bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between the Genotypes of
Staphylococcus aureus
Bloodstream Isolates and Clinical Characteristics and Outcomes of Bacteremic Patients
Authors: Lalani Tahaniyat , Federspiel Jerome J. , Boucher Helen W. , Rude Thomas H. , Bae In-Gyu , Rybak Michael J. , Tonthat Giang T. , Corey G. Ralph , Stryjewski Martin E. , Sakoulas George , Chu Vivian H. , Alder Jeff , Steenbergen Judith N. , Luperchio Steven A. , Campion Marilyn , Woods Christopher W. , Fowler Vance G.
Published: July 2008

We investigated associations between the genotypic and phenotypic features of
Staphylococcus aureus
bloodstream isolates and the clinical characteristics of bacteremic patients enrolled in a phase III trial of
S. aureus
bacteremia and endocarditis. Isolates underwent pulsed-field gel electrophoresis, PCR for 33 putative virulence genes, and screening for heteroresistant glycopeptide intermediate
S. aureus
(hGISA). A total of 230 isolates (141 methicillin-susceptible
S. aureus
and 89 methicillin-resistant
S. aureus
[MRSA]) were analyzed. North American and European
S. aureus
isolates differed in their genotypic characteristics. Overall, 26% of the MRSA bloodstream isolates were USA 300 strains. Patients with USA 300 MRSA bacteremia were more likely to be injection drug users (61% versus 15%;
P
< 0.001), to have right-sided endocarditis (39% versus 9%;
P
= 0.002), and to be cured of right-sided endocarditis (100% versus 33%;
P
= 0.01) than patients with non-USA 300 MRSA bacteremia. Patients with persistent bacteremia were less likely to be infected with Panton-Valentine leukocidin gene (
pvl
)-constitutive MRSA (19% versus 56%;
P
= 0.005). Although 7 of 89 MRSA isolates (8%) exhibited the hGISA phenotype, no association with persistent bacteremia, daptomycin resistance, or bacterial genotype was observed. This study suggests that the virulence gene profiles of
S. aureus
bloodstream isolates from North America and Europe differ significantly. In this study of bloodstream isolates collected as part of a multinational randomized clinical trial, USA 300 and
pvl
-constitutive MRSA strains were associated with better clinical outcomes.
Clinical Impact of
Mycobacterium tuberculosis
W-Beijing Genotype Strain Infection on Aged Patients in Taiwan
Authors: Feng Jia-Yih , Su Wei-Juin , Tsai Cheng-Chien , Chang Shi-Chuan
Published: July 2008

The impact of W-Beijing genotype
Mycobacterium tuberculosis
on treatment outcome was evaluated in 249 newly diagnosed tuberculosis patients. No significant difference in the treatment outcome was found between the W-Beijing and non-W-Beijing groups. However, a poor outcome was more common in the elderly patients (≥65 years) infected with the W-Beijing strain.
Human T-Cell Leukemia Virus Type 1 Infection Leads to Arrest in the G
1
Phase of the Cell Cycle
Authors: Liu Meihong , Yang Liangpeng , Zhang Ling , Liu Baoying , Merling Randall , Xia Zheng , Giam Chou-Zen
Published: July 2008

Infection by the human T-cell leukemia virus type 1 (HTLV-1) is thought to cause dysregulated T-cell proliferation, which in turn leads to adult T-cell leukemia/lymphoma. Early cellular changes after HTLV-1 infection have been difficult to study due to the poorly infectious nature of HTLV-1 and the need for cell-to-cell contact for HTLV-1 transmission. Using a series of reporter systems, we show that HeLa cells cease proliferation within one or two division cycles after infection by HTLV-1 or transduction of the HTLV-1
tax
gene. HTLV-1-infected HeLa cells, like their
tax
-transduced counterparts, expressed high levels of p21

CIP1
/
WAF1

and p27

KIP1

, developed mitotic abnormalities, and became arrested in G
1
in senescence. In contrast, cells of a human osteosarcoma lineage (HOS) continued to divide after HTLV-1 infection or Tax expression, albeit at a reduced growth rate and with mitotic aberrations. Unique to HOS cells is the dramatic reduction of p21

CIP1
/
WAF1

and p27

KIP1

expression, which is in part associated with the constitutive activation of the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) pathway. The loss of p21

CIP1
/
WAF1

and p27

KIP1

in HOS cells apparently allows HTLV-1- and Tax-induced G
1
arrest to be bypassed. Finally, HTLV-1 infection and Tax expression also cause human SupT1 T cells to arrest in the G
1
phase of the cell cycle. These results suggest that productive HTLV-1 infection ordinarily leads to Tax-mediated G
1
arrest. However, T cells containing somatic mutations that inactivate p21

CIP1
/
WAF1

and p27

KIP1

may continue to proliferate after HTLV-1 infection and Tax expression. These infected cells can expand clonally, accumulate additional chromosomal abnormalities, and progress to cancer.
Human Immunodeficiency Virus Type 1 Vif Induces Cell Cycle Delay via Recruitment of the Same E3 Ubiquitin Ligase Complex That Targets APOBEC3 Proteins for Degradation
Authors: DeHart Jason L. , Bosque Alberto , Harris Reuben S. , Planelles Vicente
Published: July 2008

Human immunodeficiency virus type 1 (HIV-1) Vif recruits a Cullin 5 ubiquitin ligase that targets APOBEC3 proteins for degradation. Recently, Vif has also been shown to induce cell cycle disturbance in G2. We show that in contrast to the expression of Vpr, the expression of Vif does not preclude cell division, and therefore, Vif causes delay and not arrest in G2. We also demonstrate that the interaction of Vif with the ubiquitin ligase is required for cell cycle disruption, as was previously shown for HIV-1 Vpr. The presence of APOBEC3 D/E, F, and G had no influence on Vif-induced alteration of the cell cycle. We conclude that cell cycle delay by Vif is a result of ubiquitination and degradation of a cellular protein that is different from the known APOBEC3 family members.
Temporal and Spatial Dynamics of Human Immunodeficiency Virus Type 1 Circulating Recombinant Forms 08_BC and 07_BC in Asia
Authors: Tee Kok Keng , Pybus Oliver G. , Li Xiao-Jie , Han Xiaoxu , Shang Hong , Kamarulzaman Adeeba , Takebe Yutaka
Published: July 2008

Human immunodeficiency virus type 1 (HIV-1) CRF08_BC and CRF07_BC are two major recombinants descended from subtypes B′ and C. Despite their massive epidemic impact in China, their migration patterns and divergence times remain unknown. Phylogenetic and population genetic analyses were performed on 228 HIV-1 sequences representing CRF08_BC, CRF07_BC, and subtype C strains from different locations across China, India, and Myanmar. Genome-specific rates of evolution and divergence times were estimated using a Bayesian Markov chain Monte Carlo framework under various evolutionary models. CRF08_BC originated in 1990.3 (95% credible region [CR], 1988.6 to 1991.9) in Yunnan province before spreading to Guangxi (south) and Liaoning (northeast) around 1995. Inside Guangxi region, the eastward expansion of CRF08_BC continued from Baise city (west) to Binyang (central) between 1997 and 1998 and later spread into Pingxiang around 1999 in the south, mainly through injecting drug users. Additionally, CRF07_BC diverged from its common ancestor in 1993.3 (95% CR, 1991.2 to 1995.2) before crossing the border into southern Taiwan in late 1990s. Phylogenetic analysis indicates that both CRF08_BC and CRF07_BC can trace their origins to Yunnan. The parental Indian subtype C lineage likely entered China around 1981.2 (95% CR, 1976.7 to 1985.9). Using a multiple unlinked locus model, we also showed that the dates of divergence calculated in this study may not be significantly affected by intrasubtype recombination among different lineages. This is the first phylodynamic study depicting the spatiotemporal dynamics of HIV/AIDS in East Asia.
Changes in Population Dynamics during Long-Term Evolution of Sabin Type 1 Poliovirus in an Immunodeficient Patient
Authors: Odoom John K. , Yunus Zaira , Dunn Glynis , Minor Philip D. , Martín Javier
Published: July 2008

The evolution of the Sabin strain of type 1 poliovirus in a hypogammaglobulinemia patient for a period of 649 days is described. Twelve poliovirus isolates from sequential stool samples encompassing days 21 to 649 after vaccination with Sabin 1 were characterized in terms of their antigenic properties, virulence in transgenic mice, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin 1 strain. Poliovirus isolates from the immunodeficient patient evolved gradually toward non-temperature-sensitive and neurovirulent phenotypes, accumulating mutations at key nucleotide positions that correlated with the observed reversion to biological properties typical of wild polioviruses. Analysis of plaque-purified viruses from stool samples revealed complex genetic and evolutionary relationships between the poliovirus strains. The generation of various coevolving genetic lineages incorporating different mutations was observed at early stages of virus excretion. The main driving force for genetic diversity appeared to be the selection of mutations at attenuation sites, particularly in the 5′ noncoding region and the VP1 BC loop. Recombination between virus strains from the two main lineages was observed between days 63 and 88. Genetic heterogeneity among plaque-purified viruses at each time point seemed to decrease with time, and only viruses belonging to a unique genotypic lineage were seen from day 105 after vaccination. The relevance of vaccine-derived poliovirus strains for disease surveillance and future polio immunization policies is discussed in the context of the Global Polio Eradication Initiative.
Autophagosome Supports Coxsackievirus B3 Replication in Host Cells
Authors: Wong Jerry , Zhang Jingchun , Si Xiaoning , Gao Guang , Mao Ivy , McManus Bruce M. , Luo Honglin
Published: July 2008

Recent studies suggest a possible takeover of host antimicrobial autophagy machinery by positive-stranded RNA viruses to facilitate their own replication. In the present study, we investigated the role of autophagy in coxsackievirus replication. Coxsackievirus B3 (CVB3), a picornavirus associated with viral myocarditis, causes pronounced intracellular membrane reorganization after infection. We demonstrate that CVB3 infection induces an increased number of double-membrane vesicles, accompanied by an increase of the LC3-II/LC3-I ratio and an accumulation of punctate GFP-LC3-expressing cells, two hallmarks of cellular autophagosome formation. However, protein expression analysis of p62, a marker for autophagy-mediated protein degradation, showed no apparent changes after CVB3 infection. These results suggest that CVB3 infection triggers autophagosome formation without promoting protein degradation by the lysosome. We further examined the role of the autophagosome in CVB3 replication. We demonstrated that inhibition of autophagosome formation by 3-methyladenine or small interfering RNAs targeting the genes critical for autophagosome formation (ATG7, Beclin-1, and VPS34 genes) significantly reduced viral replication. Conversely, induction of autophagy by rapamycin or nutrient deprivation resulted in increased viral replication. Finally, we examined the role of autophagosome-lysosome fusion in viral replication. We showed that blockage of the fusion by gene silencing of the lysosomal protein LAMP2 significantly promoted viral replication. Taken together, our results suggest that the host's autophagy machinery is activated during CVB3 infection to enhance the efficiency of viral replication.
The Enhanced DNA Replication Fidelity of a Mutant Herpes Simplex Virus Type 1 DNA Polymerase Is Mediated by an Improved Nucleotide Selectivity and Reduced Mismatch Extension Ability
Authors: Tian Wang , Hwang Ying T. , Hwang Charles B. C.
Published: July 2008

We previously demonstrated that a recombinant herpes simplex virus containing a mutation within the finger domain of DNA polymerase replicated DNA with increased fidelity. In this study, we demonstrate that, compared with wild-type polymerase, the mutant enzyme exhibited improved nucleotide selectivity and a reduced ability to extend from mismatched primer termini, which would contribute to the increased DNA replication fidelity.
Intrahepatic Expression of Genes Affiliated with Innate and Adaptive Immune Responses Immediately after Invasion and during Acute Infection with Woodchuck Hepadnavirus
Authors: Guy Clifford S. , Mulrooney-Cousins Patricia M. , Churchill Norma D. , Michalak Tomasz I.
Published: July 2008

The importance of effective immune responses in recovery from acute hepadnaviral hepatitis has been demonstrated. However, there is no conclusive delineation of virological and immunological events occurring in the liver immediately after hepadnavirus invasion and during the preacute phase of infection. These very early events might be of primary importance in determining the recovery or progression to chronic hepatitis and the intrinsic hepadnaviral propensity to persist. In this study, applying the woodchuck model of acute hepatitis B, the hepatic kinetics of hepadnavirus replication and activation of genes encoding cytokines, cytotoxicity effectors, and immune cell markers were quantified in sequential liver biopsies collected from 1 h postinoculation onward by sensitive real-time cDNA amplification assays. The results revealed that hepadnavirus replication is established in the liver as early as 1 hour after infection. In 3 to 6 h, significantly augmented intrahepatic transcription of gamma interferon and interleukin-12 were evident, suggesting activation of antigen-presenting cells. In 48 to 72 h, NK and NKT cells were activated and virus replication was transiently but significantly reduced, implying that this early innate response is at least partially successful in limiting virus propagation. Nonetheless, T cells were activated 4 to 5 weeks later when hepatitis became histologically evident. Collectively, our data demonstrate that virus replication is initiated and the innate response activated in the liver soon after exposure to a liver-pathogenic dose of hepadnavirus. Nevertheless, this response is unable to prompt a timely adaptive T-cell response, in contrast to infections caused by other viral pathogens.
Experimental Tests of General Relativity
Authors: Turyshev Slava G.
Published: July 2008

Einstein's general theory of relativity is the standard theory of gravity, especially where the needs of astronomy, astrophysics, cosmology and fundamental physics are concerned. As such, this theory is used for many practical purposes involving spacecraft navigation, geodesy, and time transfer. Here I review the foundations of general relativity, discuss recent progress in the tests of relativistic gravity in the Solar System, and present motivations for the new generation of high-accuracy gravitational experiments. I discuss the advances in our understanding of fundamental physics that are anticipated in the near future and evaluate the discovery potential of the recently proposed gravitational experiments.
Febrile temperature leads to significant stiffening of Plasmodium falciparum parasitized erythrocytes
Authors: Marinkovic Marina , Diez-Silva Monica , Pantic Ivan , Fredberg Jeffrey J. , Suresh Subra , Butler James P.
Published: July 2008

Parasitic infection with Plasmodium falciparum is responsible for the most severe form of human malaria in which patients suffer from periodic fever. It is well established that during intra-erythrocytic maturation of the parasite in the red blood cell (RBC), the RBC becomes significantly more cytoadhesive and less deformable; these and other biochemical factors together with human host factors such as compromised immune status are important contributors to the disease pathology. There is currently substantial interest in understanding the loss of RBC deformability due to P. falciparum infection, but few results are available concerning effects of febrile conditions or parasitization on RBC membrane rheology. Here, for the first time, we report rheology of the single, isolated RBC with and without P. falciparum merozoite invasion, spanning a range from room temperature to febrile conditions (41°C), over all the stages of parasite maturation. As expected, stiffness increased with parasite maturation. Surprisingly, however, stiffness increased acutely with temperature on a scale of minutes, particularly in late trophozoite and schizont stages. This acute stiffening in late falciparum stages may contribute to fever-dependent pathological consequences in the microcirculation.
Ca2+ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture
Authors: Berra-Romani Roberto , Mazzocco-Spezzia Amparo , Pulina Maria V. , Golovina Vera A.
Published: July 2008

Phenotypic modulation of vascular myocytes is important for vascular development and adaptation. A characteristic feature of this process is alteration in intracellular Ca2+ handling, which is not completely understood. We studied mechanisms involved in functional changes of inositol 1,4,5-trisphosphate (IP3)- and ryanodine (Ry)-sensitive Ca2+ stores, store-operated Ca2+ entry (SOCE), and receptor-operated Ca2+ entry (ROCE) associated with arterial myocyte modulation from a contractile to a proliferative phenotype in culture. Proliferating, cultured myocytes from rat mesenteric artery have elevated resting cytosolic Ca2+ levels and increased IP3-sensitive Ca2+ store content. ATP- and cyclopiazonic acid [CPA; a sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) inhibitor]-induced Ca2+ transients in Ca2+-free medium are significantly larger in proliferating arterial smooth muscle cells (ASMCs) than in freshly dissociated myocytes, whereas caffeine (Caf)-induced Ca2+ release is much smaller. Moreover, the Caf/Ry-sensitive store gradually loses sensitivity to Caf activation during cell culture. These changes can be explained by increased expression of all three IP3 receptors and a switch from Ry receptor type II to type III expression during proliferation. SOCE, activated by depletion of the IP3/CPA-sensitive store, is greatly increased in proliferating ASMCs. Augmented SOCE and ROCE (activated by the diacylglycerol analog 1-oleoyl-2-acetyl- sn-glycerol) in proliferating myocytes can be attributed to upregulated expression of, respectively, transient receptor potential proteins TRPC1/4/5 and TRPC3/6. Moreover, stromal interacting molecule 1 (STIM1) and Orai proteins are upregulated in proliferating cells. Increased expression of IP3 receptors, SERCA2b, TRPCs, Orai(s), and STIM1 in proliferating ASMCs suggests that these proteins play a critical role in an altered Ca2+ handling that occurs during vascular growth and remodeling.
P2X7 receptor-Pannexin1 complex: pharmacology and signaling
Authors: Iglesias R. , Locovei S. , Roque A. , Alberto A. P. , Dahl G. , Spray D. C. , Scemes E.
Published: July 2008

Pannexin 1 (Panx1), an ortholog to invertebrate innexin gap junctions, has recently been proposed to be the pore induced by P2X7 receptor (P2X7R) activation. We explored the pharmacological action of compounds known to block gap junctions on Panx1 channels activated by the P2X7R and the mechanisms involved in the interaction between these two proteins. Whole cell recordings revealed distinct P2X7R and Panx1 currents in response to agonists. Activation of Panx1 currents following P2X7R stimulation or by membrane depolarization was blocked by Panx1 small-interfering RNA (siRNA) and with mefloquine > carbenoxolone > flufenamic acid. Incubation of cells with KN-62, a P2X7R antagonist, prevented current activation by 2′(3′)- O-(4-benzoylbenzoyl)adenosine 5′-triphosphate (BzATP). Membrane permeabilization to dye induced by BzATP was also prevented by Panx1 siRNA and by carbenoxolone and mefloquine. Membrane permeant (TAT-P2X7) peptides, provided evidence that the Src homology 3 death domain of the COOH-terminus of the P2X7R is involved in the initial steps of the signal transduction events leading to Panx1 activation and that a Src tyrosine kinase is likely involved in this process. Competition assays indicated that 20 μM TAT-P2X7 peptide caused 50% reduction in Src binding to the P2X7R complex. Src tyrosine phosphorylation following BzATP stimulation was reduced by KN-62, TAT-P2X7 peptide, and by the Src tyrosine inhibitor PP2 and these compounds prevented both large-conductance Panx1 currents and membrane permeabilization. These results together with the lack Panx1 tyrosine phosphorylation in response to P2X7R stimulation indicate the involvement of an additional molecule in the tyrosine kinase signal transduction pathway mediating Panx1 activation through the P2X7R.
Actin cytoskeletal dynamics in smooth muscle: a new paradigm for the regulation of smooth muscle contraction
Authors: Gunst Susan J. , Zhang Wenwu
Published: July 2008

A growing body of data supports a view of the actin cytoskeleton of smooth muscle cells as a dynamic structure that plays an integral role in regulating the development of mechanical tension and the material properties of smooth muscle tissues. The increase in the proportion of filamentous actin that occurs in response to the stimulation of smooth muscle cells and the essential role of stimulus-induced actin polymerization and cytoskeletal dynamics in the generation of mechanical tension has been convincingly documented in many smooth muscle tissues and cells using a wide variety of experimental approaches. Most of the evidence suggests that the functional role of actin polymerization during contraction is distinct and separately regulated from the actomyosin cross-bridge cycling process. The molecular basis for the regulation of actin polymerization and its physiological roles may vary in diverse types of smooth muscle cells and tissues. However, current evidence supports a model for smooth muscle contraction in which contractile stimulation initiates the assembly of cytoskeletal/extracellular matrix adhesion complex proteins at the membrane, and proteins within this complex orchestrate the polymerization and organization of a submembranous network of actin filaments. This cytoskeletal network may serve to strengthen the membrane for the transmission of force generated by the contractile apparatus to the extracellular matrix, and to enable the adaptation of smooth muscle cells to mechanical stresses. Better understanding of the physiological function of these dynamic cytoskeletal processes in smooth muscle may provide important insights into the physiological regulation of smooth muscle tissues.
Large-scale quantitative LC-MS/MS analysis of detergent-resistant membrane proteins from rat renal collecting duct
Authors: Yu Ming-Jiun , Pisitkun Trairak , Wang Guanghui , Aranda Juan F. , Gonzales Patricia A. , Tchapyjnikov Dmitry , Shen Rong-Fong , Alonso Miguel A. , Knepper Mark A.
Published: July 2008

In the renal collecting duct, vasopressin controls transport of water and solutes via regulation of membrane transporters such as aquaporin-2 (AQP2) and the epithelial urea transporter UT-A. To discover proteins potentially involved in vasopressin action in rat kidney collecting ducts, we enriched membrane “raft” proteins by harvesting detergent-resistant membranes (DRMs) of the inner medullary collecting duct (IMCD) cells. Proteins were identified and quantified with LC-MS/MS. A total of 814 proteins were identified in the DRM fractions. Of these, 186, including several characteristic raft proteins, were enriched in the DRMs. Immunoblotting confirmed DRM enrichment of representative proteins. Immunofluorescence confocal microscopy of rat IMCDs with antibodies to DRM proteins demonstrated heterogeneity of raft subdomains: MAL2 (apical region), RalA (predominant basolateral labeling), caveolin-2 (punctate labeling distributed throughout the cells), and flotillin-1 (discrete labeling of large intracellular structures). The DRM proteome included GPI-anchored, doubly acylated, singly acylated, cholesterol-binding, and integral membrane proteins (IMPs). The IMPs were, on average, much smaller and more hydrophobic than IMPs identified in non-DRM-enriched IMCD. The content of serine 256-phosphorylated AQP2 was greater in DRM than in non-DRM fractions. Vasopressin did not change the DRM-to-non-DRM ratio of most proteins, whether quantified by tandem mass spectrometry (LC-MS/MS, n = 22) or immunoblotting ( n = 6). However, Rab7 and annexin-2 showed small increases in the DRM fraction in response to vasopressin. In accord with the long-term goal of creating a systems-level analysis of transport regulation, this study has identified a large number of membrane-associated proteins expressed in the IMCD that have potential roles in vasopressin action.
Reduced renal responses to nitric oxide synthase inhibition in mice lacking the gene for gp91phoxsubunit of NAD(P)H oxidase
Authors: Haque Mohammed Z. , Majid Dewan S. A.
Published: July 2008

Both short-term and long-term nitric oxide (NO) blockade were shown to cause an increase in O2−activity. To assess the contribution of such enhanced O2−activity in the kidney, responses to administration of the NO synthase inhibitor nitro-l-arginine methyl ester (l-NAME; 200 μg·min−1·kg body wt−1) were assessed in knockout mice the lacking NAD(P)H oxidase subunit gp91phox(KO; n = 10) and in wild-type (WT; n = 10) mice. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by PAH and inulin clearances, respectively. Baseline RBF was higher in KO compared with WT mice (5.8 ± 0.5 vs. 4.5 ± 0.3 ml·min−1·g−1; P < 0.04) without significant differences in GFR (0.62 ± 0.04 vs. 0.73 ± 0.05 ml·min−1·g−1) and in mean arterial pressure (MAP; 91 ± 6 vs. 88 ± 4 mmHg). l-NAME infusion for 60 min caused similar increases in MAP (114 ± 6 vs. 113 ± 3 mmHg) in both groups but resulted in a lesser degree of reduction in RBF in KO compared with WT mice (−7 ± 3 vs. −17 ± 3%; P < 0.02), although GFR remained unchanged in both groups. The natriuretic response to systemic l-NAME infusion was attenuated in KO compared with WT mice (Δ: 3.1 ± 0.7 vs. 5.2 ± 0.6 μmol·min−1·g−1). l-NAME increased urinary 8-isoprostane excretion rate in WT (5.9 ± 1 to 7.7 ± 1 pg·min−1·g−1; P < 0.02) but not in KO mice (5.6 ± 1 to 4.9 ± 0.3 pg·min−1·g−1). In contrast, responses to another vasoconstrictor, norepinephrine, were similar in both strains of mice. These data indicate that activation of NAD(P)H oxidase results in the enhancement of O2−activity that influences renal hemodynamics and excretory function in the condition of NO deficiency.
Fast and Accurate Detection of Action Potentials From Somatic Calcium Fluctuations
Authors: Sasaki Takuya , Takahashi Naoya , Matsuki Norio , Ikegaya Yuji
Published: July 2008

Large-scale recording from a population of neurons is a promising strategy for approaching the study of complex brain functions. Taking advantage of the fact that action potentials reliably evoke transient calcium fluctuations in the cell body, functional multineuron calcium imaging (fMCI) monitors the suprathreshold activity of hundreds of neurons. However, a limitation of fMCI is its semi-manual procedure of spike extraction from somatic calcium fluctuations, which is not only time consuming but is also associated with human errors. Here we describe a novel automatic method that combines principal-component analysis and support vector machine. This simple algorithm determines the timings of the spikes in calcium fluorescence traces more rapidly and reliably than human operators.
Subcortical Interactions Between Somatosensory Stimuli of Different Modalities and Their Temporal Profile
Authors: Costa João , Valls-Solé Josep , Valldeoriola Francesc , Rumià Jordi
Published: July 2008

Interactions between inputs of different sensory modality occur along the sensory pathway, including the thalamus. However, the temporal profile of such interaction has not been fully studied. In eight patients who had been implanted an intrathalamic electrode for deep brain stimulation as symptomatic treatment of tremor, we investigated the interactions between mechanical taps and electrical nerve stimuli. Somatosensory evoked potentials (SEPs) were recorded from Erb's point, cervical spinal cord, nucleus ventrointermedialis of the thalamus, and parietal cortex. A handheld electronic reflex hammer was used to deliver a mechanical tap to the skin overlying the first dorsal interosseous muscle and to trigger an ipsilateral digital median nerve electrical stimulus time-locked to the mechanical tap with a variable delay of 0 to 50 ms. There were significant time-dependent interactions between the two sensory volleys at the subcortical level. Thalamic SEPs were decreased in amplitude at interstimulus intervals (ISIs) from 10 to 40 ms with maximum effect at 20 ms (−42.8 ± 10.5%; P < 0.001). A similar decrease was also seen in the number and frequency of the high-frequency components of thalamic SEPs (−25 ± 4%). A smaller reduction (−18.1 ± 5.8%; P < 0.001) was present in upper cervical response at ISI = 20 ms. There were no changes in peripheral responses. Cortical SEPs were almost completely absent in some subjects at ISIs from 20 to 50 ms. There were no changes in SEP latencies. Our results indicate that significant time-dependent interactions between sensory volleys occur at the subcortical level. These observations provide further insight into the physiological mechanisms underlying afferent gating between sensory volleys of different modality.
Corticofugal Modulation of the Paradoxical Latency Shifts of Inferior Collicular Neurons
Authors: Ma Xiaofeng , Suga Nobuo
Published: July 2008

The central auditory system creates various types of neurons tuned to different acoustic parameters other than a specific frequency. The response latency of auditory neurons typically shortens with an increase in stimulus intensity. However, ∼10% of collicular neurons of the little brown bat show a “paradoxical latency-shift (PLS)”: long latencies to intense sounds but short latencies to weak sounds. These neurons presumably are involved in the processing of target distance information carried by a pair of an intense biosonar pulse and its weak echo. Our current studies show that collicular PLS neurons of the big brown bat are modulated by the corticofugal (descending) system. Electric stimulation of cortical auditory neurons evoked two types of changes in the PLS neurons, depending on the relationship in the best frequency (BF) between the stimulated cortical and recorded collicular neurons. When the BF was matched between them, the cortical stimulation did not shift the BFs of the collicular neurons and shortened their response latencies at intense sounds so that the PLS became smaller. When the BF was unmatched, however, the cortical stimulation shifted the BFs of the collicular neurons and lengthened their response latencies at intense sounds, so that the PLS became larger. Cortical electric stimulation also modulated the response latencies of non-PLS neurons. It produced an inhibitory frequency tuning curve or curves. Our findings indicate that corticofugal feedback is involved in shaping the spectrotemporal patterns of responses of subcortical auditory neurons presumably through inhibition.
Explaining Savings for Visuomotor Adaptation: Linear Time-Invariant State-Space Models Are Not Sufficient
Authors: Zarahn Eric , Weston Gregory D. , Liang Johnny , Mazzoni Pietro , Krakauer John W.
Published: July 2008

Adaptation of the motor system to sensorimotor perturbations is a type of learning relevant for tool use and coping with an ever-changing body. Memory for motor adaptation can take the form of savings: an increase in the apparent rate constant of readaptation compared with that of initial adaptation. The assessment of savings is simplified if the sensory errors a subject experiences at the beginning of initial adaptation and the beginning of readaptation are the same. This can be accomplished by introducing either 1) a sufficiently small number of counterperturbation trials (counterperturbation paradigm [ CP]) or 2) a sufficiently large number of zero-perturbation trials (washout paradigm [ WO]) between initial adaptation and readaptation. A two-rate, linear time-invariant state-space model (SSMLTI,2) was recently shown to theoretically produce savings for CP. However, we reasoned from superposition that this model would be unable to explain savings for WO. Using the same task (planar reaching) and type of perturbation (visuomotor rotation), we found comparable savings for both CP and WO paradigms. Although SSMLTI,2 explained some degree of savings for CP it failed completely for WO. We conclude that for visuomotor rotation, savings in general is not simply a consequence of LTI dynamics. Instead savings for visuomotor rotation involves metalearning, which we show can be modeled as changes in system parameters across the phases of an adaptation experiment.
Data Dependence for Ishikawa Iteration When Dealing with Contractive-Like Operators
Authors: Şoltuz ŞM , Grosan Teodor
Published: July 2008

We prove a convergence result and a data dependence for Ishikawa iteration when applied to contraction-like operators. An example is given, in which instead of computing the fixed point of an operator, we approximate the operator with a contractive-like one. For which it is possible to compute the fixed point, and therefore to approximate the fixed point of the initial operator.
A Tutorial of the Poisson Random Field Model in Population Genetics
Authors: Sethupathy Praveen , Hannenhalli Sridhar
Published: July 2008

Population genetics is the study of allele frequency changes driven by various evolutionary forces such as mutation, natural selection, and random genetic drift. Although natural selection is widely recognized as a bona‐fide phenomenon, the extent to which it drives evolution continues to remain unclear and controversial. Various qualitative techniques, or so‐called “tests of neutrality”, have been introduced to detect signatures of natural selection. A decade and a half ago, Stanley Sawyer and Daniel Hartl provided a mathematical framework, referred to as the Poisson random field (PRF), with which to determine quantitatively the intensity of selection on a particular gene or genomic region. The recent availability of large‐scale genetic polymorphism data has sparked widespread interest in genome‐wide investigations of natural selection. To that end, the original PRF model is of particular interest for geneticists and evolutionary genomicists. In this article, we will provide a tutorial of the mathematical derivation of the original Sawyer and Hartl PRF model.
An Approximate Solution for Boundary Value Problems in Structural Engineering and Fluid Mechanics
Authors: Barari A. , Omidvar M. , Ganji D. D. , Poor Abbas Tahmasebi
Published: July 2008

Variational iteration method (VIM) is applied to solve linear and nonlinear boundary value problems with particular significance in structural engineering and fluid mechanics. These problems are used as mathematical models in viscoelastic and inelastic flows, deformation of beams, and plate deflection theory. Comparison is made between the exact solutions and the results of the variational iteration method (VIM). The results reveal that this method is very effective and simple, and that it yields the exact solutions. It was shown that this method can be used effectively for solving linear and nonlinear boundary value problems.
A Novel Mechanism of PPARγ Regulation of TGFβ1: Implication in Cancer Biology
Authors: Lee Chang Ho , Kim Hyung Don , Shin Sang Mi , Kim Sang Geon
Published: July 2008

Peroxisome proliferator‐activated receptor‐γ (PPARγ) and retinoic acid X‐receptor (RXR) heterodimer, which regulates cell growth and differentiation, represses the TGFβ1 gene that encodes for the protein involved in cancer biology. This review will introduce the novel mechanism associated with the inhibition of the TGFβ1 gene by PPARγ activation, which regulates the dephosphorylation of Zf9 transcription factor. Pharmacological manipulation of TGFβ1 by PPARγ activators can be applied for treating TGFβ1‐induced pathophysiologic disorders such as cancer metastasis and fibrosis. In this article, we will discuss the opposing effects of TGFβ on tumor growth and metastasis, and address the signaling pathways regulated by PPARγ for tumor progression and suppression.
Severe Congenital Neutropenia or Hyper-IgM Syndrome? A Novel Mutation of CD40 Ligand in a Patient with Severe Neutropenia
Authors: Rezaei Nima , Aghamohammadi Asghar , Ramyar Asghar , Pan-Hammarstrom Qiang , Hammarstrom Lennart
Published: July 2008

Severe congenital neutropenia (SCN) and CD40 ligand deficiency (CD40LD) are two primary immunodeficiency diseases caused by different underlying genetic defects. In this report, we present a case who clinically presented as a SCN patient, but subsequent mutation analysis of this patient was compatible with CD40LD. The patient is a 3-year-old boy, who was referred to our center because of pneumonia, oral and anal ulcers, and periodontitis. As severe consistent neutropenia and maturation arrest in the myeloid series were observed in the bone marrow, a diagnosis of SCN was made. However, no mutations were found in the ELA2 and HAX1 genes. As functional T cell defects were observed, we suspected CD40LD. DNA sequencing showed a 17-base pair deletion in the CD40L gene. Although the patient did not have a decreased serum level of IgA, and his serum IgM level was within the normal range, the diagnosis of CD40LD was confirmed, suggesting that CD40LD should be suspected in any male patient with recurrent infections and neutropenia.
Recurrent Peanut Allergy May Not Be Prevented by Continued Peanut Ingestion
Authors: Boyle Robert J. , Tang Mimi L.-K.
Published: July 2008

Recurrent peanut allergy has been described in patients who have previously passed an oral food challenge [N Engl J Med 2002;347:1535–1536]. It has been suggested that recurrent peanut allergy might be prevented by regular ingestion of peanut subsequent to passing an oral food challenge [J Allergy Clin Immunol 2004;114:1195–1201]. We present a case that challenges this thinking by demonstrating that peanut allergy may recur during regular ingestion of significant doses of peanut protein. The case suggests that current practice cannot guarantee freedom from recurrent peanut allergy, and it is important that patients and their families are aware of this.
Chronic Erythropoietin Treatment Decreases Post-Infarct Myocardial Damage in Rats without Venous Thrombogenic Effect
Authors: Prunier F. , Pottier P. , Clairand R. , Mercier A. , Hajjar R.J. , Planchon B. , Furber A.
Published: July 2008

Objectives: Whereas administration of erythropoietin (EPO) acutely after myocardial infarction (MI) reduces infarct size and chronic EPO therapy attenuates post-MI remodeling, the safety of chronic EPO therapy following MI is unknown. Therefore, we examined the thrombogenic effects of a chronic EPO therapy after MI. Methods: Rats underwent coronary occlusion followed by reperfusion. They were assigned to one of the following groups: EPO-A, single injection of EPO 5,000 U/kg at the time of reperfusion; EPO-C, injection of EPO 5,000 U/kg at the time of reperfusion followed by 300 U/kg/week; PBS-C, injection of vehicle only. After eight weeks of treatment they were exposed to a validated prethrombotic test based on partial stenosis of the inferior vena cava. Results: As compared to the rats receiving vehicle only, the rats treated with EPO exhibited a significant reduction in MI size (28.7 ± 2.1% and 25.8 ± 1.9 vs. 39.8 ± 3.0% in EPO-A, EPO-C and PBS-C, respectively; p < 0.05). Whereas the hematocrit was significantly increased in EPO-C (59.7 ± 2.0% vs. 44.7 ± 0.9% in EPO-A, p < 0.001), the proportion of rats in which a thrombus occurred was similar in all groups (p = 0.52). Conclusion: Chronic EPO therapy added to the single high dose of EPO injected acutely did not induce venous pro-thrombotic effect in rats.
Functionalization of Single-Walled Carbon Nanotubes with Azides Derived from Amino Acids Using Click Chemistry
Authors: Kumar Indresh , Rana Sravendra , Rode Chandrashakher V. , Cho Jae Whan
Published: July 2008

Single-walled carbon nanotubes (SWCNTs) were chemically functionalized with amino acid-based moieties. The covalent functionalization of alkyne-derived SWCNTs with well defined azides derived from amino acids was accomplished through Cu(I)-catalyzed Huisgen [3 + 2] dipolar cycloaddition
click chemistry. Transmission electron microscopy, Raman spectroscopy, and infrared spectroscopic measurements confirmed the functionalization of SWCNTs by organic molecules derived from amino acids, and the resulting material showed some good solubility in the organic solvents such as tetrahydrofuran,
CH2Cl2, and CHCl3.
Framework Functionalization of Periodic Mesoporous Organosilica with 1,2-bis[3-(triethoxysilylpropyl)ureido] cyclohexane Function via Basic Co-condensation Self-Assembly
Authors: Wahab M. Abdul , Kim I. , Ha C. S.
Published: July 2008

The synthesized bis silylated long alkyl chain containing organosilicate precursor, 1,2-bis(3-(triethoxysilylpropyl)ureido)cyclohexane (BSPUCh) has been used as co-precursor with 1,2-bis (triethoxysilyl)ethane (BTSE) for the preparation of functional periodic mesoporous organosilicas
(PMOs) via surfactant-mediated basic co-condensation self-assembly method. The various characterization techniques such as X-ray diffraction patterns (XRD), transmission electron microscope (TEM), N2 adsorption–desorption isotherms (BET), FT-IR, and 13C and 29Si
CPMAS NMR spectroscopies were used to characterize the resulting structure of functionalized PMO mesostructures. Results obtained from XRD, TEM, and BET analysis clearly showed that the structural and pore arrangement of the functionalized PMOs were found to be dependent on the used concentration
of BSPUCh. The functional PMOs showed well ordered mesophases when BSPUCh concentration was ≤9 wt% in the initial mixtures, whereas higher concentration of the BSPUCh always produced disordered hierarchical mesostructures with bimodal pore size distributions. The incorporation of BSPUCh
also reduces the surface area, pore volume, pore size, and pore wall thickness of the functionalized nanostructures, indicating that the BSPUCh is incorporated in the pore channels of the PMOs. The solid-state 13C and 29Si NMR spectra showed that the BSPUCh organosilicate
with non-hydrolyzable bridging ligands propylureidocyclohexane has been successfully covalently linked in the framework of the resulting functional PMOs.
Adhesive Force Assisted Imprinting of Soft Solid Polymer Films by Flexible Foils
Authors: Mukherjee Rabibrata , Sharma Ashutosh , Gonuguntla Manoj , Patil Ganesh K.
Published: July 2008

We report a simple, rapid, room temperature, pressure-less and large area (∼cm2) imprinting technique for high fidelity patterning of soft solid polymer films and surfaces like cross-linked polydimethylsiloxane (PDMS) and polyacrylamide (PAA) based hydrogels, both on
planar and curved surfaces. The key element of the method is the use of patterned thin flexible foils that readily and rapidly attain a conformal contact with soft (shear modulus < 0.1 MPa) solid surfaces because of adhesive interfacial interactions. The conformal contact is established
at all length scales by bending of the foil at scales larger than the feature size, in conjunction with the spontaneous elastic deformations of the surface on the scale of the features. For example, we used the protective aluminum foils of commercial data storage discs, both with or without
data stored, for micron and sub-micron pattern transfer. The patterns are made permanent by UV-ozone treatment (for PDMS) or by controlled drying (for hydrogels). Interestingly, elastic contact imprinting of very thin (<300 nm) films results in about 50% miniaturization of the original
foil feature sizes. Complex two dimensional patterns could also be formed even by using a simple one dimensional master by multiple imprinting. The technique can be particularly useful for the bulk nano applications requiring routine fabrication of templates, for example, in the study of confined
chemistry phenomena, nanofluidics, bio-MEMS, micro-imprinting, optical coatings and controlled dewetting.
Novel Aspects of the Purpose-Built Materials Strategy: Evidence of Topographic Template Effect and Oriented Attachment Growth Mechanism
Authors: Leite Edson R. , Lopes Kírian P. , Ribeiro Caue , Orlandi Marcelo O. , Longo Elson
Published: July 2008

We report two novel aspects relating to the growth of oriented 3D arrays of SnO2 nanorods, based on the "purpose-built materials" (PBM) strategy. Under controlled conditions, the substrate acted as a topographic template and the growth direction of the 3D arrays of SnO2
nanorods was unrelated to the crystallographic characteristic of the substrate. A growth process based on the oriented attachment mechanism was proposed to explain this behavior, and this findings, reported here for SnO2, can be extended to include other metal oxides.
Hydrazine Based Facile Synthesis and Ordered Assembly of Metal Nanoparticles (Au, Ag) on a Bacterial Surface Layer Protein Template
Authors: Puranik Sarang S. , Joshi Hrushikesh M. , Ogale S. B. , Paknikar K. M.
Published: July 2008

An efficient and facile procedure is developed for concurrent in situ synthesis and ordered assembly of metal nanoparticles on a periodic two dimensional protein array. The S-layer protein of Bacillus subtilis exhibiting uniform pore size is used as template. Synthesis
of gold and silver nanoparticles anchoring on the pores of S-layer is achieved by chemical reduction of respective metal salt laden protein template. Transmission electron microscopy reveals formation of well ordered and separated gold and silver nanoparticles with an average diameter of 6
± 1 nm and 4 ± 1 nm, respectively. The periodic arrangement of nanoparticles is dictated by the native structure of S-layer protein array as the nanoparticle locations are found to be correlated to the nanosized pores of the crystalline S-layer array.
Single-Crystal Vanadium Pentoxide Nanowires
Authors: Gao Shaokang , Chen Yuzhen , Luo Haiyan , Jiang Lilong , Ye Binghuo , Wei Mingdeng , Wei Kemei
Published: July 2008

Single-crystal V2O5 nanowires were successfully synthesized from the starting materials V6O13 powder and water. The experimental results indicate that high purity nanowires can be obtained using this simple synthetic route in absence of templates
or catalysts. The diameter of the nanowires was found to be ca. 20∼60 nm and the length up to several tens of micrometers, and the phases of nanowires were determined by XRD and TEM measurements.
Fabrication of Gold Nanocrescents by Angle Deposition with Nanosphere Lithography for Localized Surface Plasmon Resonance Applications
Authors: Zhou Xiaodong , Virasawmy Selven , Knoll Wolfgang , Liu Kai Yu , Tse Man Siu , Yen Li Wei
Published: July 2008

The gold nanostructures fabricated on a substrate yield localized surface plasmon resonance. We describe the fabrication and characterization of nanocrescents on a silicon substrate, which are fabricated by depositing a gold film at an oblique angle through nanosphere lithography. Following
the etching of the gold perpendicular to the substrate and the removal of the nanospheres by dissolution, nanocrescents with fine nanostructures are generated. By varying the deposition angle of the gold film from 0° to 72°, nanorings, 2D and 3D nanocrescents can be obtained. During
the nanocrescent fabrication, we also compared the deposition angle difference between the e-beam and thermal evaporators for oblique depositions of the gold. The 3D nanocrescents fabricated in our experiments are expected to have improved sensitivity in localized surface plasmon resonance
measurements when compared to the previously reported 2D nanocrescents, which enable broader biosensor applications. Simulations of the profiles of these 3D nanocrescents using solid geometry show good consistency with the fabricated ones.