bluuebunny/crossref_metadata_2025 huggingface dataset:
Marburg Virus VP40 Antagonizes Interferon Signaling in a Species-Specific Manner
Authors: Valmas Charalampos , Basler Christopher F.
Published: February 2011

Marburgviruses are zoonotic pathogens that cause lethal hemorrhagic fever in humans and nonhuman primates. However, they do not cause lethal disease in immunocompetent mice unless they are adapted to this species. The adaptation process can therefore provide insight into the specific virus-host interactions that determine virulence. In primate cells, the
Lake Victoria marburgvirus
Musoke strain (MARV) VP40 matrix protein antagonizes alpha/beta interferon (IFN-α/β) and IFN-γ signaling by inhibiting the activation of the cellular tyrosine kinase Jak1. Here, VP40 from the Ravn strain (RAVV VP40)—from a distinct Marburg virus clade—is demonstrated to also inhibit IFN signaling in human cells. However, neither MARV nor RAVV VP40 effectively inhibited IFN-signaling in mouse cells, as assessed by assays of the antiviral effects of IFN-α/β and the IFN-α/β-induced phosphorylation of Jak1, STAT1, and STAT2. In contrast, the VP40 from a mouse-adapted RAVV (maRAVV) did inhibit IFN signaling. Effective Jak1 inhibition correlated with the species from which the cells were derived and did not depend upon whether Jak1 was of human or mouse origin. Of the seven amino acid changes that accumulated in VP40 during mouse adaptation, two (V57A and T165A) are sufficient to allow efficient IFN signaling antagonism by RAVV VP40 in mouse cells. The same two changes also confer efficient IFN antagonist function upon MARV VP40 in mouse cells. The mouse-adaptive changes did not affect the budding of RAVV VP40 in mouse cells, suggesting that this second major function of VP40 did not undergo adaptation. These data identify an apparent determinant of RAVV host range and virulence and define specific genetic determinants of this function.
Immunotypes of a Quaternary Site of HIV-1 Vulnerability and Their Recognition by Antibodies
Authors: Wu Xueling , Changela Anita , O'Dell Sijy , Schmidt Stephen D. , Pancera Marie , Yang Yongping , Zhang Baoshan , Gorny Miroslaw K. , Phogat Sanjay , Robinson James E. , Stamatatos Leonidas , Zolla-Pazner Susan , Kwong Peter D. , Mascola John R.
Published: February 2011

HIV-1 is neutralized by a class of antibodies that preferentially recognize a site formed on the assembled viral spike. Such quaternary structure-specific antibodies have diverse neutralization breadths, with antibodies PG16 and PG9 able to neutralize 70 to 80% of circulating HIV-1 isolates while antibody 2909 is specific for strain SF162. We show that alteration between a rare lysine and a common N-linked glycan at position 160 of HIV-1 gp120 is primarily responsible for toggling between 2909 and PG16/PG9 neutralization sensitivity. Quaternary structure-specific antibodies appear to target antigenic variants of the same epitope, with neutralization breadth determined by the prevalence of recognized variants among circulating isolates.
FOCUSING CONTROL BASED ON SPPs-SCATTERING MODULATION
Authors: HAO FENGHUAN , WANG RUI , WANG JIA
Published: February 2011

We demonstrate a design method of focusing-control device, which consists of single metallic nano-slit surrounded with the grooves at the metal exit surface. According to the principle of the constructive interference, the grooves are positioned to scatter the SPPs to the radiation lights with desired phases. The role of SPPs in the focusing control is investigated, by applying the design method in the four different types of metal film. The simulation results indicate that the focusing effects are dependant on the types of metal film, the metal film which supports the SPPs with a long propagation length can form an apparent focus spot, and the reason is discussed.
MAPPING OF QUANTUM-HALL EDGE CHANNELS BY A DILUTION-REFRIGERATOR BASED NEAR-FIELD SCANNING OPTICAL MICROSCOPE
Authors: ITO H. , FURUYA K. , SHIBATA Y. , OOTUKA Y. , NOMURA S. , KASHIWAYA S. , YAMAGUCHI M. , TAMURA H. , AKAZAKI T.
Published: February 2011

A real-space mapping of photovoltage near the edge of the Hall-bar of a GaAs/AlGaAs single heterojunction has been obtained using a dilution-refrigerator-based near-field scanning optical microscope in magnetic fields. The optical probe-sample surface distance dependence of photovoltage is investigated. We obtain photovoltage profile in the vicinity of the edge, which reflects the local chemical potential of the two-dimensional electron gas determined by the distribution of the compressible and incompressible strips.
DEPENDENCE OF DEVICE CHARACTERISTICS OF BULK-HETEROJUNCTION ORGANIC THIN-FILM SOLAR CELLS ON CONCENTRATION OF GLYCEROL AND SORBITOL ADDITION IN PEDOT: PSS SOLUTIONS FOR FABRICATING BUFFER LAYERS
Authors: YAMAKI YUSUKE , MARUMOTO KAZUHIRO , FUJIMORI TAKUYA , MORI TATSUO
Published: February 2011

We have investigated the dependence of device characteristics of bulk-heterojunction organic thin-film solar cells on the concentration of glycerol and sorbitol addition in poly(3,4-ethylenedioxy thiophene):poly(4-styrene sulfonate) (PEDOT:PSS) solutions for fabricating buffer layers. The device structure is ITO/buffer/regioregular poly(3-hexylthiophene) (P3HT):[6,6]-phenyl C 61-butyric acid methylester (PCBM)/ Al . Glycerol addition is effective for increasing power conversion efficiency (PCE) from 1.25 to 1.41% because of the increase in short-circuit current density (J sc ) without decreasing open-circuit voltage (V oc ). On the other hand, sorbitol addition decreases PCE from 1.25 to 1.04%, owing to the decrease in V oc . This difference in V oc behavior is ascribed to different work function of PEDOT:PSS with glycerol and sorbitol treatment.
HETEROINTERFACE PROPERTIES OF NOVEL HYBRID SOLAR CELLS CONSISTING OF TRANSPARENT CONDUCTIVE POLYMERS AND III-NITRIDE SEMICONDUCTOR
Authors: MATSUKI NOBUYUKI , NAKANO YOSHITAKA , IROKAWA YOSHIHIRO , SUMIYA MASATOMO
Published: February 2011

We have investigated the heterointerface properties of recently developed hybrid solar cells comprising a Schottky contact made of transparent conductive polymer (TCP) and an underlying GaN semiconductor layer. The heterointerface capacitance induced by the depletion layer under the TCP Schottky contact showed a rapid drop at a specific frequency. An intrinsic capacitance component that was derived from the capacitance–frequency (C–f) characteristics of the heterointerface showed clear correlation with the open circuit voltage. Hence, the C–f characterization using TCP Schottky contacts is indicative of the quality of the heterointerface.
ULTRA-SHORT OPTICAL PULSE GENERATION WITH SINGLE-LAYER GRAPHENE
Authors: LEE C.-C. , SCHIBLI T. R. , ACOSTA G. , BUNCH J. S.
Published: February 2011

Pulses as short as 260 fs have been generated in a diode-pumped low-gain Er:Yb: glass laser by exploiting the nonlinear optical response of single-layer graphene. The application of this novel material to solid-state bulk lasers opens up a way to compact and robust lasers with ultrahigh repetition rates.
DIELECTRIC ANALYSIS ON OPTICAL PROPERTIES OF ZrO2 THIN FILMS DISPERSED WITH SILVER NANOPARTICLES
Authors: WAKAKI MORIAKI , YOKOYAMA EISUKE
Published: February 2011

ZrO2 thin films containing silver nanoparticles were prepared using the sol-gel method with silver volume fractions from 5.3 to 53.9 %. An amorphous phase was observed for the ZrO2 matrix and a cubic crystalline phase was identified for the Ag nanoparticles by the XRD measurement. The diameter of silver nanoparticles distributed over 25 to 75 nm was analyzed by TEM measurement. The films showed an absorption band centered at 450 nm due to the surface plasmon resonance of silver nanoparticles. The absorption peak was analyzed using the effective dielectric function modeled with both Maxwell-Garnett and Bruggeman expressions. In the small Ag volume fractions, the calculated spectra using Maxwell-Garnett theory agreed well with the measured spectra. In the large Ag volume fraction, the calculated absorption spectra using the Bruggeman model gives a relatively good fitting to the experimental spectrum.
Pnck induces ligand-independent EGFR degradation by probable perturbation of the Hsp90 chaperone complex
Authors: Deb Tushar B. , Zuo Annie H. , Wang Youhong , Barndt Robert J. , Cheema Amrita K. , Sengupta Surojeet , Coticchia Christine M. , Johnson Michael D.
Published: February 2011

We have recently described a novel role for pregnancy-upregulated nonubiquitous calmodulin kinase (Pnck) in the induction of ligand-independent epidermal growth factor receptor (EGFR) degradation (Deb TB, Coticchia CM, Barndt R, Zuo H, Dickson RB, and Johnson MD. Am J Physiol Cell Physiol 295: C365–C377, 2008). In the current communication, we explore the probable mechanism by which Pnck induces ligand-independent EGFR degradation. Pnck-induced EGFR degradation is calcium/calmodulin independent and is regulated by cell density, with the highest EGFR degradation observed at low cell density. Pnck is a novel heat shock protein 90 (Hsp90) client protein that can be coimmunoprecipitated with Hsp90. Treatment of Pnck-overexpressing cells with the pharmacologic Hsp90 inhibitor geldanamycin results in enhanced EGFR degradation, and destruction of Pnck. In cells in which Pnck is inducing EGFR degradation, we observed that Hsp90 exhibits reduced electrophoretic mobility, and through mass spectrometric analysis of immunopurified Hsp90 protein we demonstrated enhanced phosphorylation at threonine 89 and 616 (in both Hsp90-α and -β) and serine 391 (in Hsp90-α). Kinase-active Pnck protein is degraded by the proteasome, concurrent with EGFR degradation. A Pnck mutant (T171A) protein with suppressed kinase activity induced EGFR degradation to essentially the same level as wild-type (WT) Pnck, suggesting that Pnck kinase activity is not required for the induction of EGFR degradation. Although EGFR is degraded, overexpression of WT Pnck paradoxically promoted cellular proliferation, whereas cells expressing mutant Pnck (T171A) were growth inhibited. WT Pnck promoted S to G2 transition, but cells expressing the mutant exhibited higher residency time in S phase. Basal MAP kinase activity was inhibited by WT Pnck but not by mutant T171A Pnck protein. Cyclin-dependent kinase (Cdk) inhibitor p21/Cip-1/Waf-1 was transcriptionally suppressed downstream to MAP kinase inhibition by WT Pnck, but not the mutant protein. Collectively, these data suggest that 1) Pnck induces ligand-independent EGFR degradation most likely through perturbation of Hsp90 chaperone activity due to Hsp90 phosphorylation, 2) EGFR degradation is coupled to proteasomal degradation of Pnck, and 3) modulation of basal MAP kinase activity, p21/Cip-1/Waf-1 expression, and cellular growth by Pnck is independent of Pnck-induced ligand-independent EGFR degradation.
Effects of maturation and acidosis on the chaos-like complexity of the neural respiratory output in the isolated brainstem of the tadpole,Rana esculenta
Authors: Straus Christian , Samara Ziyad , Fiamma Marie-Noëlle , Bautin Nathalie , Ranohavimparany Anja , Le Coz Patrick , Golmard Jean-Louis , Darré Pierre , Zelter Marc , Poon Chi-Sang , Similowski Thomas
Published: February 2011

Human ventilation at rest exhibits mathematical chaos-like complexity that can be described as long-term unpredictability mediated (in whole or in part) by some low-dimensional nonlinear deterministic process. Although various physiological and pathological situations can affect respiratory complexity, the underlying mechanisms remain incompletely elucidated. If such chaos-like complexity is an intrinsic property of central respiratory generators, it should appear or increase when these structures mature or are stimulated. To test this hypothesis, we employed the isolated tadpole brainstem model [ Rana ( Pelophylax) esculenta] and recorded the neural respiratory output (buccal and lung rhythms) of pre- ( n = 8) and postmetamorphic tadpoles ( n = 8), at physiologic (7.8) and acidic pH (7.4). We analyzed the root mean square of the cranial nerve V or VII neurograms. Development and acidosis had no effect on buccal period. Lung frequency increased with development ( P < 0.0001). It also increased with acidosis, but in postmetamorphic tadpoles only ( P < 0.05). The noise-titration technique evidenced low-dimensional nonlinearities in all the postmetamorphic brainstems, at both pH. Chaos-like complexity, assessed through the noise limit, increased from pH 7.8 to pH 7.4 ( P < 0.01). In contrast, linear models best fitted the ventilatory rhythm in all but one of the premetamorphic preparations at pH 7.8 ( P < 0.005 vs. postmetamorphic) and in four at pH 7.4 (not significant vs. postmetamorphic). Therefore, in a lower vertebrate model, the brainstem respiratory central rhythm generator accounts for ventilatory chaos-like complexity, especially in the postmetamorphic stage and at low pH. According to the ventilatory generators homology theory, this may also be the case in mammals.
Neuronal suppressor of cytokine signaling-3 deficiency enhances hypothalamic leptin-dependent phosphatidylinositol 3-kinase signaling
Authors: Metlakunta Anantha S. , Sahu Maitrayee , Yasukawa Hideo , Dhillon Sandeep S. , Belsham Denise D. , Yoshimura Akihiko , Sahu Abhiram
Published: February 2011

Suppressor of cytokine signaling-3 (SOCS3) is thought to be involved in the development of central leptin resistance and obesity by inhibiting STAT3 pathway. Because phosphatidylinositol 3-kinase (PI3K) pathway plays an important role in transducing leptin action in the hypothalamus, we examined whether SOCS3 exerted an inhibition on this pathway. We first determined whether leptin sensitivity in the hypothalamic PI3K pathway was increased in brain-specific Socs3-deficient (NesKO) mice. In NesKO mice, hypothalamic insulin receptor substrate-1 (IRS1)-associated PI3K activity was significantly increased at 30 min and remained elevated up to 2 h after leptin intraperitoneal injection, but in wild-type (WT) littermates, the significant increase was only at 30 min. Hypothalamic p-STAT3 levels were increased up to 5 h in NesKO as opposed to 2 h in WT mice. In food-restricted WT mice with reduced body weight, leptin increased hypothalamic PI3K activity only at 30 min, and p-STAT3 levels at 30–120 min postinjection. These results suggest increased leptin sensitivity in both PI3K and STAT3 pathways in the hypothalamus of NesKO mice, which was not due to a lean phenotype. In the next experiment with a clonal hypothalamic neuronal cell line expressing proopiomelanocortin, we observed that whereas leptin significantly increased IRS1-associated PI3K activity and p-JAK2 levels in cells transfected with control vector, it failed to do so in SOCS3-overexpressed cells. Altogether, these results imply a SOCS3 inhibition of the PI3K pathway of leptin signaling in the hypothalamus, which may be one of the mechanisms behind the development of central leptin resistance and obesity.
Cannabinoid receptor 1 mediates high glucose-induced apoptosis via endoplasmic reticulum stress in primary cultured rat mesangial cells
Authors: Lim Jae Cheong , Lim Seul Ki , Park Min Jung , Kim Gye Yeop , Han Ho Jae , Park Soo Hyun
Published: February 2011

The endocannabinoid system in animals and humans is involved in the onset of diverse diseases, including obesity and diabetic nephropathy, which is a major end-stage renal disease characterized by high glucose (HG)-induced apoptosis of mesangial cells. Endocannabinoids induce physiological and behavioral effects by activating two specific receptors, cannabinoid receptor 1 (CB1R) and cannabinoid receptor 2 (CB2R). However, the pathophysiology of CB1R in diabetic nephropathy has not been elucidated. We investigated the effects of HG on CB1R expression and its signaling pathways in primary cultured rat mesangial cells. HG significantly increased CB1R mRNA and protein levels in a time-dependent manner and induced CB1R internalization. NF-κB and cPLA2were involved in the HG-induced increase in CB1R levels. Using a CB1R antagonist (AM251) and CB1siRNA transfection, we showed that HG-induced CB1R is linked to apoptosis. Specifically, HG inhibited the expression of GRP78, but induced increases in endoplasmic reticulum (ER) stress proteins, including phosphorylated (p)-protein kinase-like ER-associated kinase, p-eukaryotic initiation factor 2α, p-activating transcription factor-4, and C/EBP homologous protein. In addition, HG increased the Bax/Bcl-2 ratio and increased the amounts of cleaved poly(ADP-ribose) polymerase and caspase-3. These apoptotic effects were prevented by AM251 and by the downregulation of CB1R expression by small interfering RNA. We propose a mechanism by which blockade of CB1R attenuates HG-induced apoptosis in rat mesangial cells. Our findings suggest that blockade of CB1R may be a potential therapy in diabetic nephropathy.
Using computer simulations to determine the limitations of dynamic clamp stimuli applied at the soma in mimicking distributed conductance sources
Authors: Lin Risa J. , Jaeger Dieter
Published: February 2011

In previous studies we used the technique of dynamic clamp to study how temporal modulation of inhibitory and excitatory inputs control the frequency and precise timing of spikes in neurons of the deep cerebellar nuclei (DCN). Although this technique is now widely used, it is limited to interpreting conductance inputs as being location independent; i.e., all inputs that are biologically distributed across the dendritic tree are applied to the soma. We used computer simulations of a morphologically realistic model of DCN neurons to compare the effects of purely somatic vs. distributed dendritic inputs in this cell type. We applied the same conductance stimuli used in our published experiments to the model. To simulate variability in neuronal responses to repeated stimuli, we added a somatic white current noise to reproduce subthreshold fluctuations in the membrane potential. We were able to replicate our dynamic clamp results with respect to spike rates and spike precision for different patterns of background synaptic activity. We found only minor differences in the spike pattern generation between focal or distributed input in this cell type even when strong inhibitory or excitatory bursts were applied. However, the location dependence of dynamic clamp stimuli is likely to be different for each cell type examined, and the simulation approach developed in the present study will allow a careful assessment of location dependence in all cell types.
The Effect of a Hyperdynamic Circulation on Tissue Doppler Values: A Simulation in Young Adults during Exercise
Authors: Royse Colin F. , Ruizhi Ni , Huynh Andrew L. , Royse Alistair G.
Published: February 2011

Left ventricular tissue Doppler imaging (TDI) velocities are used to monitor systolic and diastolic function, but it is not known how these may change in a hyperdynamic circulation, as often occurs in anesthesia and critical care medicine. Twenty-six healthy young volunteers were recruited and left ventricular systolic and diastolic tissue Doppler velocities measured at rest, light exercise, strenuous exercise, and recovery (10 minutes after exercise). At rest, TDI velocities significantly decreased from base to apex (). Within basal, mid, and apical sections, systolic and diastolic peak velocities differed between segments (), except for systolic middle () and late diastolic apical velocities (). Basal septal velocities differed from basal lateral, for systolic () but not diastolic peak values. Inferobasal radial values differed from basal lateral values for both systolic and diastolic velocities (). Both systolic and diastolic TDI velocities increased significantly in all segments in a proportionate manner with a hyperdynamic circulation.
Hybrid Proximal‐Point Methods for Zeros of Maximal Monotone Operators, Variational Inequalities and Mixed Equilibrium Problems
Authors: Wattanawitoon Kriengsak , Kumam Poom
Published: February 2011

We prove strong and weak convergence theorems of modified hybrid proximal‐point
algorithms for finding a common element of the zero point of a maximal monotone operator, the set
of solutions of equilibrium problems, and the set of solution of the variational inequality operators of
an inverse strongly monotone in a Banach space under different conditions. Moreover, applications to
complementarity problems are given. Our results modify and improve the recently announced ones by
Li and Song (2008) and many authors.
The Dynamics of Glutathione Species and Ophthalmate Concentrations in Plasma from the VX2 Rabbit Model of Secondary Liver Tumors
Authors: Abbas R. , Kombu R. S. , Ibarra R. A. , Goyal K. K. , Brunengraber H. , Sanabria J. R.
Published: February 2011

Purpose. Available tumor markers have low sensitivity/specificity for the diagnosis of liver tumors. The present study was designed to evaluate the oxidoreductive status of the liver as surrogates of tumor subsistence and growth.Methods. Glutathione species (GSH:GSSG), ophthalmate (OA) concentrations, and their turnover were measured in plasma of rabbits (n=6) in their healthy state and in the state of tumor growth after implantation of the VX2 carcinoma in their liver. Tumors were allowed to grow for a period of 14 days when rabbits were sacrificed. Livers were removed and cysteine concentration was measured in liver tissue.Results. Tumor growth was found in 100% of the rabbits. Concentration and labeling of GSH/GSSG were similar in experimental animals before and after tumor implantation and to sham animals. In contrast, OA concentration increased significantly in experimental animals after tumor implantation when compared to same animals prior to tumor implantation and to sham animals (P<.05). The concentration of cysteine, a precursor of GSH, was found to be significantly lower in the liver tissue adjacent to the tumor (P<.05).Conclusion. Disturbances in the oxidoreductive state of livers appear to be a surrogate of early tumor growth.
Equilibrium Conditions at a Solid‐Solid Interface
Authors: Plohr JeeYeon N.
Published: February 2011

We derive the thermodynamic conditions necessary for two elastoplastic solid phases
to coexist in equilibrium. Beyond temperature, velocity, and traction continuity, these conditions
require continuity of a generalization of the specific Gibbs free energy. We express this quantity in
the Eulerian frame as well as the Lagrangian frame. We also show that two approaches in deriving
the equilibrium conditions, one on the continuum level and the other on the atomistic scale, yield
the same results. Finally, we discuss two possible interpretations for the Gibbs free energy, which
lead to distinct generalizations, except in the case of inviscid fluids, where they coincide.
The Progression from MGUS to Smoldering Myeloma and Eventually to Multiple Myeloma Involves a Clonal Expansion of Genetically Abnormal Plasma Cells
Authors: López-Corral Lucía , Gutiérrez Norma C. , Vidriales Maria Belén , Mateos Maria Victoria , Rasillo Ana , García-Sanz Ramón , Paiva Bruno , San Miguel Jesús F.
Published: February 2011

Purpose: Genetic aberrations detected in multiple myeloma (MM) have also been reported in the premalignant conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM). Our aim was to investigate in depth the level of clonal heterogeneity of recurrent genetic abnormalities in these conditions.

Experimental Design: Immunoglobulin heavy chain (IGH) translocations, 13q14 and 17p13 deletions, and 1q21 gains using FISH were evaluated in 90 MGUS, 102 high-risk SMM, and 373 MM. To this end, we not only purified plasma cells (PC) for the FISH analysis (purity > 90%), but subsequently, we examined the correlation between the proportion of PC with cytogenetic changes and the number of clonal PC present in the same sample, as measured by multiparametric flow cytometry.

Results: We observed a significant difference between the proportion of clonal PC with specific genetic abnormalities in MGUS compared with SMM and in SMM compared with MM. Thus, the median proportion of PC with IGH translocations globally considered, t(11;14) and 13q deletions was significantly lower in MGUS than in SMM, and in SMM than in MM [IGH translocations: 34% vs. 57% vs. 76%; t(11;14): 38% vs. 61% vs. 81%; and 13q deletion: 37% vs. 61% vs. 74% in MGUS, SMM, and MM, respectively]. For t(4;14), the difference was significant in the comparison between MGUS/SMM and MM and for 1q between MGUS and SMM/MM.

Conclusions: This study demonstrates that the progression from MGUS to SMM, and eventually to MM, involves a clonal expansion of genetically abnormal PC. Clin Cancer Res; 17(7); 1692–700. ©2011 AACR.
Cytological Characteristics of Pulmonary Pleomorphic and Giant Cell Carcinomas
Authors: Hiroshima Kenzo , Dosaka-Akita Hirotoshi , Usuda Katsuo , Ogura Shigeaki , Kusunoki Yoko , Kodama Tetsuro , Saito Yasuki , Sato Masami , Tagawa Yutaka , Baba Masayuki , Hirano Takashi , Horai Takeshi , Matsuno Yoshihiro
Published: February 2011

Objective: To establish cytological features of pulmonary pleomorphic carcinoma (PC) or giant cell carcinoma (GC), we evaluated the cytological characteristics of these tumors using a multidisciplinary approach. Study Design: Samples from 13 surgically resected and histologically confirmed PC or GC patients were collected from our institutes. Eight cases without prior chemotherapy before surgery were selected, and cytological features were analyzed. Results: The background contained numerous lymphocytes and neutrophils. The tumor cells were arranged in flat loose clusters, but some were in fascicles. The shape of the tumor cell was spindle or pleomorphic, and the sizes of the tumor cells varied by more than 5-fold. The tumor cells had an abundant, thick and well-demarcated cytoplasm. The location of the nucleus was centrifugal, and the nucleus was oval or irregularly shaped. Multinucleated giant cells were frequently observed. The size of the nucleus was more than 5 times that of normal lymphocytes, and its size also varied by more than 5-fold. The nuclear membrane was thin, and nuclear chromatin was coarsely granular, while the nucleolus was single and round. Conclusion: PC or GC has characteristic cytological features, however, spindle cells tended to be hardly observed in cytological specimens in some cases.
The Efficacy of Fine Needle Aspiration Cytology in the Preoperative Evaluation of Parakeratotic Odontogenic Keratocysts
Authors: Dereci Ömür , Öztürk Adnan , Günhan Ömer
Published: February 2011

Objective: To assess the performance of fine needle aspiration cytology (FNAC) in preoperative diagnosis of parakeratotic odontogenic keratocyst. Study Design: Twenty-three cases of odontogenic keratocyst which were evaluated with FNAC prior to enucleation were included in the study. Aspiration smears were stained with Papanicolaou and hematoxylin-eosin stain. Results obtained from FNAC were compared with histopathologic data obtained from the excisional biopsies. Results: Keratotic cell clusters with or without inflammation were identified in all the cytologic smears. No dysplastic changes were seen. The evaluation of the excisional biopsies revealed cystic epithelium which is characterized by palisaded basal cells, a corrugated surface with a lumen containing keratin debris. Two of the cases which revealed satellite cysts were not associated with Gorlin-Goltz syndrome due to the absence of other findings. Conclusion: Parakeratotic odontogenic keratocyst can be substantially diagnosed preoperatively utilizing FNAC with a careful evaluation.
Discordance between Cytology and Biopsy Histology of the Cervix: What to Consider and What to Do
Authors: Anschau Fernando , Guimarães Gonçalves Manoel Afonso
Published: February 2011

Objective: Since cytology is the examination utilized for the screening of cervical cancer, it is important to determine its correlation with histologic examination, the gold standard in the diagnosis of cervical disease. Study Design: A retrospective evaluation was made of 431 patients who presented with colposcopic indication for cervical biopsy between 2003 and 2007. Results: In 90.8% (289/318) of the patients, cytology showing cervical intraepithelial neoplasia (CIN) was confirmed as CIN in the histology of the cervix, while 62.8% (71/113) of patients with normal cytology had a confirmation of a normal histology (ĸ = 0.558). Conclusion: Cytology demonstrated a sensitivity and specificity of 87.3 and 71.0%, respectively. The agreement between cervical cytology and histology, considering the presence of CIN, was moderate. Correlations between accuracy and errors of cytology are discussed with therapeutic emphasis.
Repeat Processing of Residual ThinPrep Pap Tests: Sampling of the Vial May Not Be Invariably Homogeneous
Authors: Grapsa D. , Ioakim-Liossi A. , Stergiou E. , Petrakakou E. , Nicolopoulou-Stamati P. , Patsouris E. , Athanassiadou P.
Published: February 2011

Objective: To re-evaluate the reproducibility of additional slides prepared from residual cervical ThinPrep (TP) samples. Study Design: Sixty paired specimens (conventional smears and direct-to-vial TP) were studied. Up to 10 additional slides were prepared from each TP vial. All slides were reviewed for adequacy of material, presence of abnormal cells and presence of normal flora or other pathogens. The additional TP slides were further evaluated for the presence of diagnostic elements which were not found on the conventional smear and primary TP slide. Results: Abnormal cells found on the primary TP slide were also identified on all additional slides in 48/50 cases (96%) with squamous cell lesions. The distribution of material on TP slides was evaluated as homogenous in 51 cases (85%) and as non-homogenous in 9 (15%). Using the primary slides (conventional smear and TP) as a reference, additional diagnostic cells upgrading the cytologic diagnosis were found on the repeat slides in 7 cases (11.7%) and fungi consistent with Candida in 3 (5%). Conclusion: Repeat processing of residual cervical TP samples may not be an invariably reproducible procedure and the first slide may not be necessarily representative of the specimen as a whole. Nevertheless, both primary and repeat TP slides seem to be extremely effective in detecting a lesion (regardless of grade) in abnormal cases. The exact impact of non-homogeneous sampling of the vial on the diagnostic accuracy of the TP method should be further investigated.
Agreement between Methods for Diagnosing HPV-Induced Anal Lesions in Women with Cervical Neoplasia
Authors: Heráclio Sandra de Andrade , Souza Alex Sandro Rolland de , Pinto Fátima Regina Gomes , Amorim Melania Maria Ramos , Oliveira Micheline de Lucena , Souza Paulo Roberto Eleutério de
Published: February 2011

Objective: To evaluate agreement between 3 methods for screening anal intraepithelial lesions: anal cytology, anoscopy and human papillomavirus (HPV) detection by PCR. Study Design: This prospective, cross-sectional study screened 324 women with cervical neoplasia for anal neoplasia. Agreement between methods was calculated using the ĸ coefficient. Results: Of 324 anal cytologies performed, 31.5% (n = 102) were found to be abnormal: low-grade anal lesions were detected in 19.1% (n = 62) of cases, high-grade lesions in 3.1% (n = 10) and atypical squamous cells of undetermined significance in 9.3% (n = 30). With respect to the biopsies, 25.7% (n = 20) were positive, consisting of 7 cases of HPV infection, 5 anal intraepithelial neoplasia (AIN) grade 1, 6 AIN grade 2, and 2 AIN grade 3. Twenty-one samples (6.5%) were inadequate for HPV analysis. Of the 303 adequate samples, 84.2% (n = 255) tested positive for HPV. Agreement between cytology and anoscopy was fair (ĸ = 0.31). Agreement between PCR for HPV and cytology was slight (ĸ = 0.08) and no agreement was found between PCR for HPV and anoscopy (ĸ = 0.00). Conclusion: Agreement between the different methods of diagnosing HPV-induced anal lesions is slight to fair; however, anal cytology permits identification of cases in which lesions are present, allowing them to be referred for anoscopy and biopsy.
Gorilla and Orangutan Brains Conform to the Primate Cellular Scaling Rules: Implications for Human Evolution
Authors: Herculano-Houzel Suzana , Kaas Jon H.
Published: February 2011

Gorillas and orangutans are primates at least as large as humans, but their brains amount to about one third of the size of the human brain. This discrepancy has been used as evidence that the human brain is about 3 times larger than it should be for a primate species of its body size. In contrast to the view that the human brain is special in its size, we have suggested that it is the great apes that might have evolved bodies that are unusually large, on the basis of our recent finding that the cellular composition of the human brain matches that expected for a primate brain of its size, making the human brain a linearly scaled-up primate brain in its number of cells. To investigate whether the brain of great apes also conforms to the primate cellular scaling rules identified previously, we determine the numbers of neuronal and other cells that compose the orangutan and gorilla cerebella, use these numbers to calculate the size of the brain and of the cerebral cortex expected for these species, and show that these match the sizes described in the literature. Our results suggest that the brains of great apes also scale linearly in their numbers of neurons like other primate brains, including humans. The conformity of great apes and humans to the linear cellular scaling rules that apply to other primates that diverged earlier in primate evolution indicates that prehistoric Homo species as well as other hominins must have had brains that conformed to the same scaling rules, irrespective of their body size. We then used those scaling rules and published estimated brain volumes for various hominin species to predict the numbers of neurons that composed their brains. We predict that Homo heidelbergensis and Homo neanderthalensis had brains with approximately 80 billion neurons, within the range of variation found in modern Homo sapiens. We propose that while the cellular scaling rules that apply to the primate brain have remained stable in hominin evolution (since they apply to simians, great apes and modern humans alike), the Colobinae and Pongidae lineages favored marked increases in body size rather than brain size from the common ancestor with the Homo lineage, while the Homo lineage seems to have favored a large brain instead of a large body, possibly due to the metabolic limitations to having both.
Papillary Thyroid Carcinoma: An Easy Fine Needle Aspiration Biopsy Diagnosis?
Authors: Dušková Jaroslava , Tretiník Pavel
Published: February 2011

Objective: To analyze reasons for unclear or missed diagnoses in fine needle aspiration biopsy (FNAB) of papillary thyroid carcinoma (PTC). Study Design: Among 35,000 thyroid FNAB diagnoses made during 1989–2009, 135 PTC FNAB diagnoses were divided into 3 categories by expressed probability. A group of 10 cases with histologic PTC diagnosis not mentioned in our previous FNAB sample was also analyzed. Results: Of the 75 PTC FNAB diagnoses, 71 were confirmed; the remaining 4 were hyperplastic goiters. In the group of 45 cases with PTC, in which FNAB diagnosis was the next most probable differential diagnosis, 23 were confirmed. In the group of 15 cases, in which the PTC FNAB diagnosis was considered the less probable differential diagnosis, 3 PTCs were found. The other cases in both groups were usually histologically diagnosed as lymphocytic thyroiditis. In the group of 10 cases with histologic PTC diagnosis, 6 were evaluated as suspicious for (other) malignancy, 3 were diagnosed as hyperplasia with oncocytes and 1 as low cellularity; sample reaspiration was recommended. Conclusion: FNAB diagnosis of PTC is not always possible, with success rate influenced by lesion type and size, accompanying diagnoses, representativeness of cytology sample and experience of the cytopathologist.
Reflex High Risk HPV Testing in Atypical Squamous Cells, Cannot Exclude High Grade Intraepithelial Lesion: A Large Institution’s Experience with the Significance of This Often Ordered Test
Authors: Galliano Gretchen E. , Moatamed Neda A. , Lee Susanna , Salami Nikki , Apple Sophia K.
Published: February 2011

Objective: Cervical cytology specimens diagnosed with ASC-H consist of squamous cells with equivocal cytology for high-grade dysplastic lesions. We reviewed our cases of ASC-H with reflex HPV testing to evaluate this patient population. Study Design: We retrospectively identified patients with ASC-H in Pap smears over a 3-year period. Reflex high-risk (HR) HPV DNA testing was performed by request. Follow-up results and smear characteristics were evaluated. Results: HR HPV DNA testing was positive in 60 of 82 (73%) cases tested. The risk of high grade cervical intraepithelial neoplasia (CIN) on follow-up after a positive HPV test with ASC-H is 68.3%. The risk of high grade CIN after a negative HPV test with ASC-H is 58.3%. High grade CIN lesions were found in 20% HPV-negative patients. The cellularity of atypical cells in Pap smears was not helpful in analyzing differences in HPV-positive and HPV-negative ASC-H. Conclusion: The risk of high grade dysplasia after an ASC-H Pap diagnosis was high irrespective of the reflex HPV test results in our patient population. Therefore, our findings support the continued utilization of the current ASCCP guidelines of colposcopy and caution when utilizing reflex HR HPV testing in the colposcopy triage ASC-H patients.
Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis
Authors: Sumegi Janos , Barnes Michael G. , Nestheide Shawnagay V. , Molleran-Lee Susan , Villanueva Joyce , Zhang Kejian , Risma Kimberly A. , Grom Alexei A. , Filipovich Alexandra H.
Published: February 2011

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, genetically heterogeneous autosomal recessive immune disorder that results when the critical regulatory pathways that mediate immune defense mechanisms and the natural termination of immune/inflammatory responses are disrupted or overwhelmed. To advance the understanding of FHL, we performed gene expression profiling of peripheral blood mononuclear cells from 11 children with untreated FHL. Total RNA was isolated and gene expression levels were determined using microarray analysis. Comparisons between patients with FHL and normal pediatric controls (n = 30) identified 915 down-regulated and 550 up-regulated genes with more than or equal to 2.5-fold difference in expression (P ≤ .05). The expression of genes associated with natural killer cell functions, innate and adaptive immune responses, proapoptotic proteins, and B- and T-cell differentiation were down-regulated in patients with FHL. Genes associated with the canonical pathways of interleukin-6 (IL-6), IL-10 IL-1, IL-8, TREM1, LXR/RXR activation, and PPAR signaling and genes encoding of antiapoptotic proteins were overexpressed in patients with FHL. This first study of genome-wide expression profiling in children with FHL demonstrates the complexity of gene expression patterns, which underlie the immunobiology of FHL.
Myosin-cross-reactive antigen (MCRA) protein from Bifidobacterium breve is a FAD-dependent fatty acid hydratase which has a function in stress protection
Authors: Rosberg-Cody Eva , Liavonchanka Alena , Göbel Cornelia , Ross R Paul , O'Sullivan Orla , Fitzgerald Gerald F , Feussner Ivo , Stanton Catherine
Published: February 2011

Background

The aim of this study was to determine the catalytic activity and physiological role of myosin-cross-reactive antigen (MCRA) from Bifidobacterium breve NCIMB 702258. MCRA from B. breve NCIMB 702258 was cloned, sequenced and expressed in heterologous hosts (Lactococcus and Corynebacterium) and the recombinant proteins assessed for enzymatic activity against fatty acid substrates.

Results

MCRA catalysed the conversion of palmitoleic, oleic and linoleic acids to the corresponding 10-hydroxy fatty acids, but shorter chain fatty acids were not used as substrates, while the presence of trans-double bonds and double bonds beyond the position C12 abolished hydratase activity. The hydroxy fatty acids produced were not metabolised further. We also found that heterologous Lactococcus and Corynebacterium expressing MCRA accumulated increasing amounts of 10-HOA and 10-HOE in the culture medium. Furthermore, the heterologous cultures exhibited less sensitivity to heat and solvent stresses compared to corresponding controls.

Conclusions

MCRA protein in B. breve can be classified as a FAD-containing double bond hydratase, within the carbon-oxygen lyase family, which may be catalysing the first step in conjugated linoleic acid (CLA) production, and this protein has an additional function in bacterial stress protection.
The Complete Mitochondrial Genome of an 11,450-year-old Aurochsen (Bos primigenius) from Central Italy
Authors: Lari Martina , Rizzi Ermanno , Mona Stefano , Corti Giorgio , Catalano Giulio , Chen Kefei , Vernesi Cristiano , Larson Greger , Boscato Paolo , De Bellis Gianluca , Cooper Alan , Caramelli David , Bertorelle Giorgio
Published: February 2011

Background

Bos primigenius, the aurochs, is the wild ancestor of modern cattle breeds and was formerly widespread across Eurasia and northern Africa. After a progressive decline, the species became extinct in 1627. The origin of modern taurine breeds in Europe is debated. Archaeological and early genetic evidence point to a single Near Eastern origin and a subsequent spread during the diffusion of herding and farming. More recent genetic data are instead compatible with local domestication events or at least some level of local introgression from the aurochs. Here we present the analysis of the complete mitochondrial genome of a pre-Neolithic Italian aurochs.

Results

In this study, we applied a combined strategy employing both multiplex PCR amplifications and 454 pyrosequencing technology to sequence the complete mitochondrial genome of an 11,450-year-old aurochs specimen from Central Italy. Phylogenetic analysis of the aurochs mtDNA genome supports the conclusions from previous studies of short mtDNA fragments - namely that Italian aurochsen were genetically very similar to modern cattle breeds, but highly divergent from the North-Central European aurochsen.

Conclusions

Complete mitochondrial genome sequences are now available for several modern cattle and two pre-Neolithic mtDNA genomes from very different geographic areas. These data suggest that previously identified sub-groups within the widespread modern cattle mitochondrial T clade are polyphyletic, and they support the hypothesis that modern European breeds have multiple geographic origins.
The living microarray: a high-throughput platform for measuring transcription dynamics in single cells
Authors: Rajan Saravanan , Djambazian Haig , Dang Huan Chu Pham , Sladek Rob , Hudson Thomas J
Published: February 2011

Background

Current methods of measuring transcription in high-throughput have led to significant improvements in our knowledge of transcriptional regulation and Systems Biology. However, endpoint measurements obtained from methods that pool populations of cells are not amenable to studying time-dependent processes that show cell heterogeneity.

Results

Here we describe a high-throughput platform for measuring transcriptional changes in real time in single mammalian cells. By using reverse transfection microarrays we are able to transfect fluorescent reporter plasmids into 600 independent clusters of cells plated on a single microscope slide and image these clusters every 20 minutes. We use a fast-maturing, destabilized and nuclear-localized reporter that is suitable for automated segmentation to accurately measure promoter activity in single cells. We tested this platform with synthetic drug-inducible promoters that showed robust induction over 24 hours. Automated segmentation and tracking of over 11 million cell images during this period revealed that cells display substantial heterogeneity in their responses to the applied treatment, including a large proportion of transfected cells that do not respond at all.

Conclusions

The results from our single-cell analysis suggest that methods that measure average cellular responses, such as DNA microarrays, RT-PCR and chromatin immunoprecipitation, characterize a response skewed by a subset of cells in the population. Our method is scalable and readily adaptable to studying complex systems, including cell proliferation, differentiation and apoptosis.
The maternal and early embryonic transcriptome of the milkweed bug Oncopeltus fasciatus
Authors: Ewen-Campen Ben , Shaner Nathan , Panfilio Kristen A , Suzuki Yuichiro , Roth Siegfried , Extavour Cassandra G
Published: February 2011

Background

Most evolutionary developmental biology ("evo-devo") studies of emerging model organisms focus on small numbers of candidate genes cloned individually using degenerate PCR. However, newly available sequencing technologies such as 454 pyrosequencing have recently begun to allow for massive gene discovery in animals without sequenced genomes. Within insects, although large volumes of sequence data are available for holometabolous insects, developmental studies of basally branching hemimetabolous insects typically suffer from low rates of gene discovery.

Results

We used 454 pyrosequencing to sequence over 500 million bases of cDNA from the ovaries and embryos of the milkweed bug Oncopeltus fasciatus, which lacks a sequenced genome. This indirectly developing insect occupies an important phylogenetic position, branching basal to Diptera (including fruit flies) and Hymenoptera (including honeybees), and is an experimentally tractable model for short-germ development. 2,087,410 reads from both normalized and non-normalized cDNA assembled into 21,097 sequences (isotigs) and 112,531 singletons. The assembled sequences fell into 16,617 unique gene models, and included predictions of splicing isoforms, which we examined experimentally. Discovery of new genes plateaued after assembly of ~1.5 million reads, suggesting that we have sequenced nearly all transcripts present in the cDNA sampled. Many transcripts have been assembled at close to full length, and there is a net gain of sequence data for over half of the pre-existing O. fasciatus accessions for developmental genes in GenBank. We identified 10,775 unique genes, including members of all major conserved metazoan signaling pathways and genes involved in several major categories of early developmental processes. We also specifically address the effects of cDNA normalization on gene discovery in de novo transcriptome analyses.

Conclusions

Our sequencing, assembly and annotation framework provide a simple and effective way to achieve high-throughput gene discovery for organisms lacking a sequenced genome. These data will have applications to the study of the evolution of arthropod genes and genetic pathways, and to the wider evolution, development and genomics communities working with emerging model organisms.

[The sequence data from this study have been submitted to GenBank under study accession number SRP002610 (http://www.ncbi.nlm.nih.gov/sra?term=SRP002610). Custom scripts generated are available at http://www.extavourlab.com/protocols/index.html. Seven Additional files are available.]