bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Substrates for the Characterisation of Sialate-O-Acetyltransferases
Authors: Eleutério Inês , Streicher Hansjörg
Published: November 2010

The synthesis of a series of α- and β-configured sialosides using a Koenigs–Knorr methodology is described. The target compounds can serve as substrates for the investigation of biologically relevant sialate- O-acetyltransferase activity.
Preparation and Characterisation of Self-assembled Monolayers of Long-Chain alkyl Imidazolium-Based Ionic Liquids on Glass Surface
Authors: Du Bing
Published: November 2010

Self-assembled monolayers of long-chain alkyl imidazolium-based ionic liquid [C16tespim]X (X = Br–, BF4–, PF6–, Tf2N–) were grafted onto soda glass surfaces by –Si–O– covalent bonding. These monolayers transformed the wetting behaviour of the glass from hydrophilicity to hydrophobicity as investigated by water contact angle measurement. Exchange of the counteranion of the ionic liquids could tailor the surface wettability. It was found that the contact angle could be up to 112±4° on the glass surfaces when Tf2N– was the counteranion. The transmittance of glass-grafted ionic liquid monolayers was similar to that of the common glass.
Production and Characterization of Fengycin by Indigenous Bacillus subtilis F29-3 Originating from a Potato Farm
Authors: Wei Yu-Hong , Wang Li-Chuan , Chen Wei-Chuan , Chen Shan-Yu
Published: November 2010

Fengycin, a lipopeptide biosurfactant, was produced by indigenous Bacillus subtilis F29-3 isolated from a potato farm. Although inhibiting the growth of filamentous fungi, the fengycin is ineffective against yeast and bacteria. In this study, fengycin was isolated from fermentation broth of B. subtilis F29-3 via acidic precipitation (pH 2.0 with 5 N HCl) followed by purification using ultrafiltration and nanofiltration. The purified fengycin product was characterized qualitatively by using fast atom bombardment-mass spectrometer, Fourier transform infrared spectrometer, ultraviolet-visible spectrophotometer, 13C-nuclear magnetic resonance spectrometer and matrix assisted laser desorption ionization-time of flight, followed by quantitative analysis using reversed-phase HPLC system. This study also attempted to increase fengycin production by B. subtilis F29-3 in order to optimize the fermentation medium constituents. The fermentation medium composition was optimized using response surface methodology (RSM) to increase fengycin production from B. subtilis F29-3. According to results of the five-level four-factor central composite design, the composition of soybean meal, NaNO3, MnSO4·4H2O, mannitol-mannitol, soybean meal-mannitol, soybean meal‑soybean meal, NaNO3-NaNO3 and MnSO4·4H2O-MnSO4·4H2O significantly affected production. The simulation model produced a coefficient of determination (R2) of 0.9043, capable of accounting for 90.43% variability of the data. Results of the steepest ascent and central composite design indicated that 26.2 g/L of mannitol, 21.9 g/L of soybean meal, 3.1 g/L of NaNO3 and 0.2 g/L of MnSO4·4H2O represented the optimal medium composition, leading to the highest production of fengycin. Furthermore, the optimization strategy increased the fengycin production from 1.2 g/L to 3.5 g/L.
Chemical Constituents of the Bark of Dipteryx alata Vogel, an Active Species against Bothrops jararacussu Venom
Authors: Puebla Pilar , Oshima-Franco Yoko , Franco Luiz M. , Santos Marcio G. Dos , Silva Renata V. da , Rubem-Mauro Leandro , Feliciano Arturo San
Published: November 2010

The effect of four sub-extracts prepared from the lyophilized hydroalcoholic bark of Dipteryx alata (Leguminosae-Papilionoideae) dissolved in a methanol-water (80:20) mixture through a liquid-liquid partition procedure has been investigated against the neuromuscular blockade of the venom of the snake Bothrops jararacussu. The active CH2Cl2 sub-extract has been extensively analyzed for its chemical constituents, resulting in the isolation of four lupane-type triterpenoids: lupeol (1), lupenone (2), 28-hydroxylup-20(29)-en-3-one (3), betulin (4), nine isoflavonoids: 8-O-methylretusin (5), 7-hydroxy-5,6,4’-trimethoxyisoflavone (6), afrormosin (8), 7-hydroxy-8,3’,4’-trimethoxyisoflavone (9), 7,3’-dihydroxy-8,4’-dimethoxyisoflavone (10), odoratin (11), 7,8,3’-trihydroxy-4’-methoxyisoflavone (13), 7,8,3’-trihydroxy-6,4’-dimethoxyisoflavone (15), dipteryxin (17), one chalcone: isoliquiritigenin (7), one aurone: sulfuretin (14) and three phenolic compounds: vanillic acid (12), vanillin (16), and protocatechuic acid (18). Their chemical structures were elucidated on the basis of spectroscopic analysis, including HRMS, 1D- and 2D-NMR techniques.
Crucial Role of Selenium in the Virucidal Activity of Benzisoselenazol-3(2H)-ones and Related Diselenides
Authors: Pietka-Ottlik Magdalena , Potaczek Piotr , Piasecki Egbert , Mlochowski Jacek
Published: November 2010

Various N-substituted benzisoselenazol-3(2H)-ones and their non-selenium-containing analogues have been synthesized and tested against selected viruses (HHV-1, EMCV and VSV) to determine the extent to which selenium plays a role in antiviral activity. The data presented here show that the presence of selenium is crucial for the antiviral properties of benzisoselenazol-3(2H)-ones since their isostructural analogues having different groups but lacking selenium either did not show any antiviral activity or their activity was substantially lower. The open-chain analogues of benzisoselenazol-3(2H)-ones—diselenides also exhibited high antiviral activity while selenides and disulfides were completely inactive towards model viruses.
Molecular Basis for Drug Resistance in HIV-1 Protease
Authors: Ali Akbar , Bandaranayake Rajintha M. , Cai Yufeng , King Nancy M. , Kolli Madhavi , Mittal Seema , Murzycki Jennifer F. , Nalam Madhavi N.L. , Nalivaika Ellen A. , Özen Ayşegül , Prabu-Jeyabalan Moses M. , Thayer Kelly , Schiffer Celia A.
Published: November 2010

HIV-1 protease is one of the major antiviral targets in the treatment of patients infected with HIV-1. The nine FDA approved HIV-1 protease inhibitors were developed with extensive use of structure-based drug design, thus the atomic details of how the inhibitors bind are well characterized. From this structural understanding the molecular basis for drug resistance in HIV-1 protease can be elucidated. Selected mutations in response to therapy and diversity between clades in HIV-1 protease have altered the shape of the active site, potentially altered the dynamics and even altered the sequence of the cleavage sites in the Gag polyprotein. All of these interdependent changes act in synergy to confer drug resistance while simultaneously maintaining the fitness of the virus. New strategies, such as incorporation of the substrate envelope constraint to design robust inhibitors that incorporate details of HIV-1 protease’s function and decrease the probability of drug resistance, are necessary to continue to effectively target this key protein in HIV-1 life cycle.
Human IgG1 Monoclonal Antibody against Human Collagen 17 Noncollagenous 16A Domain Induces Blisters via Complement Activation in Experimental Bullous Pemphigoid Model
Authors: Li Qiang , Ujiie Hideyuki , Shibaki Akihiko , Wang Gang , Moriuchi Reine , Qiao Hong-jiang , Morioka Hiroshi , Shinkuma Satoru , Natsuga Ken , Long Heather A. , Nishie Wataru , Shimizu Hiroshi
Published: November 2010

Bullous pemphigoid (BP) is an autoimmune blistering disease caused by IgG autoantibodies targeting the noncollagenous 16A (NC16A) domain of human collagen 17 (hCOL17), which triggers blister formation via complement activation. Previous in vitro analysis demonstrated that IgG1 autoantibodies showed much stronger pathogenic activity than IgG4 autoantibodies; however, the exact pathogenic role of IgG1 autoantibodies has not been fully demonstrated in vivo. We constructed a recombinant IgG1 mAb against hCOL17 NC16A from BP patients. In COL17-humanized mice, this mAb effectively reproduced a BP phenotype that included subepidermal blisters, deposition of IgG1, C1q and C3, neutrophil infiltration, and mast cell degranulation. Subsequently, alanine substitutions at various C1q binding sites were separately introduced to the Fc region of the IgG1 mAb. Among these mutated mAbs, the one that was mutated at the P331 residue completely failed to activate the complement in vitro and drastically lost pathogenic activity in COL17-humanized mice. These findings indicate that P331 is a key residue required for complement activation and that IgG1-dependent complement activation is essential for blister formation in BP. This study is, to our knowledge, the first direct evidence that IgG1 Abs to hCOL17 NC16A can induce blister formation in vivo, and it raises the possibility that IgG1 mAbs with Fc modification may be used to block pathogenic epitopes in autoimmune diseases.
Preexisting Vaccinia Virus Immunity Decreases SIV-Specific Cellular Immunity but Does Not Diminish Humoral Immunity and Efficacy of a DNA/MVA Vaccine
Authors: Kannanganat Sunil , Nigam Pragati , Velu Vijayakumar , Earl Patricia L. , Lai Lilin , Chennareddi Lakshmi , Lawson Benton , Wilson Robert L. , Montefiori David C. , Kozlowski Pamela A. , Moss Bernard , Robinson Harriet L. , Amara Rama Rao
Published: November 2010

The influence of preexisting immunity to viral vectors is a major issue for the development of viral-vectored vaccines. In this study, we investigate the effect of preexisting vaccinia virus immunity on the immunogenicity and efficacy of a DNA/modified vaccinia Ankara (MVA) SIV vaccine in rhesus macaques using a pathogenic intrarectal SIV251 challenge. Preexisting immunity decreased SIV-specific CD8 and CD4 T cell responses but preserved the SIV-specific humoral immunity. In addition, preexisting immunity did not diminish the control of an SIV challenge mediated by the DNA/MVA vaccine. The peak and set point viremia was 150- and 17-fold lower, respectively, in preimmune animals compared with those of control animals. The peak and set point viremia correlated directly with colorectal virus at 2 wk postchallenge suggesting that early control of virus replication at the site of viral challenge was critical for viral control. Factors that correlated with early colorectal viral control included 1) the presence of anti-SIV IgA in rectal secretions, 2) high-avidity binding Ab for the native form of Env, and 3) low magnitude of vaccine-elicited SIV-specific CD4 T cells displaying the CCR5 viral coreceptor. The frequency of SIV-specific CD8 T cells in blood and colorectal tissue at 2 wk postchallenge did not correlate with early colorectal viral control. These results suggest that preexisting vaccinia virus immunity may not limit the potential of recombinant MVA vaccines to elicit humoral immunity and highlight the importance of immunodeficiency virus vaccines achieving early control at the mucosal sites of challenge.
Antibodies and Lentiviruses That Specifically Recognize a T Cell Epitope Derived from HIV-1 Nef Protein and Presented by HLA-C
Authors: Herschhorn Alon , Marasco Wayne A. , Hizi Amnon
Published: November 2010

HIV selectively downregulates HLA-A and -B from the surfaces of infected cells to avoid detection by the immune system. In contrast, the HLA-C molecules are highly resistant to this downregulation. High expression level of HLA-C on the cell surface, which correlates with a single nucleotide polymorphism, is also associated with lower viral loads and slower progression to AIDS. These findings strongly suggest that HIV-1–derived peptides are efficiently presented by HLA-C and trigger the elimination of infected cells. Accordingly, the ability to detect these HLA-C–peptide complexes may be used for therapeutic targeting of HIV-1–infected cells and for measuring effective presentation of vaccine candidates after immunization with HIV-1–related proteins or genes. However, low level of HLA-C expression on the cell surface has impeded the development of such complex-recognizing reagents. In this study, we describe the development of a high-affinity human Ab that specifically interacts, at low pM concentrations, with a conserved viral T cell epitope derived from HIV-1 Nef protein and presented by HLA-C. The human Ab selectively detects this complex on different cells and does not interact with a control complex that differed only in the presented peptide. Engineering lentiviruses to display this Ab endowed them with the same specificity as the Ab, whereas coexpressing the Ab and Fas ligand enables the lentiviruses to kill specifically Nef-presenting cells. Abs and pseudoviruses with such specificity are likely to be highly valuable as building blocks for specific targeting and killing of HIV-1–infected cells.
CD8 T Cell-Intrinsic GITR Is Required for T Cell Clonal Expansion and Mouse Survival following Severe Influenza Infection
Authors: Snell Laura M. , McPherson Ann J. , Lin Gloria H. Y. , Sakaguchi Shimon , Pandolfi Pier Paolo , Riccardi Carlo , Watts Tania H.
Published: November 2010

The regulation of T cell expansion by TNFR family members plays an important role in determining the magnitude of the immune response to pathogens. As several members of the TNFR family, including glucocorticoid-induced TNFR-related protein (GITR), are found on both regulatory and effector T cells, there is much interest in understanding how their effects on these opposing arms of the immune system affect disease outcome. Whereas much work has focused on the role of GITR on regulatory T cells, little is known about its intrinsic role on effector T cells in an infectious disease context. In this study, we demonstrate that GITR signaling on CD8 T cells leads to TNFR-associated factor (TRAF) 2/5-dependent, TRAF1-independent NF-κB induction, resulting in increased Bcl-xL. In vivo, GITR on CD8 T cells has a profound effect on CD8 T cell expansion, via effects on T cell survival. Moreover, GITR is required on CD8 T cells for enhancement of influenza-specific CD8 T cell expansion upon administration of agonistic anti-GITR Ab, DTA-1. Remarkably, CD8 T cell-intrinsic GITR is essential for mouse survival during severe, but dispensable during mild respiratory influenza infection. These studies highlight the importance of GITR as a CD8 T cell costimulator during acute viral infection, and argue that despite the similarity among several TNFR family members in inducing T lymphoctye survival, they clearly have nonredundant functions in protection from severe infection.
A Dendritic Cell Population Generated by a Fusion of GM-CSF and IL-21 Induces Tumor-Antigen–Specific Immunity
Authors: Williams Patrick , Bouchentouf Manaf , Rafei Moutih , Romieu-Mourez Raphaëlle , Hsieh Jeremy , Boivin Marie-Noëlle , Yuan Shala , Forner Kathy Ann , Birman Elena , Galipeau Jacques
Published: November 2010

We have previously shown that the fusion of GM-CSF and IL-21 (GIFT-21) possesses a potent immune stimulatory effect on myeloid cells. In this study, we define the effect of GIFT-21 on naive murine monocytes (GIFT-21 dendritic cells [DCs]), which express increased levels of Gr-1, CD45R, MHC class I, CD80, CD86, and CXCR4 and suppress CD11c and MHC class II. Compared with conventional dendritic cells, GIFT-21 DCs produced substantially more CCL2, IL-6, TNF-α, and IFN-α and induced significantly greater production of IFN-γ by CD8+ T cells in MHC class I-restricted Ag presentation assays. B16 melanoma and D2F2 Neu breast cancer growth was inhibited in mice treated with Ag-naive GIFT-21 DCs. This effect was lost in CD8−/− and CCR2−/− mice and when mice were treated with β2-microglobulin–deficient GIFT-21 DCs, indicating that GIFT-21 DCs migrated to and sampled from the tumors to present tumor Ags to CCL2 recruited CD8+ T cells via MHC class I. We propose that autologous GIFT-21 DCs may serve as a cell therapy platform for the treatment of cancer.
Immunological Effects of Sublingual Immunotherapy: Clinical Efficacy Is Associated with Modulation of Programmed Cell Death Ligand 1, IL-10, and IgG4
Authors: Piconi Stefania , Trabattoni Daria , Rainone Veronica , Borgonovo Linda , Passerini Simone , Rizzardini Giuliano , Frati Franco , Iemoli Enrico , Clerici Mario
Published: November 2010

Sublingual immunotherapy (SLIT) is an alternate route of administration of allergen-specific immunotherapy with an improved safety profile; to clarify the immune mechanisms elicited by this therapy, we analyzed the clinical and immunologic effects of SLIT in patients with a clinical history of ragweed sensitization. To analyze possible difference among immunotherapeutic protocols, we also compared patients receiving preseasonal, seasonal, or prolonged sublingual therapy (≥3 y); patients receiving symptomatic therapy alone were enrolled as well in the study. Clinical and immunological parameters were measured twice in and out of the pollination period. Clinical benefits, as measured by the visual analog scale for symptoms and for use of drugs, were evident in all three groups of individuals receiving immunotherapy, but were significantly better in patients undergoing prolonged SLIT. Immunologically, SLIT resulted in increased IL-10 production, programmed cell death ligand 1 expression, and concentration of allergen-specific IgG4, as well as in the reduction of CD80 and CD86 expression and IL-4 production. SLIT, thus, is associated with modulation of programmed cell death ligand 1 expression and IL-10 synthesis and favors the production of allergen-specific IgG4. These effects are evident from the first pollen season, independently from therapeutic regimen (preseasonal or seasonal) even if a prolonged treatment is necessary to obtain full clinical efficacy. A more detailed understanding of the interaction of allergen and APCs within the oral mucosa will allow improved targeting of allergy vaccine.
NKG2D Is Required for NK Cell Activation and Function in Response to E1-Deleted Adenovirus
Authors: Zhu Jiangao , Huang Xiaopei , Yang Yiping
Published: November 2010

Despite high transduction efficiency in vivo, the application of recombinant E1-deleted adenoviral vectors for in vivo gene therapy has been limited by the attendant innate and adaptive immune responses to adenoviral vectors. NK cells have been shown to play an important role in innate immune elimination of adenoviral vectors in vivo. However, the mechanisms underlying NK cell activation and function in response to adenoviral vectors remain largely undefined. In this study, we showed that NK cell activation upon adenoviral infection was dependent on accessory cells such as dendritic cells and macrophages and that cell contact-dependent signals from the accessory cells are necessary for NK cell activation. We further demonstrated that ligands of the NK activating receptor NKG2D were upregulated in accessory cells upon adenoviral infection and that blockade of NKG2D inhibited NK cell activation upon adenoviral infection, leading to a delay in adenoviral clearance in vivo. In addition, NKG2D was required for NK cell-mediated cytolysis on adenovirus-infected targets. Taken together, these results suggest that efficient NK cell activation and function in response to adenoviral infection is critically dependent on the NKG2D pathway, which understanding may assist in the design of effective strategies to improve the outcome of adenovirus-mediated gene therapy.
Cutting Edge: Lymphoproliferation Caused by Fas Deficiency Is Dependent on the Transcription Factor Eomesodermin
Authors: Kinjyo Ichiko , Gordon Scott M. , Intlekofer Andrew M. , Dowdell Kennichi , Mooney Erin C. , Caricchio Roberto , Grupp Stephan A. , Teachey David T. , Rao V. Koneti , Lindsten Tullia , Reiner Steven L.
Published: November 2010

A hallmark of autoimmune lymphoproliferative syndrome (ALPS), caused by mutation of the Fas death receptor, is massive lymphadenopathy from aberrant expansion of CD4−CD8− (double-negative [DN]) T cells. Eomesodermin (Eomes) is a member of the T-box family of transcription factors and plays critical roles in effector cell function and memory cell fitness of CD8+ T lymphocytes. We provide evidence in this study that DN T cells exhibit dysregulated expression of Eomes in humans and mice with ALPS. We also find that T cell-specific deletion of Eomes prevents lymphoid hypertrophy and accumulation of DN T cells in Fas-mutant mice. Although Eomes has critical physiological roles in the function and homeostasis of CD8+ T cells, overexpression of Eomes appears to enable pathological induction or expansion of unusual CD8-related T cell subsets. Thus, antagonism of Eomes emerges as a therapeutic target for DN T cell ablation in ALPS.
Specific coping behaviors in relation to adolescent depression and suicidal ideation
Authors: Horwitz Adam G. , Hill Ryan M. , King Cheryl A.
Published: November 2010

The coping strategies used by adolescents to deal with stress may have implications for the development of depression and suicidal ideation. This study examined coping categories and specific coping behaviors used by adolescents to assess the relation of coping to depression and suicidal ideation. In hierarchical regression models, the specific coping behaviors of behavioral disengagement and self‐blame were predictive of higher levels of depression; depression and using emotional support were predictive of suicidal ideation. Results suggest that specific behaviors within the broad coping categories of emotion‐focused coping (e.g., self‐blame) and avoidant coping (e.g., behavioral disengagement) account for these categories’ associations with depression and suicidal ideation. Specific problem‐focused coping strategies did not independently predict lower levels of depression or suicidal ideation. It may be beneficial for interventions to focus on eliminating maladaptive coping behaviors in addition to introducing or enhancing positive coping behaviors.
Using discrete choice experiments to inform randomised controlled trials: an application to chronic low back pain management in primary care
Authors: Yi Deokhee , Ryanl Mandy , Campbelll Susan , Elliottl Alison , Torrancel Nicola , Chambersl Alastair , Johnstonl Marie , Hannafordl Philip , Smithl Blair H.
Published: November 2010

Pain Management Programmes (PMPs) are a multi‐disciplinary approach to the management of chronic low back pain (CLBP). Notwithstanding evidence of effectiveness, successful take‐up of programmes requires acceptability to patients. We used a discrete choice experiment to investigate patient preferences for alternative PMPs for managing CLBP in primary care. Specifically, we estimated the probability of uptake of alternative configurations of PMPs. Potential attributes and associated levels influencing take‐up were identified through a systematic literature review, survey of current PMPs, expert consultation, and focus groups. Five attributes were included: content; provider; schedule; group size; and travel time to clinic. Four hundred and fourteen questionnaires were mailed to patients attending clinics and 124 questionnaires were returned suitable for analysis. Method of delivery influenced probability of take‐up, with small group sizes and low intensity programmes over a prolonged period increasing the probabilities. Travel time was also important. However, providers and contents of PMPs were not main drivers of preferences, though those with more severe pain did prefer PMPs provided by more specialists. Probability of take‐up increases when PMPs better reflect patient preferences. Given preferences, resource constraints, and evidence on clinical outcomes of alternative configurations it is suggested more resource‐intensive PMPs be reserved for those with the most severe and disabling pain and less intensive programmes delivered over a longer time period in smaller groups for those with less severe pain. These findings can inform future randomised trials to evaluate acceptable PMPs in primary care.
How Good are Orthopaedic Surgeons at Interpreting ECGs?
Authors: Raheel Shariff , Safa Attar , Attar Fahad G.
Published: November 2010

This study is to find out how good orthopaedic surgeons are at interpreting electrocardiograms and to compare the results between surgical specialties with physicians. It showed that surgeons were considerably weaker than physicians in this aspect. The difference between the surgical specialities was not significant, but the orthopaedic surgeons were marginally better than other surgical specialists. Improper interpretation of electrocardiogram may compromise patient care. A formal training may be required in surgical portfolio.
Anterior Elbow Subluxation after Radial Head Arthroplasty for Fracture Dislocation of the Elbow
Authors: Wai-Kit Chan , Tun-Hing Lui
Published: November 2010

We describe a case of elbow dislocation with Hotchkiss type III radial head fracture and Regan-Morrey type II coronoid process fracture, which was treated with radial head replacement. It was complicated with oversizing of prosthesis, resulting in elbow subluxation. It was treated with radial shaft shortening osteotomy. The clinical result was satisfactory.
Validation on Efficiency Pattern Analysis for Geriatric Hip Fractures Rehabilitation
Authors: Fran Lai Ho-Yin , Eric Wong Ming-Chung , Carey Poon Mei-Yee , Stephanie Louie Wai-Shan , Simon Wong Kam-Man
Published: November 2010

Seven hundred and sixty-three elderly patients with hip fractures were recruited in the study. The Functional Independence Measure (FIM) was used to measure their functional status on admission and upon discharge, and their difference was defined as functional change. An Efficiency Pattern Analysis Matrix was formed with Efficiency Pattern Analysis (EPA) and was used for in-depth matrix characteristics analysis. A validation study was also conducted with another group of patients (n = 455) so that the stability of EPA across time was affirmed. We found that 23.3% of patients are in “higher efficiency” group [higher motor-FIM gains with shorter length of stay (LOS)], 8.5% in “higher gain and longer stay” group (higher motor-FIM gains with longer LOS), 32.5% in “average efficiency” group, 12% in “lower gain and shorter stay” (lower motor-FIM gain and shorter LOS), and 23.7% of patients in “lower efficiency” group (intermediate motor-FIM gains with longer LOS). The demographic and functional characteristics among these groups would be also analysed.
The Diagnosis of Osteolymphoma: A Case Report and Review of the Literature
Authors: Alistair Spiers , Gregory Freeman
Published: November 2010

Osteolymphoma, also known as primary non-Hodgkin's lymphoma of the bone, is an unusual disease which can be difficult to diagnose. This case study concerns a 51-year-old patient who presented with right leg pain initially diagnosed as osteomyelitis. Failure of treatment and further investigation revealed an unusual primary tumour. We review the sequence of events leading to the diagnosis of osteolymphoma and the literature relating to the diagnosis.
Finger Stiffness Measured by Goniometry Method—A Simple useful Tool for Early Diagnosis of Reflex Sympathetic Dystrophy after Colles’ Fracture
Authors: Rajesh Garg
Published: November 2010

We assess the finger joint stiffness by measuring the active range of motion of all metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of the involved hand with a hand goniometer. It is then compared with the normal hand for the effective range of total motion and thereby using it as a quantitative, qualitative, and reproducible method for early diagnosis of reflex sympathetic dystrophy after Colles’ fracture. It is sensitive and specific.
Scavenger receptor class B type I (SR-BI) regulates perivascular macrophages and modifies amyloid pathology in an Alzheimer mouse model
Authors: Thanopoulou Kalliopi , Fragkouli Apostolia , Stylianopoulou Fotini , Georgopoulos Spiros
Published: November 2010

Scavenger receptor class B type I (SR-BI) is a high-density lipoprotein receptor that regulates cholesterol efflux from the peripheral tissues to the liver. SR-BI has been identified on astrocytes and vascular smooth muscle cells in Alzheimer's disease brain and has been shown to mediate adhesion of microglia to fibrillar amyloid-β (Aβ). Here we report that SR-BI mediates perivascular macrophage response and regulates Aβ-related pathology and cerebral amyloid angiopathy in an Alzheimer's mouse model. Reduction or deletion of
SR-BI
gene in heterozygous or homozygous deficient mice (
SR-BI
+/−
,
−/−
) resulted in a significant increase in perivascular macrophages in the brain. SR-BI deletion had no effect on apolipoprotein E or apolipoprotein AI levels in the mouse brain. Our analysis revealed increased levels of SR-BI expression in the brains of human amyloid precursor protein (Swedish, Indiana) transgenic mice (J20 line). To evaluate the role of SR-BI in Alzheimer's disease pathogenesis, we inactivated one
SR-BI
allele in J20 transgenic mice. SR-BI reduction in J20/
SR-BI
+/−
mice enhanced fibrillar amyloid deposition and cerebral amyloid angiopathy and also exacerbated learning and memory deficits compared with J20 littermates. Immunohistochemical analysis revealed localization of SR-BI on perivascular macrophages in tight association with Aβ deposits. Our data suggest that SR-BI reduction impairs the response of perivascular macrophages to Aβ and enhances the Aβ-related phenotype and cerebral amyloid angiopathy in J20 mice. These results reveal that SR-BI, a scavenger receptor primarily involved in high-density lipoprotein cholesterol transport, plays an essential role in Alzheimer's disease and cerebral amyloid angiopathy.
Mechanism of replication blocking and bypass of Y-family polymerase η by bulky acetylaminofluorene DNA adducts
Authors: Schorr Stephanie , Schneider Sabine , Lammens Katja , Hopfner Karl-Peter , Carell Thomas
Published: November 2010

Heterocyclic aromatic amines produce bulky C8 guanine lesions in vivo, which interfere and disrupt DNA and RNA synthesis. These lesions are consequently strong replication blocks. In addition bulky adducts give rise to point and frameshift mutations. The translesion synthesis (TLS) DNA polymerase η is able to bypass slowly C8 bulky adduct lesions such as the widely studied 2-aminofluorene-dG and its acetylated analogue mainly in an error-free manner. Replicative polymerases are in contrast fully blocked by the acetylated lesion. Here, we show that TLS efficiency of Pol η depends critically on the size of the bulky adduct forming the lesion. Based on the crystal structure, we show why the bypass reaction is so difficult and we provide a model for the bypass reaction. In our model, TLS is accomplished without rotation of the lesion into the
anti
conformation as previously thought.
A naturally chimeric type IIA topoisomerase in
Aquifex aeolicus
highlights an evolutionary path for the emergence of functional paralogs
Authors: Tretter Elsa M. , Lerman Jeffrey C. , Berger James M.
Published: November 2010

Bacteria frequently possess two type IIA DNA topoisomerases, gyrase and topo IV, which maintain chromosome topology by variously supercoiling, relaxing, and disentangling DNA. DNA recognition and functional output is thought to be controlled by the C-terminal domain (CTD) of the topoisomerase DNA binding subunit (GyrA/ParC). The deeply rooted organism
Aquifex aeolicus
encodes one type IIA topoisomerase conflictingly categorized as either DNA gyrase or topo IV. To resolve this enzyme’s catalytic properties and heritage, we conducted a series of structural and biochemical studies on the isolated GyrA/ParC CTD and the holoenzyme. Whereas the CTD displays a global structure similar to that seen in bone fide GyrA and ParC paralogs, it lacks a key functional motif (the “GyrA-box”) and fails to wrap DNA. Biochemical assays show that the
A. aeolicus
topoisomerase cannot supercoil DNA, but robustly removes supercoils and decatenates DNA, two hallmark activities of topo IV. Despite these properties, phylogenetic analyses place all functional domains except the CTD squarely within a gyrase lineage, and the
A. aeolicus
GyrB subunit is capable of supporting supercoiling with
Escherichia coli
GyrA, but not DNA relaxation with
E. coli
ParC. Moreover, swapping the
A. aeolicus
GyrA/ParC CTD with the GyrA CTD from
Thermotoga maritima
creates an enzyme that negatively supercoils DNA. These findings identify
A. aeolicus
as the first bacterial species yet found to exist without a functional gyrase, and suggest an evolutionary path for generation of bacterial type IIA paralogs.
Syntaxin clusters assemble reversibly at sites of secretory granules in live cells
Authors: Barg S. , Knowles M. K. , Chen X. , Midorikawa M. , Almers Wolfhard
Published: November 2010

Syntaxin resides in the plasma membrane, where it helps to catalyze membrane fusion during exocytosis. The protein also forms clusters in cell-free and granule-free plasma-membrane sheets. We imaged the interaction between syntaxin and single secretory granules by two-color total internal reflection microscopy in PC12 cells. Syntaxin-GFP assembled in clusters at sites where single granules had docked at the plasma membrane. Clusters were intermittently present at granule sites, as syntaxin molecules assembled and disassembled in a coordinated fashion. Recruitment to granules required the N-terminal domain of syntaxin, but not the entry of syntaxin into SNARE complexes. Clusters facilitated exocytosis and disassembled once exocytosis was complete. Syntaxin cluster formation defines an intermediate step in exocytosis.
Two-dimensional effects in the problem of tearing modes control by electron cyclotron current drive
Authors: Comisso L. , Lazzaro E.
Published: November 2010

The design of means to counteract robustly the classical and neoclassical tearing modes in a tokamak by localized injection of an external control current requires an ever growing understanding of the physical process, beyond the Rutherford-type zero-dimensional models. Here a set of extended magnetohydrodynamic nonlinear equations for four continuum fields is used to investigate the two-dimensional effects in the response of the reconnecting modes to specific inputs of the localized external current. New information is gained on the space- and time-dependent effects of the external action on the two-dimensional structure of magnetic islands, which is very important to formulate applicable control strategies.
The relation between upstream density and temperature widths in the scrape-off layer and the power width in an attached divertor
Authors: Stangeby P.C. , Canik J.M. , Whyte D.G.
Published: November 2010

The target power width
is one of the most critical practical quantities in the development of magnetic fusion energy. It is essential to know how to scale this quantity to future devices. At present the controlling physics is not adequately understood, making reliable prediction difficult. It seems likely that two important processes effecting
are (a) cross-field transport, e.g. D
⊥,
and (b) volumetric power loss processes in the edge plasma, with the latter tending to occur mainly in the divertor for attached divertor conditions. It is hypothesized that a simple relation exists between the ‘upstream’ radial profiles of n
e and T
e in the main scrape-off layer,
,
, and the parallel power flux density at the divertor entrance,
. Such a simple relation is found here in 2D SOLPS edge code simulations of attached divertor conditions, which contain a wide range of more or less complex edge physics effects. It is found that
, as can be expected on the basis of flux-limited parallel heat conduction, rather than Spitzer–Harm conduction for which
is expected. For the relatively open divertor configuration considered, and for attached divertor conditions, it is found that the flux-limited relationship also holds for the SOLPS power flux density deposited on the target
, even including the radiation load; this despite the fact that up to half the power into the SOL is dissipated radiatively. Comparing with experimentally measured target power widths for H-mode discharges, better agreement is found assuming flux limited rather than Spitzer–Harm transport although definitive conclusions will require analysis of specific discharges in specific tokamaks. This study is a necessary preliminary work to an equivalent treatment of the case where volumetric losses in the divertor are stronger, including the detached, strongly radiating divertor case with momentum loss.
The ecton mechanism of unipolar arcing in magnetic confinement fusion devices
Authors: Barengolts S.A. , Mesyats G.A. , Tsventoukh M.M.
Published: November 2010

It has been shown that the source of current and erosion plasma in a unipolar arc is explosive electron emission, which occurs as ejection of individual portions of electrons named ectons. This phenomenon is responsible for the numerous microcraters left by unipolar arcs on metal surfaces. An arc of this type is self-sustained due to the interaction of the erosion plasma with the electrode surface. The duration of an arc is determined by the conditions of its initiation: the higher the arc current, and hence, the number of cells in the spot formed on arc initiation, the longer the arc operation.
Is laser cooling for heavy-ion fusion feasible?
Authors: Ho D.D.-M. , Brandon S.T.
Published: November 2010

Heavy-ion beams, each with current in the kiloampere range and particle energy in the giga-electronvolt range, must be focused onto a millimetre-size spot to provide the power required for ignition of high-gain targets for inertial confinement fusion. However, the focal spot size is always enlarged by chromatic aberration generated by the thermal spread of the beam ions in the direction of beam propagation. Enlarged focal spot degrades the target performance. For high-current beams, the conventional remedy for chromatic aberration using sextupole magnets has been shown to be ineffective. If novel correction schemes can be found, then the spot size can be reduced to below that previously believed possible. Smaller spots can mean lower energy targets so that the heavy-ion fusion (HIF) scenario can look more attractive. Success in laser cooling of ion beams in storage rings has inspired us to explore the feasibility of applying laser cooling for HIF, and the recirculator configuration proposed for HIF appears to be well suited for this purpose. However, using particle-in-cell simulations and theoretical arguments, we demonstrate in this paper that although laser cooling of heavy-ion beams is feasible in principle, the rapid velocity-space diffusion of ions in the bump-in-tail distribution, set up by the cooling lasers, limits the velocity-space compressibility of the thermal spread along the beam. Consequently, laser cooling is impractical for high-current, heavy-ion beams for the proposed recirculator configuration. Nevertheless, if the recirculator architecture or the target requirement can reduce the beam current, then the cooling scheme described here would be useful. This scheme may also be applicable to the RF linac and storage ring approach to HIF.
Assigning duplication events to relative temporal scales in genome-wide studies
Authors: Huerta-Cepas Jaime , Gabaldón Toni
Published: November 2010

Motivation: In genome-wide analyses, the relative age of gene duplications is often estimated by measuring the rate of synonymous substitutions (dS) between paralogous sequences. On the other hand, recent studies have shown the feasibility of inferring, at genomic scales, the relative age of duplication events from the topology of gene family trees. This represents a promising alternative for large surveys requiring an automatic methodology to establish a timeline of duplication events and that are usually limited to the use of dS, which presents known limitations such as a fast saturation of the signal. However, both measures have never been compared in a common framework.

Results: Topology-based placement of duplications on a relative time scale corresponding to periods between speciation events were found to be highly consistent, providing the same placement for 67–84% of a reliable set of gene pairs duplicated in a single event. For recent evolutionary periods, dS and topological measures showed a strong correlation. We conclude that the topology-based approach is more appropriate for assigning duplications to temporal scales when analyses need to include ancient events, and that the study of recent duplications may benefit from a combination of dS and topology information.

Contact:  tgabaldon@crg.es

Supplementary information:  Supplementary data are available at Bioinformatics online.
Inference of gene networks—application toBifidobacterium
Authors: Lai Darong , Yang Xinyi , Wu Gang , Liu Yuanhua , Nardini Christine
Published: November 2010

Motivation: The reliable and reproducible identification of gene interaction networks represents one of the grand challenges of both modern molecular biology and computational sciences. Approaches based on careful collection of literature data and network topological analysis, applied to unicellular organisms, have proven to offer results applicable to medical therapies. However, when little a priori knowledge is available, other approaches, not relying so strongly on previous literature, must be used. We propose here a novel algorithm (based on ordinary differential equations) able to infer the interactions occurring among genes, starting from gene expression steady state data.

Results: The algorithm was first validated on synthetic and real benchmarks. It was then applied to the reconstruction of the core of the amino acids metabolism in Bifidobacterium longum, an essential, yet poorly known player in the human gut intestinal microbiome, known to be related to the onset of important diseases, such as metabolic syndromes. Our results show how computational approaches can offer effective tools for applications with the identification of potential new biological information.

Availability: The software is available at www.bioconductor.org and at www.picb.ac.cn/ClinicalGenomicNTW/temp2.html.

Contact:  christine@picb.ac.cn

Supplementary information:  Supplementary data are available at Bioinformatics online.
The uniqueome: a mappability resource for short-tag sequencing
Authors: Koehler Ryan , Issac Hadar , Cloonan Nicole , Grimmond Sean M.
Published: November 2010

Summary: Quantification applications of short-tag sequencing data (such as CNVseq and RNAseq) depend on knowing the uniqueness of specific genomic regions at a given threshold of error. Here, we present the ‘uniqueome’, a genomic resource for understanding the uniquely mappable proportion of genomic sequences. Pre-computed data are available for human, mouse, fly and worm genomes in both color-space and nucletotide-space, and we demonstrate the utility of this resource as applied to the quantification of RNAseq data.

Availability: Files, scripts and supplementary data are available from http://grimmond.imb.uq.edu.au/uniqueome/; the ISAS uniqueome aligner is freely available from http://www.imagenix.com/.

Contact:  n.cloonan@uq.edu.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
Calidifontibacter indicus gen. nov., sp. nov., a member of the family Dermacoccaceae isolated from a hot spring, and emended description of the family Dermacoccaceae
Authors: Ruckmani Arunachalam , Kaur Ishwinder , Schumann Peter , Klenk Hans-Peter , Mayilraj Shanmugam
Published: November 2010

During the course of a study on the bacterial diversity in Western Ghats, India, an actinobacterial strain, designated PC IW02T, was isolated and characterized by a polyphasic taxonomic approach. Strain PC IW02T was a non-motile, Gram-positive, short rod that formed creamish white to yellow coloured colonies. 16S rRNA gene sequence analysis showed that the novel strain showed highest sequence similarity with type strains of members of the genus Dermacoccus: Dermacoccus barathri (96.6 %), Dermacoccus profundi (96.5 %), Dermacoccus abyssi (96.4 %) and Dermacoccus nishinomiyaensis (95.9 %). The phylogenetic tree suggested that strain PC IW02T could represent a member of a new genus of the family Dermacoccaceae with the genus Demetria as closest clade. Pairwise sequence alignment with Demetria terragena HKI 0089T and Kytococcus sedentarius DSM 20547T showed similarities of 94.2 and 93.7 %, respectively. Strain PC IW02T had MK-8(H4) as the major menaquinone. The major fatty acids were iso-C16 : 0 (43.4 %), iso-C16 : 1 H (17.2 %) and anteiso-C17 : 0 (9.9 %). The diagnostic cell-wall amino acid at position 3 of the peptide subunit was lysine; the interpeptide bridge consisted of Gly–Ser–Asp. The polar lipids present were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannosides and phosphatidylserine, along with two unknown phospholipids. The genomic DNA G+C content of the isolate was 77 mol%. On the basis of phenotypic characteristics, including chemotaxonomic data, and 16S rRNA gene sequence similarities, strain PC IW02T represents a novel species in a new genus of the family Dermacoccaceae for which the name Calidifontibacter indicus gen. nov., sp. nov. is proposed. The type strain of Calidifontibacter indicus is PC IW02T ( = MTCC 8338T = DSM 22967T = JCM 16038T). An emended description of the family Dermacoccaceae is provided.
Rhizobium pseudoryzae sp. nov., isolated from the rhizosphere of rice
Authors: Zhang Xiaoxia , Sun Lei , Ma Xiaotong , Sui Xin Hua , Jiang Ruibo
Published: November 2010

A Gram-stain-negative, aerobic, rod-shaped bacterium, designated strain J3-A127T, was isolated from the roots of fresh rice plants (Oryza sativa). Cells were non-motile and no flagellum was detected. Comparison of 16S rRNA gene sequences indicated that the strain was phylogenetically related to species of the genusRhizobium, with closest similarity toRhizobium oryzaeAlt 505T(96.4 %). The low levels of 16S rRNA gene sequence similarity (<90 %) found between thegyrB,atpD,recAandglnIIgene sequences of strain J3-A127Tand the type strains of recognized species of the genusRhizobiumalso indicated that it represented a separate species. The temperature range for growth was 10–40 °C (optimum around 28 °C) and the pH range was 6.0–11.0 (optimum pH 7.0–8.0). Strain J3-A127Ttolerated NaCl concentrations up to 5.0 % (w/v). The strain was catalase- and oxidase-positive. The main cellular fatty acids were summed feature 8 (C18 : 1ω7cand/or C18 : 1ω6; 46.7 %). The DNA G+C content of strain J3-A127Twas 59.5 mol%. Strain J3-A127Tdid not form any nodules on four different legumes and thenodDandnifHgenes were not detected by PCR. According to physiological and biochemical characteristics and genotypic data, strain J3-A127Tis considered to represent a novel species of the genusRhizobium, for which the nameRhizobium pseudoryzaesp. nov. is proposed. The type strain is J3-A127T( = ACCC 10380T = KCTC 23294T).
Corynebacterium nuruki sp. nov., isolated from an alcohol fermentation starter
Authors: Shin Na-Ri , Jung Mi-Ja , Kim Min-Soo , Roh Seong Woon , Nam Young-Do , Bae Jin-Woo
Published: November 2010

A novel Gram-positive, strictly aerobic and non-motile bacterial strain, S6-4T, was isolated from a Korean alcohol fermentation starter. Optimal growth occurred at 37 °C, at pH 8 and in 1 % (w/v) NaCl. The isolate was positive for oxidase and catalase. It assimilated various sugars and acids were produced from several carbohydrates. The major cell-wall sugars were galactose and arabinose. The major fatty acids of strain S6-4T were C16 : 0, C17 : 1ω9c, C18 : 1ω9c and 10-methyl C18 : 0 (tuberculostearic acid). The predominant isoprenoid quinone was menaquinone MK-9(H2) and peptidoglycan amino acids were meso-diaminopimelic acid, alanine, glycine and glutamic acid. The strain contained mycolic acids. According to phylogenetic analysis based on 16S rRNA gene sequences, strain S6-4T was most closely related to Corynebacterium variabile DSM 20132T (98.1 % similarity). The genomic DNA G+C content of strain S6-4T was 73.6 mol% and DNA–DNA hybridization values with related strains were below 33±4 %. On the basis of phenotypic, genotypic and phylogenetic data, strain S6-4T represents a novel species in the genus Corynebacterium, for which the name Corynebacterium nuruki sp. nov. is proposed; the type strain is S6-4T ( = KACC 15032T  = JCM 17162T).