bluuebunny/crossref_metadata_2025 huggingface dataset:
The FoxO Family in Cardiac Function and Dysfunction
Authors: Ronnebaum Sarah M. , Patterson Cam
Published: February 2010

The Forkhead family of transcription factors mediates many aspects of physiology, including stress response, metabolism, commitment to apoptosis, and development. The Forkhead box subfamily O (FoxO) proteins have garnered particular interest due to their involvement in the modulation of cardiovascular biology. In this review, we discuss the mechanisms of FoxO regulation and outcomes of FoxO signaling under normal and pathological cardiovascular contexts.
Systems Biology of Mammalian Circadian Clocks
Authors: Ukai Hideki , Ueda Hiroki R.
Published: February 2010

Systems biology is a natural extension of molecular biology; it can be defined as biology after identification of key gene(s). Systems-biological research is a multistage process beginning with (a) the comprehensive identification and (b) quantitative analysis of individual system components and their networked interactions, which lead to the ability to (c) control existing systems toward the desired state and (d) design new ones based on an understanding of the underlying structure and dynamical principles. In this review, we use the mammalian circadian clock as a model system and describe the application of systems-biological approaches to fundamental problems in this model. This application has allowed the identification of transcriptional/posttranscriptional circuits, the discovery of a temperature-insensitive period-determining process, and the discovery of desynchronization of individual clock cells underlying the singularity behavior of mammalian clocks.
Cellular Maintenance and Repair of the Kidney
Authors: Guo Jian-Kan , Cantley Lloyd G.
Published: February 2010

The mammalian kidney is a highly complex organ that requires the precise structural arrangement of multiple cell types for effective function. The need to filter large volumes of plasma at the glomerulus followed by active reabsorption of nearly 99% of that filtrate by the tubules creates vulnerability in both compartments for cell injury. Thus maintenance of cell viability and replacement of those cells that are lost are essential for functional stability of the kidney. This review addresses our current understanding of how cells from the glomerular, tubular, and interstitial compartments arise during development and the manner in which they may be regenerated in the adult organ. In addition, we discuss the data regarding the role of organ-specific and bone marrow–derived stem and progenitor cells in the replacement/repair process, as well as the potential for ex vivo programming of stem cells toward a renal lineage.
T-type current modulation by the actin-binding protein Kelch-like 1
Authors: Aromolaran K. A. , Benzow K. A. , Cribbs L. L. , Koob M. D. , Piedras-Rentería E. S.
Published: February 2010

We report a novel form of modulation of T-type calcium currents carried out by the neuronal actin-binding protein (ABP) Kelch-like 1 (KLHL1). KLHL1 is a constitutive neuronal ABP localized to the soma and dendritic arbors; its genetic elimination in Purkinje neurons leads to dendritic atrophy and motor insufficiency. KLHL1 participates in neurite outgrowth and upregulates voltage-gated P/Q-type calcium channel function; here we investigated KLHL1's role as a modulator of low-voltage-gated calcium channels and determined the molecular mechanism of this modulation with electrophysiology and biochemistry. Coexpression of KLHL1 with CaV3.1 or CaV3.2 (α1G or α1H subunits) caused increases in T-type current density (35%) and calcium influx (75–83%) when carried out by α1H but not by α1G. The association between KLHL1 and α1H was determined by immunoprecipitation and immunolocalization in brain membrane fractions and in vitro in HEK-293 cells. Noise analysis showed that neither α1H single-channel conductance nor open probability was altered by KLHL1, yet a significant increase in channel number was detected and further corroborated by Western blot analysis. KLHL1 also induced an increase in α1H current deactivation time (τdeactivation). Interestingly, the majority of KLHL1's effects were eliminated when the actin-binding motif (kelch) was removed, with the exception of the calcium influx increase during action potentials, indicating that KLHL1 interacts with α1H and actin and selectively regulates α1H function by increasing the number of α1H channels. This constitutes a novel regulatory mechanism of T-type calcium currents and supports the role of KLHL1 in the modulation of cellular excitability.
Odors activate dual pathways, a TRPC2 and a AA-dependent pathway, in mouse vomeronasal neurons
Authors: Zhang Peng , Yang Chun , Delay Rona J.
Published: February 2010

Located at the anterior portion of the nose, the paired vomeronasal organs (VNO) detect odors and pheromones. In vomeronasal sensory neurons (VSNs) odor responses are mainly mediated by phospholipase C (PLC), stimulation of which elevates diacylglycerol (DAG). DAG activates a transient receptor potential channel (TRPC2) leading to cell depolarization. In this study, we used a natural stimulus, urine, to elicit odor responses in VSNs and found urine responses persisted in TRPC2−/−mice, suggesting the existence of a TRPC2-independent signal transduction pathway. Using perforated patch-clamp recordings on isolated VSNs from wild-type (WT) and TRPC2−/−mice, we found a PLC inhibitor blocked urine responses from all VSNs. Furthermore, urine responses were reduced by blocking DAG lipase, an enzyme that produces arachidonic acid (AA), in WT mice and abolished in TRPC2−/−mice. Consistently, direct stimulation with AA activated an inward current that was independent of TRPC2 channels but required bath Ca2+and was blocked by Cd2+. With the use of inside-out patches from TRPC2−/−VSNs, we show that AA activated a channel that also required Ca2+. Together, these data from WT and TRPC2−/−mice suggest that both DAG and its metabolite, AA, mediate excitatory odor responses in VSNs, by activating two types of channels, a TRPC2 and a separate Ca2+-permeable channel.
Interstitial cells of Cajal in the cynomolgus monkey rectoanal region and their relationship to sympathetic and nitrergic nerves
Authors: Cobine C. A. , Hennig G. W. , Bayguinov Y. R. , Hatton W. J. , Ward S. M. , Keef K. D.
Published: February 2010

The morphology of interstitial cells of Cajal (ICC) in the circular muscle layer of the cynomolgus monkey internal anal sphincter (IAS) and rectum and their relationship to sympathetic and nitrergic nerves were compared by dual-labeling immunohistochemistry. Contractile studies confirmed that nitrergic nerves participate in neural inhibition in both regions whereas sympathetic nerves serve as excitatory motor nerves only in the IAS. Muscle bundles extended from myenteric to submucosal edge in rectum but in the IAS bundles were further divided into “minibundles” each surrounded by connective tissue. Dual labeling of KIT and smooth muscle myosin revealed KIT-positive stellate-shaped ICC (ICC-IAS) within each minibundle. In the rectum intramuscular ICC (ICC-IM) were spindle shaped whereas stellate-shaped ICC were located at the myenteric surface (ICC-MY). ICC were absent from both the myenteric and submucosal surfaces of the IAS. Nitrergic nerves (identified with anti-neuronal nitric oxide synthase antibodies or NADPH diaphorase activity) and sympathetic nerves (identified with anti-tyrosine hydroxylase antibody) each formed a plexus at the myenteric surface of the rectum but not the IAS. Intramuscular neuronal nitric oxide synthase- and tyrosine hydroxylase-positive fibers were present in both regions but were only closely associated with ICC-IM in rectum. Minimal association was also noted between ICC-IAS and cells expressing the nonspecific neuronal marker PGP9.5. In conclusion, the morphology of rectal ICC-IM and ICC-MY is similar to that described elsewhere in the gastrointestinal tract whereas ICC-IAS are unique. The distribution of stellate-shaped ICC-IAS throughout the musculature and their absence from both the myenteric and submucosal surfaces suggest that ICC-IAS may serve as pacemaker cells in this muscle whereas their limited relationship to nerves suggests that they are not involved in neuromuscular transmission. Additionally, the presence of numerous minibundles, each containing both ICC-IAS and nerves, suggests that this muscle functions as a multiunit type muscle.
Lymphocyte responses exacerbate angiotensin II-dependent hypertension
Authors: Crowley Steven D. , Song Young-Soo , Lin Eugene E. , Griffiths Robert , Kim Hyung-Suk , Ruiz Phillip
Published: February 2010

Activation of the immune system by ANG II contributes to the pathogenesis of hypertension, and pharmacological suppression of lymphocyte responses can ameliorate hypertensive end-organ damage. Therefore, to examine the mechanisms through which lymphocytes mediate blood pressure elevation, we studied ANG II-dependent hypertension in scid mice lacking lymphocyte responses and wild-type controls. Scid mice had a blunted hypertensive response to chronic ANG II infusion and accordingly developed less cardiac hypertrophy. Moreover, lymphocyte deficiency led to significant reductions in heart and kidney injury following 4 wk of angiotensin. The muted hypertensive response in the scid mice was associated with increased sodium excretion, urine volumes, and weight loss beginning on day 5 of angiotensin infusion. To explore the mechanisms underlying alterations in blood pressure and renal sodium handling, we measured gene expression for vasoactive mediators in the kidney after 4 wk of ANG II administration. Scid mice and controls had similar renal expression for interferon-γ, interleukin-1β, and interleukin-6. By contrast, lymphocyte deficiency (i.e., scid mice) during ANG II infusion led to upregulation of tumor necrosis factor-α, endothelial nitric oxide synthase (eNOS), and cyclooxygenase-2 (COX-2) in the kidney. In turn, this enhanced eNOS and COX-2 expression in the scid kidneys was associated with exaggerated renal generation of nitric oxide, prostaglandin E2, and prostacyclin, all of which promote natriuresis. Thus, the absence of lymphocyte activity protects from hypertension by allowing blood pressure-induced sodium excretion, possibly via stimulation of eNOS- and COX-2-dependent pathways.
Dietary fructose accelerates the development of diabetes in UCD-T2DM rats: amelioration by the antioxidant, α-lipoic acid
Authors: Cummings Bethany P. , Stanhope Kimber L. , Graham James L. , Evans Joseph L. , Baskin Denis G. , Griffen Steven C. , Havel Peter J.
Published: February 2010

Sustained fructose consumption has been shown to induce insulin resistance and glucose intolerance, in part, by promoting oxidative stress. Alpha-lipoic acid (LA) is an antioxidant with insulin-sensitizing activity. The effect of sustained fructose consumption (20% of energy) on the development of T2DM and the effects of daily LA supplementation in fructose-fed University of California, Davis-Type 2 diabetes mellitus (UCD-T2DM) rats, a model of polygenic obese T2DM, was investigated. At 2 mo of age, animals were divided into three groups: control, fructose, and fructose + LA (80 mg LA·kg body wt−1·day−1). One subset was followed until diabetes onset, while another subset was euthanized at 4 mo of age for tissue collection. Monthly fasted blood samples were collected, and an intravenous glucose tolerance test (IVGTT) was performed. Fructose feeding accelerated diabetes onset by 2.6 ± 0.5 mo compared with control ( P < 0.01), without affecting body weight. LA supplementation delayed diabetes onset in fructose-fed animals by 1.0 ± 0.7 mo ( P < 0.05). Fructose consumption lowered the GSH/GSSG ratio, while LA attenuated the fructose-induced decrease of oxidative capacity. Insulin sensitivity, as assessed by IVGTT, decreased in both fructose-fed and fructose + LA-supplemented rats. However, glucose excursions in fructose-fed LA-supplemented animals were normalized to those of control via increased glucose-stimulated insulin secretion. Fasting plasma triglycerides were twofold higher in fructose-fed compared with control animals at 4 mo, and triglyceride exposure during IVGTT was increased in both the fructose and fructose + LA groups compared with control. In conclusion, dietary fructose accelerates the onset of T2DM in UCD-T2DM rats, and LA ameliorates the effects of fructose by improving glucose homeostasis, possibly by preserving β-cell function.
Activation of a latent nuclear localization signal in the NH2terminus of γ-ENaC initiates feedback regulation of channel activity
Authors: Mironova Elena , Stockand James D.
Published: February 2010

Proteolytic enzymes cleave the epithelial Na+channel (ENaC) at several positions releasing, in part, the NH2terminus of the γ-subunit. Cleavage increases ENaC activity by increasing open probability; however, the role of polypeptides cleaved from the channel core remains unclear. We find that the cytosolic NH2terminus of γ-ENaC unexpectedly targets to the nucleus being particularly strong in nucleoli. In contrast, the cytosolic COOH terminus targets to the cytoplasm and plasma membrane in a manner similar to full-length subunits. Targeting of the cytosolic NH2terminus of γ-ENaC to the nucleus has functional consequences for coexpression of eGFP-fusion proteins containing this segment of the channel, but not the COOH terminus, decrease ENaC activity in a dose-dependent manner. The mechanism of this negative regulation is associated with a decrease in the functional half-life of ENaC at the plasma membrane. Inspection of the primary amino acid sequence of γ-ENaC reveals possible nuclear localization signals (NLS) conserved at the extreme NH2terminus and just preceding the first transmembrane domain. Disruption of the putative NLS preceding the first transmembrane domain in γ-ENaC but not that at the extreme NH2terminus abolishes both targeting to the nucleus and negative regulation of ENaC activity. These findings are consistent with the release of the NH2terminus of γ-ENaC following cleavage being functionally important for signaling to the nucleus in a manner similar to Notch signaling and release of the cytosolic COOH-terminal tail of polycystin-1.
Role of the hypothalamic PVN in the regulation of renal sympathetic nerve activity and blood flow during hyperthermia and in heart failure
Authors: Badoer Emilio
Published: February 2010

The hypothalamic paraventricular nucleus is a key integrative area in the brain involved in influencing sympathetic nerve activity and in the release of hormones or releasing factors that contribute to regulating body fluid homeostasis and endocrine function. The endocrine and hormonal regulatory function of the paraventricular nucleus is well studied, but the regulation of sympathetic nerve activity and blood flow by this region is less clear. Here we review the critical role of the paraventricular nucleus in regulating renal blood blow during hyperthermia and the evidence pointing to an important pathophysiological role of the paraventricular nucleus in the elevated renal sympathetic nerve activity that is a characteristic of heart failure.
Responses in the Inferior Colliculus of the Guinea Pig to Concurrent Harmonic Series and the Effect of Inactivation of Descending Controls
Authors: Nakamoto Kyle T. , Shackleton Trevor M. , Palmer Alan R.
Published: February 2010

One of the fundamental questions of auditory research is how sounds are segregated because, in natural environments, multiple sounds tend to occur at the same time. Concurrent sounds, such as two talkers, physically add together and arrive at the ear as a single input sound wave. The auditory system easily segregates this input into a coherent percept of each of the multiple sources. A common feature of speech and communication calls is their harmonic structure and in this report we used two harmonic complexes to study the role of the corticofugal pathway in the processing of concurrent sounds. We demonstrate that, in the inferior colliculus (IC) of the anesthetized guinea pig, deactivation of the auditory cortex altered the temporal and/or the spike response to the concurrent, monaural harmonic complexes. More specifically, deactivating the auditory cortex altered the representation of the relative level of the complexes. This suggests that the auditory cortex modulates the representation of the level of two harmonic complexes in the IC. Since sound level is a cue used in the segregation of auditory input, the corticofugal pathway may play a role in this segregation.
Biochanin A Modulates Cell Viability, Invasion, and Growth Promoting Signaling Pathways in HER-2-Positive Breast Cancer Cells
Authors: Sehdev Vikas , Lai James C. K. , Bhushan Alok
Published: February 2010

Overexpression of HER-2 receptor is associated with poor prognosis and aggressive forms of breast cancer. Scientific literature indicates a preventive role of isoflavones in cancer. Since activation of HER-2 receptor initiates growth-promoting events in cancer cells, we studied the effect of biochanin A (an isoflavone) on associated signaling events like receptor activation, downstream signaling, and invasive pathways. HER-2-positive SK-BR-3 breast cancer cells, MCF-10A normal breast epithelial cells, and NIH-3T3 normal fibroblast cells were treated with biochanin A (2–100 μM) for 72 hours. Subsequently cell viability assay, western blotting and zymography were carried out. The data indicate that biochanin A inhibits cell viability, signaling pathways, and invasive enzyme expression and activity in SK-BR-3 cancer cells. Biochanin A did not inhibit MCF-10A and NIH-3T3 cell viability. Therefore, biochanin A could be a unique natural anticancer agent which can selectively target cancer cells and inhibit multiple signaling pathways in HER-2-positive breast cancer cells.
Constructing Physical and Genomic Maps forPuccinia striiformisf. sp.tritici, the Wheat Stripe Rust Pathogen, by Comparing Its EST Sequences to the Genomic Sequence ofP. graminisf. sp.tritici, the Wheat Stem Rust Pathogen
Authors: Ma Jinbiao , Chen Xianming , Wang Meinan , Kang Zhensheng
Published: February 2010

The wheat stripe rust fungus,Puccinia striiformisf. sp.tritici(Pst), does not have a known alternate host for sexual reproduction, which makes it impossible to study gene linkages through classic genetic and molecular mapping approaches. In this study, we compared 4,219Pstexpression sequence tags (ESTs) to the genomic sequence ofP. graminisf. sp.tritici(Pgt), the wheat stem rust fungus, using BLAST searches. The percentages of homologous genes varied greatly among differentPstlibraries with 54.51%, 51.21%, and 13.61% for the urediniospore, germinated urediniospore, and haustorial libraries, respectively, with an average of 33.92%. The 1,432Pstgenes with significant homology withPgtsequences were grouped into physical groups corresponding to 237Pgtsupercontigs. The physical relationship was demonstrated by 12 pairs (57%), out of 21 selectedPstgene pairs, through PCR screening of aPstBAC library. The results indicate that thePgtgenome sequence is useful in constructingPstphysical maps.
Si Incorporation in InP Nanowires Grown by Au‐Assisted Molecular Beam Epitaxy
Authors: Rigutti Lorenzo , De Luna Bugallo Andres , Tchernycheva Maria , Jacopin Gwenole , Julien François H. , Cirlin George , Patriarche Gilles , Lucot Damien , Travers Laurent , Harmand Jean-Christophe
Published: February 2010

We report on the growth, structural characterization, and conductivity studies of Si‐doped InP nanowires grown by Au‐assisted molecular beam epitaxy. It is shown that Si doping reduces the mean diffusion length of adatoms on the lateral nanowire surface and consequently reduces the nanowire growth rate and promotes lateral growth. A resistivity as low as 5.1 ± 0.3 × 10−5 Ω ·cm is measured for highly doped nanowires. Two dopant incorporation mechanisms are discussed: incorporation via catalyst particle and direct incorporation on the nanowire sidewalls. The first mechanism is shown to be less efficient than the second one, resulting in inhomogeneous radial dopant distribution.
Concept for Mobility and Interconnections Aspects in Converged NGN-Based IPTV Architecture
Authors: Mikoczy Eugen , Kadlic Radovan , Podhradsky Pavol
Published: February 2010

The progress and evolution trends in the area of ICT and ICT infrastructure based on convergence processes create new opportunities. Service providers and network operators can provide a wide spectrum of multimedia services and applications to end users. The IPTV services represent a specific group of multimedia services which are in the sphere of interest of the telecommunication technical community but also subscribers. Standardization bodies like ETSI TISPAN or ITU-T have defined standards for NGN-based IPTV architecture and services (IMS and non-IMS). The paper evaluates possibilities and potential architecture for concept of converged NGN IPTV. New vision of the converged NGN IPTV architecture is presented together with proposed enhancements compared to IMS-based IPTV where single converged platform can serve fixed, mobile, or wireless terminals. The concept for IPTV service roaming with mobility support and different interconnection scenarios are discussed with intention to show potential user benefits.
Manipulation of Energy Transfer Processes in Nanochannels
Authors: Devaux André , Calzaferri Gion
Published: February 2010

The realisation of molecular assemblies featuring specific macroscopic properties is a prime example for the versatility of supramolecular organisation. Microporous materials such as zeolite L are well suited for the preparation of host‐guest composites containing dyes, complexes, or clusters. This short tutorial focuses on the possibilities offered by zeolite L to study and influence Förster resonance energy transfer inside of its nanochannels. The highly organised host‐guest materials can in turn be structured on a larger scale to form macroscopic patterns, making it possible to create large‐scale structures from small, highly organised building blocks for novel optical applications.
Prevalence of Joint Hypermobility and Patterns of Articular Manifestations in Patients with Inflammatory Bowel Disease
Authors: Vounotrypidis P. , Efremidou E. , Zezos P. , Pitiakoudis M. , Maltezos E. , Lyratzopoulos N. , Kouklakis G.
Published: February 2010

Objective. The objective is the investigation of Joint Hypermobility (JH) and the Hypermobility Syndrome (HMS) in patients with inflammatory bowel disease (IBD).Methods. We examined 83 patients with IBD and 67 healthy individuals for the presence of JH. Patients were excluded if they were under 18 or over 50 years of age and if they had other conditions which affect joint mobility. Thex2and the Fisher exact test were used appropriately between study groups. Odds ratios (ORs) for the risk of JH and HMS in IBD groups were calculated.Results. A total of 150 individuals (83 IBD patients and 67 healthy controls) participated in the study. 69 IBD patients, 41 with Crohn's Disease (CD) and 28 with ulcerative colitis (UC), were finally eligible. JH was detected in 29 CD patients (70.7%), in 10 UC patients (35.7%), and in 17 healthy control subjects (25.4%). Significant difference was detected on JH in CD patients as compared to UC patients (P=.0063) and controls (P<.0001). The estimated OR for JH was 7.108 (95% CI: 2.98–16.95) in CD and 1.634 (95% CI: 0.63–4.22) in UC patients. HMS was detected in 5 (12.2%) CD and in 1 (3.57%) UC patients. The OR for HMS in CD was 3.75 (95% CI: 0.41–34.007), while 7 (17.1%) CD patients had overlapping symptoms for both HMS and early spondylarthropathy.Conclusions. JH and the HMS are common in CD patients, thus articular manifestations should be carefully interpreted. This implies an involvement of collagen varieties in the pathogenesis of IBD.
Protein Viability on Au Nanoparticles during an Electrospray and Electrostatic‐Force‐Directed Assembly Process
Authors: Mao Shun , Lu Ganhua , Yu Kehan , Chen Junhong
Published: February 2010

We study the protein viability on Au nanoparticles during an electrospray and electrostatic‐force‐directed assembly process, through which Au nanoparticle‐antibody conjugates are assembled onto the surface of carbon nanotubes (CNTs) to fabricate carbon nanotube field‐effect transistor (CNTFET) biosensors. Enzyme‐linked immunosorbent assay (ELISA) and field‐effect transistor (FET) measurements have been used to investigate the antibody activity after the nanoparticle assembly. Upon the introduction of matching antigens, the colored reaction from the ELISA and the change in the electrical characteristic of the CNTFET device confirm that the antibody activity is preserved during the assembly process.
Telomeric Heterochromatin inPlasmodium falciparum
Authors: Hernandez-Rivas Rosaura , Pérez-Toledo Karla , Herrera Solorio Abril-Marcela , Delgadillo Dulce María , Vargas Miguel
Published: February 2010

Until very recently, little was known about the chromatin structure of the telomeres and subtelomeric regions inPlasmodium falciparum. In yeast andDrosophila melanogaster, chromatin structure has long been known to be an important aspect in the regulation and functioning of these regions. Telomeres and subtelomeric regions are enriched in epigenetic marks that are specific to heterochromatin, such as methylation of lysine 9 of histone H3 and lysine 20 of histone H4. InP. falciparum, histone modifications and the presence of both the heterochromatin “writing” (PfSir2, PKMT) and “reading” (PfHP1) machinery at telomeric and subtelomeric regions indicate that these regions are likely to have heterochromatic structure that is epigenetically regulated. This structure may be important for telomere functions such as the silencing of thevargene family implicated in the cytoadherence and antigenic variation of these parasites.
High‐Rate Redundant Space‐Time Coding
Authors: Manssour Jawad , Osseiran Afif , Ben Slimane Slimane
Published: February 2010

We present a new space‐time encoder
based on packet‐level redundancy which can increase the space‐time encoder rate beyond unity without compromising diversity
gains. A complementary low‐complexity decoding algorithm
based on maximum ratio combining and successive interference
cancelation is further proposed. A major merit of the decoding
algorithm is that it allows to adaptively tradeoff between
diversity and multiplexing gains based on the estimated channel
parameters at the receiver without requiring any channel state
information at the transmitter. System level simulation results
give insight into the advantages of the proposed scheme when
compared to its Alamouti and MIMO multiplexing based on
single value decomposition counterparts.
Update on Instrumentations for Cholecystectomies Performed via Transvaginal Route: State of the Art and Future Prospectives
Authors: Pulvirenti Elia , Toro Adriana , Di Carlo Isidoro
Published: February 2010

Natural Orifice Transluminal Endoscopic Surgery (NOTES) is an innovative approach in which a flexible endoscope enters the abdominal cavity via the transesophageal, transgastric, transcolonic, transvaginal or transvescical route, combining the technique of minimally invasive surgery with flexible endoscopy. Several groups have described different modifications by using flexible endoscopes with different levels of laparoscopic assistance. Transvaginal cholecystectomy (TVC) consists in accessing the abdominal cavity through a posterior colpotomy and using the vaginal incision as a visual or operative port. An increasing interest has arisen around the TVC; nevertheless, the most common and highlighted concern is about the lack of specific instruments dedicated to the vaginal access route. TVC should be distinguished between “pure”, in which the entire operation is performed through the transvaginal route, and “hybrid”, in which the colpotomy represents only a support to introduce instruments and the operation is performed mainly by the classic transabdominal-introduced instruments. Although this new technique seems very appealing for patients, on the other hand it is very challenging for the surgeon because of the difficulties related to the mode of access, the limited technology currently available and the risk of complications related to the organ utilized for access. In this brief review all the most recent advancements in the field of TVC's techniques and instrumentations are listed and discussed.
Gene Expression in Trypanosomatid Parasites
Authors: Martínez-Calvillo Santiago , Vizuet-de-Rueda Juan C. , Florencio-Martínez Luis E. , Manning-Cela Rebeca G. , Figueroa-Angulo Elisa E.
Published: February 2010

The parasitesLeishmaniaspp.,Trypanosoma brucei,andTrypanosoma cruziare the trypanosomatid protozoa that cause the deadly human diseases leishmaniasis, African sleeping sickness, and Chagas disease, respectively. These organisms possess unique mechanisms for gene expression such as constitutive polycistronic transcription of protein-coding genes and trans-splicing. Little is known about either the DNA sequences or the proteins that are involved in the initiation and termination of transcription in trypanosomatids.In silicoanalyses of the genome databases of these parasites led to the identification of a small number of proteins involved in gene expression. However, functional studies have revealed that trypanosomatids have more general transcription factors than originally estimated. Many posttranslational histone modifications, histone variants, and chromatin modifying enzymes have been identified in trypanosomatids, and recent genome-wide studies showed that epigenetic regulation might play a very important role in gene expression in this group of parasites. Here, we review and comment on the most recent findings related to transcription initiation and termination in trypanosomatid protozoa.
Mixed Approximation for Nonexpansive Mappings in Banach Spaces
Authors: Zhang Qing-Bang , Xia Fu-Quan , Liu Ming-Jie
Published: February 2010

The mixed viscosity approximation is proposed for finding fixed points of nonexpansive mappings, and the strong convergence of the scheme to a fixed point of the nonexpansive mapping is proved in a real Banach space with uniformly Gâteaux differentiable norm. The theorem about Halpern type approximation for nonexpansive mappings is shown also. Our theorems extend and improve the correspondingly results shown recently.
Anosognosia for Behavioral Disturbances in Frontotemporal Dementia and Corticobasal Syndrome: A Voxel-Based Morphometry Study
Authors: Zamboni G. , Grafman J. , Krueger F. , Knutson K.M. , Huey E.D.
Published: February 2010

Background: Patients with syndromes of the frontotemporal dementia spectrum are frequently unaware of their behavioral changes. Methods: Seventy patients with a clinical diagnosis of behavioral variant frontotemporal dementia (bv-FTD, n = 27), aphasic variant frontotemporal dementia (a-FTD, n = 12) and corticobasal syndrome (CBS, n = 31) participated in the study. Anosognosia for behavioral disturbances was measured as discrepancy between caregiver’s and patient’s ratings on the Frontal Systems Behavior Scale for present and premorbid behavioral symptoms. Voxel-based morphometry analysis of MRI data was performed to explore the association between anosognosia and gray matter loss. Results: Although behavioral symptoms were reported in all the groups, the comparison between present and premorbid anosognosia revealed that bv-FTD patients not only underestimated their present behavioral disturbances compared to their caregivers, but also overestimated their premorbidbehavioral disturbances. Across all groups, the degree of anosognosia for present behavioral impairment correlated with gray matter atrophy in a posterior region of the right superior temporal sulcus (adjacent to the temporoparietal junction). Conclusion: These results confirm the role of the right temporoparietal cortex in the genesis of anosognosia and suggest that, in clinical syndromes of the frontotemporal dementia spectrum, anosognosia is associated with the dysfunction of temporoparietal mechanisms of self versus others knowledge.
Effects of a Physical Training Programme on Cognitive Function and Walking Efficiency in Elderly Persons with Dementia
Authors: Kemoun Gilles , Thibaud Marie , Roumagne Nicolas , Carette Pierre , Albinet Cédric , Toussaint Lucette , Paccalin Marc , Dugué Benoit
Published: February 2010

Objectives: To study the effects of physical stimulation based on walking exercises, equilibrium and endurance on cognitive function and walking efficiency in patients with dementia. Methods: Randomized controlled trial including 31 subjects suffering from dementia (age: 81.8 ± 5.3 years). The intervention group (n = 16) benefited from a 15-week physical activity programme involving three 1-hour sessions per week. The control group (n = 15) did not practice any physical activities. Before and after rehabilitation, all subjects were evaluated with the Rapid Evaluation of Cognitive Functions test (ERFC French version) and walking analysis. Results: After the 15 weeks of rehabilitation, the subjects from the intervention group improved their overall ERFC score (p < 0.01), while those in the control group decreased their overall ERFC score. Interactions were also observed between walking parameters and groups (p < 0.01); the intervention group improved walking capacities through heightened walking speed, stride length and a reduction in double limb support time. Lastly, the subjects from the control group presented a reduction in both walking speed and stride length. Conclusion: This study shows that a physical activity programme can slow cognitive decline and improve quality of walking in elderly persons suffering from dementia.
Predicting Gains in Dementia Caregiving
Authors: Liew Tau Ming , Luo Nan , Ng Wai Yee , Chionh Hui Ling , Goh Jenny , Yap Philip
Published: February 2010

Background: Caregiver gain is an important yet less-explored phenomenon. Being conceptually distinct from burden, factors associated with burden and gain can differ. This study aims to explore factors associated with the experience of gains in dementia caregiving. Method: Cross-sectional study involving caregivers recruited from a tertiary hospital dementia clinic and the local Alzheimer’s Association. Caregivers completed a questionnaire containing the following scales: gain in Alzheimer’s care Instrument (GAIN), General Health Questionnaire (GHQ-28), Dementia Management Strategies Scale (DMSS), Revised Memory and Behavioral Problems Checklist (RMBPC) and Zarit Burden Interview (ZBI). Demographic information for the person with dementia (PWD) and the caregiver was also recorded. Initial screening with univariate analyses (t tests, ANOVAs, Pearson’s correlations) was performed to identify significant (p < 0.05) variables, which were then entered into a multiple regression model to identify variables associated with gain. Result: The final sample comprised 334 caregivers with a mean age of 51.5 years (SD = 10.9, range = 22–85), the majority of whom where Chinese (94.6%) females (71%). Mean GAIN score was 30 (SD = 6.6, range = 7–40). Regression analysis identified 3 factors significantly associated with gains (adjusted R2 32.3%): mental well-being of the caregiver, use of active management as a caregiving strategy, and participation in caregiver educational and support group programmes. Conclusion: The results have important implications for caregiver interventions. Interventions should target maintaining mental well-being, encouraging participation in educational and support programmes, and teaching appropriate coping and dementia specific management strategies to derive good outcomes.
Comparative Effect of Green Tea, Chokeberry and Honeysuckle Polyphenols on Nutrients and Mineral Absorption and Digestibility in Rats
Authors: Frejnagel Slawomir , Wroblewska Monika
Published: February 2010

Background/Aims: Natural polyphenols are chemically and biologically active. This study aimed at examining the physiological effects of high doses of polyphenol extracts from green tea and new polyphenol-rich sources (chokeberry and honeysuckle fruits) on nutrient absorption. Methods: 32 male Wistar rats were divided into four groups and fed a diet supplemented with one of the three polyphenolic extracts (at 0.4%) or a control diet for 4 weeks. A perfusion technique was used to study the effects at intestinal level. Pure polyphenols from the three sources were introduced into perfusion fluid at a concentration of 0.4% and allowed to cross the intestinal tract in 1.5 h. Results: In the perfusion experiment, addition of the extracts caused a strong and statistically significant reduction in absorption of the selected nutrients (water, glucose, cholesterol, amino acids and minerals) compared to control animals. In the nutritional experiment, we recorded a slight decrease in diet utilization and growth in rats on polyphenolic diets relative to control group. In the same experiment, we observed a reduction of Zn and Cu absorption, but this was not accompanied by diminished concentrations in the bone femur. Conclusions: The presence of the polyphenolic extracts in the perfusion liquids significantly reduced absorption from the small intestine, but the nutritional experiment did not confirm deleterious consequences of the consumption of high extract doses.
Round Window Membrane Implantation with an Active Middle Ear Implant: A Study of the Effects on the Performance of Round Window Exposure and Transducer Tip Diameter in Human Cadaveric Temporal Bones
Authors: Tringali Stéphane , Koka Kanthaiah , Deveze Arnaud , Holland N. Julian , Jenkins Herman A. , Tollin Daniel J.
Published: February 2010

Objectives: To assess the importance of 2 variables, transducer tip diameter and resection of the round window (RW) niche, affecting the optimization of the mechanical stimulation of the RW membrane with an active middle ear implant (AMEI). Materials and Methods: Ten temporal bones were prepared with combined atticotomy and facial recess approach to expose the RW. An AMEI stimulated the RW with 2 ball tip diameters (0.5 and 1.0 mm) before and after the resection of the bony rim of the RW niche. The RW drive performance, assessed by stapes velocities using laser Doppler velocimetry, was analyzed in 3 frequency ranges: low (0.25–1 kHz), medium (1–3 kHz) and high (3–8 kHz). Results: Driving the RW produced mean peak stapes velocities (HEV) of 0.305 and 0.255 mm/s/V at 3.03 kHz, respectively, for the 1- and 0.5-mm tips, with the RW niche intact. Niche drilling increased the HEV to 0.73 and 0.832 mm/s/V for the 1- and 0.5-mm tips, respectively. The tip diameter produced no difference in output at low and medium frequencies; however, the 0.5-mm tip was 5 and 6 dB better than the 1-mm tip at high frequencies before and after niche drilling, respectively. Drilling the niche significantly improved the output by 4 dB at high frequencies for the 1-mm tip, and by 6 and 10 dB in the medium- and high-frequency ranges for the 0.5-mm tip. Conclusion: The AMEI was able to successfully drive the RW membrane in cadaveric temporal bones using a classical facial recess approach. Stimulation of the RW membrane with an AMEI without drilling the niche is sufficient for successful hearing outputs. However, the resection of the bony rim of the RW niche significantly improved the RW stimulation at medium and higher frequencies. Drilling the niche enhances the exposure of the RW membrane and facilitates positioning the implant tip.
Effects of Age and Working Memory Capacity on Pitch Pattern Sequence Test and Dichotic Listening
Authors: Mukari Siti Z. , Umat C. , Othman Nor I.
Published: February 2010

This study assessed the effects of age and working memory capacity on dichotic listening and temporal sequencing. Double Dichotic Digit Test (DDT), Pitch Pattern Sequence Test (PPST) and Digit Span Test were administered on 40 healthy adults with hearing thresholds of not greater than 30 dB HL across octave frequencies from 250 to 4000 Hz. Twenty young (20–30 years old) and 20 older (50–65 years old) adults were included in the study. Results showed that the older group had significantly lower scores in DDT, PPST and working memory capacity measures than the young subjects. Working memory capacity was positively correlated with PPST but not with DDT, suggesting that DDT might be more auditory-modality-specific than PPST.
The Gene-Environment Interactions in Respiratory Diseases (GEIRD) Project
Authors: de Marco R. , Accordini S. , Antonicelli L. , Bellia V. , Bettin M.D. , Bombieri C. , Bonifazi F. , Bugiani M. , Carosso A. , Casali L. , Cazzoletti L. , Cerveri I. , Corsico A.G. , Ferrari M. , Fois A.G. , Lo Cascio V. , Marcon A. , Marinoni A. , Olivieri M. , Perbellini L. , Pignatti P. , Pirina P. , Poli A. , Rolla G. , Trabetti E. , Verlato G. , Villani S. , Zanolin M.E. ,   for the GEIRD Study Group
Published: February 2010

The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions.
Activity of Lymphocyte Subpopulations in Polymicrobial Sepsis and DHEA Treatment in IL-6 Knockout Mice
Authors: Zeckey Christian , Hildebrand Frank , Hoevel Petra , Müller Kathrin , Krettek Christian , Barkhausen Tanja , van Griensven Martijn
Published: February 2010

Introduction: Sepsis with subsequent multiorgan dysfunction remains the leading cause of mortality in trauma patients. A gender dimorphism in the host response after trauma and sepsis has been revealed. Dehydroepiandrosterone (DHEA), one of the most abundant adrenal sexual steroid hormones, seems to have a protective immunological effect in sepsis. Knowledge of the pathway is sparse; however, a cellular modulation mediated by interleukin-6 (IL-6) has been proposed. Materials and Methods: The effect of DHEA on survival, clinical parameters and the cellular immune system (T lymphocytes and NK cells) was examined in a model of polymicrobial sepsis induced by cecal ligation and puncture. For clarification of the role of IL-6 in the protective effect of DHEA, we used IL-6 knockout mice (IL-6–/–). As controls, experiments were performed on wild-type mice (WT). Results: The administration of DHEA in IL-6–/– mice did not affect mortality, as it was not significantly different from WT mice without DHEA application. The cellular immune response was influenced, as seen by a significant reduction in the percentage of CD8+ and NK cells in WT animals. Conclusions: Mortality rates in IL-6–/– mouse strains were not lowered by DHEA; therefore, a limited effect of IL-6 on this pathway has to be proposed. NK cells may be one of the effector cells of the protective mechanisms of DHEA, whilst the role of CD8+ lymphocytes remains unclear. Consequently, DHEA might be presented as a possible adjuvant therapy after septic insult for modulation of the dysregulated immune system.
SERCA2b Activity Is Regulated by Cyclophilins in Human Platelets
Authors: Rosado Juan A. , Pariente Jose A. , Salido Gines M. , Redondo Pedro C.
Published: February 2010

Objective—

The role of cyclophilins (chaperones that are widely expressed in different cell types, including human platelets) was explored in sarcoendoplasmic calcium (Ca
2+
) adenosine triphosphatase (SERCA) activity.

Methods and Results—

Cyclophilin inhibition by cyclosporin A (CsA) evoked a time- and concentration-dependent reduction of Ca
2+
uptake by SERCA2b. However, other Ca
2+
-adenosine triphosphatases expressed in platelets, such as SERCA3 and plasma membrane Ca
2+
adenosine triphophatase, remained unaltered after CsA treatment. Cypermethrin, a non–CsA-related calcineurin inhibitor, did not alter SERCA2b activity. Furthermore, SERCA2b was affected by other CsA analogues, which do not interfere with calcineurin, such as PKF-211-811-NX5 (NIM811) and sanglifehrin A. Inhibition of the immunophilin family members using FK506 (tacrolimus) did not alter SERCA2b ability to sequester Ca
2+
into the dense tubular system. Coimmunoprecipitation experiments confirmed that cyclophilin A associates with SERCA2b and stromal interaction molecule-1 in resting platelets. This interaction is attenuated by the physiological agonist thrombin but enhanced by treatment with CsA or sanglifehrin A.

Conclusion—

Cyclophilin A is a regulator of SERCA2b in human platelets.
Rivaroxaban: A New Oral Factor Xa Inhibitor
Authors: Perzborn Elisabeth , Roehrig Susanne , Straub Alexander , Kubitza Dagmar , Mueck Wolfgang , Laux Volker
Published: February 2010

Rivaroxaban is a direct inhibitor of factor Xa, a coagulation factor at a critical juncture in the blood coagulation pathway leading to thrombin generation and clot formation. It is selective for human factor Xa, for which it has >10 000-fold greater selectivity than for other biologically relevant serine proteases (half-maximal inhibitory concentration [IC
50
], >20 μmol/L). Rivaroxaban inhibits factor Xa in a concentration-dependent manner (inhibitory constant [K
i
], 0.4 nmol/L) and binds rapidly (kinetic association rate constant [k
on
], 1.7×10
7
mol/L
−1
s
−1
) and reversibly (kinetic dissociation rate constant [k
off
], 5×10
−3
s
−1
). By inhibiting prothrombinase complex-bound (IC
50
, 2.1 nmol/L) and clot-associated factor Xa (IC
50
, 75 nmol/L), rivaroxaban reduces the thrombin burst during the propagation phase. In animal models of venous and arterial thrombosis, rivaroxaban showed dose-dependent antithrombotic activity. In healthy individuals, rivaroxaban was found to have predictable pharmacokinetics and pharmacodynamics across a 5- to 80-mg total daily dose range, inhibiting factor Xa activity and prolonging plasma clotting time. In phase III clinical trials, rivaroxaban regimens reduced rates of venous thromboembolism in patients after total hip or knee arthroplasty compared with enoxaparin regimens, without significant differences in rates of major bleeding, showing that rivaroxaban has a favorable benefit-to-risk profile.