bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping the interactome of overexpressed RAF kinase inhibitor protein in a gastric cancer cell line
Authors: Gu Huan , Zhan Xianquan , Zhang Guiying , Yan Lu , Cho William CS , Li Maoyu , Liu Ting , Chen Zhuchu
Published: November 2013

Background

Gastric cancer (GC) is a threat to human health with increasing incidence and mortality worldwide. Down-regulation or absence of RAF kinase inhibitor protein (RKIP) was associated with the occurrence, differentiation, invasion, and metastasis of GC. This study aims to investigate the molecular mechanisms and biological functions of RKIP in the GC biology.

Methods

The fusion expression plasmid pcDNA3.1-RKIP-3xFLAG was transfected into SGC7901 cells, the RKIP fusion proteins were purified with anti-flag M2 magnetic beads, and the RKIP-interacting proteins were identified with tandem mass spectrometry (MS/MS), and were analyzed with bioinformatics tools. Western blot and co-immunoprecipitation were used to confirm the interaction complex.

Results

A total of 72 RKIP-interacting proteins were identified by MS/MS. Those proteins play roles in enzyme metabolism, molecular chaperoning, biological oxidation, cytoskeleton organization, signal transduction, and enzymolysis. Three RKIP-interaction protein network diagrams were constructed with Michigan Molecular Interactions, functional linage network, and Predictome analysis to address the molecular pathways of the functional activity of RKIP. The MS/MS-characterized components of the existing interaction complex (RKIP, HSP90, 14-3-3ϵ, and keratin 8) were confirmed by Western blot analysis and co-immunoprecipitation.

Conclusion

This study is the first discovery of the interaction of RKIP with HSP90, 14-3-3, and keratin. The present data would provide insight into the molecular mechanisms of how RKIP inhibits the occurrence and development of GC.
Different patterns of cortical excitability in major depression and vascular depression: a transcranial magnetic stimulation study
Authors: Concerto Carmen , Lanza Giuseppe , Cantone Mariagiovanna , Pennisi Manuela , Giordano Daniela , Spampinato Concetto , Ricceri Riccardo , Pennisi Giovanni , Aguglia Eugenio , Bella Rita
Published: November 2013

Background

Clinical and functional studies consider major depression (MD) and vascular depression (VD) as different neurobiological processes. Hypoexcitability of the left frontal cortex to transcranial magnetic stimulation (TMS) is frequently reported in MD, whereas little is known about the effects of TMS in VD. Thus, we aimed to assess and compare motor cortex excitability in patients with VD and MD.

Methods

Eleven VD patients, 11 recurrent drug-resistant MD patients, and 11 healthy controls underwent clinical, neuropsychological and neuroimaging evaluations in addition to bilateral resting motor threshold, cortical silent period, and paired-pulse TMS curves of intracortical excitability. All patients continued on psychotropic drugs, which were unchanged throughout the study.

Results

Scores on one of the tests evaluating frontal lobe abilities (Stroop Color-Word interference test) were worse in patients compared with controls. The resting motor threshold in patients with MD was significantly higher in the left hemisphere compared with the right (p < 0.05), and compared with the VD patients and controls. The cortical silent period was bilaterally prolonged in MD patients compared with VD patients and controls, with a statistically significant difference in the left hemisphere (p < 0.01). No differences were observed in the paired-pulse curves between patients and controls.

Conclusions

This study showed distinctive patterns of motor cortex excitability between late-onset depression with subcortical vascular disease and early-onset recurrent drug resistant MD. The data provide a TMS model of the different processes underlying VD and MD. Additionally, our results support the “Vascular depression hypothesis” at the neurophysiological level, and confirm the inter-hemispheric asymmetry to TMS in patients with MD. We were unable to support previous findings of impaired intracortical inhibitory mechanisms to TMS in patients with MD, although a drug-induced effect on our results cannot be excluded. This study may aid the understanding of the pathogenetic differences underlying the clinical spectrum of depressive disorders.
Development of a new pre-vascularized tissue-engineered construct using pre-differentiated rADSCs, arteriovenous vascular bundle and porous nano-hydroxyapatide-polyamide 66 scaffold
Authors: Yang Pei , Huang Xin , Shen Jacson , Wang Chunsheng , Dang Xiaoqian , Mankin Henry , Duan Zhenfeng , Wang Kunzheng
Published: November 2013

Background

Development of a pre-vascularized tissue-engineered construct with intrinsic vascular system for cell growth and tissue formation still faces many difficulties due to the complexity of the vascular network of natural bone tissue. The present study was to design and form a new vascularized tissue-engineered construct using pre-differentiated rADSCs, arteriovenous vascular bundle and porous nHA-PA 66 scaffold.

Methods

rADSCs were pre-differentiated to endothelial cells (rADSCs-Endo) and then incorporated in nHA-PA 66 scaffolds in vitro. Subsequently, in vivo experiments were carried out according to the following groups: Group A (rADSCs-Endo/nHA-PA 66 scaffold with arteriovenous vascular bundle), Group B (rADSCs/nHA-PA 66 scaffold with arteriovenous vascular bundle); Group C (nHA-PA66 scaffold with arteriovenous vascular bundle), Group D (nHA-PA 66 scaffold only). The vessel density and vessel diameter were measured based on histological and immunohistochemical evaluation, furthermore, the VEGF-C, FGF-2 and BMP-2 protein expressions were also evaluated by western blot analysis.

Results

The results of in vivo experiments showed that the vessel density and vessel diameter in group A were significantly higher than the other three groups. Between Group B and C, no statistical difference was observed at each time point. In accordance with the results, there were dramatically higher expressions of VEGF-C and FGF-2 protein in Group A than that of Group B, C and D at 2 or 4 weeks. Statistical differences were not observed in VEGF-C and FGF-2 expression between Group B and C. BMP-2 was not expressed in any group at each time point.

Conclusions

Compared with muscular wrapping method, arteriovenous vascular bundle implantation could promote vascularization of the scaffold; and the angiogenesis of the scaffold was significantly accelerated when pre-differentiated rADSCs (endothelial differentiation) were added. These positive results implicate the combination of pre-differentiated rADSCs (endothelial differentiation) and arteriovenous vascular bundle may achieve rapidly angiogenesis of biomaterial scaffold.
Effect of intracellular loop 3 on intrinsic dynamics of human β2-adrenergic receptor
Authors: Ozcan Ozer , Uyar Arzu , Doruker Pemra , Akten Ebru Demet
Published: November 2013

Background

To understand the effect of the long intracellular loop 3 (ICL3) on the intrinsic dynamics of human β2-adrenergic receptor, molecular dynamics (MD) simulations were performed on two different models, both of which were based on the inactive crystal structure in complex with carazolol (after removal of carazolol and T4-lysozyme). In the so-called loop model, the ICL3 region that is missing in available crystal structures was modeled as an unstructured loop of 32-residues length, whereas in the clipped model, the two open ends were covalently bonded to each other. The latter model without ICL3 was taken as a reference, which has also been commonly used in recent computational studies. Each model was embedded into POPC bilayer membrane with explicit water and subjected to a 1 μs molecular dynamics (MD) simulation at 310 K.

Results

After around 600 ns, the loop model started a transition to a “very inactive” conformation, which is characterized by a further movement of the intracellular half of transmembrane helix 6 (TM6) towards the receptor core, and a close packing of ICL3 underneath the membrane completely blocking the G-protein’s binding site. Concurrently, the binding site at the extracellular part of the receptor expanded slightly with the Ser207-Asp113 distance increasing to 18 Å from 11 Å, which was further elaborated by docking studies.

Conclusions

The essential dynamics analysis indicated a strong coupling between the extracellular and intracellular parts of the intact receptor, implicating a functional relevance for allosteric regulation. In contrast, no such transition to the “very inactive” state, nor any structural correlation, was observed in the clipped model without ICL3. Furthermore, elastic network analysis using different conformers for the loop model indicated a consistent picture on the specific ICL3 conformational change being driven by global modes.
RETRACTED ARTICLE: Neuroprotective effect of Buyang Huanwu Decoction on spinal ischemia-reperfusion injury in rats is linked with inhibition of cyclin-dependent kinase 5
Authors: Wang Lei , Jiang Dian-Ming
Published: November 2013

Background

Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine formula, has been shown to exert a variety of pharmacological effects including neuroprotective properties. However, the mechanism of neuroprotection is not fully understood. This study was designed to explore the mechanism of BYHWD in the treatment of spinal ischemia-reperfusion injury in rats.

Methods

Twenty-eight male Sprague–Dawley rats, weighting 250–280 g, were used, and were randomly divided into four groups with 7 animals in each: sham operation group (Control), spinal ischemia with saline (SI + Saline), spinal ischemia with BYHWD (SI + BYHWD), and spinal ischemia with roscovitine (SI + R). After 60 minutes of spinal ischemia followed by 72 hours of reperfusion, motor function of hind limbs, spinal ischemic infarction volume, the number of apoptotic cells, and cyclin-dependent kinase 5 (Cdk5) were examined.

Result

Ischemia-reperfusion resulted in injury of the spines, while BYHWD significantly improved spinal function. The spinal infarction volume, number of apoptotic cells, and Cdk5 were decreased by administration of BYHWD. The similar improvements were seen with the pre-treatment of roscovitine.

Conclusions

BYHWD prevented the ischemia-reperfusion-induced spinal injury in rats. The protective function of BYHWD was, in part, linked with inhibition of Cdk5.
A comparison of calibration data from full field digital mammography units for breast density measurements
Authors: Fowler Erin EE , Lu Beibei , Heine John J
Published: November 2013

Background

Breast density is a significant breast cancer risk factor measured from mammograms. The most appropriate method for measuring breast density for risk applications is still under investigation. Calibration standardizes mammograms to account for acquisition technique differences prior to making breast density measurements. We evaluated whether a calibration methodology developed for an indirect x-ray conversion full field digital mammography (FFDM) technology applies to direct x-ray conversion FFDM systems.

Methods

Breast tissue equivalent (BTE) phantom images were used to establish calibration datasets for three similar direct x-ray conversion FFDM systems. The calibration dataset for each unit is a function of the target/filter combination, x-ray tube voltage, current × time (mAs), phantom height, and two detector fields of view (FOVs). Methods were investigated to reduce the amount of calibration data by restricting the height, mAs, and FOV sampling. Calibration accuracy was evaluated with mixture phantoms. We also compared both intra- and inter-system calibration characteristics and accuracy.

Results

Calibration methods developed previously apply to direct x-ray conversion systems with modification. Calibration accuracy was largely within the acceptable range of ± 4 standardized units from the ideal value over the entire acquisition parameter space for the direct conversion units. Acceptable calibration accuracy was maintained with a cubic-spline height interpolation, representing a modification to previous work. Calibration data is unit specific, can be acquired with the large FOV, and requires a minimum of one reference mAs sample. The mAs sampling, calibration accuracy, and the necessity for machine specific calibration data are common characteristics and in agreement with our previous work.

Conclusion

The generality of our calibration approach was established under ideal conditions. Evaluation with patient data using breast cancer status as the endpoint is required to demonstrate that the approach produces a breast density measure associated with breast cancer.
Novel compound heterozygous mutations in the MYO15A gene in autosomal recessive hearing loss identified by whole-exome sequencing
Authors: Gao Xue , Zhu Qing-yan , Song Yue-Shuai , Wang Guo-Jian , Yuan Yong-Yi , Xin Feng , Huang Sha-Sha , Kang Dong-Yang , Han Ming-Yu , Guan Li-ping , Zhang Jian-guo , Dai Pu
Published: November 2013

Background

Inherited genetic defects play an important role in congenital hearing loss, contributing to about 60% of deafness occurring in infants. Hereditary nonsyndromic hearing loss is highly heterogeneous, and most patients with a presumed genetic etiology lack a specific molecular diagnosis.

Methods

By whole exome sequencing, we identified responsible gene of family 4794 with autosomal recessively nonsyndromic hearing loss (ARNSHL). We also used DNA from 56 Chinese familial patients with ARNSHL (autosomal recessive nonsyndromic hearing loss) and 108 ethnicity-matched negative samples to perform extended variants analysis.

Results

We identified MYO15A c.IVS25 + 3G > A and c.8375 T > C (p.V2792A) as the disease-causing mutations. Both mutations co-segregated with hearing loss in family 4794, but were absent in the 56 index patients and 108 ethnicity-matched controls.

Conclusions

Our results demonstrated that the hearing loss of family 4794 was caused by novel compound heterozygous mutations in MYO15A.
Chitosan-based intelligent theragnosis nanocomposites enable pH-sensitive drug release with MR-guided imaging for cancer therapy
Authors: Lim Eun-Kyung , Sajomsang Warayuth , Choi Yuna , Jang Eunji , Lee Hwunjae , Kang Byunghoon , Kim Eunjung , Haam Seungjoo , Suh Jin-Suck , Chung Sang Jeon , Huh Yong-Min
Published: November 2013

Smart drug delivery systems that are triggered by environmental conditions have been developed to enhance cancer therapeutic efficacy while limiting unwanted effects. Because cancer exhibits abnormally high local acidities compared to normal tissues (pH 7.4) due to Warburg effects, pH-sensitive systems have been researched for effective cancer therapy. Chitosan-based intelligent theragnosis nanocomposites, N-naphthyl-O-dimethymaleoyl chitosan-based drug-loaded magnetic nanoparticles (N Chitosan-DMNPs), were developed in this study. N Chitosan-DMNPs are capable of pH-sensitive drug release with MR-guided images because doxorubicin (DOX) and magnetic nanocrystals (MNCs) are encapsulated into the designed N-naphthyl-O-dimethymaleoyl chitosan (N-nap-O-MalCS). This system exhibits rapid DOX release as acidity increases, high stability under high pH conditions, and sufficient capacity for diagnosing and monitoring therapeutic responses. These results demonstrate that N Chitosan-DMNPs have potential as theragnosis nanocomposites for effective cancer therapy.
Plasmonic Fano resonance and dip of Au-SiO2-Au nanomatryoshka
Authors: Liaw Jiunn-Woei , Chen Huang-Chih , Kuo Mao-Kuen
Published: November 2013

This study theoretically investigates Fano resonances and dips of an Au-SiO2-Au nanomatryoshka that is excited by a nearby electric dipole. An analytical solution of dyadic Green's functions is used to analyze the radiative and nonradiative power spectra of a radial dipole in the proximity of a nanomatryoshka. From these spectra, the plasmon modes and Fano resonances that accompany the Fano dips are identified. In addition, the scattering and absorption spectra of a nanomatryoshka that is illuminated by a plane wave are investigated to confirm these modes and Fano dips. Our results reveal that a Fano dip splits each of the dipole and quadrupole modes into bonding and anti-bonding modes. The Fano dip and resonance result from the destructive interference of the plasmon modes of the Au shell and the Au core. The Fano factors that are obtained from the nonradiative power spectra of the Au shell and the Au core of a nanomatryoshka are in accordance with those obtained from the absorption cross section spectra. Moreover, these Fano factors increase as the plasmonic coupling of the Au shell with the core increases for both dipole and quadrupole modes.
Dirac cone in α-graphdiyne: a first-principles study
Authors: Niu Xiaoning , Mao Xingze , Yang Dezheng , Zhang Zhiya , Si Mingsu , Xue Desheng
Published: November 2013

We investigate the Dirac cone in α-graphdiyne, which is a predicted flat one-atom-thick allotrope of carbon using first-principles calculations. α-graphdiyne is derived from graphene where two acetylenic linkages (-C ≡C-) are inserted into the single bonds (-C-C-). Thus, α-graphdiyne possesses a larger lattice constant which subsequently affects its electronic properties. Band structures show that α-graphdiyne exhibits similar Dirac points and cone to graphene. Further, the tight-binding method is used to exploit the linear dispersion in the vicinity of Dirac points. Thanks to the larger lattice constant, α-graphdiyne yields a lower Fermi velocity, which might make itself an ideal material to serve the anomalous integer quantum Hall effect.
Annealing effect and photovoltaic properties of nano-ZnS/textured p-Si heterojunction
Authors: Ji Liang-Wen , Hsiao Yu-Jen , Tang I-Tseng , Meen Teen-Hang , Liu Chien-Hung , Tsai Jenn-Kai , Wu Tien-Chuan , Wu Yue-Sian
Published: November 2013

The preparation and characterization of heterojunction solar cell with ZnS nanocrystals synthesized by chemical bath deposition method were studied in this work. The ZnS nanocrystals were characterized by X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM). Lower reflectance spectra were found as the annealing temperature of ZnS film increased on the textured p-Si substrate. It was found that the power conversion efficiency (PCE) of the AZO/ZnS/textured p-Si heterojunction solar cell with an annealing temperature of 250°C was η = 3.66%.
Asymptotic behavior for third-order quasi-linear differential equations
Authors: Qin Guixiang , Huang Chuangxia , Xie Yongqin , Wen Fenghua
Published: November 2013

In this paper, a class of third-order quasi-linear differential equations withcontinuously distributed delay is studied. Applying the generalized Riccatitransformation, integral averaging technique of Philos type and Young’sinequality, a set of new criteria for oscillation or certain asymptoticbehavior of nonoscillatory solutions of this equations is given. Our resultsessentially improve and complement some earlier publications.
Differentiation between genomic and non-genomic feedback controls yields an HPA axis model featuring Hypercortisolism as an irreversible bistable switch
Authors: Zarzer Clemens A , Puchinger Martin G , Köhler Gottfried , Kügler Philipp
Published: November 2013

Background

The hypothalamic-pituitary-adrenal axis (HPA axis) is a major part of the neuroendocrine system responsible for the regulation of the response to physical or mental stress and for the control of the synthesis of the stress hormone cortisol. Dysfunctions of the HPA axis characterized by either low (hypocortisolism) or increased (hypercortisolism) cortisol levels are implicated in various pathological conditions. Their understanding and therapeutic correction may be supported by mathematical modeling and simulation of the HPA axis.

Methods

Mass action and Michaelis Menten enzyme kinetics were used to provide a mechanistic description of the feedback mechanisms within the pituitary gland cells by which cortisol inhibits its own production. A separation of the nucleus from the cytoplasm by compartments enabled a differentiation between slow genomic and fast non-genomic processes. The model in parts was trained against time resolved ACTH stress response data from an in vitro cell culture of murine AtT-20 pituitary tumor cells and analyzed by bifurcation discovery tools.

Results

A recently found pituitary gland cell membrane receptor that mediates rapid non-genomic actions of glucocorticoids has been incorporated into our model of the HPA axis. As a consequence of the distinction between genomic and non-genomic feedback processes our model possesses an extended dynamic repertoire in comparison to existing HPA models. In particular, our model exhibits limit cycle oscillations and bistable behavior associated to hypocortisolism but also features a (second) bistable switch which captures irreversible transitions in hypercortisolism to elevated cortisol levels.

Conclusions

Model predictive control and inverse bifurcation analysis have been previously applied in the simulation-based design of therapeutic strategies for the correction of hypocortisolism. Given the HPA model extension presented in this paper, these techniques may also be used in the study of hypercortisolism. As an example, we show how sparsity enforcing penalization may suggest network interventions that allow the return from elevated cortisol levels back to nominal ones.
Genetic evidence of extra-pair paternity and intraspecific brood parasitism in the monk parakeet
Authors: Martínez Juan José , de Aranzamendi María Carla , Masello Juan F , Bucher Enrique H
Published: November 2013

Introduction

The monk parakeet (Myiopsitta monachus) is a widespread invasive species native to southern South America that has become established in many regions of the world. Monk parakeets breed in a large, fully enclosed structure built from twigs, which consist of one to many individual brooding chambers. The species has been considered to be socially and genetically monogamous. However, genetic relatedness of adults to juveniles in the native area was found to be lower than expected for monogamy. To assess the significance of this discrepancy, we examined individual and population genetic patterns of microsatellite loci at two sites in Córdoba province, Argentina.

Results

We sampled 154 nestlings and 42 adults in Córdoba, Argentina. Mean value of pairwise relatedness of nestlings within chambers was about 0.40. Contrarily, relatedness of nestlings between chambers was close to zero. We found a considerable degree of variation in nestling pairwise relatedness and parentage within chambers, including chambers with combinations of unrelated, half-sib, and full-sib nestlings. The proportion of sibling relatedness indicated monogamy in 47% and extra pair-paternity in 40% of the chambers. We also found intra-brood parasitism in 3% of the chambers.

Conclusions

Our results indicate that the monk parakeet is sexually polygamous in its native range in Argentina, which is consistent with the observed mean value of relatedness of adults to juveniles of about 0.4. We also confirm the existence of intra-brood parasitism. High density of monk parakeets may favor occurrence of extra-pair paternity and intra-brood parasitism in the native sites.
Transcriptional profiling of left ventricle and peripheral blood mononuclear cells in a rat model of postinfarction heart failure
Authors: Tulacz Dorota , Mackiewicz Urszula , Maczewski Michal , Maciejak Agata , Gora Monika , Burzynska Beata
Published: November 2013

Background

Myocardial infarction (MI) often results in left ventricular (LV) remodeling followed by heart failure (HF). It is of great clinical importance to understand the molecular mechanisms that trigger transition from compensated LV injury to HF and to identify relevant diagnostic biomarkers. The aim of this study was to investigate gene expression in the LV and to evaluate their reflection in peripheral blood mononuclear cells (PBMCs).

Methods

MI was induced in rats by ligation of the proximal left coronary artery. Rats with small, moderate, and large MI size were included into the experiment two months after the operation. The development of heart failure was estimated by echocardiography and catheterization. Microarrays were used to compare the LV and PBMCs transcriptomes of control and experimental animals.

Results

Only rats with a large MI developed extensive LV remodeling and heart failure. 840 transcripts were altered in LV of failing hearts, and especially numerous were those associated with the extracellular matrix. In contrast, no significant gene expression changes were seen in LVs of rats with moderate or small MI that had compensated LV injury. We showed that ceruloplasmin was similarly overexpressed in the heart and blood in response to HF, whereas downregulation of tetraspanin 12 was significant only in the PBMCs.

Conclusion

A large size of infarcted area is critical for progression of LV remodeling and HF development, associated with altered gene expression in the heart. Ceruloplasmin and tetraspanin 12 are potential convenient markers in readily obtainable PBMCs.
A new double right border binary vector for producing marker-free transgenic plants
Authors: Matheka Jonathan M , Anami Sylvester , Gethi James , Omer Rasha A , Alakonya Amos , Machuka Jesse , Runo Steven
Published: November 2013

Background

Once a transgenic plant is developed, the selectable marker gene (SMG) becomes unnecessary in the plant. In fact, the continued presence of the SMG in the transgenic plant may cause unexpected pleiotropic effects as well as environmental or biosafety issues. Several methods for removal of SMGs that have been reported remain inaccessible due to protection by patents, while development of new ones is expensive and cost prohibitive. Here, we describe the development of a new vector for producing marker-free plants by simply adapting an ordinary binary vector to the double right border (DRB) vector design using conventional cloning procedures.

Findings

We developed the DRB vector pMarkfree5.0 by placing the bar gene (representing genes of interest) between two copies of T-DNA right border sequences. The β-glucuronidase (gus) and nptII genes (representing the selectable marker gene) were cloned next followed by one copy of the left border sequence. When tested in a model species (tobacco), this vector system enabled the generation of 55.6% kanamycin-resistant plants by Agrobacterium-mediated transformation. The frequency of cotransformation of the nptII and bar transgenes using the vector was 66.7%. Using the leaf bleach and Basta assays, we confirmed that the nptII and bar transgenes were coexpressed and segregated independently in the transgenic plants. This enable separation of the transgenes in plants cotransformed using pMarkfree5.0.

Conclusions

The results suggest that the DRB system developed here is a practical and effective approach for separation of gene(s) of interest from a SMG and production of SMG-free plants. Therefore this system could be instrumental in production of “clean” plants containing genes of agronomic importance.
Domestic pigs as potential reservoirs of human and animal trypanosomiasis in Northern Tanzania
Authors: Hamill Louise C , Kaare Magai T , Welburn Susan C , Picozzi Kim
Published: November 2013

Background

Pig keeping is becoming increasingly common across sub-Saharan Africa. Domestic pigs from the Arusha region of northern Tanzania were screened for trypanosomes using PCR-based methods to examine the role of pigs as a reservoir of human and animal trypanosomiasis.

Methods

A total of 168 blood samples were obtained from domestic pigs opportunistically sampled across four districts in Tanzania (Babati, Mbulu, Arumeru and Dodoma) during December 2004. A suite of PCR-based methods was used to identify the species and sub-species of trypanosomes including: Internally Transcribed Sequence to identify multiple species; species specific PCR to identify T. brucei s. l. and T. godfreyi and a multiplex PCR reaction to distinguish T. b. rhodesiense from T. brucei s. l.

Results

Of the 168 domestic pigs screened for animal and human infective trypanosome DNA, 28 (16.7%) were infected with one or more species of trypanosome; these included: six pigs infected with Trypanosoma vivax (3.6%); three with Trypanosoma simiae (1.8%); two with Trypanosoma congolense (Forest) (1%) and four with Trypanosoma godfreyi (2.4%). Nineteen pigs were infected with Trypanosoma brucei s. l. (10.1%) of which eight were identified as carrying the human infective sub-species Trypanosoma brucei rhodesiense (4.8%).

Conclusion

These results show that in Tanzania domestic pigs may act as a significant reservoir for animal trypanosomiasis including the cattle pathogens T. vivax and T. congolense, the pig pathogen T. simiae, and provide a significant reservoir for T. b. rhodesiense, the causative agent of acute Rhodesian sleeping sickness.
Models to quantify excretion of dry matter, nitrogen, phosphorus and carbon in growing pigs fed regional diets
Authors: Jørgensen Henry , Prapaspongsa Trakarn , Vu Van Thi Khanh , Poulsen Hanne Damgaard
Published: November 2013

Modern pig production contributes to many environmental problems that relate to manure, especially in areas with highly intensive production systems and in regions like Asia where the regulative control is not effective. Therefore, the objective of this study was to use three different pig diets varying in dietary protein, fibre and fat as representative for Danish (DK), Thai (TH) and Vietnamese (VN) pig production to develop and evaluate different approaches to predict/calculate excretion from growing pigs in comparison with the experimentally determined values.

Nine female growing pigs were used in a digestibility and balance experiment. Excretion of dry matter (DM), nitrogen (N), phosphorus (P) and carbon (C) of the experimental diets were determined.

Due to the highest dietary fibre content, VN had the lowest digestibility of N, P and C (73, 49, and 73%, respectively) compared with the DK and TH pig diets. From the known diet composition using standard table values on chemical and nutrient digestibly, high accuracy (bias) and low variation was found and the results could be used for prediction on chemical composition and excretion in faeces and urine in growing pigs. Calculation based on standard values regarding nutrient retention in the pig body as used in the Danish manure normative system (DMNS) showed likewise to be quite useful for quantifying the total excretion of N and P.

Overall, the results demonstrate that simple models that require cheap and normally available information on dietary nutrients can give useful information on nutrient excretion in growing pigs.
Neoadjuvant treatment of melanoma: case reports and review
Authors: Laks Shachar , Brueske Kevin A , Hsueh Eddy C
Published: November 2013

Neoadjuvant therapy is an under-utilized regimen for the treatment of metastatic melanoma. The use of this approach has been increasing in other tumor types. Neoadjuvant therapy may reduce occult circulating tumor cell burden in the face of bulky disease and afford a real time evaluation of treatment effectiveness. Neoadjuvant approach can also provide preoperative histologic and molecular analysis of treated tissue that may guide the postoperative treatment planning in patients with resectable metastatic melanoma lesions. The putative benefits of better margin control and clearance of occult systemic disease would theoretically improve surgical outcome. With the advent of effective agents against metastatic melanoma, this common approach to the treatment of rectal cancer, metastatic colon cancer, and breast cancer should also be evaluated as a viable treatment strategy for advanced stage melanoma.
Development of a PCR based marker system for easy identification and classification of aerobic endospore forming bacilli
Authors: Kadyan Sangeeta , Panghal Manju , Singh Khushboo , Yadav Jaya Parkash
Published: November 2013

Restriction fragment length analysis of 16S rRNA gene of 52 different aerobic endospore forming Bacilli (AEFB) strains with HaeIII enzyme has revealed the presence of a 460 bp long fragment in 50 AEFB strains. BLAST analysis revealed that the fragment was 463 bp long and it was located at 3’ end of 16S rRNA gene. Further specificity of this fragment for AEFB strains was checked by PCR and in silico methods. In PCR based method a primer pair (463 F and 463R) specific to this fragment was designed and this primer pair has shown amplification of 463 bp fragment in AEFB strains only. In in silico methods homology of primer pair and presence of restriction enzyme site in 16S rRNA genes were checked in 268 species of AEFB. Almost all species of AEFB have shown positive results for both of the tests. Further multiple alignments of 463 bp sequences of different species of AEFB have shown that it is a good marker for identification and classification of AEFB.
Racemic ketamine in adult head injury patients: use in endotracheal suctioning
Authors: Caricato Anselmo , Tersali Alessandra , Pitoni Sara , De Waure Chiara , Sandroni Claudio , Bocci Maria Grazia , Annetta Maria Giuseppina , Pennisi Mariano Alberto , Antonelli Massimo
Published: November 2013

Introduction

Endotracheal suctioning (ETS) is essential for patient care in an ICU but may represent a cause of cerebral secondary injury. Ketamine has been historically contraindicated for its use in head injury patients, since an increase of intracranial pressure (ICP) was reported; nevertheless, its use was recently suggested in neurosurgical patients. In this prospective observational study we investigated the effect of ETS on ICP, cerebral perfusion pressure (CPP), jugular oxygen saturation (SjO2) and cerebral blood flow velocity (mVMCA) before and after the administration of ketamine.

Methods

In the control phase, ETS was performed on patients sedated with propofol and remifentanil in continuous infusion. If a cough was present, patients were assigned to the intervention phase, and 100 γ/kg/min of racemic ketamine for 10 minutes was added before ETS.

Results

In the control group ETS stimulated the cough reflex, with a median cough score of 2 (interquartile range (IQR) 1 to 2). Furthermore, it caused an increase in mean arterial pressure (MAP) (from 89.0 ± 11.6 to 96.4 ± 13.1 mmHg; P <0.001), ICP (from 11.0 ± 6.7 to 18.5 ± 8.9 mmHg; P <0.001), SjO2 (from 82.3 ± 7.5 to 89.1 ± 5.4; P = 0.01) and mVMCA (from 76.8 ± 20.4 to 90.2 ± 30.2 cm/sec; P = 0.04). CPP did not vary with ETS. In the intervention group, no significant variation of MAP, CPP, mVMCA, and SjO2 were observed in any step; after ETS, ICP increased if compared with baseline (15.1 ± 9.4 vs. 11.0 ± 6.4 mmHg; P <0.05). Cough score was significantly reduced in comparison with controls (P <0.0001).

Conclusions

Ketamine did not induce any significant variation in cerebral and systemic parameters. After ETS, it maintained cerebral hemodynamics without changes in CPP, mVMCA and SjO2, and prevented cough reflex. Nevertheless, ketamine was not completely effective when used to control ICP increase after administration of 100 γ/kg/min for 10 minutes.
The two faces of heterologous immunity: protection or immunopathology
Authors: Sharma Shalini , Thomas Paul G
Published: November 2013

Immunity to previously encountered viruses can alter responses to unrelated pathogens. This phenomenon, which is known as heterologous immunity, has been well established in animal model systems. Heterologous immunity appears to be relatively common and may be beneficial by boosting protective responses. However, heterologous reactivity can also result in severe immunopathology. The key features that define heterologous immune modulation include alterations in the CD4+ and CD8+ T cell compartments and changes in viral dynamics and disease progression. In this review, we discuss recent advances and the current understanding of antiviral immunity in heterologous infections. The difficulties of studying these complex heterologous infections in humans are discussed, with special reference to the variations in HLA haplotypes and uncertainties about individuals' infection history. Despite these limitations, epidemiological analyses in humans and the data from mouse models of coinfection can be applied toward advancing the design of therapeutics and vaccination strategies.
Characteristics of TCR/CD3 complex CD3ɛ chains of regulatory CD4+ T (Treg) lymphocytes: role in Treg differentiation in vitro and impact on Treg in vivo
Authors: Rojo Jose M , Ojeda Gloria , Acosta Yenny Y , Montes-Casado Maria , Criado Gabriel , Portolés Pilar
Published: November 2013

Tregs are anergic CD4+CD25+Foxp3+ T lymphocytes exerting active suppression to control immune and autoimmune responses. However, the factors in TCR recognition underlying Treg differentiation are unclear. Based on our previous data, we hypothesized that Treg TCR/CD3 antigen receptor complexes might differ from those of CD4+CD25− Tconv. Expression levels of TCR/CD3, CD3ɛ,ζ chains, or other molecules involved in antigen signaling and the characteristics of CD3ɛ chains were analyzed in thymus or spleen Treg cells from normal mice. Tregs had quantitative and qualitatively distinct TCR/CD3 complexes and CD3ɛ chains. They expressed significantly lower levels of the TCR/CD3 antigen receptor, CD3ɛ chains, TCR-ζ chain, or the CD4 coreceptor than Tconv. Levels of kinases, adaptor molecules involved in TCR signaling, and early downstream activation pathways were also lower in Tregs than in Tconv. Furthermore, TCR/CD3 complexes in Tregs were enriched in CD3ɛ chains conserving their N-terminal, negatively charged amino acid residues; this trait is linked to a higher activation threshold. Transfection of mutant CD3ɛ chains lacking these residues inhibited the differentiation of mature CD4+Foxp3− T lymphocytes into CD4+Foxp3+ Tregs, and differences in CD3ɛ chain recognition by antibodies could be used to enrich for Tregs in vivo. Our results show quantitative and qualitative differences in the TCR/CD3 complex, supporting the hyporesponsive phenotype of Tregs concerning TCR/CD3 signals. These differences might reconcile avidity and flexible threshold models of Treg differentiation and be used to implement therapeutic approaches involving Treg manipulation.
More Native than Tomorrow: Grace Ndiritu in Conversation with Brendan Wattenberg
Authors: Wattenberg Brendan
Published: November 2013

In this conversation Brendan Wattenberg and Grace Ndiritu discuss several of Ndiritu’s videos, in particular The Nightingale, Natural Disasters, and Journey’s North. They talk about Ndiritu’s filmmaking practice, the concept of self-portraiture, shamanic journeying, and the three schools of contemporary African art.
Postcolonial Artists and Global Aesthetics, by Akin Adesokan
Authors: Gilvin Amanda
Published: November 2013

Scholars of African visual culture will be well served by Akin Adesokan’s recent book Postcolonial Artists and Global Aesthetics, which offers a model for interpreting artworks within the many cultural and economic contexts in which they function. The book is structured as a collection of case studies of writers and filmmakers, and while each chapter focuses on a specific cultural producer, Adesokan builds connections between his figures of analysis across time and space. Adesokan offers a successful, rigorous example of a project that demonstrates the political urgency and conceptual depth of African artists, as well as artists’ investment in mercurial global political networks that stretch across generations and continents.
The Delight of the Yearner: Ernst May and Erica Mann in Nairobi, 1933–1953
Authors: Tiven Benjamin
Published: November 2013

This article engages the German architect Ernst May and the complex legacies of his work in colonial Kenya from 1933 to 1953. Tiven examines three structures and parses their political, aesthetic, and biographical dimensions: one proposed, but never built (the Native House for Concrete Pre-manufacture); one still inhabited today (the Delamere Flats); and one demolished ca. 2005 (the Oceanic Hotel). The article explores May’s impulse for gardening as a kind of anti-architecture and crosses his narrative with those of two other architect-horticulturalists: Erica Mann, a Jewish Romanian refugee and May’s architectural colleague in Nairobi; and Albert Speer, Hitler’s architect and armaments minister.
Frantz Fanon’s Oeuvres: A Metamorphic Thought
Authors: Mbembe Achille
Published: November 2013

Frantz Fanon is one of the very few thinkers to have risked something that resembles a theory of decolonization. In this essay Achille Mbembe reflects on the dialectics of the end/closure and the boundless possibilities evoked by Fanon, and the ways these are played out under contemporary conditions. Mbembe also assesses the place contemporary struggles for emancipation assign to the key Fanonian concepts of time, creation, and reconstitution, and the extent to which they truly transcend the “law of repetition,” which Fanon foresaw as the biggest threat to newness.
An Echo without a Medium: An Artist's Project
Authors: Tiven Benjamin
Published: November 2013

This article engages the German architect Ernst May and the complex legacies of his work in colonial Kenya from 1933 to 1953. Tiven examines three structures and parses their political, aesthetic, and biographical dimensions: one proposed, but never built (the Native House for Concrete Pre-manufacture); one still inhabited today (the Delamere Flats); and one demolished ca. 2005 (the Oceanic Hotel). The article explores May’s impulse for gardening as a kind of anti-architecture and crosses his narrative with those of two other architect-horticulturalists: Erica Mann, a Jewish Romanian refugee and May’s architectural colleague in Nairobi; and Albert Speer, Hitler’s architect and armaments minister.
Dispersal, eddies, and the diversity of marine phytoplankton
Authors: Clayton Sophie , Dutkiewicz Stephanie , Jahn Oliver , Follows Michael J.
Published: November 2013

Lay Abstract

Phytoplankton are the “plants” of the ocean; they fix carbon dioxide from the atmosphere and make up the base of the oceanic food chain. Phytoplankton are incredibly diverse, but the reason for their high biodiversity is not well understood. Generally speaking, phytoplankton might be present in a given location either because they are “happy” and able to grow there, or if they are unable to grow there, because they have been transported in from elsewhere (i.e., via dispersal). Previous studies have suggested that “hotspots” of high phytoplankton diversity found in the most dynamic oceanic regions can be explained by dispersal. We explored this question by using a set of computer simulations of phytoplankton ecology coupled to a realistic ocean circulation. We show that dispersal can only partly explain diversity hotspots. The mixing of populations by ocean currents and eddies is important, but a plentiful supply of nutrients and variable environmental conditions also enhance phytoplankton diversity. This work has generated hypotheses that will stimulate new projects to test them in the field.
ModelingMycobacterium tuberculosisearly granuloma formation in experimental human lung tissue
Authors: Parasa Venkata Ramanarao , Rahman Muhammad Jubayer , Ngyuen Hoang Anh Thu , Svensson Mattias , Brighenti Susanna , Lerm Maria
Published: November 2013

The widely used animal models for tuberculosis (TB) display fundamental differences from human TB. Therefore, a validated model that recapitulates human lung TB is attractive for TB research. Here, we describe a unique method for establishment of TB infection in an experimental human lung tissue model. The model is based on cell lines derived from human lungs and primary macrophages from peripheral blood, and display characteristics of human lung tissue including evenly integrated macrophages throughout the epithelium, production of extracellular matrix, stratified epithelia and mucus secretion. Establishment of experimental infection in the model tissue with Mycobacterium tuberculosis, the bacterium that causes TB, resulted in clustering of macrophages at the site of infection, reminiscent of early TB granuloma formation. We quantitated the extent of granuloma formation induced by different strains of mycobacteria and validated our model against findings in other TB models. We found that early granuloma formation is dependent on ESAT-6, which is secreted via the Type VII secretion machinery of virulent mycobacteria. Our model, which can facilitate the discovery of the interactions between mycobacteria and host cells in a physiological environment, is the first lung tissue model described for TB.
Oncogenic deletion mutants of gp130 signal from intracellular compartments
Authors: Schmidt-Arras Dirk , Müller Miryam , Stevanovic Marija , Horn Silke , Schütt Antje , Bergmann Juri , Wilkens Ruven , Lickert Annett , Rose-John Stefan
Published: November 2013

Interleukin 6 and hence activation of the IL-6 receptor signalling subunit gp130 have been linked to inflammation and tumour formation. Recently, deletion mutations in gp130 have been identified in inflammatory hepatocellular adenoma. The mutations clustered around one IL-6 binding epitope and rendered gp130 constitutively active in a ligand-independent manner. Here we can show that gp130 deletion mutants, but not wildtype gp130 localise predominantly to intracellular compartments, notably the ER and early endosomes. One of the most frequent mutants gp130 Y186-Y190del (ΔYY) is retained in the ER quality control by its association with the chaperone calnexin. Furthermore, we can show that gp130 ΔYY induces downstream signalling from both, ER and endosomes and that both signals contribute to ligand-independent cell proliferation. We also demonstrate that endosomal localisation of gp130 ΔYY is crucial for full-fledged STAT3 activation. Therefore aberrant signalling from intracellular compartments might explain the tumourigenic potential of naturally occurring somatic mutations of gp130.
Osh proteins regulate COPII-mediated vesicular transport of ceramide from the endoplasmic reticulum in budding yeast
Authors: Kajiwara Kentaro , Ikeda Atsuko , Aguilera-Romero Auxiliadora , Castillon Guillaume A. , Kagiwada Satoshi , Hanada Kentaro , Riezman Howard , Muñiz Manuel , Funato Kouichi
Published: November 2013

Lipids synthesized at the endoplasmic reticulum (ER) are delivered to the Golgi by vesicular and non-vesicular pathways. ER-to-Golgi transport is critical for maintaining the different membrane lipid composition and identities of organelles. Despite their importance, mechanisms regulating transport remain elusive. Here we report that coat protein complex II (COPII) vesicle-mediated transport of ceramide from the ER to the Golgi requires the yeast oxysterol-binding protein homologs, Osh proteins, which have been implicated in lipid homeostasis. Because Osh proteins are not required to transport proteins to the Golgi, these results indicate a specific requirement for the Osh proteins in the transport of ceramide. In addition, we provide evidence that Osh proteins play a negative role in COPII vesicle biogenesis. Together, our data suggest that ceramide transport and sphingolipid levels between the ER and Golgi are maintained by two distinct functions of Osh proteins, which negatively regulate COPII vesicle formation and positively control the late stage, presumably fusion of ceramide-enriched vesicles with Golgi compartments.