bluuebunny/crossref_metadata_2025 huggingface dataset:
A Diagnostic for Evaluating the Representation of Turbulence in Atmospheric Models at the Kilometric Scale
Authors: Honnert Rachel , Masson Valéry , Couvreux Fleur
Published: June 2011

Turbulence is well represented by atmospheric models at very fine grid sizes, from 10 to 100 m, for which turbulent movements are mainly resolved, and by atmospheric models with grid sizes greater than 2 km, for which those movements are entirely parameterized. But what happens at intermediate scales, Wyngaard’s so-called terra incognita?

Here an original method is presented that provides a new diagnostic by calculating the subgrid and resolved parts of five variables at different scales: turbulent kinetic energy (TKE), heat and moisture fluxes, and potential temperature and mixing ratio variances. They are established at intermediate scales for dry and cumulus-topped convective boundary layers. The similarity theorem allows the determination of the dimensionless variables of the problem. When the subgrid and resolved parts are studied, a new dimensionless variable, the dimensionless mesh size , needs to be added to the Deardorff free convective scaling variables, where h is the boundary layer height and hc is the height of the cloud layer. Similarity functions for the subgrid and resolved parts are assumed to be the product of the similarity function of the total (subgrid plus resolved) variables and a “partial” similarity function that depends only on . In order to determine the partial similarity function form, large-eddy simulations (LES) of five dry and cloudy convective boundary layers are used. The resolved and subgrid parts of the variables at coarser grid sizes are then deduced from the LES fields.

The evolution of the subgrid and resolved parts in the boundary layer with is as follows: fine grids mainly resolve variables. As the mesh becomes coarser, more eddies are subgrid. Finally, for very large meshes, turbulence is entirely subgrid. A scale therefore exists for which the subgrid and resolved parts are equal. This is obtained for in the case of TKE, 0.4 for the potential temperature variance, and 0.8 for the mixing ratio variance, indicating that the velocity structures are smaller than those for the potential temperature, which are smaller than those for the mixing ratio. Furthermore, boundary layers capped by convective clouds have structures larger than dry boundary layer ones as displayed by the scaling in the partial similarity functions.

This new diagnostic gives a reference for evaluating current and future parameterizations at kilometric scales. As an illustration, the parameterizations of a mesoscale model are eventually evaluated at intermediate scales. In its standard version, the model produces too many resolved movements, as the turbulence scheme does not sufficiently represent the impact of the subgrid thermal. This is not true when a mass-flux scheme is introduced. However in this case, a completely subgrid thermal is modeled leading to an overestimation of the subgrid part.
Optimized Determination of Viscous Mud Properties Using a Nonlinear Wave–Mud Interaction Model
Authors: Tahvildari Navid , Kaihatu James M.
Published: June 2011

The complex process of surface wave propagation over areas of cohesive sediments has generally been treated by assuming a particular rheological behavior for the mud layer, thereby fixing the description of the mud characteristics into the specification of parameters relevant to the selected rheology. The capability of inverting data to recover these parameters is investigated here. Representing the mud layer as a thin viscous fluid, a nonlinear wave–mud interaction model, coupled with a nonlinear optimization technique (Levenberg–Marquardt), is used to deduce mud characteristics from estimates of wave energy. A set of numerical tests with a deterministic phase-coherent cnoidal wave are conducted to individually estimate viscosity and mud layer depth (keeping one fixed while estimating the other), and to determine the limits of convergence of the inversion algorithm. It is shown that instances of convergence or nonconvergence can be traced to the shape of the dissipation rate curve as a function of the parameter under consideration as well as the location of the initial guesses of the target parameter along that curve. It is found that the estimation of viscosity is less problematic than the estimation of mud layer depth. Tests with random waves are also performed, using both root-mean-square wave height (representation of wave energy) and wave skewness (representation of nonlinear wave properties) as input for the inversion. The use of random waves appears to ameliorate many of the convergence difficulties encountered with the cnoidal wave tests, while the use of wave skewness, while promising, is somewhat less successful. Finally, the inversion algorithm is tested against laboratory data and the deduction of both mud layer depth and viscosity proceed well. Implications for general mud property deduction are discussed.
Are sports desks losing their nerve?
Authors: Engel Matthew
Published: June 2011

Wall-to-wall newspaper sports coverage doesn’t signify high quality: the magic of 50 years ago is missing, argues this sports aficionado
Teratoma With Somatic-Type Malignant Components in Germ Cell Tumors of the Testis: A Clinicopathologic Analysis of 40 Cases With Outcome Correlation
Authors: Colecchia Maurizio , Necchi Andrea , Paolini Biagio , Nicolai Nicola , Salvioni Roberto
Published: June 2011

Teratoma with a malignant somatic component (MSC) is a rare phenomenon recognized when a somatic type malignancy occurs in the context of a germ cell tumor (GCT). The authors present their 29-year experience with 40 patients treated from 1981 to 2009 in their institution. The average age was 31 years. All patients underwent radical orchiectomy, which demonstrated a GCT in 19 with an MSC. The MSC was observed in the other 21 cases in metastatic sites, including lung (13), liver (3), pleura (1), mediastinum (7), supraclavicular lymph nodes (1), and retroperitoneal lymph nodes (9). The most common histologic types were rhabdomyosarcoma (n = 11) and primitive neuroectodermal tumors (n = 10), followed by adenocarcinoma (n = 9), sarcoma, not otherwise specified (n = 5), well-differentiated liposarcoma (n = 2), leiomyosarcoma (n = 2), chondrosarcoma (n = 2), nephroblastoma (Wilms’s tumor), carcinoid, malignant peripheral nerve sheath tumor, and a gemistiocytic astrocytoma with choroid plexus tumor (each n = 1). Clinical data were collected through a dedicated database and are available for all 40 cases. After a median follow-up of 37 months, 29/40 (72.5%) were alive and disease-free. Stage-specific survival was 100% for stage I, 87.5% for stage II, and 53% for stage III patients suggesting that patients with MSC confined to the testis have a good prognosis. A lower sensitivity to chemotherapy for a MSC when compared with typical GCT is reported. Surgical excision of the MSC is therefore an essential part of the management.
Endothelial cell substrate stiffness influences neutrophil transmigration via myosin light chain kinase-dependent cell contraction
Authors: Stroka Kimberly M. , Aranda-Espinoza Helim
Published: June 2011

A vast amount of work has been dedicated to the effects of shear flow and cytokines on leukocyte transmigration. However, no studies have explored the effects of substrate stiffness on transmigration. Here, we investigated important aspects of endothelial cell contraction-mediated neutrophil transmigration using an in vitro model of the vascular endothelium. We modeled blood vessels of varying mechanical properties using fibronectin-coated polyacrylamide gels of varying physiologic stiffness, plated with human umbilical vein endothelial cell (HUVEC) monolayers, which were activated with tumor necrosis factor-α. Interestingly, neutrophil transmigration increased with increasing substrate stiffness below the endothelium. HUVEC intercellular adhesion molecule-1 expression, stiffness, cytoskeletal arrangement, morphology, and cell-substrate adhesion could not account for the dependence of transmigration on HUVEC substrate stiffness. We also explored the role of cell contraction and observed that large holes formed in endothelium on stiff substrates several minutes after neutrophil transmigration reached a maximum. Further, suppression of contraction through inhibition of myosin light chain kinase normalized the effects of substrate stiffness by reducing transmigration and eliminating hole formation in HUVECs on stiff substrates. These results provide strong evidence that neutrophil transmigration is regulated by myosin light chain kinase-mediated endothelial cell contraction and that this event depends on subendothelial cell matrix stiffness.
Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy: a report from the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS)
Authors: Armenian Saro H. , Sun Can-Lan , Kawashima Toana , Arora Mukta , Leisenring Wendy , Sklar Charles A. , Baker K. Scott , Francisco Liton , Teh Jennifer Berano , Mills George , Wong F. Lennie , Rosenthal Joseph , Diller Lisa R. , Hudson Melissa M. , Oeffinger Kevin C. , Forman Stephen J. , Robison Leslie L. , Bhatia Smita
Published: June 2011

HSCT is being increasingly offered as a curative option for children with hematologic malignancies. Although survival has improved, the long-term morbidity ascribed to the HSCT procedure is not known. We compared the risk of chronic health conditions and adverse health among children with cancer treated with HSCT with survivors treated conventionally, as well as with sibling controls. HSCT survivors were drawn from BMTSS (N = 145), whereas conventionally treated survivors (N = 7207) and siblings (N = 4020) were drawn from CCSS. Self-reported chronic conditions were graded with CTCAEv3.0. Fifty-nine percent of HSCT survivors reported ≥ 2 conditions, and 25.5% reported severe/life-threatening conditions. HSCT survivors were more likely than sibling controls to have severe/life-threatening (relative risk [RR] = 8.1, P < .01) and 2 or more (RR = 5.7, P < .01) conditions, as well as functional impairment (RR = 7.7, P < .01) and activity limitation (RR = 6.3, P < .01). More importantly, compared with CCSS survivors, BMTSS survivors demonstrated significantly elevated risks (severe/life-threatening conditions: RR = 3.9, P < .01; multiple conditions: RR = 2.6, P < .01; functional impairment: RR = 3.5, P < .01; activity limitation: RR = 5.8, P < .01). Unrelated donor HSCT recipients were at greatest risk. Childhood HSCT survivors carry a significantly greater burden of morbidity not only compared with noncancer populations but also compared with conventionally treated cancer patients, providing evidence for close monitoring of this high-risk population.
Blood doping and its detection
Authors: Jelkmann Wolfgang , Lundby Carsten
Published: June 2011

Hemoglobin mass is a key factor for maximal exercise capacity. Some athletes apply prohibited techniques and substances with intent to increase hemoglobin mass and physical performance, and this is often difficult to prove directly. Autologous red blood cell transfusion cannot be traced on reinfusion, and also recombinant erythropoietic proteins are detectable only within a certain timeframe. Novel erythropoietic substances, such as mimetics of erythropoietin (Epo) and activators of the Epo gene, may soon enter the sports scene. In addition, Epo gene transfer maneuvers are imaginable. Effective since December 2009, the World Anti-Doping Agency has therefore implemented “Athlete Biologic Passport Operating Guidelines,” which are based on the monitoring of several parameters for mature red blood cells and reticulocytes. Blood doping may be assumed, when these parameters change in a nonphysiologic way. Hematologists should be familiar with blood doping practices as they may play an important role in evaluating blood profiles of athletes with respect to manipulations, as contrasted with the established diagnosis of clinical disorders and genetic variations.
Requirement for LMP1-induced RON receptor tyrosine kinase in Epstein-Barr virus–mediated B-cell proliferation
Authors: Chou Ya-Ching , Lin Sue-Jane , Lu Jean , Yeh Te-Huei , Chen Chi-Long , Weng Pei-Lun , Lin Jiun-Han , Yao Ming , Tsai Ching-Hwa
Published: June 2011

EBV, an oncogenic human herpesvirus, can transform primary B lymphocytes into immortalized lymphoblastoid cell lines (LCLs) through multiple regulatory mechanisms. However, the involvement of protein tyrosine kinases in the infinite proliferation of B cells is not clear. In this study, we performed kinase display assays to investigate this subject and identified a specific cellular target, Recepteur d'Origine Nantais (RON) tyrosine kinase, expressed in LCLs but not in primary B cells. Furthermore, we found that latent membrane protein 1 (LMP1), an important EBV oncogenic protein, enhanced RON expression through its C-terminal activation region-1 (CTAR1) by promoting NF-κB binding to the RON promoter. RON knockdown decreased the proliferation of LCLs, and transfection with RON compensated for the growth inhibition caused by knockdown of LMP1. Immunohistochemical analysis revealed a correlation between LMP1 and RON expression in biopsies from posttransplantation lymphoproliferative disorder (PTLD), suggesting that LMP1-induced RON expression not only is essential for the growth of LCLs but also may contribute to the pathogenesis of EBV-associated PTLD. Our study is the first to reveal the impact of RON on the proliferation of transformed B cells and to suggest that RON may be a novel therapeutic target for EBV-associated lymphoproliferative diseases.
Comparative promoter analysis in vivo: identification of a dendritic cell-specific promoter module
Authors: Edelmann Stephanie L. , Nelson Peter J. , Brocker Thomas
Published: June 2011

Dendritic cells (DCs) are important immune cells. This study focused on transcriptional networks active in murine DCs, but DCs are difficult to study using conventional molecular techniques. Therefore, comparative promoter analysis was used to identify evolutionarily conserved features between the murine CD11c and DC-STAMP promoters. A promoter framework consisting of 4 transcription factor binding sites was identified that included signal transducer and activator of transcription, homeodomain transcription factors, and 2 members of the Brn POU domain factors family. This promoter module was functionally verified by in vivo promoter analysis and site-directed mutagenesis. Hematopoietic stem cells were engineered by lentiviral vectors and expression of green fluorescent protein reporter was monitored in primary hematopoietic cell types that develop without further manipulation in irradiated recipient mice. The verified promoter module was then modeled and used in a bioinformatics-based search for other potential coregulated genes in murine DCs. A promoter database search identified 2 additional genes, Ppef2 and Pftk1, which have a similar promoter organization and are preferentially expressed in murine DCs. The results define a regulatory network linked to development of murine DCs.
Thrombotic risk during oral contraceptive use and pregnancy in women with factor V Leiden or prothrombin mutation: a rational approach to contraception
Authors: van Vlijmen Elizabeth F. W. , Veeger Nic J. G. M. , Middeldorp Saskia , Hamulyák Karly , Prins Martin H. , Büller Harry R. , Meijer Karina
Published: June 2011

Current guidelines discourage combined oral contraceptive (COC) use in women with hereditary thrombophilic defects. However, qualifying all hereditary thrombophilic defects as similarly strong risk factors might be questioned. Recent studies indicate the risk of venous thromboembolism (VTE) of a factor V Leiden mutation as considerably lower than a deficiency of protein C, protein S, or antithrombin. In a retrospective family cohort, the VTE risk during COC use and pregnancy (including postpartum) was assessed in 798 female relatives with or without a heterozygous, double heterozygous, or homozygous factor V Leiden or prothrombin G20210A mutation. Overall, absolute VTE risk in women with no, single, or combined defects was 0.13 (95% confidence interval 0.08-0.21), 0.35 (0.22-0.53), and 0.94 (0.47-1.67) per 100 person-years, while these were 0.19 (0.07-0.41), 0.49 (0.18-1.07), and 0.86 (0.10-3.11) during COC use, and 0.73 (0.30-1.51), 1.97 (0.94-3.63), and 7.65 (3.08-15.76) during pregnancy. COC use and pregnancy were independent risk factors for VTE, with highest risk during pregnancy postpartum, as demonstrated by adjusted hazard ratios of 16.0 (8.0-32.2) versus 2.2 (1.1-4.0) during COC use. Rather than strictly contraindicating COC use, we advocate that detailed counseling on all contraceptive options, including COCs, addressing the associated risks of both VTE and unintended pregnancy, enabling these women to make an informed choice.
FlnA-null megakaryocytes prematurely release large and fragile platelets that circulate poorly
Authors: Jurak Begonja Antonija , Hoffmeister Karin M. , Hartwig John H. , Falet Hervé
Published: June 2011

Filamin A (FlnA) is a large cytoplasmic protein that crosslinks actin filaments and anchors membrane receptors and signaling intermediates. FlnAloxP PF4-Cre mice that lack FlnA in the megakaryocyte (MK) lineage have a severe macrothrombocytopenia because of accelerated platelet clearance. Macrophage ablation by injection of clodronate-encapsulated liposomes increases blood platelet counts in FlnAloxP PF4-Cre mice and reveals the desintegration of FlnA-null platelets into microvesicles, a process that occurs spontaneously during storage. FlnAloxP PF4-Cre bone marrows and spleens have a 2.5- to 5-fold increase in MK numbers, indicating increased thrombopoiesis in vivo. Analysis of platelet production in vitro reveals that FlnA-null MKs prematurely convert their cytoplasm into large CD61+ platelet-sized particles, reminiscent of the large platelets observed in vivo. FlnA stabilizes the platelet von Willebrand factor receptor, as surface expression of von Willebrand factor receptor components is normal on FlnA-null MKs but decreased on FlnA-null platelets. Further, FlnA-null platelets contain multiple GPIbα degradation products and have increased expression of the ADAM17 and MMP9 metalloproteinases. Together, the findings indicate that FlnA-null MKs prematurely release large and fragile platelets that are removed rapidly from the circulation by macrophages.
Malaria prevalence pattern observed in the highland fringe of Butajira, Southern Ethiopia: A longitudinal study from parasitological and entomological survey
Authors: Tesfaye Solomon , Belyhun Yeshambel , Teklu Takele , Mengesha Tesfaye , Petros Beyene
Published: June 2011

Background

In Ethiopia, information regarding highland malaria transmission is scarce, and no report has been presented from Butajira highland so far whether the appearance of malaria in the area was due to endemicity or due to highland malaria transmission. Thus this study aimed to determine the presence and magnitude of malaria transmission in Butajira.

Methods

For parasitological survey, longitudinal study was conducted from October to December 2006. The entomological surveys were done from October to December 2006 and continued from April to May 2007. Both parasitological and entomological surveys were done using standard procedures.

Results

The parasitological result in all the survey months (October-December) showed an overall detection rate of 4.4% (48/1082) (CI 95%; 3.2-5.7%) malaria parasite. Among infected individuals, 32 (3.0%) of the infection was due to Plasmodium vivax and the rest 16 (1.5%) were due to Plasmodium falciparum. The highest prevalence 39(3.6%) of the parasite was observed in age groups of above 15 years old. Among the total tested, 25(2.3%) of males and 23(2.1%) of females had malaria infection. Among tested individuals, 38(5.3%) and 10 (2.7%) of infection was occurred in Misrak-Meskan (2100 m a.s.l) and Mirab-Meskan (2280 m a.s.l), respectively which was statistically significant (X2 = 3.72, P < 0.05). Although the prevalence pattern of Plasmodium species declined from October to December, the trend was non-significant (X2 for trend = 0.49, P > 0.05). The entomological survey showed a collection of 602 larvae and 80 adult Anopheles. Anopheles christyi was the dominant species both in the first (45.3%) and in the second (35.4%) surveys; where as, Anopheles gambiae sensu lato comprised 4.7% and 14.6%, in the first and second surveys, respectively. Anopheles gambiae
s.l comprises 55% of the adult collection, and both species were collected more from outdoors (57.5%). The number of An. christyi was higher in Mirab-Meskan (58. 3%) than Misrak-Meskan (41.7%) (P < 0.05).

Conclusion

Malaria parasite and its vectors were found to be common during transmission periods in the highland fringes of Butajira. Thus, health education about the risk of malaria and its control programme in the area must be given adequate attention to minimize potential epidemics. In addition, the current study should be complemented from sero-epidemiological, prospective longitudinal and retrospective studies along with metrological and ecological factors, and socio-demographic data before concluding in favour of highland malaria transmission in the area. In light of its abundance, which coincided with the malaria transmission seasons, the possible role of An. christyi as a secondary vector in the highlands must be further investigated by including blood meal sources detection.
Evaluation of formalin-fixed paraffin-embedded tissues in the proteomic analysis of parathyroid glands
Authors: Donadio Elena , Giusti Laura , Cetani Filomena , Da Valle Ylenia , Ciregia Federica , Giannaccini Gino , Pardi Elena , Saponaro Federica , Torregrossa Liborio , Basolo Fulvio , Marcocci Claudio , Lucacchini Antonio
Published: June 2011

Background

Proteomic research in the field of parathyroid tissues is limited by the very small dimension of the glands and by the low incidence of cancer lesions (1%). Formalin-fixed paraffin-embedded (FFPE) tissue specimens are a potentially valuable resource for discovering protein cancer biomarkers. In this study we have verified the applicability of a heat induced protein extraction from FFPE parathyroid adenoma tissues followed by a gel-based or gel-free proteomic approach in order to achieve protein separation and identification.

Results

The best results for high quality MS spectra and parameters, were obtained by using a gel-free approach, and up to 163 unique proteins were identified. Similar results were obtained by applying both SDS-out and SDS-out + TCA/Acetone techniques during the gel-free method. Western blot analysis carried out with specific antibodies suggested that the antigenicity was not always preserved, while specific immunoreactions were detected for calmodulin, B box and SPRY domain-containing protein (BSPRY), peroxiredoxin 6 (PRDX 6) and parvalbumin.

Conclusions

In spite of some limitations mainly due to the extensive formalin-induced covalent cross-linking, our results essentially suggest the applicability of a proteomic approach to FFPE parathyroid specimens. From our point of view, FFPE extracts might be an alternative source, especially in the validation phase of protein biomarkers when a large cohort of samples is required and the low availability of frozen tissues might be constraining.
Intracisternal Administration of NR2 Subunit Antagonists Attenuates the Nociceptive Behavior and p-p38 MAPK Expression Produced by Compression of the Trigeminal Nerve Root
Authors: Jeon Hye J , Han Seung R , Lim Koang H , Won Kyoung A , Bae Yong C , Ahn Dong K
Published: June 2011

Background:

We investigated the role of the central NMDA receptor NR2 subunits in the modulation of nociceptive behavior and p-p38 MAPK expression in a rat model with compression of the trigeminal nerve root. To address this possibility, changes in air-puff thresholds and pin-prick scores were determined following an intracisternal administration of NR2 subunit antagonists. We also examined effects of NR2 subunit antagonists on the p-p38 MAPK expression.

Results:

Experiments were carried out using male Sprague-Dawley rats weighing (200-230 g). Compression of the trigeminal nerve root was performed under pentobarbital sodium (40 mg/kg) anesthesia. Compression of the trigeminal nerve root produced distinct nociceptive behavior such as mechanical allodynia and hyperalgesia. Intracisternal administration of 10 or 20 μg of D-AP5 significantly increased the air-puff threshold and decreased the pin-prick scores in a dose-dependent manner. The intracisternal administration of PPPA (1,10 μg), or PPDA (5, 10 μg) increased the air-puff threshold and decreased the pin-prick scores ipsilateral as well as contralateral to the compression of the trigeminal root. Compression of the trigeminal nerve root upregulated the expression of p-p38 MAPK in the ipsilateral medullary dorsal horn which was diminished by D-AP5, PPPA, PPDA, but not Ro25-6981.

Conclusions:

Our findings suggest that central NMDA receptor NR2 subunits play an important role in the central processing of trigeminal neuralgia-like nociception in rats with compression of the trigeminal nerve root. Our data further indicate that the targeted blockade of NR2 subunits is a potentially important new treatments strategy for trigeminal neuralgia-like nociception.
Indigenous knowledge of HIV/AIDS among High School students in Namibia
Authors: Chinsembu Kazhila C , Shimwooshili-Shaimemanya Cornelia N , Kasanda Choshi D , Zealand Donovan
Published: June 2011

Background

The use of Indigenous Knowledge (IK) can help students to form schemas for interpreting local phenomena through the prism of what they already know. The formation of schemas related to HIV/AIDS risk perception and prevention is important for individuals to form local meanings of the HIV/AIDS epidemic. The objective of this study was to explore the indigenous names and symptoms of HIV/AIDS among High School students in Namibia

Methods

Focus group discussions were used to collect qualitative data on indigenous names and symptoms of HIV/AIDS from students in 18 secondary schools located in six education regions. Data were grouped into themes.

Results

People living with HIV/AIDS were called names meaning prostitute: ihule, butuku bwa sihule, and shikumbu. Names such askibutu bwa masapo (bone disease),katjumba (a young child),kakithi (disease), andshinangele (very thin person) were used to describe AIDS. Derogatory names like mbwa (dog), esingahogo (pretender), ekifi (disease), and shinyakwi noyana (useless person) were also used. Other terms connoted death (zeguru, heaven; omudimba, corpse), fear (simbandembande, fish eagle; katanga kamufifi, (hot ball), and subtle meaning using slang words such as 4 × 4, oondanda ne (four letters), desert soul, and mapilelo (an AIDS service organization). Typical (body wasting) and non-typical (big head, red eyes) symptoms of HIV were also revealed.

Conclusions

The study determined students' IK of the names and symptoms of HIV/AIDS. Programmes to prevent/manage adolescent HIV infection and stigma may be strengthened if they take students' indigenous understandings of the disease on board.
Pontine tegmental cap dysplasia: developmental and cognitive outcome in three adolescent patients
Authors: Briguglio Marilena , Pinelli Lorenzo , Giordano Lucio , Ferraris Alessandro , Germanò Eva , Micheletti Serena , Severino Mariasavina , Bernardini Laura , Loddo Sara , Tortorella Gaetano , Ormitti Francesca , Gasparotti Roberto ,   the CBCD Study Group, Rossi Andrea , Valente Enza Maria
Published: June 2011

Pontine Tegmental Cap Dysplasia (PTCD) is a recently described, rare disorder characterized by a peculiar cerebellar and brainstem malformation. Nineteen patients have been reported to date, of which only one in the adolescent age, and data on the clinical, cognitive and behavioural outcome of this syndrome are scarce.

Here we describe three adolescent patients with PTCD. All presented bilateral deafness and multiple cranial neuropathies, variably associated with skeletal, cardiac and gastro-intestinal malformations. Feeding and swallowing difficulties, that are often causative of recurrent aspiration pneumonias and death in the first years of life, completely resolved with age in all three patients. Neuropsychological assessment showed borderline to moderate cognitive impairment, with delay in adaptive functioning, visual-spatial and language deficits. Two of three patients also showed mild behavioural problems, although their overall socialization abilities were well preserved. Cochlear implantation in two patients significantly improved their relational and learning abilities. Fibre tractography confirmed the abnormal bundle of transversely oriented fibres forming the typical pontine "tegmental cap" and absence of decussation of the superior cerebellar peduncles, supporting the hypothesis that PTCD results from abnormal axonal guidance and/or migration.

These data indicate that PTCD may have a favourable long-term outcome, with borderline cognitive deficit or even normal cognition and partially preserved speech.
Effect of a 6-week dynamic neuromuscular training programme on ankle joint function: A Case report
Authors: O'Driscoll Jeremiah , Kerin Fearghal , Delahunt Eamonn
Published: June 2011

Background

Ankle joint sprain and the subsequent development of chronic ankle instability (CAI) are commonly encountered by clinicians involved in the treatment and rehabilitation of musculoskeletal injuries. It has recently been advocated that ankle joint post-sprain rehabilitation protocols should incorporate dynamic neuromuscular training to enhance ankle joint sensorimotor capabilities. To date no studies have reported on the effects of dynamic neuromuscular training on ankle joint positioning during landing from a jump, which has been reported as one of the primary injury mechanisms for ankle joint sprain. This case report details the effects of a 6-week dynamic neuromuscular training programme on ankle joint function in an athlete with CAI.

Methods

The athlete took part in a progressive 6-week dynamic neuromuscular training programme which incorporated postural stability, strengthening, plyometric, and speed/agility drills. The outcome measures chosen to assess for interventional efficacy were: [1] Cumberland Ankle Instability Tool (CAIT) scores, [2] Star Excursion Balance Test (SEBT) reach distances, [3] ankle joint plantar flexion during drop landing and drop vertical jumping, and [4] ground reaction forces (GRFs) during walking.

Results

CAIT and SEBT scores improved following participation in the programme. The angle of ankle joint plantar flexion decreased at the point of initial contact during the drop landing and drop vertical jumping tasks, indicating that the ankle joint was in a less vulnerable position upon landing following participation in the programme. Furthermore, GRFs were reduced whilst walking post-intervention.

Conclusions

The 6-week dynamic neuromuscular training programme improved parameters of ankle joint sensorimotor control in an athlete with CAI. Further research is now required in a larger cohort of subjects to determine the effects of neuromuscular training on ankle joint injury risk factors.
Technical Advance: Immunophenotypical characterization of human neutrophil differentiation
Authors: Mora-Jensen Helena , Jendholm Johan , Fossum Anna , Porse Bo , Borregaard Niels , Theilgaard-Mönch Kim
Published: June 2011

The current study reports a flow cytometry-based protocol for the prospective purification of human BM populations representing six successive stages of terminal neutrophil differentiation, including early promyelocytes and late promyelocytes, myelocytes, metamyelocytes, band cells, and PMN neutrophilic granulocytes. Validation experiments revealed a high purity of each bone marrow population and biological meaningful expression profiles for marker genes of neutrophil differentiation at a hitherto unprecedented resolution. Hence, the present protocol should be useful for studying neutrophil differentiation in vivo in the human setting and constitutes an important alternative to models that are based on in vitro differentiation of myeloid cell lines and HPCs.
Nod-like receptors in intestinal homeostasis, inflammation, and cancer
Authors: Werts Catherine , Rubino Stephen , Ling Arthur , Girardin Stephen E , Philpott Dana J
Published: June 2011

NLRs have been shown in a number of models to protect against microbial infection through their ability to participate in “pattern recognition” and their triggering of inflammatory pathways to control infection. Over the past few years, however, the role of NLRs, especially Nod1, Nod2, and NLRP3, in intestinal homeostasis has been highlighted. Indeed, these specific NLRs have been implicated in IBD, in particular, the association of Nod2 with CD, yet a clear understanding of how dysfunctional NLR activation leads to aberrant inflammation is still the focus of much investigation. In this review, we will examine how NLRs participate in the maintenance of gut homeostasis and how upset of this regulation can tip the balance toward chronic inflammation and intestinal cancer.
Systemic mast cell degranulation increases mortality during polymicrobial septic peritonitis in mice
Authors: Seeley Eric J , Sutherland Rachel E , Kim Sophia S , Wolters Paul J
Published: June 2011

MCs are required for an effective host response during septic peritonitis. Local MC degranulation facilitates neutrophil recruitment, activation, and bacterial killing. However, the role of MCs located distant from the site of infection is unknown. We studied the temporal and spacial degranulation of MCs following CLP-induced septic peritonitis. The functional importance of systemic MC degranulation during infection was evaluated by compartment-specific MC reconstitution. Serum histamine, reflecting MC degranulation, was elevated 4 h after onset of septic peritonitis. Histologic examination revealed progressive MC degranulation in select tissues during the first 24 h of infection. MC-deficient Wsh mice, reconstituted only in the peritoneal compartment, had improved survival after CLP compared with controls. However, reconstitution in peritoneal plus systemic compartments worsened survival after CLP. IL-6 contributed to the detrimental effects of systemic MCs on survival, as mice systemically reconstituted with IL-6−/− MCs were more likely to survive than control mice. These results indicate that in contrast to the benefits of local MC activation during infection, systemic MC activation worsens survival during CLP-induced sepsis.
Frequencies of FoxP3+ naïve T cells are related to both viral load and naïve T cell proliferation responses in HIV disease
Authors: Rodriguez Benigno , Bazdar Douglas A , Funderburg Nicholas , Asaad Robert , Luciano Angel A , Yadavalli Gopal , Kalayjian Robert C , Lederman Michael M , Sieg Scott F
Published: June 2011

HIV infection results in depletion and dysfunction of naïve CD4+ T cells. The mechanisms underlying these deficiencies are not understood. We investigated the frequencies of CD4+ naïve subsets in HIV disease as defined by expression of CD25 and/or FoxP3 and the relationship of these frequencies to naïve T cell proliferation function. We observed increased proportions of CD25+FoxP3+ and CD25+FoxP3– cells and decreased proportions of CD25–FoxP3– cells within the naïve CD4+ cell compartment from HIV-infected persons compared with findings in healthy donors. These perturbations were related to higher plasma HIV RNA levels but not with higher immune activation, as measured by the proportions of CD38+ memory CD4+ T cells. Naïve T cell proliferation responses to mitogen stimulation were inversely related to the frequencies and absolute numbers of FoxP3+ naïve T cells. MDA, a marker of oxidative stress, and sCD14, a marker of monocyte activation and a surrogate for microbial translocation, were increased in serum samples from HIV+ donors; however, neither marker was related to naïve T cell function in HIV+ donors. These observations suggest that alterations in naïve T cell subset frequencies could contribute to naïve T cell dysfunction in HIV disease, but these alterations are not necessarily the result of chronic immune activation.
Acquisition of Sexual Receptivity: Roles of Chromatin Acetylation, Estrogen Receptor-α, and Ovarian Hormones
Authors: Bonthuis Paul J. , Patteson James K. , Rissman Emilie F.
Published: June 2011

Sexually naïve, hormone-primed, C57BL/6J female mice are not receptive to mating attempts by conspecific males. Repeated experience with sexually active males and concurrent treatment with estradiol and progesterone gradually increases female receptivity over the course of five trials to maximal levels. Ovarian hormones activate their cognate nuclear steroid receptors estrogen receptor-α and progesterone receptor to induce female sexual receptivity. Nuclear receptors recruit coactivators of transcription that include histone acetyltransferases to hormone responsive genes. In this set of studies, we found that the histone deacetylase inhibitor sodium butyrate enhances the experiential acquisition of receptivity. Evidence is provided that the actions of sodium butyrate on receptivity require activated estrogen receptor-α and progesterone.
Tarzan's White Flights: Terrorism and Fantasy before and after the Airplane
Authors: Bady Aaron
Published: June 2011

By placing the Tarzan novels and films in the historical context of the development of aviation and aerial bombardment, Bady traces how changing fantasies of flight mediate the Tarzan franchise's changing relationship to white supremacist violence. Edgar Rice Burroughs's original novels were published contemporaneously with the popular “airmindedness” that accompanied the invention of the airplane, and Tarzan's ability to “fly” expresses the types of fantasy by which this advance was popularly understood. For Burroughs, Tarzan's flight signified the white race's “natural” superiority over nature. By the time the novels were adapted into films, however, aerial bombardment had come to seem monstrously unnatural, a technology serving racialized colonial governance. The Tarzan films made in the 1930s, this essay argues, use flight to describe a very different fantasy, the desire to forget and transcend the very histories of racial violence that the Tarzan character was once unthinkable without.
Identifying an uptake mechanism for the antiepileptic and bipolar disorder treatment valproic acid using the simple biomedical modelDictyostelium
Authors: Terbach Nicole , Shah Rishita , Kelemen Rachel , Klein Peter S. , Gordienko Dmitri , Brown Nigel A. , Wilkinson Christopher J. , Williams Robin S. B.
Published: June 2011

Valproic acid (VPA) is the most highly prescribed epilepsy treatment worldwide and is also used to prevent bipolar disorder and migraine. Surprisingly, very little is known about its mechanisms of cellular uptake. Here, we employ a range of cellular, molecular and genetic approaches to characterize VPA uptake using a simple biomedical model, Dictyostelium discoideum. We show that VPA is taken up against an electrochemical gradient in a dose-dependent manner. Transport is protein-mediated, dependent on pH and the proton gradient and shows strong substrate structure specificity. Using a genetic screen, we identified a protein homologous to a mammalian solute carrier family 4 (SLC4) bicarbonate transporter that we show is involved in VPA uptake. Pharmacological and genetic ablation of this protein reduces the uptake of VPA and partially protects against VPA-dependent developmental effects, and extracellular bicarbonate competes for VPA uptake in Dictyostelium. We further show that this uptake mechanism is likely to be conserved in both zebrafish (Danio rerio) and Xenopus laevis model systems. These results implicate, for the first time, an uptake mechanism for VPA through SLC4-catalysed activity.
Dive behaviour impacts the ability of heart rate to predict oxygen consumption in Steller sea lions (Eumetopias jubatus) foraging at depth
Authors: Young Beth L. , Rosen David A. S. , Hindle Allyson G. , Haulena Martin , Trites Andrew W.
Published: June 2011

The predictive relationship between heart rate (fH) and oxygen consumption () has been derived for several species of marine mammals swimming horizontally or diving in tanks to shallow depths. However, it is unclear how dive activity affects the relationship and whether the existing equations apply to animals diving to deeper depths. We investigated these questions by simultaneously measuring the fH and of Steller sea lions (Eumetopias jubatus) under different activity states (surface resting or diving), types of dives (single dives or dive bouts), and depths (10 or 40 m). We examined the relationship over dives only and also over dive cycles (dive + surface interval). We found that fH could only predict over a complete single dive cycle or dive bout cycle (i.e. surface intervals had to be included). The predictive equation derived for sea lions resting on the surface did not differ from that for single dive cycles. However, the equation derived over dive bout cycles (multiple dives + surface intervals) differed from those for single dive cycles or surface resting, with similar fH for multiple dive bout equations yielding higher predicted than that for single dive bout cycles (or resting). The relationships were not significantly affected by dive duration, dive depth, water temperature or cumulative food consumed under the conditions tested. Ultimately, our results demonstrate that fH can be used to predict activity-specific metabolic rates of diving Steller sea lions, but only over complete dive cycles that include a post-dive surface recovery period.
Honeybee flight: a novel ‘streamlining’ response
Authors: Luu Tien , Cheung Allen , Ball David , Srinivasan Mandyam V.
Published: June 2011

Animals that move rapidly through the air can save considerable energy by reducing the drag that they need to overcome during flight. We describe a novel ‘streamlining’ response in tethered, flying honeybees in which the abdomen is held in a raised position when the visual system is exposed to a pattern of image motion that is characteristic of forward flight. This visually evoked response, which can be elicited without exposing the insect to any airflow, presumably serves to reduce the aerodynamic drag that would otherwise be produced by the abdomen during real flight. The response is critically dependent on the presence of appropriate image motion everywhere within the large field of view of the insect. Thus, our results also underscore the importance of using panoramic stimulation for the study of visually guided flight in insects, and reveal the relative importance of various regions of the visual field in assessing the speed of flight through the environment.
Renal responses to salinity change in snakes with and without salt glands
Authors: Babonis Leslie S. , Miller Stephanie N. , Evans David H.
Published: June 2011

To understand renal responses to salinity change in aquatic reptiles, we examined the structure and function of the kidney in three species of snake: a marine species with a salt gland (Laticauda semifasciata), a marine species without a salt gland (Nerodia clarkii clarkii) and a freshwater species without a salt gland (Nerodia fasciata). Both marine species maintained relatively constant plasma ions, even after acclimation to saltwater. By contrast, both plasma Cl– and mortality increased with salinity in the freshwater species. To investigate putative renal ion regulatory mechanisms, we examined the distribution and abundance of Na+/K+-ATPase (NKA) and the Na+/K+/2Cl– cotransporter (NKCC2). In all species, NKA localized to the basolateral membranes of the distal tubule and the connecting segments and collecting ducts only; there was no effect of salinity on the distribution of NKA or on the abundance of NKA mRNA in any species. NKCC2 protein was undetectable in the kidney of any of the species and there was no effect of salinity on NKCC2 mRNA abundance. We also examined the distribution and abundance of aquaporin 3 (AQP3) in the kidney of these species; although putative AQP3 localized to the basolateral membranes of the connecting segments and collecting ducts of all three species, there was no effect of salinity on the localization of the protein or the abundance of the transcript. Interestingly, we found very few differences across species, suggesting that the snake kidney may play a trivial role in limiting habitat use.
Effects of shell morphology on mechanics of zebra and quagga mussel locomotion
Authors: Peyer Suzanne M. , Hermanson John C. , Lee Carol Eunmi
Published: June 2011

Although zebra mussels (Dreissena polymorpha) initially colonized shallow habitats within the North American Great Lakes, quagga mussels (Dreissena bugensis) are becoming dominant in both shallow- and deep-water habitats. Shell morphology differs among zebra, shallow quagga and deep quagga mussels but functional consequences of such differences are unknown. We examined effects of shell morphology on locomotion for the three morphotypes on hard (typical of shallow habitats) and soft (characteristic of deep habitats) sedimentary substrates. We quantified morphology using the polar moment of inertia, a parameter used in calculating kinetic energy that describes shell area distribution and resistance to rotation. We quantified mussel locomotion by determining the ratio of rotational (Krot) to translational kinetic energy (Ktrans). On hard substrate, Krot:Ktrans of deep quagga mussels was fourfold greater than for the other morphotypes, indicating greater energy expenditure in rotation relative to translation. On soft substrate, Krot:Ktrans of deep quagga mussels was approximately one-third of that on hard substrate, indicating lower energy expenditure in rotation on soft substrate. Overall, our study demonstrates that shell morphology correlates with differences in locomotion (i.e. Krot:Ktrans) among morphotypes. Although deep quagga mussels were similar to zebra and shallow quagga mussels in terms of energy expenditure on sedimentary substrate, their morphology was energetically maladaptive for linear movement on hard substrate. As quagga mussels can possess two distinct morphotypes (i.e. shallow and deep morphs), they might more effectively utilize a broader range of substrates than zebra mussels, potentially enhancing their ability to colonize a wider range of habitats.