bluuebunny/crossref_metadata_2025 huggingface dataset:
Conformation-Dependent High-Affinity Potent Ricin-Neutralizing Monoclonal Antibodies
Authors: Hu Wei-Gang , Yin Junfei , Chau Damon , Hu Charles Chen , Lillico Dustin , Yu Justin , Negrych Laurel M. , Cherwonogrodzky John W.
Published: December 2012

Ricin is a potential biothreat agent with no approved antidote available for ricin poisoning. The aim of this study was to develop potent antibody-based antiricin antidotes. Four strong ricin resistant hybridoma clones secreting antiricin monoclonal antibodies (mAbs) were developed. All four mAbs are bound to conformational epitopes of ricin toxin B (RTB) with high affinity (KDvalues from 2.55 to 36.27 nM). RTB not only triggers cellular uptake of ricin, but also facilitates transport of the ricin toxin A (RTA) from the endoplasmic reticulum to the cytosol, where RTA exerts its toxic activity. The four mAbs were found to have potent ricin-neutralizing capacities and synergistic effects among them as determined by anin vitroneutralization assay.In vivoprotection assay demonstrated that all four mAbs had strong efficacy against ricin challenges. D9 was found to be exceptionally effective. Intraperitoneal (i.p.) administration of D9, at a dose of 5 μg, 6 weeks before or 6 hours after an i.p. challenge with 5 × LD50 of ricin was able to protect or rescue 100% of the mice, indicating that mAb D9 is an excellent candidate to be developed as a potent antidote against ricin poisoning for both prophylactic and therapeutic purposes.
What Is Recent in Pancreatic Cancer Immunotherapy?
Authors: Niccolai Elena , Prisco Domenico , D'Elios Mario Milco , Amedei Amedeo
Published: December 2012

Pancreatic cancer (PC) represents an unresolved therapeutic challenge, due to the poor prognosis and the reduced response to currently available treatments. Pancreatic cancer is the most lethal type of digestive cancers, with a median survival of 4–6 months. Only a small proportion of PC patients is curative by surgical resection, whilst standard chemotherapy for patients in advanced disease generates only modest effects with considerable toxic damages. Thus, new therapeutic approaches, specially specific treatments such as immunotherapy, are needed. In this paper we analyze recent preclinical and clinical efforts towards immunotherapy of pancreatic cancer, including passive and active immunotherapy approaches, designed to target pancreatic-cancer-associated antigens and to elicit an antitumor responsein vivo.
Corticospinal Reorganization after Locomotor Training in a Person with Motor Incomplete Paraplegia
Authors: Hajela Nupur , Mummidisetty Chaithanya K. , Smith Andrew C. , Knikou Maria
Published: December 2012

Activity-dependent plasticity as a result of reorganization of neural circuits is a fundamental characteristic of the central nervous system that occurs simultaneously in multiple sites. In this study, we established the effects of subthreshold transcranial magnetic stimulation (TMS) over the primary motor cortex region on the tibialis anterior (TA) long-latency flexion reflex. Neurophysiological tests were conducted before and after robotic gait training in one person with a motor incomplete spinal cord injury (SCI) while at rest and during robotic-assisted stepping. The TA flexion reflex was evoked following nonnociceptive sural nerve stimulation and was conditioned by TMS at 0.9 TA motor evoked potential resting threshold at conditioning-test intervals that ranged from 70 to 130 ms. Subthreshold TMS induced a significant facilitation on the TA flexion reflex before training, which was reversed to depression after training with the subject seated at rest. During stepping, corticospinal facilitation of the flexion reflex at early and midstance phases before training was replaced with depression at early and midswing followed by facilitation at late swing after training. These results constitute the first neurophysiologic evidence that locomotor training reorganizes the cortical control of spinal interneuronal circuits that generate patterned motor activity, modifying spinal reflex function, in the chronic lesioned human spinal cord.
Cell Mechanosensitivity: Mechanical Properties and Interaction with Gravitational Field
Authors: Ogneva I. V.
Published: December 2012

This paper addressed the possible mechanisms of primary reception of a mechanical stimulus by different cells. Data concerning the stiffness of muscle and nonmuscle cells as measured by atomic force microscopy are provided. The changes in the mechanical properties of cells that occur under changed external mechanical tension are presented, and the initial stages of mechanical signal transduction are considered. The possible mechanism of perception of different external mechanical signals by cells is suggested.
Quantification of Cigarette Smoke Particle DepositionIn VitroUsing a Triplicate Quartz Crystal Microbalance Exposure Chamber
Authors: Adamson Jason , Thorne David , McAughey John , Dillon Deborah , Meredith Clive
Published: December 2012

There are a variety of smoke exposure systems available to the tobacco industry and respiratory toxicology research groups, each with their own way of diluting/delivering smoke to cell cultures. Thus a simple technique to measure dosein vitroneeds to be utilised. Dosimetry—assessment of dose—is a key element in linking the biological effects of smoke generated by various exposure systems. Microbalance technology is presented as a dosimetry tool and a way of measuring whole smoke dose. Described here is a new tool to quantify diluted smoke particulate depositionin vitro. The triplicate quartz crystal microbalance (QCM) chamber measured real-time deposition of smoke at a range of dilutions 1 : 5–1 : 400 (smoke : air). Mass was read in triplicate by 3 identical QCMs installed into onein vitroexposure chamber, each in the location in which a cell culture would be exposed to smoke at the air-liquid interface. This resulted in quantification of deposited particulate matter in the range 0.21–28.00 μg/cm2. Results demonstrated that the QCM could discriminate mass between dilutions and was able to give information of regional deposition where cell cultures would usually be exposed within the chamber. Our aim is to use the QCM to support the preclinical (in vitro) evaluation of tobacco products.
ToxocaraSeroprevalence in Patients with Idiopathic Parkinson's Disease: Chance Association or Coincidence?
Authors: Çelik Tuncay , Kaplan Yüksel , Ataş Eser , Öztuna Derya , Berilgen Said
Published: December 2012

Most cases of idiopathic Parkinson disease (IPD) are believed to be due to a combination of genetic and environmental factors. The purpose of this study is to investigate the relationship between toxocariasis and Parkinson disease (PD). Patients were selected from people who were admitted to the Movement Disorders Branch, Neurology Department of Elazığ University Faculty of Medicine Elazığ, Turkey. We studied specific IgG antibodies againstToxocara canis(T. canis) in 50 patients with idiopathic Parkinson and 50 healthy volunteers. We investigated the clinical history of three patients infected withT. canis. We also studied specific IgG antibodies againstToxoplasma gondiiin these groups. Antibodies anti-Toxocara caniswere found in 3 idiopathic PD (6%) (P=0.121) and antibody titer was not found in control. A patient had history of the presence of dog in current dog ownership. We did not detect any statistically significant association betweenT. canisand IPD. But, we believe that further comprehensive studies are required for understanding whether there is a causal relation between toxocariasis and PD. We didn’t find possible association betweenToxoplasma gondiiand IPD (P=0.617).
Is the Second Sodium Pump Electrogenic?
Authors: Thomas L. E. , Rocafull M. A. , del Castillo J. R.
Published: December 2012

Transepithelial sodium transport is a process that involves active Na+transport at the basolateral membrane of the epithelial cell. This process is mediated by the Na+/K+pump, which exchanges 3 internal Na+by 2 external K+inducing a net charge movement and the second Na+pump, which transports Na+accompanied by Cl−and water. It has been suggested that this pump could also be electrogenic. Herein, we evaluated, in MDCK cells, the short-circuit current (Isc) generated by these Na+pumps at the basolateral membrane of the epithelial cells, using amphotericin B as an apical permeabilizing agent. In Cl−-containing media,Iscinduced by amphotericin B is totally inhibited by ouabain, indicating that only the electrogenic Na+/K+pump is detectable in the presence of Cl−. Electrogenicity of the second Na+pump can be demonstrated in Cl−-free media. The existence of a furosemide-sensitive component ofIsc, in addition to an ouabain-sensitive one, was identified in absence of chloride. Passive Cl−movement associated with the function of the second Na+pump seems to be regulated by the pump itself. These results demonstrate that the second Na+pump is an electroneutral mechanism result from the stoichiometric movement of Na+and Cl−across the basolateral plasma membrane of the epithelial cell.
Essential Oils from Fruits with Different Colors and Leaves ofNeomitranthes obscura(DC.) N. Silveira: An Endemic Species from Brazilian Atlantic Forest
Authors: Amaral Raquel R. , Fernandes Caio P. , Caramel Otávio P. , Tietbohl Luis A. C. , Santos Marcelo G. , Carvalho José C. T. , Rocha Leandro
Published: December 2012

Neomitranthes obscura(DC.) N. Silveira is an endemic plant of Brazilian Atlantic Forest and widely spread in the sandbanks of “Restinga de Jurubatiba” National Park. It is popularly known by local population as “camboim-de-cachorro” or “cambuí-preto” and recognized by its black ripe fruits. However, specimens with yellow ripe fruits were localized in the “Restinga de Jurubatiba” National Park. The aim of the present study was to evaluate chemical composition of essential oils obtained from leaves and fruits ofN. obscuraspecimens with different fruit color (black and yellow) by GC and GC-MS. Essential oils from leaves of specimens with black and yellow fruits indicated a predominance of sesquiterpenes (81.1% and 84.8%, resp.). Meanwhile, essential oil from black fruits presented a predominance of monoterpenes (50.5%), while essential oil from yellow fruits had sesquiterpenes (39.9%) as major substances. Despite previous studies about this species, including essential oil extraction, to our knowledge this is the first report onN. obscurafruits with different colors. Our results suggest the occurrence of unless two different varieties for this species.
Oxidative Stress Induces Mitochondrial DNA Damage and Cytotoxicity through Independent Mechanisms in Human Cancer Cells
Authors: Han Yue , Chen Junjian Z.
Published: December 2012

Intrinsic oxidative stress through increased production of reactive oxygen species (ROS) is associated with carcinogenic transformation, cell toxicity, and DNA damage. Mitochondrial DNA (mtDNA) is a natural surrogate to oxidative DNA damage. MtDNA damage results in the loss of its supercoiled structure and is readily detectable using a novel, supercoiling-sensitive real-time PCR method. Our studies have demonstrated that mtDNA damage, as measured by DNA strand breaks and copy number depletion, is very sensitive to exogenous H2O2but independent of endogenous ROS production in both prostate cancer and normal cells. In contrast, aggressive prostate cancer cells exhibit a more than 10-fold sensitivity to H2O2-induced cell toxicity than normal cells, and a cascade of secondary ROS production is a critical determinant to the differential response. We propose a new paradigm to account for different mechanisms governing cellular oxidative stress, cell toxicity, and DNA damage with important ramifications in devising new techniques and strategies in prostate cancer prevention and treatment.
Patients' Attitudes towards the Surplus Frozen Embryos in China
Authors: Jin Xuan , Wang GongXian , Liu SiSun , Liu Ming , Zhang Jing , Shi YuFa
Published: December 2012

Background. Assisted reproductive techniques have been used in China for more than 20 years. This study investigates the attitudes of surplus embryo holders towards embryos storage and donation for medical research.Methods. A total of 363 couples who had completed in vitro fertilization (IVF) treatment and had already had biological children but who still had frozen embryos in storage were invited to participate. Interviews were conducted by clinics in a narrative style.Results. Family size was the major reason for participants’ (dis)continuation of embryo storage; moreover, the moral status of embryos was an important factor for couples choosing embryo storage, while the storage fee was an important factor for couples choosing embryo disposal. Most couples discontinued the storage of their embryos once their children were older than 3 years. In our study, 58.8% of the couples preferred to dispose of surplus embryos rather than donate them to research, citing a lack of information and distrust in science as significant reasons for their decision.Conclusions. Interviews regarding frozen embryos, including patients’ expectations for embryo storage and information to assist them with decisions regarding embryo disposal, are beneficial for policies addressing embryo disposition and embryo donation in China.
Quilts
Authors: Higgs Elizabeth , Radosh Polly F.
Published: December 2012

Across time and culture, women connect generations through traditions. Women often bequeath family mementos to succeeding women. Quilts made by women commemorate, illustrate, or express important events. While these items have economic value, their primary worth is in the connections they make within families. Quilts are frequently passed on in matrilineal gifts and bequests. Their value is in the familial networks and reflects a moral economy that embraces matrilineal norms and values. As a nearly exclusively female artistic expression, the meanings embedded in quilts reflect knowledge across time. This article reviews the historical significance of quilts and analyzes the matrilineal connections in quilts in multicultural contexts.
In ovo serial skeletal muscle diffusion tractography of the developing chick embryo using DTI: feasibility and correlation with histology
Authors: Zhou Zien , DelProposto Zachary , Wu Lianming , Xu Jianrong , Hua Jia , Zhou Yan , Ye Yongquan , Zhang Zishu , Hu Jiani , Haacke E Mark
Published: December 2012

Background

Magnetic resonance imaging is a noninvasive method of evaluating embryonic development. Diffusion tensor imaging (DTI), based on the directional diffusivity of water molecules, is an established method of evaluating tissue structure. Yet embryonic motion degrades the in vivo acquisition of long-duration DTI. We used a dual-cooling technique to avoid motion artifact and aimed to investigate whether DTI can be used to monitor chick embryonic skeletal muscle development in ovo, and to investigate the correlation between quantitative DTI parameters fractional anisotropy (FA) and fiber length and quantitative histologic parameters fiber area percentage (FiberArea%) and limb length.

Results

From 84 normally developing chick embryos, 5 were randomly chosen each day from incubation days 5 to 18 and scanned using 3.0 Tesla magnetic resonance imaging. A dual-cooling technique is used before and during imaging. Eggs were cracked for making histological specimen after imaging. 3 eggs were serially imaged from days 5 to 18. We show that skeletal muscle fibers can be tracked in hind limb in DTI beginning with incubation day 8. Our data shows a good positive correlation between quantitative DTI and histologic parameters (FA vs FiberArea%: r= 0.943, p<0.0001; Fiber_length vs Limb_length: r=0.974, p<0.0001). The result of tracked fibers in DTI during incubation corresponds to the development of chick embryonic skeletal muscle as reported in the literature.

Conclusion

Diffusion tensor imaging can provide a noninvasive means of evaluating skeletal muscle development in ovo.
Evolution of cichlid vision via trans-regulatory divergence
Authors: O’Quin Kelly E , Schulte Jane E , Patel Zil , Kahn Nadia , Naseer Zan , Wang Helena , Conte Matthew A , Carleton Karen L
Published: December 2012

Background

Phenotypic evolution may occur through mutations that affect either the structure or expression of protein-coding genes. Although the evolution of color vision has historically been attributed to structural mutations within the opsin genes, recent research has shown that opsin regulatory mutations can also tune photoreceptor sensitivity and color vision. Visual sensitivity in African cichlid fishes varies as a result of the differential expression of seven opsin genes. We crossed cichlid species that express different opsin gene sets and scanned their genome for expression Quantitative Trait Loci (eQTL) responsible for these differences. Our results shed light on the role that different structural, cis-, and trans-regulatory mutations play in the evolution of color vision.

Results

We identified 11 eQTL that contribute to the divergent expression of five opsin genes. On three linkage groups, several eQTL formed regulatory “hotspots” associated with the expression of multiple opsins. Importantly, however, the majority of the eQTL we identified (8/11 or 73%) occur on linkage groups located trans to the opsin genes, suggesting that cichlid color vision has evolved primarily via trans-regulatory divergence. By modeling the impact of just two of these trans-regulatory eQTL, we show that opsin regulatory mutations can alter cichlid photoreceptor sensitivity and color vision at least as much as opsin structural mutations can.

Conclusions

Combined with previous work, we demonstrate that the evolution of cichlid color vision results from the interplay of structural, cis-, and especially trans-regulatory loci. Although there are numerous examples of structural and cis-regulatory mutations that contribute to phenotypic evolution, our results suggest that trans-regulatory mutations could contribute to phenotypic divergence more commonly than previously expected, especially in systems like color vision, where compensatory changes in the expression of multiple genes are required in order to produce functional phenotypes.
Genome-wide annotation and analysis of zebra finch microRNA repertoire reveal sex-biased expression
Authors: Luo Guan-Zheng , Hafner Markus , Shi Zhimin , Brown Miguel , Feng Gui-Hai , Tuschl Thomas , Wang Xiu-Jie , Li XiaoChing
Published: December 2012

Background

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally in a wide range of biological processes. The zebra finch (Taeniopygia guttata), an oscine songbird with characteristic learned vocal behavior, provides biologists a unique model system for studying vocal behavior, sexually dimorphic brain development and functions, and comparative genomics.

Results

We deep sequenced small RNA libraries made from the brain, heart, liver, and muscle tissues of adult male and female zebra finches. By mapping the sequence reads to the zebra finch genome and to known miRNAs in miRBase, we annotated a total of 193 miRNAs. Among them, 29 (15%) are avian specific, including three novel zebra finch specific miRNAs. Many of the miRNAs exhibit sequence heterogeneity including length variations, untemplated terminal nucleotide additions, and internal substitution events occurring at the uridine nucleotide within a GGU motif. We also identified seven Z chromosome-encoded miRNAs. Among them, miR-2954, an avian specific miRNA, is expressed at significantly higher levels in males than in females in all tissues examined. Target prediction analysis reveals that miR-2954, but not other Z-linked miRNAs, preferentially targets Z chromosome-encoded genes, including several genes known to be expressed in a sexually dimorphic manner in the zebra finch brain.

Conclusions

Our genome-wide systematic analysis of mature sequences, genomic locations, evolutionary sequence conservation, and tissue expression profiles of the zebra finch miRNA repertoire provides a valuable resource to the research community. Our analysis also reveals a miRNA-mediated mechanism that potentially regulates sex-biased gene expression in avian species.
Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum
Authors: Hitomi Yuki , Adachi Takahiro , Tsuchiya Naoyuki , Honda Zen-Ichiro , Tokunaga Katsushi , Tsubata Takeshi
Published: December 2012

Background

CD72 is an inhibitory co-receptor expressed on B cells. We previously demonstrated significant association of the polymorphism of theCD72gene with susceptibility to human systemic lupus erythematosus (SLE) in individuals carrying a SLE-susceptibleFCGR2Bgenotype (FCGR2B-232Thr/Thr). The humanCD72locus generates a splicing isoform that lacks exon 8 (CD72Δex8) as well as full-length CD72 (CD72fl), and theCD72polymorphism regulates exon 8 skipping.

Results

Here we demonstrated that individuals carrying the disease-protectiveCD72genotype exhibit significantly lower serum immunoglobulin levels than do individuals carrying otherCD72genotypes (P< 0.05). Although expression level of CD72fl in the peripheral blood B cells was similar regardless ofCD72genotype, the protein level of CD72Δex8 was increased in individuals carrying the disease-protectiveCD72genotype, suggesting a crucial role of CD72Δex8 in regulation of antibody production. By expressing these human CD72 isoforms in mouse cell lines, we further demonstrated that CD72Δex8 is accumulated in endoplasmic reticulum (ER) and fails to regulate BCR signaling whereas human CD72fl is efficiently transported to the cell surface and inhibits signaling through the B cell antigen receptor (BCR), as is the case for mouse CD72.

Conclusion

HumanCD72polymorphism appears to regulate antibody production as well as susceptibility to SLE by regulating expression of ER-localizing CD72Δex8.
Some ethylene biosynthesis and AP2/ERF genes reveal a specific pattern of expression during somatic embryogenesis in Hevea brasiliensis
Authors: Piyatrakul Piyanuch , Putranto Riza-Arief , Martin Florence , Rio Maryannick , Dessailly Florence , Leclercq Julie , Dufayard Jean-François , Lardet Ludovic , Montoro Pascal
Published: December 2012

Background

Ethylene production and signalling play an important role in somatic embryogenesis, especially for species that are recalcitrant in in vitro culture. The AP2/ERF superfamily has been identified and classified in Hevea brasiliensis. This superfamily includes the ERFs involved in response to ethylene. The relative transcript abundance of ethylene biosynthesis genes and of AP2/ERF genes was analysed during somatic embryogenesis for callus lines with different regeneration potential, in order to identify genes regulated during that process.

Results

The analysis of relative transcript abundance was carried out by real-time RT-PCR for 142 genes. The transcripts of ERFs from group I, VII and VIII were abundant at all stages of the somatic embryogenesis process. Forty genetic expression markers for callus regeneration capacity were identified. Fourteen markers were found for proliferating calli and 35 markers for calli at the end of the embryogenesis induction phase. Sixteen markers discriminated between normal and abnormal embryos and, lastly, there were 36 markers of conversion into plantlets. A phylogenetic analysis comparing the sequences of the AP2 domains of Hevea and Arabidopsis genes enabled us to predict the function of 13 expression marker genes.

Conclusions

This first characterization of the AP2/ERF superfamily in Hevea revealed dramatic regulation of the expression of AP2/ERF genes during the somatic embryogenesis process. The gene expression markers of proliferating callus capacity to regenerate plants by somatic embryogenesis should make it possible to predict callus lines suitable to be used for multiplication. Further functional characterization of these markers opens up prospects for discovering specific AP2/ERF functions in the Hevea species for which somatic embryogenesis is difficult.
A cohort evaluation on arterial stiffness and hypertensive disorders in pregnancy
Authors: Lim Wai Yee , Saw Seang Mei , Tan Kok Hian , Yeo George SH , Kwek Kenneth YC
Published: December 2012

Background

Hypertensive disorders in pregnancy are associated with systemic endothelial dysfunction leading to impaired physiological vasodilation. Recent evidence has shown central aortic pressures obtained through pulse wave analysis, at less than 14 weeks of gestation, to be predictive of pre-eclampsia. In light of this, we aimed to evaluate the role of central aortic stiffness in the prediction and discrimination of hypertensive disorders in pregnancy.

Methods

A cohort study of women with viable, singleton pregnancies at less than 14 weeks of amenorrhoea, and without multiple pregnancies, autoimmune or renal disease, diagnosed with aneuploidy or fetal anomaly will be recruited from a single maternity hospital and followed up till delivery and puerperium. A targeted sample size of 1000 eligible pregnant women will be enrolled into the study from antenatal clinics. Main exposure under study is central aortic pulse pressure using radial pulse wave recording, and the outcomes under follow-up are gestational hypertension and pre-eclampsia. Other measures include lifestyle factors such as smoking, physical exercise, psychometric evaluations, vasoactive factors, uterine artery pulsatility index, height and weight measurements. These measures will be repeated over 4 antenatal visits at 11-14, 18-22, 28-32 and above 34 weeks of gestation. Double data entry will be performed on Microsoft Access, and analysis of data will include the use of random effect models and receiver operating characteristic curves on Stata 11.2.

Discussion

The proposed study design will enable a longitudinal evaluation of the central aortic pressure changes as a marker for vascular compliance during pregnancy. As measures are repeated over time, the timing and severity of changes are detectable, and findings may yield important information on how aberrant vascular responses occur and its role in the early detection and prediction of hypertensive disorders.
Dynamics of circulating endothelial cells and endothelial progenitor cells in breast cancer patients receiving cytotoxic chemotherapy
Authors: Kuo Yu-Hsuan , Lin Ching-Hung , Shau Wen-Yi , Chen Te-Jung , Yang Shih-Hung , Huang Shu-Min , Hsu Chun , Lu Yen-Shen , Cheng Ann-Lii
Published: December 2012

Background

The abundance of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPs), which serve as surrogate markers for angiogenesis, may be affected by chemotherapy. We studied their dynamic change during consecutive cycles of chemotherapy.

Methods

We collected blood samples from 15 breast cancer patients, who received a total of 56 courses of systemic chemotherapy, and measured the CECs, viable CECs (V-CECs), and CEPs by six-color flow cytometry within the seven days prior to chemotherapy, twice a week during the first and second cycles of chemotherapy, and then once a week during the subsequent cycles.

Results

The CEC, V-CEC, and CEP levels all significantly decreased from day 1 of treatment to the first week of chemotherapy. After one week of chemotherapy, the CEC and V-CEC levels returned to a level similar to day 1. The CEP level remained significantly reduced after the first week of chemotherapy, but gradually rebounded until the next course of chemotherapy. After six cycles of chemotherapy, the total number of CEC and V-CEC cells trended toward a decrease and the CEP cells toward an increase. Clinical factors, including the existence of a tumor, chemotherapy regimens, and the use of granulocyte colony stimulating factor, did not significantly affect these results.

Conclusions

The CEC and CEP counts change dynamically during each course of chemotherapy and after the chemotherapy cycles, providing background data for any future study planning to use CECs and CEPs as surrogate markers of angiogenesis in antiangiogenesis treatments combined with chemotherapy.
Thoughts of death or suicidal ideation are common in young people aged 12 to 30 years presenting for mental health care
Authors: Scott Elizabeth M , Hermens Daniel F , Naismith Sharon L , White Django , Whitwell Bradley , Guastella Adam J , Glozier Nick , Hickie Ian B
Published: December 2012

Background

Reducing suicidal behaviour is a major public health goal. Expanding access to care has been identified as a key strategy. In Australia, a national network of primary-care based services (headspace) has been established for young people with mental ill-health. This study determines the socio-demographic, psychopathological and illness-stage correlates of suicidal ideation in young persons attending headspace services.

Methods

Suicidal ideation was recorded using the specific suicide item of the Hamilton Depression Rating Scale (HDRS) in a cohort of subjects aged 12-30 years (N = 494) attending headspace services.

Results

Of the 494 young persons assessed, 32% (158/494) had a positive response to any level of the HDRS suicide item, consisting of 16% (77/494) reporting that life was not worth living and a further 16% (81/494) reported thoughts of death or suicidal ideation. Young women (19%; 94/494) were more likely to report any positive response as compared with young men (13%; 64/494) [χ2(2,494) = 13.6, p < .01]. Those with ‘attenuated syndromes’ reported positive responses at rates comparable to those with more established disorders (35% vs. 34%; χ2(1,347) = 0.0, p = 0.87). However, more serious levels of suicidal ideation were more common in those with depressive disorders or later stages of illness. In multivariate analyses, the major predictors of the degree of suicidal ideation were increasing levels of clinician-rated depressive symptoms (beta = 0.595, p < .001), general psychopathology (beta = 0.198, p < .01), and self-reported distress (beta = 0.172, p < .05).

Conclusions

Feelings that life is not worth living, thoughts of death or suicidal ideation are common in young people seeking mental health care. These at-risk cognitions are evident before many of these individuals develop severe or persistent mental disorders. Thoughts of death or suicidal ideation may well need to be a primary intervention target in these young people.
Cloning and recombinant expression of a cellulase from the cellulolytic strain Streptomyces sp. G12 isolated from compost
Authors: Amore Antonella , Pepe Olimpia , Ventorino Valeria , Birolo Leila , Giangrande Chiara , Faraco Vincenza
Published: December 2012

Background

The use of lignocellulosic materials for second generation ethanol production would give several advantages such as minimizing the conflict between land use for food and fuel production, providing less expensive raw materials than conventional agricultural feedstock, allowing lower greenhouse gas emissions than those of first generation ethanol. However, cellulosic biofuels are not produced at a competitive level yet, mainly because of the high production costs of the cellulolytic enzymes. Therefore, this study was aimed at discovering new cellulolytic microorganisms and enzymes.

Results

Different bacteria isolated from raw composting materials obtained from vegetable processing industry wastes were screened for their cellulolytic activity on solid medium containing carboxymethylcellulose. Four strains belonging to the actinomycetes group were selected on the basis of their phenotypic traits and cellulolytic activity on solid medium containing carboxymethylcellulose. The strain showing the highest cellulolytic activity was identified by 16S rRNA sequencing as belonging to Streptomyces genus and it was designated as Streptomyces sp. strain G12. Investigating the enzymes responsible for cellulase activity produced by Streptomyces G12 by proteomic analyses, two endoglucanases were identified. Gene coding for one of these enzymes, named CelStrep, was cloned and sequenced. Molecular analysis showed that the celstrep gene has an open reading frame encoding a protein of 379 amino acid residues, including a signal peptide of 37 amino acid residues. Comparison of deduced aminoacidic sequence to the other cellulases indicated that the enzyme CelStrep can be classified as a family 12 glycoside hydrolase. Heterologous recombinant expression of CelStrep was carried out in Escherichia coli, and the active recombinant enzyme was purified from culture supernatant and characterized. It catalyzes the hydrolysis of carboxymethylcellulose following a Michaelis–Menten kinetics with a KM of 9.13 mg/ml and a vmax of 3469 μM min-1. The enzyme exhibits a half life of around 24 h and 96 h at 60°C and 50°C, respectively and shows a retention of around 80% of activity after 96 h at 40°C.

Conclusions

In this manuscript, we describe the isolation of a new cellulolytic strain, Streptomyces sp. G12, from industrial waste based compost, the identification of the enzymes putatively responsible for its cellulolytic activity, the cloning and the recombinant expression of the gene coding for the Streptomyces sp. G12 cellulase CelStrep, that was characterized showing to exhibit a relevant thermoresistance increasing its potential for cellulose conversion.
Bone morphogenetic protein-15 in follicle fluid combined with age may differentiate between successful and unsuccessful poor ovarian responders
Authors: Wu Yan-Ting , Wang Ting-Ting , Chen Xi-Jing , Zhu Xiao-Ming , Dong Min-Yue , Sheng Jian-Zhong , Xu Chen-Ming , Huang He-Feng
Published: December 2012

Background

The counselling of poor ovarian responders about the probability of pregnancy remains a puzzle for gynaecologists. The aim of this study was to optimise the management of poor responders by investigating the role of the oocyte-derived factor bone morphogenetic protein-15 (BMP-15) combined with chronological age in the prediction of the outcome of in-vitro fertilisation-embryo transfer (IVF-ET) in poor responders.

Methods

A retrospective study conducted in a university hospital. A total of 207 poor ovarian responders who reached the ovum pick-up stage undergoing IVF/intracytoplasmic sperm injection (ICSI) with three or fewer follicles no less than 14 mm on the day of oocyte retrieval were recruited from July 1, 2008 to December 31, 2009. Another 215 coinstantaneous cycles with normal responses were selected as controls. The BMP-15 levels in the follicular fluid (FF) of the 207 poor responders were analysed by western blot. Based on the FF BMP-15 level and age, poor responders were sub-divided into four groups. The main outcome measures were the FF BMP-15 level, implantation rate, pregnancy rate, and live birth rate.

Results

The implantation rate (24.2% vs. 15.3%), chemical pregnancy rate (40% vs. 23.7%), clinical pregnancy rate (36.5% vs. 20.4%) and live birth rate (29.4% vs. 15.1%) in the high BMP-15 group were significantly higher than those in the low BMP-15 group. Furthermore, poor responders aged less than or equal to 35 years with a higher FF BMP-15 level had the best implantation, pregnancy and live birth rates, which were comparable with those of normal responders.

Conclusions

Our study suggests a potential role of BMP-15 in the prediction of the IVF outcome. A high FF BMP-15 combined with an age less than or equal to 35 years may be used as a potential indicator for repeating IVF cycles in poor ovarian responders.
The globular heads of the C1q receptor regulate apoptosis in human cervical squamous carcinoma cells via a p53-dependent pathway
Authors: Chen Zheng-lin , Gu Ping-qing , Liu Kangsheng , Su Ya-juan , Gao Ling-juan
Published: December 2012

Background

The globular heads of the human C1q receptor (gC1qR) localize predominantly to the mitochondrial matrix. gC1qR mediates many biological responses, including growth perturbation, morphological abnormalities and the initiation of apoptosis. The purpose of this study was to investigate the relationship between mitochondrial dysfunction, p53 status and gC1qR expression and the regulation of apoptosis in human cervical squamous carcinoma cells (C33a and SiHa).

Methods

Here, gC1qR expression was examined in human cervical tissues using real-time PCR and Western blot analysis. Apoptotic death of C33a and SiHa cells was assessed by flow cytometric analysis that detected the subG1 population. Mitochondrial function was assessed via ROS generation, the content of cytosolic Ca2+, and the change in mitochondrial membrane potential (Δψm). The viability and migration of C33a and SiHa cells were detected via the water-soluble tetrazolium salt (WST-1) assay and the transwell assay, respectively.

Results

gC1qR expression was decreased in cervical squamous cell carcinoma tissues compared with normal tissues. C33a and SiHa cells transfected with a vector encoding gC1qR displayed mitochondrial dysfunction and apoptosis, which was abrogated by the addition of a mutant form of p53 or p53 small interference RNA (siRNA). Furthermore, upon overexpression of gC1qR, cell viability and migration were significantly enhanced, and the apoptosis of C33a and SiHa cells were decreased when cells were treated with mutant p53 or p53 siRNA.

Conclusions

These data support a mechanism whereby gC1qR induces apoptosis through the mitochondrial and p53-dependent pathways in cervical squamous cell carcinoma.
Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines
Authors: Hu Shan , Mao-Ying Qi-Liang , Wang Jun , Wang Zhi-Fu , Mi Wen-Li , Wang Xiao-Wei , Jiang Jian-Wei , Huang Ya-Lin , Wu Gen-Cheng , Wang Yan-Qing
Published: December 2012

Background

The neuroinflammatory responses in the spinal cord following bone cancer development have been shown to play an important role in cancer-induced bone pain (CIBP). Lipoxins (LXs), endogenous lipoxygenase-derived eicosanoids, represent a unique class of lipid mediators that possess a wide spectrum of anti-inflammatory and pro-resolving actions. In this study, we investigated the effects of intrathecal injection with lipoxin and related analogues on CIBP in rats.

Methods

The CIBP model was induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells. Mechanical thresholds were determined by measuring the paw withdrawal threshold to probing with a series of calibrated von Frey filaments. Lipoxins and analogues were administered by intrathecal (i.t.) or intravenous (i.v.) injection. The protein level of LXA4 receptor (ALX) was tested by western blot. The localization of lipoxin receptor in spinal cord was assessed by fluorescent immunohistochemistry. Real-time PCR was carried out for detecting the expression of pro-inflammatory cytokines.

Results

Our results demonstrated that: 1) i.t. injection with the same dose (0.3 nmol) of lipoxin A4 (LXA4), lipoxin B4 (LXB4) or aspirin-triggered-15-epi-lipoxin A4 (ATL) could alleviate the mechanical allodynia in CIBP on day 7 after surgery. ATL showed a longer effect than the others and the effect lasted for 6 hours. ATL administered through i.v. injection could also attenuate the allodynia in cancer rats. 2) The results from western blot indicate that there is no difference in the expression of ALX among the naive, sham or cancer groups. 3) Immunohistochemistry showed that the lipoxin receptor (ALX)-like immunoreactive substance was distributed in the spinal cord, mainly co-localized with astrocytes, rarely co-localized with neurons, and never co-localized with microglia. 4) Real-time PCR analysis revealed that, compared with vehicle, i.t. injection with ATL could significantly attenuate the expression of the mRNA of proinflammatory cytokines (IL-1β and TNF-α) in the spinal cord in CIBP.

Conclusions

Taken together, the results of our study suggest that LXs and analogues exert strong analgesic effects on CIBP. These analgesic effects in CIBP are associated with suppressing the expression of spinal proinflammatory cytokines.
Concordances and discrepancies between ICD-10 and DSM-IV criteria for anxiety disorders in childhood and adolescence
Authors: Adornetto Carmen , Suppiger Andrea , In-Albon Tina , Neuschwander Murielle , Schneider Silvia
Published: December 2012

Background

Mental disorders are classified by two major nosological systems, the ICD-10 and the DSM-IV-TR, consisting of different diagnostic criteria. The present study investigated the diagnostic concordance between the two systems for anxiety disorders in childhood and adolescence, in particular for separation anxiety disorder (SAD), specific phobia, social phobia, and generalized anxiety disorder (GAD).

Methods

A structured clinical interview, the Kinder-DIPS, was administered to 210 children and 258 parents. The percentage of agreement, kappa, and Yule’s Y coefficients were calculated for all diagnoses. Specific criteria causing discrepancies between the two classification systems were identified.

Results

DSM-IV-TR consistently classified more children than ICD-10 with an anxiety disorder, with a higher concordance between DSM-IV-TR and the ICD-10 child section (F9) than with the adult section (F4) of the ICD-10. This result was found for all four investigated anxiety disorders. The results revealed low to high levels of concordance and poor to good agreement between the classification systems, depending on the anxiety disorder.

Conclusions

The two classification systems identify different children with an anxiety disorder. However, it remains an open question, whether the research results can be generalized to clinical practice since DSM-IV-TR is mainly used in research while ICD-10 is widely established in clinical practice in Europe. Therefore, the population investigated by the DSM (research population) is not identical with the population examined using the ICD (clinical population).
Association of genetic polymorphisms with chronic obstructive pulmonary disease in the Chinese Han population: a case–control study
Authors: Guo Yi , Gong Yi , Pan Chunming , Qian Yanrong , Shi Guochao , Cheng Qijian , Li Qingyun , Ren Lei , Weng Qiuling , Chen Yi , Cheng Ting , Fan Liang , Jiang Zhihong , Wan Huanying
Published: December 2012

Background

Chronic obstructive pulmonary disease (COPD) is influenced by both environmental and genetic factors. Few gene studies of the Chinese population have focused on COPD. We investigated candidate genes associated with susceptibility to COPD in the Chinese Han population.

Methods

A total of 331 COPD patients and 213 control subjects were recruited for this study. Nighty-seven single-nucleotide polymorphisms (SNPs) of 46 genes were selected for genotyping. Genotypes were determined using multiplex polymerase chain reaction (PCR).

Results

Significant differences between patients and healthy controls were observed in the allele frequencies of seven SNPs: rs1205 C, rs2353397 C, rs20541 T, rs2070600 G, rs10947233 G, rs1800629 G, and rs2241712 A. After Bonferroni correction, rs2353397 C was most strongly associated with susceptibility to COPD. Haplotype analysis showed that the frequencies of the GC, GT haplotypes of rs2241718 (TGF-β1 gene), and rs6957 (CDC97 gene) were significantly higher in the control group than in the COPD case group (p=1.88×10-9); the frequencies of the TT haplotype of rs1205 and rs2808630 (CRP gene) were significantly higher in the control group (p=0.0377).

Conclusion

Our study suggests some genetic variants associated with the susceptibility of COPD in the Chinese Han population.
Capnocytophaga canimorsus infection presenting with complete splenic infarction and thrombotic thrombocytopenic purpura: a case report
Authors: Brichacek Michal , Blake Peter , Kao Raymond
Published: December 2012

Background

Animal bites are typically harmless, but in rare cases infections introduced by such bites can be fatal. Capnocytophaga canimorsus, found in the normal oral flora of dogs, has the potential to cause conditions ranging from minor cellulitis to fatal sepsis. The tendency of C. canimorsus infections to present with varied symptoms, the organism’s fastidious nature, and difficulty of culturing make this a challenging diagnosis. Rarely, bacterial cytotoxins such as those produced by C. canimorsus may act as causative agents of TTP, further complicating the diagnosis. Early recognition is crucial for survival, and the variability of presentation must be appreciated. We present the first known case of C. canimorsus infection resulting in TTP that initially presented as splenic infarction.

Case presentation

72-year-old Caucasian male presented with a four-day history of abdominal pain, nausea, vomiting, diarrhea, and intermittent confusion. On presentation, vital signs were stable and the patient was afebrile. Physical examination was unremarkable apart from petechiae on the inner left thigh, and extreme diffuse abdominal pain to palpation and percussion along with positive rebound tenderness. Initial investigations revealed leukocytosis with left shift and thrombocytopenia, but normal liver enzymes, cardiac enzymes, lipase, INR and PTT. Abdominal CT demonstrated a non-enhancing spleen and hemoperitoneum, suggesting complete splenic infarction. Although the patient remained afebrile, he continued deteriorating over the next two days with worsening thrombocytopenia. After becoming febrile, he developed microangiopathic hemolytic anemia and hemodynamic instability, and soon after was intubated due to hypoxic respiratory failure and decreased consciousness. Plasma exchange was initiated but subsequently stopped when positive blood cultures grew a gram-negative organism. The patient progressively improved following therapy with piperacillin-tazobactam, which was switched to imipenem, then meropenem when Capnocytophaga was identified.

Conclusions

There is a common misconception amongst practitioners that the presence of systemic infection excludes the possibility of TTP and vice versa. This case emphasizes that TTP may occur secondary to a systemic infection, thereby allowing the two processes to coexist. It is important to maintain a wide differential when considering the diagnosis of either TTP or C. canimorsus infection since delays in treatment may have fatal consequences.