosis comprised of ileus, mild abdominal pain, and indeterminate imaging. Blood urea nitrogen, lactic acidosis, diagnostic workup, and IL-6 were predictors of diagnosis in univariate analysis. In multivariate analysis, IL-6 ( P < 0.001) and diagnostic workup ( P < 0.01) were independent predictors of the definite diagnosis. Neurotensin and IL-8 did not differentiate among groups. Considering clinically doubtful cases, IL-6 perfectly differentiates mesenteric ischaemia (of infarction/embolic/occlusive aetiology) from the rest of the indeterminate pathologies. The optimum cut-off point for IL-6 was 27.66 pg/mL. The value of serum IL-6 (27.66 pg/mL) had sensitivity = 1 and specificity = 1. In conclusion, plasma IL-6 measurement on admission might be an additional diagnostic tool that can predict bowel ischaemia in doubtful clinical situations.
Transcriptomic and phylogenetic analysis of a bacterial cell cycle reveals strong associations between gene co-expression and evolution
Authors: Fang Gang , Passalacqua Karla D , Hocking Jason , Llopis Paula Montero , Gerstein Mark , Bergman Nicholas H , Jacobs-Wagner Christine
Published: July 2013

Background

The genetic network involved in the bacterial cell cycle is poorly understood even though it underpins the remarkable ability of bacteria to proliferate. How such network evolves is even less clear. The major aims of this work were to identify and examine the genes and pathways that are differentially expressed during the Caulobacter crescentus cell cycle, and to analyze the evolutionary features of the cell cycle network.

Results

We used deep RNA sequencing to obtain high coverage RNA-Seq data of five C. crescentus cell cycle stages, each with three biological replicates. We found that 1,586 genes (over a third of the genome) display significant differential expression between stages. This gene list, which contains many genes previously unknown for their cell cycle regulation, includes almost half of the genes involved in primary metabolism, suggesting that these “house-keeping” genes are not constitutively transcribed during the cell cycle, as often assumed. Gene and module co-expression clustering reveal co-regulated pathways and suggest functionally coupled genes. In addition, an evolutionary analysis of the cell cycle network shows a high correlation between co-expression and co-evolution. Most co-expression modules have strong phylogenetic signals, with broadly conserved genes and clade-specific genes predominating different substructures of the cell cycle co-expression network. We also found that conserved genes tend to determine the expression profile of their module.

Conclusion

We describe the first phylogenetic and single-nucleotide-resolution transcriptomic analysis of a bacterial cell cycle network. In addition, the study suggests how evolution has shaped this network and provides direct biological network support that selective pressure is not on individual genes but rather on the relationship between genes, which highlights the importance of integrating phylogenetic analysis into biological network studies.
Measurement of tumour size with mammography, sonography and magnetic resonance imaging as compared to histological tumour size in primary breast cancer
Authors: Gruber Ines V , Rueckert Miriam , Kagan Karl O , Staebler Annette , Siegmann Katja C , Hartkopf Andreas , Wallwiener Diethelm , Hahn Markus
Published: July 2013

Background

Tumour size in breast cancer influences therapeutic decisions. The purpose of this study was to evaluate sizing of primary breast cancer using mammography, sonography and magnetic resonance imaging (MRI) and thereby establish which imaging method most accurately corresponds with the size of the histological result.

Methods

Data from 121 patients with primary breast cancer were analysed in a retrospective study. The results were divided into the groups “ductal carcinoma in situ (DCIS)”, invasive ductal carcinoma (IDC) + ductal carcinoma in situ (DCIS)”, “invasive ductal carcinoma (IDC)”, “invasive lobular carcinoma (ILC)” and “other tumours” (tubular, medullary, mucinous and papillary breast cancer). The largest tumour diameter was chosen as the sizing reference in each case. Bland-Altman analysis was used to determine to what extent the imaging tumour size correlated with the histopathological tumour sizes.

Results

Tumour size was found to be significantly underestimated with sonography, especially for the tumour groups IDC + DCIS, IDC and ILC. The greatest difference between sonographic sizing and actual histological tumour size was found with invasive lobular breast cancer. There was no significant difference between mammographic and histological sizing. MRI overestimated non-significantly the tumour size and is superior to the other imaging techniques in sizing of IDC + DCIS and ILC.

Conclusions

The histological subtype should be included in imaging interpretation for planning surgery in order to estimate the histological tumour size as accurately as possible.
The dyslipidemia-associated SNP on the APOA1/C3/A5 gene cluster predicts post-surgery poor outcome in Taiwanese breast cancer patients: a 10-year follow-up study
Authors: Hsu Mei-Chi , Lee Kuo-Ting , Hsiao Wei-Chiang , Wu Chih-Hsing , Sun Hung-Yu , Lin I-Ling , Young Kung-Chia
Published: July 2013

Background

Post-surgery therapies are given to early-stage breast cancer patients due to the possibility of residual micrometastasis, and optimized by clincopathological parameters such as tumor stage, and hormone receptor/lymph node status. However, current efficacy of post-surgery therapies is unsatisfactory, and may be varied according to unidentified patient genetic factors. Increases of breast cancer occurrence and recurrence have been associated with dyslipidemia, which can attribute to other known risk factors of breast cancer including obesity, diabetes and metabolic syndrome. Thus we reasoned that dyslipidemia-associated nucleotide polymorphisms (SNPs) on the APOA1/C3/A5 gene cluster may predict breast cancer risk and tumor progression.

Methods

We analyzed the distribution of 5 selected APOA1/C3/A5 SNPs in recruited Taiwanese breast cancer patients (n=223) and healthy controls (n=162). The association of SNP (APOA1 rs670) showing correlation with breast cancer with baseline and follow-up parameters was further examined.

Results

APOA1 rs670 A allele carriage was higher in breast cancer patients than controls (59.64% vs. 48.77%, p=0.038). The rs670 A allele carrying patients showed less favorable baseline phenotype with positive lymph nodes (G/A: OR=3.32, 95% CI=1.77-6.20, p<0.001; A/A: OR=2.58, 95% CI=1.05-6.32, p=0.039) and negative hormone receptor expression (A/A: OR=4.85, 95%CI=1.83-12.83, p=0.001) in comparison to G/G carriers. Moreover, rs670 A/A carrying patients had higher risks in both tumor recurrence (HR=3.12, 95% CI=1.29-7.56, p=0.012) and mortality (HR=4.36, 95% CI=1.52-12.47, p=0.006) than patients with no A alleles after adjustments for associated baseline parameters. Furthermore, the prognostic effect of rs670 A/A carriage was most evident in lymph node-negative patients, conferring to the highest risks of recurrence (HR=4.98, 95% CI=1.40-17.70, p=0.013) and mortality (HR=9.87, 95%CI=1.60-60.81, p=0.014) than patients with no A alleles.

Conclusions

APOA1 rs670 A/A carriage showed poor post-surgery prognosis in Taiwanese lymph node-negative breast cancer patients, whose prognosis were considered better and adjuvant treatment might be less stringent according to currently available assessment protocols. Our findings suggest that APOA1 rs670 indicate a post-surgery risk of breast cancer disease progression, and that carriers of this SNP may benefit from more advanced disease monitoring and therapy regimens than the current regular standards. Furthermore, control of lipid homeostasis might protect APOA1 rs670 minor allele carriers from breast cancer occurrence and progression.
Effects of hypoxia on human cancer cell line chemosensitivity
Authors: Strese Sara , Fryknäs Mårten , Larsson Rolf , Gullbo Joachim
Published: July 2013

Background

Environment inside even a small tumor is characterized by total (anoxia) or partial oxygen deprivation, (hypoxia). It has been shown that radiotherapy and some conventional chemotherapies may be less effective in hypoxia, and therefore it is important to investigate how different drugs act in different microenvironments. In this study we perform a large screening of the effects of 19 clinically used or experimental chemotherapeutic drugs on five different cell lines in conditions of normoxia, hypoxia and anoxia.

Methods

A panel of 19 commercially available drugs: 5-fluorouracil, acriflavine, bortezomib, cisplatin, digitoxin, digoxin, docetaxel, doxorubicin, etoposide, gemcitabine, irinotecan, melphalan, mitomycin c, rapamycin, sorafenib, thalidomide, tirapazamine, topotecan and vincristine were tested for cytotoxic activity on the cancer cell lines A2780 (ovarian), ACHN (renal), MCF-7 (breast), H69 (SCLC) and U-937 (lymphoma). Parallel aliquots of the cells were grown at different oxygen pressures and after 72 hours of drug exposure viability was measured with the fluorometric microculture cytotoxicity assay (FMCA).

Results

Sorafenib, irinotecan and docetaxel were in general more effective in an oxygenated environment, while cisplatin, mitomycin c and tirapazamine were more effective in a low oxygen environment. Surprisingly, hypoxia in H69 and MCF-7 cells mostly rendered higher drug sensitivity. In contrast ACHN appeared more sensitive to hypoxia, giving slower proliferating cells, and consequently, was more resistant to most drugs.

Conclusions

A panel of standard cytotoxic agents was tested against five different human cancer cell lines cultivated at normoxic, hypoxic and anoxic conditions. Results show that impaired chemosensitivity is not universal, in contrast different cell lines behave different and some drugs appear even less effective in normoxia than hypoxia.
Aboriginal birth cohort (ABC): a prospective cohort study of early life determinants of adiposity and associated risk factors among Aboriginal people in Canada
Authors: Wahi Gita , Wilson Julie , Miller Ruby , Anglin Rebecca , McDonald Sarah , Morrison Katherine M , Teo Koon K , Anand Sonia S
Published: July 2013

Background

Aboriginal people living in Canada have a high prevalence of obesity, type 2 diabetes, and cardiovascular disease (CVD). To better understand the pre and postnatal influences on the development of adiposity and related cardio-metabolic factors in adult Aboriginal people, we will recruit and follow prospectively Aboriginal pregnant mothers and their children – the Aboriginal Birth Cohort (ABC) study.

Methods/design

We aim to recruit 300 Aboriginal pregnant mothers and their newborns from the Six Nations Reserve, and follow them prospectively to age 3 years. Key details of environment and health including maternal nutrition, glucose tolerance, physical activity, and weight gain will be collected. At birth, cord blood and placenta samples will be collected, as well as newborn anthropometric measurements. Mothers and offspring will be followed annually with serial measurements of diet and physical activity, growth trajectory, and adiposity.

Discussion

There is an urgent need to understand maternal and child factors that underlie the early development of adiposity and type 2 diabetes in Aboriginal people. The information generated from this cohort will assist the Six Nations community in developing interventions to prevent early adiposity in Aboriginal children.
Monoclonal antibody humanness score and its applications
Authors: Gao Sean H , Huang Kexin , Tu Hua , Adler Adam S
Published: July 2013

Background

Monoclonal antibody therapeutics are rapidly gaining in popularity for the treatment of a myriad of diseases, ranging from cancer to autoimmune diseases and neurological diseases. Multiple forms of antibody therapeutics are in use today that differ in the amount of human sequence present in both the constant and variable regions, where antibodies that are more human-like usually have reduced immunogenicity in clinical trials.

Results

Here we present a method to quantify the humanness of the variable region of monoclonal antibodies and show that this method is able to clearly distinguish human and non-human antibodies with excellent specificity. After creating and analyzing a database of human antibody sequences, we conducted an in-depth analysis of the humanness of therapeutic antibodies, and found that increased humanness score is correlated with decreased immunogenicity of antibodies. We further discovered a surprisingly similarity in the immunogenicity of fully human antibodies and humanized antibodies that are more human-like based on their humanness score.

Conclusions

Our results reveal that in most cases humanizing an antibody and confirming the humanness of the final form may be sufficient to eliminate immunogenicity issues to the same extent as using fully human antibodies. We created a public website to calculate the humanness score of any input antibody sequence based on our human antibody database. This tool will be of great value during the preclinical drug development process for new monoclonal antibody therapeutics.
Genetic variation in Tanis was associated with elevating plasma triglyceride level in Chinese nondiabetic subjects
Authors: Gao Ying , Xie Xiang , Ma Yi-Tong , Yang Yi-Ning , Li Xiao-Mei , Fu Zhen-Yan , Zheng Ying-Ying , Ma Xiang , Chen Bang-Dang , Liu Fen , Huang Ying
Published: July 2013

Background

The association of genetic polymorphisms of Tanis with triglyceride concentration in human has not been thoroughly examined. We aimed to investigate the relationship between triglyceride concentrations and Tanis genetic polymorphisms.

Methods

All participants (n=1497) selected from subjects participating in the Cardiovascular Risk Survey (CRS) study were divided into two groups according to ethnicity (Han: n=1059; Uygur: n= 438). Four tagging SNPs (rs12910524, rs1384565, rs2101171, rs4965814) of Tanis gene were genotyped using TaqMan® assays from Applied Biosystems following the manufacturer’s suggestions and analyzed in an ABI 7900HT Fast Real-Time PCR System.

Results

We found that the SNP rs12910524 was associated with triglyceride levels by analyses of a dominant model (P<0.001), recessive model (P <0.001) and additive model (P < 0.001) not only in Han ethnic but also in Uygur ethnic group, and the difference remained significant after the adjustment of sex, age, alcohol intake, smoking, BMI and plasma glucose (GLU) level (All P < 0.001). However, this relationship was not observed in rs1384565, rs2101171, and rs4965814 before and after multivariate adjustment (All P > 0.05). Furthermore, there were significant interactions between rs12910524 and GLU on TG both in Han (P=0.001) and Uygur population (P=2.60×10-4).

Conclusion

Our results indicated that the rs12910524 in the Tanis gene was associated with triglyceride concentrations in subjects without diabetes in China.
Correction of microplate location effects improves performance of the thrombin generation test
Authors: Liang Yideng , Woodle Samuel A , Shibeko Alexey M , Lee Timothy K , Ovanesov Mikhail V
Published: July 2013

Background

Microplate-based thrombin generation test (TGT) is widely used as clinical measure of global hemostatic potential and it becomes a useful tool for control of drug potency and quality by drug manufactures. However, the convenience of the microtiter plate technology can be deceiving: microplate assays are prone to location-based variability in different parts of the microtiter plate.

Methods

In this report, we evaluated the well-to-well consistency of the TGT variant specifically applied to the quantitative detection of the thrombogenic substances in the immune globulin product. We also studied the utility of previously described microplate layout designs in the TGT experiment.

Results

Location of the sample on the microplate (location effect) contributes to the variability of TGT measurements. Use of manual pipetting techniques and applications of the TGT to the evaluation of procoagulant enzymatic substances are especially sensitive. The effects were not sensitive to temperature or choice of microplate reader. Smallest location effects were observed with automated dispenser-based calibrated thrombogram instrument. Even for an automated instrument, the use of calibration curve resulted in up to 30% bias in thrombogenic potency assignment.

Conclusions

Use of symmetrical version of the strip-plot layout was demonstrated to help to minimize location artifacts even under the worst-case conditions. Strip-plot layouts are required for quantitative thrombin-generation based bioassays used in the biotechnological field.
Room-temperature violet luminescence and ultraviolet photodetection of Sb-doped ZnO/Al-doped ZnO homojunction array
Authors: Chen Wei-Jen , Wu Jen-Kai , Lin Jheng-Cyuan , Lo Shun-Tsung , Lin Huang-De , Hang Da-Ren , Shih Ming Feng , Liang Chi-Te , Chang Yuan Huei
Published: July 2013

A Sb-doped ZnO microrod array was fabricated on an Al-doped ZnO thin film by electrodeposition. Strong violet luminescence, originated from free electron-to-acceptor level transitions, was identified by temperature-dependent photoluminescence measurements. This acceptor-related transition was attributed to substitution of Sb dopants for Zn sites, instead of O sites, to form a complex with two Zn vacancies (VZn), the SbZn-2VZn complex. This SbZn-2VZn complex has a lower formation energy and acts as a shallow acceptor which can induce the observed strong violet luminescence. The photoresponsivity of our ZnO p-n homojunction device under a negative bias demonstrated a nearly 40-fold current gain, illustrating that our device is potentially an excellent candidate for photodetector applications in the ultraviolet wavelength region.
3D-image-guided high-dose-rate intracavitary brachytherapy for salvage treatment of locally persistent nasopharyngeal carcinoma
Authors: Ren Yu Feng , Cao Xin Ping , Xu Jia , Ye Wei Jun , Gao Yuan Hong , Teh Bin S , Wen Bi Xiu
Published: July 2013

Background

To evaluate the therapeutic benefit of 3D-image-guided high-dose-rate intracavitary brachytherapy (3D-image-guided HDR-BT) used as a salvage treatment of intensity modulated radiation therapy (IMRT) in patients with locally persistent nasopharyngeal carcinoma (NPC).

Methods

Thirty-two patients with locally persistent NPC after full dose of IMRT were evaluated retrospectively. 3D-image-guided HDR-BT treatment plan was performed on a 3D treatment planning system (PLATO BPS 14.2). The median dose of 16 Gy was delivered to the 100% isodose line of the Gross Tumor Volume.

Results

The whole procedure was well tolerated under local anesthesia. The actuarial 5-y local control rate for 3D-image-guided HDR-BT was 93.8%, patients with early-T stage at initial diagnosis had 100% local control rate. The 5-y actuarial progression-free survival and distant metastasis-free survival rate were 78.1%, 87.5%. One patient developed and died of lung metastases. The 5-y actuarial overall survival rate was 96.9%.

Conclusions

Our results showed that 3D-image-guided HDR-BT would provide excellent local control as a salvage therapeutic modality to IMRT for patients with locally persistent disease at initial diagnosis of early-T stage NPC.
Retinoic acid regulates olfactory progenitor cell fate and differentiation
Authors: Paschaki Marie , Cammas Laura , Muta Yuko , Matsuoka Yoko , Mak Siu-Shan , Rataj-Baniowska Monika , Fraulob Valurie , Dolle Pascal , Ladher Raj K
Published: July 2013

Background

In order to fulfill their chemosensory function, olfactory neurons are in direct contact with the external environment and are therefore exposed to environmental aggressive factors. Olfaction is maintained through life because, unlike for other sensory neuroepithelia, olfactory neurons have a unique capacity to regenerate after trauma. The mechanisms that control the ontogenesis and regenerative ability of these neurons are not fully understood. Here, we used various experimental approaches in two model systems (chick and mouse) to assess the contribution of retinoic acid signaling in the induction of the olfactory epithelium, the generation and maintenance of progenitor populations, and the ontogenesis and differentiation of olfactory neurons.

Results

We show that retinoic acid signaling, although dispensable for initial induction of the olfactory placode, plays a key role in neurogenesis within this neuroepithelium. Retinoic acid depletion in the olfactory epithelium, both in chick and mouse models, results in a failure of progenitor cell maintenance and, consequently, differentiation of olfactory neurons is not sustained. Using an explant system, we further show that renewal of olfactory neurons is hindered if the olfactory epithelium is unable to synthesize retinoic acid.

Conclusions

Our data show that retinoic acid is not a simple placodal inductive signal, but rather controls olfactory neuronal production by regulating the fate of olfactory progenitor cells. Retinaldehyde dehydrogenase 3 (RALDH3) is the key enzyme required to generate retinoic acid within the olfactory epithelium.
Transcriptome response to alkane biofuels in Saccharomyces cerevisiae: identification of efflux pumps involved in alkane tolerance
Authors: Ling Hua , Chen Binbin , Kang Aram , Lee Jong-Min , Chang Matthew Wook
Published: July 2013

Background

Hydrocarbon alkanes have been recently considered as important next-generation biofuels because microbial production of alkane biofuels was demonstrated. However, the toxicity of alkanes to microbial hosts can possibly be a bottleneck for high productivity of alkane biofuels. To tackle this toxicity issue, it is essential to understand molecular mechanisms of interactions between alkanes and microbial hosts, and to harness these mechanisms to develop microbial host strains with improved tolerance against alkanes. In this study, we aimed to improve the tolerance of Saccharomyces cerevisiae, a model eukaryotic host of industrial significance, to alkane biofuels by exploiting cellular mechanisms underlying alkane response.

Results

To this end, we first confirmed that nonane (C9), decane (C10), and undecane (C11) were significantly toxic and accumulated in S. cerevisiae. Transcriptome analyses suggested that C9 and C10 induced a range of cellular mechanisms such as efflux pumps, membrane modification, radical detoxification, and energy supply. Since efflux pumps could possibly aid in alkane secretion, thereby reducing the cytotoxicity, we formed the hypothesis that those induced efflux pumps could contribute to alkane export and tolerance. In support of this hypothesis, we demonstrated the roles of the efflux pumps Snq2p and Pdr5p in reducing intracellular levels of C10 and C11, as well as enhancing tolerance levels against C10 and C11. This result provided the evidence that Snq2p and Pdr5p were associated with alkane export and tolerance in S. cerevisiae.

Conclusions

Here, we investigated the cellular mechanisms of S. cerevisiae response to alkane biofuels at a systems level through transcriptome analyses. Based on these mechanisms, we identified efflux pumps involved in alkane export and tolerance in S. cerevisiae. We believe that the results here provide valuable insights into designing microbial engineering strategies to improve cellular tolerance for highly efficient alkane biofuel production.
Rapid assay to assess colonization patterns following in-vivo probiotic ingestion
Authors: Tobin Jacinta M , Garland Suzanne M , Jacobs Susan E , Pirotta Marie , Tabrizi Sepehr N
Published: July 2013

Background

Colonization of the intestine with some microorganisms has been shown to have beneficial health effects. The association of bacteria with its human host starts soon after birth; however in infants born prematurely establishment of normal intestinal flora is interrupted with colonization with potential pathogenic organisms Probiotic supplementation may therefore be beneficial to the health of preterm infants. As most probiotic organisms are difficult to culture, confirmation of their colonization after supplementation is difficult. In this study, rapid qPCR assays for detection of presence of probiotic species in the intestine by faecal sampling is described in both preterm infant and adult participants.

Findings

Probiotic colonization was determined using qPCR directed at amplification of organisms present in the ingested probiotic Streptococcus thermophilus, Bifidobacterium animalis subsp. lactis and B. longum subsp. infantis. Overall, differential detection of probiotic strains in faeces were found between adult and preterm infants, with 50% of infants continuing to shed at least two probiotic strains three weeks after probiotic ingestion had ceased.

Conclusions

This study demonstrated rapid assessment of the preterm infant gut for colonization with probiotic strains using real-time PCR. This method would be of great importance in studies of probiotics in prevention of diseases and adverse clinical outcomes.
High EpCAM expression is linked to proliferation and lauren classification in gastric cancer
Authors: Kroepil Feride , Dulian Agnieszka , Vallböhmer Daniel , Geddert Helene , Krieg Andreas , Vay Christian , Topp Stefan A , Schulte am Esch Jan , Baldus Stephan E , Gires Olivier , Knoefel Wolfram T , Stoecklein Nikolas H
Published: July 2013

Background

The association of EpCAM expression with the progression of gastric cancer remains unclear. Here, we investigated the expression of EpCAM in gastric cancer subtypes and correlated the data to tumor cell proliferation and clinicopathologic factors.

Methods

The intratumoral expression of EpCAM was assessed in 163 primary gastric cancers (61 diffuse-, 62 intestinal-, 32 mixed-type and 8 unclassified tumors) by immunohistochemistry, using the monoclonal antibody Ber-EP4. Intensity of staining was classified according the HercepTest-score using a standardized scoring system. Ki-67 was used to examine the proliferation in tumor tissue.

Results

Strong EpCAM expression was observed in 77% of the tumors and in 85% of the corresponding lymph nodes. Of the primary tumors, 58% (n=74) presented a homogeneous intratumoral EpCAM expression while 42% were characterised by a heterogenous expression pattern. Tumors with high EpCAM expression at the invasive front were associated with significantly (p=0.03) higher proportion of lymph node metastases and lower median overall survival (p=0.001). Diffuse type tumors presented a significantly higher EpCAM expression at the invasion front compared with the tumor centre (p=0.036). Multivariate survival analysis identified high EpCAM expression at the invasive front as an independent prognostic factor.

We observed a significant (p=0.001) correlation between high EpCAM expression and higher tumor cell proliferation.

Conclusion

High EpCAM expression associates with proliferation and progression of gastric cancer, especially in the diffuse type. Considering the discontenting results of the current adjuvant concepts for gastric cancer patients, EpCAM might be target in the adjuvant therapy of this malignant disease.
A quantitative atlas of histone modification signatures from human cancer cells
Authors: LeRoy Gary , DiMaggio Peter A , Chan Eric Y , Zee Barry M , Blanco M Andres , Bryant Barbara , Flaniken Ian Z , Liu Sherry , Kang Yibin , Trojer Patrick , Garcia Benjamin A
Published: July 2013

Background

An integral component of cancer biology is the understanding of molecular properties uniquely distinguishing one cancer type from another. One class of such properties is histone post-translational modifications (PTMs). Many histone PTMs are linked to the same diverse nuclear functions implicated in cancer development, including transcriptional activation and epigenetic regulation, which are often indirectly assayed with standard genomic technologies. Thus, there is a need for a comprehensive and quantitative profiling of cancer lines focused on their chromatin modification states.

Results

To complement genomic expression profiles of cancer lines, we report the proteomic classification of 24 different lines, the majority of which are cancer cells, by quantifying the abundances of a large panel of single and combinatorial histone H3 and H4 PTMs, and histone variants. Concurrent to the proteomic analysis, we performed transcriptomic analysis on histone modifying enzyme abundances as a proxy for quantifying their activity levels. While the transcriptomic and proteomic results were generally consistent in terms of predicting histone PTM abundance from enzyme abundances, several PTMs were regulated independently of the modifying enzyme expression. In addition, combinatorial PTMs containing H3K27 methylation were especially enriched in breast cell lines. Knockdown of the predominant H3K27 methyltransferase, enhancer of zeste 2 (EZH2), in a mouse mammary xenograft model significantly reduced tumor burden in these animals and demonstrated the predictive utility of proteomic techniques.

Conclusions

Our proteomic and genomic characterizations of the histone modification states provide a resource for future investigations of the epigenetic and non-epigenetic determinants for classifying and analyzing cancer cells.
Functional impact of Aurora A-mediated phosphorylation of HP1γ at serine 83 during cell cycle progression
Authors: Grzenda Adrienne , Leonard Phoebe , Seo Seungmae , Mathison Angela J , Urrutia Guillermo , Calvo Ezequiel , Iovanna Juan , Urrutia Raul , Lomberk Gwen
Published: July 2013

Background

Previous elegant studies performed in the fission yeastSchizosaccharomyces pombehave identified a requirement for heterochromatin protein 1 (HP1) for spindle pole formation and appropriate cell division. In mammalian cells, HP1γ has been implicated in both somatic and germ cell proliferation. High levels of HP1γ protein associate with enhanced cell proliferation and oncogenesis, while its genetic inactivation results in meiotic and mitotic failure. However, the regulation of HP1γ by kinases, critical for supporting mitotic progression, remains to be fully characterized.

Results

We report for the first time that during mitotic cell division, HP1γ colocalizes and is phosphorylated at serine 83 (Ser83) in G2/M phase by Aurora A. Since Aurora A regulates both cell proliferation and mitotic aberrations, we evaluated the role of HP1γ in the regulation of these phenomena using siRNA-mediated knockdown, as well as phosphomimetic and nonphosphorylatable site-directed mutants. We found that genetic downregulation of HP1γ, which decreases the levels of phosphorylation of HP1γ at Ser83(P-Ser83-HP1γ), results in mitotic aberrations that can be rescued by reintroducing wild type HP1γ, but not the nonphosphorylatable S83A-HP1γ mutant. In addition, proliferation assays showed that the phosphomimetic S83D-HP1γ increases 5-ethynyl-2´-deoxyuridine (EdU) incorporation, whereas the nonphosphorylatable S83A-HP1γ mutant abrogates this effect. Genome-wide expression profiling revealed that the effects of these mutants on mitotic functions are congruently reflected in G2/M gene expression networks in a manner that mimics the on and off states for P-Ser83-HP1γ.

Conclusions

This is the first description of a mitotic Aurora A-HP1γ pathway, whose integrity is necessary for the execution of proper somatic cell division, providing insight into specific types of posttranslational modifications that associate to distinct functional outcomes of this important chromatin protein.
Optimization of L-asparaginase production by Serratia marcescens (NCIM 2919) under solid state fermentation using coconut oil cake
Authors: Ghosh Sangita , Murthy Sonam , Govindasamy Sharmila , Chandrasekaran Muthukumaran
Published: July 2013

Background

The present study focused on utilization of agrowaste byproducts generated from oil mill for L-asparaginase enzyme production using Serratia marcescens under solid state fermentation. Classical and statistical methods were employed to optimize the process variables and the results were compared.

Results

The classical one factor at a time (OFAT) and response surface methodology (RSM) are employed to optimize the fermentation process. When used as the sole carbon source in SSF, coconut oil cake (COC) showed maximum enzyme production. The optimal values of substrate amount, initial moisture content, pH and temperature were found to be 6 g, 40%, 6 and 35°C respectively under classical optimization method with maximum enzyme activity of 3.87 (U gds-1). Maximum enzyme activity of 5.86 U gds-1 was obtained at the predicted optimal conditions of substrate amount 7.6 g of COC, initial moisture content of substrate 50%, temperature 35.5°C and pH 7.4. Validation results proved that a good relation existed between the experimental and the predicted model.

Conclusions

RSM optimization approach enhances the enzyme production to 33% when compared to classical method. Utilization of coconut oil cake as a low cost substrate in SSF for L-asparaginase production makes the process economical and also reduces the environmental pollution by converting the oil mill solid waste into a useful bioproduct.
Temporal factors in the extinction of fear in inbred mouse strains differing in extinction efficacy
Authors: MacPherson Kathryn , Whittle Nigel , Camp Marguerite , Gunduz-Cinar Ozge , Singewald Nicolas , Holmes Andrew
Published: July 2013

Background

Various neuropsychiatric conditions, including posttraumatic stress disorder (PTSD), are characterized by deficient fear extinction, but individuals differ greatly in risk for these. While there is growing evidence that fear extinction is influenced by certain procedural variables, it is unclear how these influences might vary across individuals and subpopulations. To model individual differences in fear extinction, prior studies identified a strain of inbred mouse, 129S1/SvImJ (S1), which exhibits a profound deficit in fear extinction, as compared to other inbred strains, such as C57BL/6J (B6).

Methods

Here, we assessed the effects of procedural variables on the impaired extinction phenotype of the S1 strain and, by comparison, the extinction-intact B6 strain. The variables studied were 1) the interval between conditioning and extinction, 2) the interval between cues during extinction training, 3) single-cue exposure before extinction training, and 4) extinction of a second-order conditioned cue.

Results

Conducting extinction training soon after (‘immediately’) conditioning attenuated fear retrieval in S1 mice and impaired extinction in B6 mice. Spacing cue presentations with long inter-trial intervals during extinction training augmented fear in S1 and B6 mice. The effect of spacing was lost with one-trial fear conditioning in B6, but not S1 mice. A single exposure to a conditioned cue before extinction training did not alter extinction retrieval, either in B6 or S1 mice. Both the S1 and B6 strains exhibited robust second-order fear conditioning, in which a cue associated with footshock was sufficient to serve as a conditioned exciter to condition a fear association to a second cue. B6 mice extinguished the fear response to the second-order conditioned cue, but S1 mice failed to do so.

Conclusions

These data provide further evidence that fear extinction is strongly influenced by multiple procedural variables and is so in a highly strain-dependent manner. This suggests that the efficacy of extinction-based behavioral interventions, such as exposure therapy, for trauma-related anxiety disorders will be determined by the procedural parameters employed and the degree to which the patient can extinguish.
Bacillus subtilis natto: a non-toxic source of poly-γ-glutamic acid that could be used as a cryoprotectant for probiotic bacteria
Authors: Bhat Aditya R , Irorere Victor U , Bartlett Terry , Hill David , Kedia Gopal , Morris Mark R , Charalampopoulos Dimitris , Radecka Iza
Published: July 2013

It is common practice to freeze dry probiotic bacteria to improve their shelf life. However, the freeze drying process itself can be detrimental to their viability. The viability of probiotics could be maintained if they are administered within a microbially produced biodegradable polymer - poly-γ-glutamic acid (γ-PGA) - matrix. Although the antifreeze activity of γ-PGA is well known, it has not been used for maintaining the viability of probiotic bacteria during freeze drying. The aim of this study was to test the effect of γ-PGA (produced by B. subtilis natto ATCC 15245) on the viability of probiotic bacteria during freeze drying and to test the toxigenic potential of B. subtilis natto. 10% γ-PGA was found to protect Lactobacillus paracasei significantly better than 10% sucrose, whereas it showed comparable cryoprotectant activity to sucrose when it was used to protect Bifidobacterium breve and Bifidobacterium longum. Although γ-PGA is known to be non-toxic, it is crucial to ascertain the toxigenic potential of its source, B. subtilis natto. Presence of six genes that are known to encode for toxins were investigated: three component hemolysin (hbl D/A), three component non-haemolytic enterotoxin (nheB), B. cereus enterotoxin T (bceT), enterotoxin FM (entFM), sphingomyelinase (sph) and phosphatidylcholine-specific phospholipase (piplc). From our investigations, none of these six genes were present in B. subtilis natto. Moreover, haemolytic and lecithinase activities were found to be absent. Our work contributes a biodegradable polymer from a non-toxic source for the cryoprotection of probiotic bacteria, thus improving their survival during the manufacturing process.