bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Implementation of a Double-Blind Corticosteroid-Tapering Regimen for a Clinical Trial
Authors: Collinson Neil , Tuckwell Katie , Habeck Frank , Chapman Monique , Klearman Micki , Stone John H.
Published: March 2015

We describe the design and operationalization of a blinded corticosteroid-tapering regimen for a randomized trial of tocilizumab in giant cell arteritis (GCA). To our knowledge, no clinical trial in any disease has ever employed a blinded corticosteroid-tapering regimen, but this was necessary to the design of our trial which is likely to be relevant to other investigations of steroid-sparing regimens. Two standardized corticosteroid-tapering regimens are required for this GCA trial: a 6-month regimen in 3 arms (taken with tocilizumab 162 mg subcutaneously weekly or every other week or with placebo) and a 12-month regimen with placebo (fourth arm). Investigators select initial prednisone doses, tapered in an open-label fashion until 20 mg/day. Doses <20 mg/day are blinded. At least 27 blinded blister packs are required to ensure blinding and encourage compliance. This permits all possible daily doses but requires ≤5 capsules/day. The number of capsules taken at any point during tapering is identical across groups. Our approach may be extrapolated to trials beyond GCA.
Parallel Dynamical Systems over Graphs and Related Topics: A Survey
Authors: Aledo Juan A. , Martinez Silvia , Valverde Jose C.
Published: March 2015

In discrete processes, as computational or genetic ones, there are many entities and each entity has a state at a given time. The update of states of the entities constitutes an evolution in time of the system, that is, a discrete dynamical system. The relations among entities are usually represented by a graph. The update of the states is determined by the relations of the entities and some local functions which together constitute (global) evolution operator of the dynamical system. If the states of the entities are updated in a synchronous manner, the system is called aparallel dynamical system. This paper is devoted to review the main results on the dynamical behavior of parallel dynamical systems over graphs which constitute a generic tool for modeling discrete processes.
Vitamin A, Cancer Treatment and Prevention: The New Role of Cellular Retinol Binding Proteins
Authors: Doldo Elena , Costanza Gaetana , Agostinelli Sara , Tarquini Chiara , Ferlosio Amedeo , Arcuri Gaetano , Passeri Daniela , Scioli Maria Giovanna , Orlandi Augusto
Published: March 2015

Retinol and vitamin A derivatives influence cell differentiation, proliferation, and apoptosis and play an important physiologic role in a wide range of biological processes. Retinol is obtained from foods of animal origin. Retinol derivatives are fundamental for vision, while retinoic acid is essential for skin and bone growth. Intracellular retinoid bioavailability is regulated by the presence of specific cytoplasmic retinol and retinoic acid binding proteins (CRBPs and CRABPs). CRBP-1, the most diffuse CRBP isoform, is a small 15 KDa cytosolic protein widely expressed and evolutionarily conserved in many tissues. CRBP-1 acts as chaperone and regulates the uptake, subsequent esterification, and bioavailability of retinol. CRBP-1 plays a major role in wound healing and arterial tissue remodelling processes. In the last years, the role of CRBP-1-related retinoid signalling during cancer progression became object of several studies. CRBP-1 downregulation associates with a more malignant phenotype in breast, ovarian, and nasopharyngeal cancers. Reexpression of CRBP-1 increased retinol sensitivity and reduced viability of ovarian cancer cellsin vitro. Further studies are needed to explore new therapeutic strategies aimed at restoring CRBP-1-mediated intracellular retinol trafficking and the meaning of CRBP-1 expression in cancer patients’ screening for a more personalized and efficacy retinoid therapy.
Regulating Rac in the Nervous System: Molecular Function and Disease Implication of Rac GEFs and GAPs
Authors: Bai Yanyang , Xiang Xiaoliang , Liang Chunmei , Shi Lei
Published: March 2015

Rho family GTPases, including RhoA, Rac1, and Cdc42 as the most studied members, are master regulators of actin cytoskeletal organization. Rho GTPases control various aspects of the nervous system and are associated with a number of neuropsychiatric and neurodegenerative diseases. The activity of Rho GTPases is controlled by two families of regulators, guanine nucleotide exchange factors (GEFs) as the activators and GTPase-activating proteins (GAPs) as the inhibitors. Through coordinated regulation by GEFs and GAPs, Rho GTPases act as converging signaling molecules that convey different upstream signals in the nervous system. So far, more than 70 members of either GEFs or GAPs of Rho GTPases have been identified in mammals, but only a small subset of them have well-known functions. Thus, characterization of important GEFs and GAPs in the nervous system is crucial for the understanding of spatiotemporal dynamics of Rho GTPase activity in different neuronal functions. In this review, we summarize the current understanding of GEFs and GAPs for Rac1, with emphasis on the molecular function and disease implication of these regulators in the nervous system.
Cytotoxic T Lymphocyte-Associated Antigen 4 Gene Polymorphisms and Autoimmune Thyroid Diseases: An Updated Systematic Review and Cumulative Meta-Analysis
Authors: Hou Hai-Feng , Jin Xu , Sun Tao , Li Cheng , Jiang Bao-Fa , Li Qun-Wei
Published: March 2015

The association of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene and susceptibility to autoimmune thyroid diseases (AITDs) has been studied extensively. However, the results were not the same in different ethnic groups. We updated the meta-analysis of association of CTLA-4 gene polymorphisms with AITDs and summarized the results in specific ethnicity. The associations of A49G gene polymorphism with GD, A49G gene polymorphism with HT, CT60 gene polymorphism with GD, and CT60 gene polymorphism with HT were summarized based on the literatures published up to October 30, 2014, in English or Chinese languages. The participants involved in the studies of A49G with GD, A49G with HT, CT60 with GD, and CT60HT were 39004 subjects (in 51 studies), 13102 subjects (in 22 studies), 31446 subjects (in 22 studies), and 6948 subjects (in 8 studies), respectively. The pooled ORs of CTLA-4 gene polymorphisms with AITDs were larger than 1.00, and the 95% CIs of ORs were statistically significant among whole population analyses. However, the subgroup analysis demonstrated that pooled ORs of A49G polymorphisms with GD among Africans or Americans are less than 1.00. The accumulated evidence suggests that the G allele mutant of A49G and CT60 increased the risks of HT and GD.
NULL Convention Floating Point Multiplier
Authors: Albert Anitha Juliette , Ramachandran Seshasayanan
Published: March 2015

Floating point multiplication is a critical part in high dynamic range and computational intensive digital signal processing applications which require high precision and low power. This paper presents the design of an IEEE 754 single precision floating point multiplier using asynchronous NULL convention logic paradigm. Rounding has not been implemented to suit high precision applications. The novelty of the research is that it is the first ever NULL convention logic multiplier, designed to perform floating point multiplication. The proposed multiplier offers substantial decrease in power consumption when compared with its synchronous version. Performance attributes of the NULL convention logic floating point multiplier, obtained from Xilinx simulation and Cadence, are compared with its equivalent synchronous implementation.
Evaluation of the Efficacy of a Bacteriophage in the Treatment of Pneumonia Induced by Multidrug ResistanceKlebsiella pneumoniaein Mice
Authors: Cao Fang , Wang Xitao , Wang Linhui , Li Zhen , Che Jian , Wang Lili , Li Xiaoyu , Cao Zhenhui , Zhang Jiancheng , Jin Liji , Xu Yongping
Published: March 2015

Multidrug-resistantKlebsiella pneumoniae(MRKP) has steadily grown beyond antibiotic control. However, a bacteriophage is considered to be a potential antibiotic alternative for treating bacterial infections. In this study, a lytic bacteriophage, phage 1513, was isolated using a clinical MRKP isolate KP 1513 as the host and was characterized. It produced a clear plaque with a halo and was classified as Siphoviridae. It had a short latent period of 30 min, a burst size of 264 and could inhibit KP 1513 growthin vitrowith a dose-dependent pattern. Intranasal administration of a single dose of 2 × 109 PFU/mouse 2 h after KP 1513 inoculation was able to protect mice against lethal pneumonia. In a sublethal pneumonia model, phage-treated mice exhibited a lower level ofK. pneumoniaeburden in the lungs as compared to the untreated control. These mice lost less body weight and exhibited lower levels of inflammatory cytokines in their lungs. Lung lesion conditions were obviously improved by phage therapy. Therefore, phage 1513 has a great effectin vitroandin vivo, which has potential to be used as an alternative to an antibiotic treatment of pneumonia that is caused by the multidrug-resistantK. pneumoniae.
Exploring Some Aspects Associated with Dentine Hypersensitivity in Children
Authors: Shitsuka Caleb , Mendes Fausto Medeiros , Corrêa Maria Salete Nahás Pires , Leite Mariana Ferreira
Published: March 2015

Background. The etiology of dentine hypersensitivity (DH) is still inconclusive and there are few studies concerning it in children. Aim. To evaluate clinical, dietary, and salivary variables in children with DH complaints. Design. Forty‐eight children were asked about DH. Data regarding dietary habits were collected from the children’s parents and an examination was performed to determine dental erosion. Dental biofilm was estimated by oral hygiene status, according to Greene and Vermillion’s Simplified Oral Hygiene Index (OHI‐S). Whole saliva was collected under mechanical stimulation and evaluated salivary flow rate, initial pH, buffer capacity, and calcium and phosphate concentrations. The temperature of soft drinks, drinking method, sense of bitter taste, and other variables were also determined. Possible factors associated with DH were analyzed by univariate and multiple Poisson regression analyses. The prevalence ratio (PR) values and 95% confidence intervals (95% CI) were calculated. Results. DH was associated with the presence of dental erosion (PR; 95% CI = 2.23; 1.05 to 4.71) and salivary flow rate (2.49; 1.05 to 5.91). When the presence of erosion was not included, other variables were retained as follows: bitter taste (2.36; 1.38 to 4.03), OHI‐S (0.47; 0.23 to 0.97). Conclusion. DH in children is associated with factors related to dental erosion.
Tactile-Foot Stimulation Can Assist the Navigation of People with Visual Impairment
Authors: Velázquez Ramiro , Pissaloux Edwige , Lay-Ekuakille Aimé
Published: March 2015

Background.Tactile interfaces that stimulate the plantar surface with vibrations could represent a step forward toward the development of wearable, inconspicuous, unobtrusive, and inexpensive assistive devices for people with visual impairments.Objective.To study how people understand information through their feet and to maximize the capabilities of tactile-foot perception for assisting human navigation.Methods.Based on the physiology of the plantar surface, three prototypes of electronic tactile interfaces for the foot have been developed. With important technological improvements between them, all three prototypes essentially consist of a set of vibrating actuators embedded in a foam shoe-insole. Perceptual experiments involving direction recognition and real-time navigation in space were conducted with a total of 60 voluntary subjects.Results.The developed prototypes demonstrated that they are capable of transmitting tactile information that is easy and fast to understand. Average direction recognition rates were 76%, 88.3%, and 94.2% for subjects wearing the first, second, and third prototype, respectively. Exhibiting significant advances in tactile-foot stimulation, the third prototype was evaluated in navigation tasks. Results show that subjects were capable of following directional instructions useful for navigating spaces.Conclusion.Footwear providing tactile stimulation can be considered for assisting the navigation of people with visual impairments.
Spindle Cell Lipoma of the Soft Palate
Authors: Hançer Ahmet , Özbay Can , Karaarslan Serap , Balaban Muzaffer
Published: March 2015

Intraoral spindle cell lipomas (SCL) are very rare and comprise ranging between 1.4%–9.8% of all intraoral lipomas. To our knowledge, no case of a SCL located on the soft palate has been reported in the English-language literature. A 31-year-old female was admitted with a swelling in her soft palate. On examination, a 3 cm sessile, nontender swelling was observed on her soft palate. After surgical excision, it was diagnosed as a SCL.
Quadrupole Excitations in Magnetic Susceptibility of Magnetic Nanoparticle Fe8
Authors: Yousefi Yousef
Published: March 2015

Magnetic susceptibility dependence on temperatures in different magnetic fields will be discussed. Until today, to calculate magnetization and magnetic susceptibility, only dipole excitations have been considered, but, due to the symmetry of operators in Hamiltonian and also to achieve more accuracy, other multiple excitations must be taken into account too. To this end, here, both dipole and quadruple excitations are considered and then the resulting curves will be plotted in presence of different magnetic fields. Finally, seen that the graphs obtained using the multipole excitations more accurately with results taken by experimental data.
Ghrelin Improves Functional Survival of Engrafted Adipose-Derived Mesenchymal Stem Cells in Ischemic Heart through PI3K/Akt Signaling Pathway
Authors: Han Dong , Huang Wei , Ma Sai , Chen Jiangwei , Gao Lina , Liu Tong , Zhang Rongqing , Li Xiujuan , Li Congye , Fan Miaomiao , Chen Yundai , Cao Feng
Published: March 2015

Mesenchymal stem cells (MSCs) have been proposed as a promising cell population for cell therapy and regenerative medicine applications. However, the low retention and poor survival of engrafted cells hampered the therapeutic efficacy of engrafted MSCs. Ghrelin is a 28-amino-acid peptide hormone and is proved to exert a protective effect on the cardiovascular system. This study is designed to investigate the protective effects of ghrelin on engrafted adipose-derived mesenchymal stem cells (ADMSCs) and its beneficial effects with cellular therapy in mice myocardial infarction (MI). Results showed that intramyocardial injection of ADMSCs combining with ghrelin administration inhibited host cardiomyocyte apoptosis, reduced fibrosis, and improved cardiac function. To reveal possible mechanisms, ADMSCs were subjected to hypoxia/serum deprivation (H/SD) injury to simulate ischemic conditionsin vivo. Ghrelin (10−8 M, 33712 pg/ml) improved ADMSCs survival under H/SD condition. Western blot assay revealed that ghrelin increased AKT phosphorylation bothin vivoandin vitro, decreased the proapoptotic protein Bax, and increased the antiapoptotic protein Bcl-2in vitro, while these effects were abolished by PI3K inhibitor LY294002. These revealed that ghrelin may serve as a promising candidate for hormone-driven approaches to improve the efficacy of mesenchymal stem cell-based therapy for cardiac ischemic diseaseviaPI3K/AKT pathway.
Three‐Dimensional Finite Element Analysis of Anterior Two‐Unit Cantilever Resin‐Bonded Fixed Dental Prostheses
Authors: Keulemans Filip , Shinya Akikazu , Lassila Lippo V. J. , Vallittu Pekka K. , Kleverlaan Cornelis J. , Feilzer Albert J. , De Moor Roeland J. G.
Published: March 2015

The aim of this study was to evaluate the influence of different framework materials on biomechanical behaviour of anterior two‐unit cantilever resin‐bonded fixed dental prostheses (RBFDPs). A three‐dimensional finite element model of a two‐unit cantilever RBFDP replacing a maxillary lateral incisor was created. Five framework materials were evaluated: direct fibre‐reinforced composite (FRC‐Z250), indirect fibre‐reinforced composite (FRC‐ES), gold alloy (M), glass ceramic (GC), and zirconia (ZI). Finite element analysis was performed and stress distribution was evaluated. A similar stress pattern, with stress concentrations in the connector area, was observed in RBFDPs for all materials. Maximal principal stress showed a decreasing order: ZI > M > GC > FRC‐ES > FRC‐Z250. The maximum displacement of RBFDPs was higher for FRC‐Z250 and FRC‐ES than for M, GC, and ZI. FE analysis depicted differences in location of the maximum stress at the luting cement interface between materials. For FRC‐Z250 and FRC‐ES, the maximum stress was located in the upper part of the proximal area of the retainer, whereas, for M, GC, and ZI, the maximum stress was located at the cervical outline of the retainer. The present study revealed differences in biomechanical behaviour between all RBFDPs. The general observation was that a RBFDP made of FRC provided a more favourable stress distribution.
Comparative Analysis of Anterior Segment Parameters in Normal and Keratoconus Eyes Generated by Scheimpflug Tomography
Authors: Orucoglu Faik , Toker Ebru
Published: March 2015

Purpose. To assess and compare the anterior and posterior corneal surface parameters, keratoconus indices, thickness profile data, and data from enhanced elevation maps of keratoconic and normal corneas with the Pentacam Scheimpflug corneal tomography and to determine the sensitivity and specificity of these parameters in discriminating keratoconus from normal eyes.Methods. The study included 656 keratoconus eyes and 515 healthy eyes with a mean age of30.95±9.25and32.90±14.78years, respectively. Forty parameters obtained from the Pentacam tomography were assessed by the receiver operating characteristic curve analysis for their efficiency.Results. Receiver operating characteristic curve analyses showed excellent predictive accuracy (area under the curve, ranging from 0.914 to 0.972) for 21 of the 40 parameters evaluated. Among all parameters indices of vertical asymmetry, keratoconus index, front elevation at thinnest location, back elevation at thinnest location, Ambrósio Relational Thickness (ARTmax), deviation of average pachymetric progression, deviation of ARTmax, and total deviation showed excellent (>90%) sensitivity and specificity in addition to excellent area under the receiver operating characteristic curve (AUROC).Conclusions. Parameters derived from the topometric and Belin-Ambrósio enhanced ectasia display maps very effectively discriminate keratoconus from normal corneas with excellent sensitivity and specificity.
Prognostic Value ofTc99m-Pertechnetate Thyroid Scintigraphy in Radioiodine Therapy in a Cohort of Chinese Graves’ Disease Patients: A Pilot Clinical Study
Authors: Hou Haifeng , Hu Shu , Fan Rong , Sun Wen , Zhang Xiaofei , Tian Mei
Published: March 2015

Objectives. This study is to assess the prognostic value ofTc99m-pertechnetate thyroid scintigraphy for predicting the outcomes of fixed low dose of radioiodine therapy (RIT) in a cohort of Chinese Graves’ disease (GD) patients.Materials and Methods. This is a retrospective study of GD patients who received RIT with a single dose of radioiodine (5 mCi). All the patients receivedTc99m-pertechnetate thyroid scintigraphy prior to RIT. Thyroid mass,Tc99m-pertechnetate uptake, gender, age at diagnosis, duration of the disease, ophthalmopathy, and serum levels of FT4, FT3, TT4, and TT3 prior to RIT were analyzed as potential interference factors for outcomes of RIT.Results. One hundred and eighteen GD patients who completed RIT were followed up for 12 months. The outcomes (euthyroidism, hypothyroidism, and hyperthyroidism) were found to be significantly associated with thyroid mass andTc99m-pertechnetate uptake. Patients with thyroid mass ≤ 40.1 g orTc99m-pertechnetate uptake ≤ 15.2% had higher treatment success.Conclusions. A fixed low dose of 5 mCi radioiodine seems to be practical and effective for the treatment of Chinese GD patients with thyroid mass ≤ 40.1 g andTc99m-pertechnetate uptake ≤ 15.2%. This study demonstratesTc99m-pertechnetate thyroid scintigraphy is an important prognostic factor for predicting the outcomes of RIT.
Mechanical Force-Induced Specific MicroRNA Expression in Human Periodontal Ligament Stem Cells
Authors: Wei F.L. , Wang J.H. , Ding G. , Yang S.Y. , Li Y. , Hu Y.J. , Wang S.L.
Published: March 2015

It remains unclear how the expression of microRNAs (miRNAs) in human periodontal ligament stem cells (PDLSCs) might respond to mechanical stretch. To investigate specific miRNA expression in stretched PDLSCs, we used a Flexcell® FX-5000™ tension system to achieve external mechanical stimulation. Then, a custom-designed microarray assay was performed to investigate and describe the genome-wide differential expression of miRNAs in normal and stretched PDLSCs. Finally, we implemented integrative miRNA target prediction and network analysis approaches to construct an interaction network of the key miRNAs and their putative targets. We found that stretching induced morphological changes and increased alkaline phosphatase (ALP) activity, runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and bone sialoprotein (BSP) expression in PDLSCs. The microarray data showed that 53 miRNAs were differentially expressed with stretching. With an interaction network, we examined the connections between 10 selected key miRNAs and their putative target genes, which were related to mechanical force. The results from the interaction network provided a basis for postulating the functional roles of miRNAs in PDLSCs.
French Nationwide Cohort Temporary Utilization Authorization Survey of GranuPAS® in MDR-TB Patients
Authors: Kibleur Yves , Veziris Nicolas
Published: March 2015

Background: Para-aminosalicylic acid (PAS) is again needed for the treatment of multidrug and extensively drug-resistant tuberculosis (M/XDR-TB). The study of a new granulated formulation (PAS-GR, ‘GranuPAS®'), which might have fewer adverse events, was made possible by the statutory requirement that data be collected regarding its use in France in multidrug-resistant TB (MDR-TB) patients under a ‘therapeutic utilization' follow-up for safety and efficacy system called ‘Autorisation Temporaire d'Utilisation' (ATU). Methods: In May 2011 an ATU cohort was established to monitor the named patient use of PAS-GR. All patients were included in a follow-up protocol developed by Lucane Pharma and the French Medicines Agency (ANSM) which recorded demographics, dosing characteristics, concomitant medications, adverse events, and outcome. Following EU marketing authorization, the ATU terminated about 3 years after initiation. Results: PAS-GR was used for the treatment of 231 MDR-TB patients. PAS-GR was used at 12 g/day in 114 cases and 8 g/day in 80 cases. PAS-GR-containing combinations resulted in sputum conversion in a median of 94 days (IQR 48-143) in the 55 patients with information after treatment initiation. Adverse effects of PAS-GR-containing combinations were mostly gastrointestinal (GI; 9% of patients experiencing a GI event at any time) and led to interrupt PAS-GR in 6% of cases (2.1% GI). Conclusions: The efficacy of PAS-GR appears equivalent to that of PAS, and its tolerance improved over earlier PAS formulations, thus supporting the use of PAS-GR as part of drug combinations for the treatment of MDR and XDR-TB.
Packing to Tamponade Severe Intracranial Hemorrhage in Pediatric Patients
Authors: Winston Ken R. , Byers Joshua T. , Freeman Jacob , Beauchamp Kathryn
Published: March 2015

The medical records of all children in whom packing was used to control severe intracranial hemorrhage were reviewed. Eight children, with ages ranging from newborn to 4 years, met the inclusion criteria and all survived. Five were victims of severe closed head trauma, 2 had received penetrating cranial injuries, and 1 developed severe bleeding while undergoing surgery for a malignant tumor in the posterior fossa. Blood loss at the time of removal of the packing was minimal in 7 patients and was surgically controllable in the other. Packing is a simple, efficient, and safe maneuver which can very often halt intracranial bleeding that is considered to be otherwise uncontrollable, and can thereby limit the consequences of prolonged or repeated periods of hypotension and possible exsanguination.
Soluble CD40 Ligand Promotes Macrophage Foam Cell Formation in the Etiology of Atherosclerosis
Authors: Yuan Ming , Fu Hongjie , Ren Lifen , Wang Haichang , Guo Wenyi
Published: March 2015

Objective: High levels of soluble CD40 ligand (sCD40L) in the circulation have been suggested as an important indicator of cardiovascular diseases such as atherosclerosis and acute coronary syndromes. In the present study, we explored the role of sCD40L in the formation of foam cells. Methods: Lipid deposition and foam cell formation was measured by high-performance liquid chromatography and Nile Red staining, respectively. Gene expressions were detected by quantitative real-time PCR and Western blot analysis. The interaction between CD40 and sCD40L were blocked by CD40 small interfering RNA or anti-CD40 antibody. Results: sCD40L significantly increased lipid deposition and foam cell formation associated with upregulation of scavenger receptor type A and CD36. Additionally, sCD40L increased adipocyte enhancer-binding protein 1 and cholesterol efflux, and activated NF-κB in macrophages. sCD40L promoted foam cell formation via CD40 ligation and disruption of the ligation between CD40 and CD40L either by small interfering RNA or by a blocking anti-CD40 antibody apparently inhibiting foam cell formation in response to sCD40L. Conclusion: Our data suggests a novel insight into the role of sCD40L in foam cell formation during atherosclerosis, which further confirms the importance of sCD40L in atherosclerosis and as a target for the treatment of this disease.
Does Caspase-6 Have a Role in Perinatal Brain Injury?
Authors: Baburamani Ana A. , Miyakuni Yasuka , Vontell Regina , Supramaniam Veena G. , Svedin Pernilla , Rutherford Mary , Gressens Pierre , Mallard Carina , Takeda Satoru , Thornton Claire , Hagberg Henrik
Published: March 2015

Apoptotic mechanisms are centre stage for the development of injury in the immature brain, and caspases have been shown to play a pivotal role during brain development and in response to injury. The inhibition of caspases using broad-spectrum agents such as Q-VD-OPh is neuroprotective in the immature brain. Caspase-6, an effector caspase, has been widely researched in neurodevelopmental disorders and found to be important following adult stroke, but its function in the neonatal brain has yet to be detailed. Furthermore, caspases may be important in microglial activation; microglia are required for optimal brain development and following injury, and their close involvement during neuronal cell death suggests that apoptotic cues such as caspase activation may be important in microglial activation. Therefore, in this study we aimed to investigate the possible apoptotic and non-apoptotic functions caspase-6 may have in the immature brain in response to hypoxia-ischaemia. We examined whether caspases are involved in microglial activation. We assessed cleaved caspase-6 expression following hypoxia-ischaemia and conducted primary microglial cultures to assess whether the broad-spectrum inhibitor Q-VD-OPh or caspase-6 gene deletion affected lipopolysaccharide (LPS)-mediated microglial activation and phenotype. We observed cleaved caspase-6 expression to be low but present in the cell body and cell processes in both a human case of white matter injury and 72 h following hypoxia-ischaemia in the rat. Gene deletion of caspase-6 did not affect the outcome of brain injury following mild (50 min) or severe (60 min) hypoxia-ischaemia. Interestingly, we did note that cleaved caspase-6 was co-localised with microglia that were not of apoptotic morphology. We observed that mRNA of a number of caspases was modulated by low-dose LPS stimulation of primary microglia. Q-VD-OPh treatment and caspase-6 gene deletion did not affect microglial activation but modified slightly the M2b phenotype response by changing the time course of SOCS3 expression after LPS administration. Our results suggest that the impact of active caspase-6 in the developing brain is subtle, and we believe there are predominantly other caspases (caspase-2, -3, -8, -9) that are essential for the cell death processes in the immature brain.
Sex Chromosome Conservation, DMRT1 Phylogeny and Gonad Morphology in Diploid Palearctic Green Toads (Bufo viridis Subgroup)
Authors: Tamschick Stephanie , Rozenblut-Kościsty Beata , Bonato Lucio , Dufresnes Christophe , Lymberakis Petros , Kloas Werner , Ogielska Maria , Stöck Matthias
Published: March 2015

Due to the prevailing sex chromosome homomorphy and large genome size, the knowledge on sex determination systems, sex chromosomes and sex-determining genes in amphibians remains scarce. Using 3 cross-amplifying sex-linked microsatellite markers, we uncover sex determination systems and sex chromosomes in purebred, diploid Palearctic green toads (Bufo viridis subgroup), which had so far only been characterized in laboratory-bred hybrids. Our data support an XY system in B. balearicus, B. viridis and B. variabilis. While females show recombination, it is strongly suppressed (or not detectable) in males. Markers corroborate the largest chromosome pair 1 (homologous to linkage group 1 of Xenopus tropicalis) to represent the sex chromosomes in diploid species of the B. viridis subgroup (B. siculus, B. shaartusiensis, B. balearicus, B. turanensis, B. variabilis, B. viridis, and probably B. boulengeri). This chromosome harbors DMRT1, a key gene of the sexual pathway in deeply divergent animal taxa. However, our phylogenetic analysis of a 600-bp fragment of that gene in diploid green toad taxa reveals that X and Y alleles cluster by species and not by gametolog. This suggests that XY-sequence similarity stems from occasional XY recombination within DMRT1, and we preliminarily reject its role as the master sex determination gene, pending future extension of this evidence to the entire DMRT1 gene. We further create a chain of evidence, which supports the hypothesis that linkage group 1 of X. tropicalis appears to be maintained as the largest chromosome (1), and thus is homologous in anuran karyotype evolution from pipid to hylid, bufonid and ranid anurans.
Haptoglobin Enhances Cardiac Transplant Rejection
Authors: Shen Hua , Heuzey Elizabeth , Mori Daniel N. , Wong Christine K. , Colangelo Christopher M. , Chung Lisa M. , Bruce Can , Slizovskiy Ilya B. , Booth Carmen J. , Kreisel Daniel , Goldstein Daniel R.
Published: March 2015

Rationale:

Early graft inflammation enhances both acute and chronic rejection of heart transplants, but it is unclear how this inflammation is initiated.

Objective:

To identify specific inflammatory modulators and determine their underlying molecular mechanisms after cardiac transplantation.

Methods and Results:

We used a murine heterotopic cardiac transplant model to identify inflammatory modulators of early graft inflammation. Unbiased mass spectrometric analysis of cardiac tissue before and ≤72 hours after transplantation revealed that 22 proteins including haptoglobin, a known antioxidant, are significantly upregulated in our grafts. Through the use of haptoglobin-deficient mice, we show that 80% of haptoglobin-deficient recipients treated with perioperative administration of the costimulatory blocking agent CTLA4 immunoglobulin exhibited >100-day survival of full major histocompatibility complex mismatched allografts, whereas all similarly treated wild-type recipients rejected their transplants by 21 days after transplantation. We found that haptoglobin modifies the intra-allograft inflammatory milieu by enhancing levels of the inflammatory cytokine interleukin-6 and the chemokine MIP-2 (macrophage inflammatory protein 2) but impair levels of the immunosuppressive cytokine interleukin-10. Haptoglobin also enhances dendritic cell graft recruitment and augments antidonor T-cell responses. Moreover, we confirmed that the protein is present in human cardiac allograft specimens undergoing acute graft rejection.

Conclusions:

Our findings provide new insights into the mechanisms of inflammation after cardiac transplantation and suggest that, in contrast to its prior reported antioxidant function in vascular inflammation, haptoglobin is an enhancer of inflammation after cardiac transplantation. Haptoglobin may also be a key component in other sterile inflammatory conditions.
Pulmonary Vascular and Right Ventricular Reserve in Patients With Normalized Resting Hemodynamics After Pulmonary Endarterectomy
Authors: Claessen Guido , La Gerche Andre , Dymarkowski Steven , Claus Piet , Delcroix Marion , Heidbuchel Hein
Published: March 2015

Background

Patients with normalized mean pulmonary artery pressure (
mPAP
) after pulmonary endarterectomy (
PEA
) for chronic thromboembolic pulmonary hypertension (
CTEPH
) do not always regain normal exercise capacity. We evaluated right ventricular function, its interaction with both pulsatile and resistive afterload, and the effect of sildenafil during exercise in these patients.

Methods and Results

Fourteen healthy controls, 15
CTEPH
patients, and 7 patients with normalized resting
mPAP
(≤25 mm Hg) post‐
PEA
underwent cardiopulmonary exercise testing, followed by cardiac magnetic resonance imaging with simultaneous invasive
mPAP
measurement during incremental supine cycling exercise. Peak oxygen consumption and peak heart rate were significantly reduced in post‐
PEA
and
CTEPH
patients compared to controls. The
mPAP
–cardiac output slope was steeper in post‐
PEA
patients than in controls and similar to
CTEPH
. Relative to controls, resting right ventricular ejection fraction was reduced in
CTEPH
, but not in post‐
PEA
patients. In contrast, peak exercise right ventricular ejection fraction was reduced both in post‐
PEA
and
CTEPH
patients. Exercise led to reduction of pulmonary arterial compliance in all groups. Nevertheless, resting pulmonary arterial compliance values in
CTEPH
and post‐
PEA
patients were even lower than those in controls at peak exercise. In post‐
PEA
patients, sildenafil did not affect resting hemodynamics nor right ventricular function, but decreased the
mPAP
/cardiac output slope and increased peak exercise right ventricular ejection fraction.

Conclusions

Exercise intolerance in post‐
PEA
patients is explained by abnormal pulmonary vascular reserve and chronotropic incompetence. The
mPAP
/cardiac output slope and pulmonary arterial compliance are sensitive measures demonstrating abnormal resistive and pulsatile pulmonary vascular function in post‐
PEA
patients. These abnormalities are partially attenuated with sildenafil.
The Timing of Regular Sequences: Production, Perception, and Covariation
Authors: Schwartze Michael , Kotz Sonja A.
Published: March 2015

The temporal structure of behavior provides information that allows the tracking of temporal regularity in the sensory and sensorimotor domains. In turn, temporal regularity allows the generation of predictions about upcoming events and to adjust behavior accordingly. These mechanisms are essential to ensure behavior beyond the level of mere reaction. However, efficient temporal processing is required to establish adequate internal representations of temporal structure. The current study used two simple paradigms, namely, finger-tapping at a regular self-chosen rate (spontaneous motor tempo) and ERPs of the EEG (EEG/ERP) recorded during attentive listening to temporally regular and irregular “oddball” sequences to explore the capacity to encode and use temporal regularity in production and perception. The results show that specific aspects of the ability to time a regular sequence of events in production covary with the ability to time a regular sequence in perception, probably pointing toward the engagement of domain-general mechanisms.
Auditory Perceptual Category Formation Does Not Require Perceptual Warping
Authors: Caruso Valeria C. , Balaban Evan
Published: March 2015

Categorical perception occurs when a perceiver's stimulus classifications affect their ability to make fine perceptual discriminations and is the most intensively studied form of category learning. On the basis of categorical perception studies, it has been proposed that category learning proceeds by the deformation of an initially homogeneous perceptual space (“perceptual warping”), so that stimuli within the same category are perceived as more similar to each other (more difficult to tell apart) than stimuli that are the same physical distance apart but that belong to different categories. Here, we present a significant counterexample in which robust category learning occurs without these differential perceptual space deformations. Two artificial categories were defined along the dimension of pitch for a perceptually unfamiliar, multidimensional class of sounds. A group of participants (selected on the basis of their listening abilities) were trained to sort sounds into these two arbitrary categories. Category formation, verified empirically, was accompanied by a heightened sensitivity along the entire pitch range, as indicated by changes in an EEG index of implicit perceptual distance (mismatch negativity), with no significant resemblance to the local perceptual deformations predicted by categorical perception. This demonstrates that robust categories can be initially formed within a continuous perceptual dimension without perceptual warping. We suggest that perceptual category formation is a flexible, multistage process sequentially combining different types of learning mechanisms rather than a single process with a universal set of behavioral and neural correlates.
Art and Science as Creative Catalysts
Authors: Gates-Stuart Eleanor , Nguyen Chuong , Adcock Matt , Bradley Jay , Morell Matthew , Lovell David
Published: March 2015

Science, Art and Science Art collaborations are generally presented and understood in terms of their products. The authors argue that the process of Science Art can be a significant—perhaps the principal—benefit of these collaborations even though the process may be largely invisible to anyone other than the collaborators. Hosting the Centenary of Canberra Science Art Commission at the Commonwealth Scientific and Industrial Research Organisation (CSIRO) has shown the authors that while Science and Art pursue orthogonal dimensions of creativity and innovation, collaborators can combine these directions to access new areas of imagination and ideas.
Atopobathynella paraoperculata n. sp. (Syncarida, Bathynellacea, Parabathynellidae) from the River Krishna, southeastern India
Authors: Ranga Reddy Yenumula , Totakura Venkateswara Rao
Published: March 2015

To date, the genusAtopobathynellaSchminke, 1973, is known by 11 species in the world. Here,Atopobathynella paraoperculatan. sp., the second species of this genus from India, is described from the interstitial hyporheic zone of the River Krishna in Andhra Pradesh state. It has closest similarity with its Indian congener,AtopobathynellaoperculataRanga Reddy, Drewes & Schminke, 2008, as borne out by the fusion of the inner flagellum of the antennule with the first segment of the outer flagellum, the presence of a seta on the subdistal outer surface of the uropodal sympod; the antennal organ consists exclusively of two massive lobes; the antenna has three instead of four armature elements; the proximal segment of the maxillule has two instead of four distinct claws; the uropodal sympod has an inhomonomous row of spines; and the anal operculum is massive. However, the new species can be easily separated fromA. operculataby several other criteria such as the labrum without vs. with tubular pores; the second endopodal segment of Th I has two setae vs. one seta; the uropodal sympod has four vs. eight spines; the uropodal endopod has two weak setae vs. one normal seta; the pleotelson is unarmed vs. armed; and the anal operculum has a subacute vs. a rounded tip. Further, based on the novelties observed in the two Indian congeners, some of the principal generic characters and their states are briefly discussed, and also some ecological notes are added.
Feeding ecology of Apocyclops procerus (Copepoda, Cyclopoida) under experimental conditions
Authors: Guenther M. , Durst R. , Felismino W. S. , Pessoa V. T. , Neumann-Leitão S.
Published: March 2015

Copepods are key links between primary producers and higher pelagics. We investigated, for the first time, under laboratory conditions, some aspects of the reproductive behaviour and feeding preferences of Apocyclops procerus (Copepoda: Cyclopoida) under different conditions of salinity and food supply. This is also its first record for Pernambuco (NE Brazil). The females carry their eggs until their eclosion and present several cycles of egg production without being further fecundated. Egg production and adult life span were not affected by differences in salinity or food supply. Offspring predation was also observed. From the three microalgae species offered to A. procerus individuals, Thalassiosira weissflogii, Chaetoceros muelleri (Ochrophyta) and Isochrysis galbana (Haptophyta), the small round-shaped I. galbana was preferred over the large and spiny diatoms, in spite of its lower nutritional value. The high salinity tolerance and apparently omnivorous feeding habits of A. procerus may enable it to predominate in estuarine waters.
When Justice Demands Inequality
Authors: Thrasher John , Hankins Keith
Published: March 2015

In Rescuing Justice and Equality G.A. Cohen argues that justice requires an uncompromising commitment to equality. Cohen also argues, however, that justice must be sensitive to other values, including a robust commitment to individual freedom and to the welfare of the community. We ask whether a commitment to these other values means that, despite Cohen’s commitment to equality, his view requires that we make room for inequality in the name of justice? We argue that even on Cohen’s version of egalitarianism equality, freedom, and welfare are not always compatible. Justice will require trade-offs between these values. Sometimes, equality will need to be sacrificed. This is a surprising result and to show it, we use two informal impossibility proofs drawn from examples in Rescuing Justice and Equality.
Revision of the genus Pseudopomatias and its relatives (Gastropoda: Cyclophoroidea: Pupinidae)
Authors: PÁLL-GERGELY BARNA , FEHÉR ZOLTÁN , HUNYADI ANDRÁS , ASAMI TAKAHIRO
Published: March 2015

The present paper revises all species that have been assigned to Pseudopomatias Möllendorff, 1885 and Nodopomatias Gude, 1921. The following new species are described: Pseudopomatias abletti Páll-Gergely, n. sp. (northeastern India), Pseudopomatias harli Páll-Gergely, n. sp. (northeastern India), Pseudopomatias linanprietoae Páll-Gergely n. sp. (Laos), Pseudopomatias maasseni Páll-Gergely & Hunyadi, n. sp. (Vietnam and China), Pseudopomatias nitens Páll-Gergely n. sp. (Vietnam), Pseudopomatias prestoni Páll-Gergely, n. sp. (northeastern India), Pseudopomatias reischuetzi Páll-Ger-gely, n. sp. (north-eastern India), Pseudopomatias shanensis Páll-Gergely n. sp. (Myanmar) and Pseudopomatias sophiae Páll-Gergely, n. sp. (Vietnam). Pseudopomatias fulvus is moved to the synonymy of P. amoenus. Csomapupa n. gen. is erected for Pseudopomatias grandis and P. luyorensis. Another new genus, Vargapupa is erected with two species, namely Vargapupa biheli Páll-Gergely, n. sp. (Vietnam) and V. oharai Páll-Gergely, n. sp. (Laos). Both new genera are probably closely related to Pseudopomatias and Nodopomatias. All the currently available type specimens of species in these groups are figured. Anatomical information of P. eos and DNA sequence data of two Pseudopomatias species indicate that the genus is a member of the family Pupinidae. The other pre-existing hypothesis, namely that Pseudopomatias is a member of the Cochlostomatidae, is not supported by our results.
Description of a new species of Sparassocynus (Marsupialia: Didelphoidea: Sparassocynidae) from the late Miocene of Jujuy (Argentina) and taxonomic review of Sparassocynus heterotopicus from the Pliocene of Bolivia
Authors: ABELLO MARÍA ALEJANDRA , REYES MARTÍN DE LOS , CANDELA ADRIANA MAGDALENA , PUJOS FRANCOIS , VOGLINO DAMIÁN , QUISPE BERNARDINO MAMANI
Published: March 2015

A new species of sparassocynid marsupial, Sparassocynus maimarai n. sp. from the late Miocene of Maimará Formation (Jujuy Province, Argentina) is described from a left mandibular fragment with a complete p2–m4 series. It differs from the remaining species of the genus S. bahiai (Montehermosan—late Miocene/early Pliocene—of Buenos Aires Province, Argentina) and S. derivatus (Chapadmalalan and Marplatan–Pliocene of Buenos Aires Province) by its smaller size, the relatively longer m1 with respect to the m4, the presence of a lingual cingulum extended between para- and metaconid on the m1–3, and its more robust entoconids. As part of this study the taxonomic status of Sparassocynus heterotopicus (Montehermosan, Umala, Bolivia; Pliocene) was reviewed concluding that this taxon should be referred to as ‘Sparassocynus’ heterotopicus and considered a Didelphoidea of uncertain affinities. Sparassocynus maimarai n. sp. is the oldest records of the genus, adding new information to evaluate the origins and early diversification of sparassocynids. Sparassocynus maimarai n. sp. was recovered with precise stratigraphic control, highlighting its potential biostratigraphic significance to the temporal correlations between Maimará Formation and other Mio–Pliocene stratigraphic units from the northwestern Argentina.
Studies of Bolivian Ptiliidae (Coleoptera) 1: The genus Cissidium Motschulsky with six new species
Authors: DARBY MICHAEL
Published: March 2015

This is the first report on a collection of Ptiliidae from Bolivian forest leaf litter made by Dr Petr Baňař of the Brno Museum (Czech Republic). Six new species in the genus Cissidium Motschulsky, are described and figured: C. amboroensis, sp. n., C. globosum, sp. n., C. elongatum, sp. n., C. lisae sp. n., C. petri sp. n. and C. tigrum, sp. n.. The relationship of Cissidium to Dacrysoma Grebennikov and its position in the tribe Discheramocephalini is discussed, and the generic description revised so as to encompass all valid species.