bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of thin descending limb urea transport in renal urea handling and the urine concentrating mechanism
Authors: Lei Tianluo , Zhou Lei , Layton Anita T. , Zhou Hong , Zhao Xuejian , Bankir Lise , Yang Baoxue
Published: August 2011

Urea transporters UT-A2 and UT-B are expressed in epithelia of thin descending limb of Henle's loop and in descending vasa recta, respectively. To study their role and possible interaction in the context of the urine concentration mechanism, a UT-A2 and UT-B double knockout (UT-A2/B knockout) mouse model was generated by targeted deletion of the UT-A2 promoter in embryonic stem cells with UT-B gene knockout. The UT-A2/B knockout mice lacked detectable UT-A2 and UT-B transcripts and proteins and showed normal survival and growth. Daily urine output was significantly higher in UT-A2/B knockout mice than that in wild-type mice and lower than that in UT-B knockout mice. Urine osmolality in UT-A2/B knockout mice was intermediate between that in UT-B knockout and wild-type mice. The changes in urine osmolality and flow rate, plasma and urine urea concentration, as well as non-urea solute concentration after an acute urea load or chronic changes in protein intake suggested that UT-A2 plays a role in the progressive accumulation of urea in the inner medulla. These results suggest that in wild-type mice UT-A2 facilitates urea absorption by urea efflux from the thin descending limb of short loops of Henle. Moreover, UT-A2 deletion in UT-B knockout mice partially remedies the urine concentrating defect caused by UT-B deletion, by reducing urea loss from the descending limbs to the peripheral circulation; instead, urea is returned to the inner medulla through the loops of Henle and the collecting ducts.
Selectivity for the rate of frequency-modulated sweeps in the mouse auditory cortex
Authors: Trujillo Michael , Measor Kevin , Carrasco Maria Magdalena , Razak Khaleel A.
Published: August 2011

Frequency-modulated (FM) sweeps are common components of vocalizations, including human speech. Both sweep direction and rate influence discrimination of vocalizations. Across species, relatively less is known about FM rate selectivity compared with direction selectivity. In this study, FM rate selectivity was studied in the auditory cortex of anesthetized 1- to 3-mo-old C57bl/6 mice. Neurons were classified as fast pass, band pass, slow pass, or all pass depending on their selectivity for rates between 0.08 and 20 kHz/ms. Multiunit recordings were used to map FM rate selectivity at depths between 250 and 450 μm across both primary auditory cortex (A1) and the anterior auditory field (AAF). In terms of functional organization of rate selectivity, three patterns were found. First, in both A1 and AAF, neurons clustered according to rate selectivity. Second, most (∼60%) AAF neurons were either fast-pass or band-pass selective. Most A1 neurons (∼72%) were slow-pass selective. This distribution supports the hypothesis that AAF is specialized for faster temporal processing than A1. Single-unit recordings ( n = 223) from A1 and AAF show that the mouse auditory cortex is best poised to detect and discriminate a narrow range of sweep rates between 0.5 and 3 kHz/ms. Third, based on recordings obtained at different depths, neurons in the infragranular layers were less rate selective than neurons in the granular layers, suggesting FM processing undergoes changes within the cortical column. On average, there was very little direction selectivity in the mouse auditory cortex. There was also no correlation between characteristic frequency and direction selectivity. The narrow range of rate selectivity in the mouse cortex indicates that FM rate processing is a useful physiological marker for studying contributions of genetic and environmental factors in auditory system development, aging, and disease.
Stereotypical spatiotemporal activity patterns during slow-wave activity in the neocortex
Authors: Fucke Thomas , Suchanek Dymphie , Nawrot Martin P. , Seamari Yamina , Heck Detlef H. , Aertsen Ad , Boucsein Clemens
Published: August 2011

Alternating epochs of activity and silence are a characteristic feature of neocortical networks during certain sleep cycles and deep states of anesthesia. The mechanism and functional role of these slow oscillations (<1 Hz) have not yet been fully characterized. Experimental and theoretical studies show that slow-wave oscillations can be generated autonomously by neocortical tissue but become more regular through a thalamo-cortical feedback loop. Evidence for a functional role of slow-wave activity comes from EEG recordings in humans during sleep, which show that activity travels as stereotypical waves over the entire brain, thought to play a role in memory consolidation. We used an animal model to investigate activity wave propagation on a smaller scale, namely within the rat somatosensory cortex. Signals from multiple extracellular microelectrodes in combination with one intracellular recording in the anesthetized animal in vivo were utilized to monitor the spreading of activity. We found that activity propagation in most animals showed a clear preferred direction, suggesting that it often originated from a similar location in the cortex. In addition, the breakdown of active states followed a similar pattern with slightly weaker direction preference but a clear correlation to the direction of activity spreading, supporting the notion of a wave-like phenomenon similar to that observed after strong sensory stimulation in sensory areas. Taken together, our findings support the idea that activity waves during slow-wave sleep do not occur spontaneously at random locations within the network, as was suggested previously, but follow preferred synaptic pathways on a small spatial scale.
Distributed representation of social odors indicates parallel processing in the antennal lobe of ants
Authors: Brandstaetter Andreas Simon , Kleineidam Christoph Johannes
Published: August 2011

In colonies of eusocial Hymenoptera cooperation is organized through social odors, and particularly ants rely on a sophisticated odor communication system. Neuronal information about odors is represented in spatial activity patterns in the primary olfactory neuropile of the insect brain, the antennal lobe (AL), which is analog to the vertebrate olfactory bulb. The olfactory system is characterized by neuroanatomical compartmentalization, yet the functional significance of this organization is unclear. Using two-photon calcium imaging, we investigated the neuronal representation of multicomponent colony odors, which the ants assess to discriminate friends (nestmates) from foes (nonnestmates). In the carpenter ant Camponotus floridanus, colony odors elicited spatial activity patterns distributed across different AL compartments. Activity patterns in response to nestmate and nonnestmate colony odors were overlapping. This was expected since both consist of the same components at differing ratios. Colony odors change over time and the nervous system has to constantly adjust for this (template reformation). Measured activity patterns were variable, and variability was higher in response to repeated nestmate than to repeated nonnestmate colony odor stimulation. Variable activity patterns may indicate neuronal plasticity within the olfactory system, which is necessary for template reformation. Our results indicate that information about colony odors is processed in parallel in different neuroanatomical compartments, using the computational power of the whole AL network. Parallel processing might be advantageous, allowing reliable discrimination of highly complex social odors.
Adipokines and Osteoarthritis: Novel Molecules Involved in the Pathogenesis and Progression of Disease
Authors: Conde Javier , Scotece Morena , Gómez Rodolfo , Lopez Veronica , Gómez-Reino Juan Jesus , Gualillo Oreste
Published: August 2011

Obesity has been considered a risk factor for osteoarthritis and it is usually accepted that obesity contributes to the development and progression of osteoarthritis by increasing mechanical load of the joints. Nevertheless, recent advances in the physiology of white adipose tissue evidenced that fat cells produce a plethora of factors, called adipokines, which have a critical role in the development of ostearthritis, besides to mechanical effects. In this paper, we review the role of adipokines and highlight the cellular and molecular mechanisms at play in osteoarthritis elicited by adipokines. We also emphasize how defining the role of adipokines has broadned our understanding of the diversity of factors involved in the genesis and progression of osteoarthritis in the hope of modifying it to prevent and treat diseases.
Histaminergic Mechanisms for Modulation of Memory Systems
Authors: Köhler Cristiano André , da Silva Weber Cláudio , Benetti Fernando , Bonini Juliana Sartori
Published: August 2011

Encoding for several memory types requires neural changes and the activity of distinct regions across the brain. These areas receive broad projections originating in nuclei located in the brainstem which are capable of modulating the activity of a particular area. The histaminergic system is one of the major modulatory systems, and it regulates basic homeostatic and higher functions including arousal, circadian, and feeding rhythms, and cognition. There is now evidence that histamine can modulate learning in different types of behavioral tasks, but the exact course of modulation and its mechanisms are controversial. In the present paper we review the involvement of the histaminergic system and the effects histaminergic receptor agonists/antagonists have on the performance of tasks associated with the main memory types as well as evidence provided by studies with knockout models. Thus, we aim to summarize the possible effects histamine has on modulation of circuits involved in memory formation.
The Existence of Solutions for a Nonlinear Fractional Multi‐Point Boundary Value Problem at Resonance
Authors: Han Xiaoling , Wang Ting
Published: August 2011

We discuss the existence of solution for a multipoint boundary value problem of fractional differential equation. An existence result is obtained with the use of the coincidence degree theory.
Tobacco and the Escalating Global Cancer Burden
Authors: Oppeltz Richard F. , Jatoi Ismail
Published: August 2011

The global burden of cancer is escalating as a result of dramatic increases in the use of tobacco in the developing world. The use of tobacco is linked to the development of a broad variety of cancers, mainly lung cancer, the single most common cancer in the world. Tobacco smoking-attributable deaths extends beyond cancer and include stroke, heart attack and COPD. Widening disparities in cancer-related mortality have shifted towards a more dramatic burden in the developing world. Appropriate interventions must be implemented to reduce tobacco use and prevent global mortality that has escalated to epidemic levels. Tobacco control policies, including public health advertisement campaigns, warning labels, adoption of smoke-free laws, comprehensive bans and tax policies are highly effective measures to control tobacco use. Clinicians and academic institutions have to be actively committed to support tobacco control initiatives. The reduction in cancer related morbidity and mortality should be viewed as a global crisis and definitive results will depend on a multilevel effort to effectively reduce the burden of cancer, particularly in underprivileged regions of the world.
Group‐Invariant Solutions for Two‐Dimensional Free, Wall, and Liquid Jets Having Finite Fluid Velocity at Orifice
Authors: Naz R.
Published: August 2011

The group‐invariant solutions for nonlinear third‐order partial differential equation (PDE) governing flow in two‐dimensional jets (free, wall, and liquid) having finite fluid velocity at orifice are constructed. The symmetry associated with the conserved vector that was used to derive the conserved quantity for the jets (free, wall, and liquid) generated the group invariant solution for the nonlinear third‐order PDE for the stream function. The comparison between results for two‐dimensional jet flows having finite and infinite fluid velocity at orifice is presented. The general form of the group invariant solution for two‐dimensional jets is given explicitly.
Genetics and Function of Neocortical GABAergic Interneurons in Neurodevelopmental Disorders
Authors: Rossignol E.
Published: August 2011

A dysfunction of cortical and limbic GABAergic circuits has been postulated to contribute to multiple neurodevelopmental disorders in humans, including schizophrenia, autism, and epilepsy. In the current paper, I summarize the characteristics that underlie the great diversity of cortical GABAergic interneurons and explore how the multiple roles of these cells in developing and mature circuits might contribute to the aforementioned disorders. Furthermore, I review the tightly controlled genetic cascades that determine the fate of cortical interneurons and summarize how the dysfunction of genes important for the generation, specification, maturation, and function of cortical interneurons might contribute to these disorders.
Friedel-Crafts Polyketones: Synthesis, Characterization and Antimicrobial Properties of Unsaturated Polyketones and Copolyketones Based on Difurfurylidene Cycloheptanone
Authors: Al-Muaikel Nayef S.
Published: August 2011

A new type of unsaturated polyketones and copolyketones having cycloheptanone moiety in a p-conjugated main chain were synthesized via Friedel-Crafts reaction through the polymerization of the monomer: 2,7-bis furfurylidene cycloheptanoneIwith different diacid chlorides. The model compound was synthesized by reactingIwith benzoyl chloride and characterized by1H-NMR, IR, and elemental analyses. The polyketones and copolyketones were soluble easily in protic solvents like H2SO4and trifluoroacetic acid. The thermal properties of these polyketones and copolyketones were evaluated and correlated to their structural units by TGA and DSC measurements. The crystallinity of some polymers was tested by X-ray analyses; also the morphological properties of selected examples of poly and copolyketones were detected by SEM. All the polyketones were tested for their biological activity against bacteria, fungi, and yeast. It was observed that the majority of the polyketones and its copolymers synthesized can be used as antibacterial and antifungal agents.
Nanoporous PdCo Catalyst for Microfuel Cells: Electrodeposition and Dealloying
Authors: Tominaka Satoshi , Osaka Tetsuya
Published: August 2011

PdCo alloy is a promising catalyst for oxygen reduction reaction of direct methanol fuel cells because of its high activity and the tolerance to methanol. We have applied this catalyst in order to realize on‐chip fuel cell which is a membraneless design. The novel design made the fuel cells to be flexible and integratable with other microdevices. Here, we summarize our recent research on the synthesis of nanostructured PdCo catalyst by electrochemical methods, which enable us to deposit the alloy onto microelectrodes of the on‐chip fuel cells. First, the electrodeposition of PdCo is discussed in detail, and then, dealloying for introducing nanopores into the electrodeposits is described. Finally, electrochemical response and activities are fully discussed.
Synthesis, Crystal Structure, and DNA-Binding Studies of a Nickel(II) Complex with the Bis(2-benzimidazolymethyl)amine Ligand
Authors: Wu Huilu , Sun Tao , Li Ke , Liu Bin , Kou Fan , Jia Fei , Yuan Jingkun , Bai Ying
Published: August 2011

A V-shaped ligand Bis(2-benzimidazolymethyl)amine (bba) and its nickel(II) picrate (pic) complex, with composition [Ni(bba)2](pic)2⋅3MeOH, have been synthesized and characterized on the basis of elemental analyses, molar conductivities, IR spectra, and UV/vis measurements. In the complex, the Ni(II) ion is six-coordinated with a N2O4ligand set, resulting in a distorted octahedron coordination geometry. In addition, the DNA-binding properties of the Ni(II) complex have been investigated by electronic absorption, fluorescence, and viscosity measurements. The experimental results suggest that the nickel(II) complex binds to DNA by partial intercalation binding mode.
Comparison of Newly Diagnosed Ocular Hypertension and Open-Angle Glaucoma: Ocular Variables, Risk Factors, and Disease Severity
Authors: Buys Yvonne M. , Harasymowycz Paul , Gaspo Rania , Kwok Kenneth , Hutnik Cindy M. L. , Blondeau Pierre , Birt Catherine M. , Piemontesi Robert L. G. , Gould Lisa F. , Lesk Mark R. , Ahmed Iqbal K.
Published: August 2011

Purpose. To describe the distribution of ocular variables, risk factors, and disease severity in newly diagnosed ocular hypertension (OH) or open-angle glaucoma (OAG).Methods. Eligible subjects underwent a complete history and examination. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) obtained from multiple logistic regression models were used to compare OAG to OH and advanced to early/moderate OAG.Results. 405 subjects were enrolled: 292 (72.1%) with OAG and 113 (27.9%) with OH. 51.7% had early, 27.1% moderate, and 20.9% advanced OAG. The OR for OAG versus OH was 8.19 (P<0.0001) for disc notch, 5.36 (P<0.0001) for abnormal visual field, 1.45 (P=0.001) for worsening mean deviation, 1.91 (P<0.0001) for increased cupping, 1.03 for increased age (P=0.030), and 0.36 (P=0.010) for smoking.Conclusions. Increased age was a risk for OAG, and smoking decreased the risk of OAG compared to OH. Almost half of the OAG subjects had moderate/advanced disease at diagnosis.
Identification of Epstein-Barr Virus–Induced Gene 3 as a Novel Serum and Tissue Biomarker and a Therapeutic Target for Lung Cancer
Authors: Nishino Ryohei , Takano Atsushi , Oshita Hideto , Ishikawa Nobuhisa , Akiyama Hirohiko , Ito Hiroyuki , Nakayama Haruhiko , Miyagi Yohei , Tsuchiya Eiju , Kohno Nobuoki , Nakamura Yusuke , Daigo Yataro
Published: August 2011

Purpose: This study aims to identify novel biomarkers and therapeutic targets for lung cancer.

Experimental Design: We carried out gene expression profile analysis of 120 lung cancers to screen for genes encoding transmembrane/secretory molecules that are commonly transactivated in lung cancers. Epstein-Barr virus–induced gene 3 (EBI3), which encodes a secretory glycoprotein, was selected as a good candidate. Immunohistochemical staining using tissue microarray consisting of 414 non–small cell lung cancers was applied to examine the expression level and prognostic value of EBI3. Serum EBI3 levels in 400 individuals for training assays (274 lung cancers and 126 healthy volunteers) and those in 173 individuals for validation analysis (132 lung cancers and 41 healthy volunteers) were measured by ELISA. The role of EBI3 in cancer cell growth was examined by siRNA and cell growth assays, using cells stably expressing exogenous EBI3.

Results: Immunohistochemical staining of EBI3 using tissue microarrays revealed that a high level of EBI3 expression was associated with a poor prognosis of lung cancer (P = 0.0014) and multivariate analysis confirmed it to be an independent prognostic factor (P = 0.0439). Serum levels of EBI3 in the training set were found to be significantly higher in lung cancer patients than in healthy volunteers; this result was also observed in the validation set. Furthermore, reduction in EBI3 expression by siRNA suppressed cancer cell proliferation whereas induction of exogenous EBI3 conferred growth-promoting activity.

Conclusions: EBI3 is a potential serum and tissue biomarker as well as therapeutic target for lung cancer. Clin Cancer Res; 17(19); 6272–86. ©2011 AACR.
BAD Phosphorylation Determines Ovarian Cancer Chemosensitivity and Patient Survival
Authors: Marchion Douglas C. , Cottrill Hope M. , Xiong Yin , Chen Ning , Bicaku Elona , Fulp William J. , Bansal Nisha , Chon Hye Sook , Stickles Xiaomang B. , Kamath Siddharth G. , Hakam Ardeshir , Li Lihua , Su Dan , Moreno Carolina , Judson Patricia L. , Berchuck Andrew , Wenham Robert M. , Apte Sachin M. , Gonzalez-Bosquet Jesus , Bloom Gregory C. , Eschrich Steven A. , Sebti Said , Chen Dung-Tsa , Lancaster Johnathan M.
Published: August 2011

Purpose: Despite initial sensitivity to chemotherapy, ovarian cancers (OVCA) often develop drug resistance, which limits patient survival. Using specimens and/or genomic data from 289 patients and a panel of cancer cell lines, we explored genome-wide expression changes that underlie the evolution of OVCA chemoresistance and characterized the BCL2 antagonist of cell death (BAD) apoptosis pathway as a determinant of chemosensitivity and patient survival.

Experimental Design: Serial OVCA cell cisplatin treatments were performed in parallel with measurements of genome-wide expression changes. Pathway analysis was carried out on genes associated with increasing cisplatin resistance (EC50). BAD-pathway expression and BAD protein phosphorylation were evaluated in patient samples and cell lines as determinants of chemosensitivity and/or clinical outcome and as therapeutic targets.

Results: Induced in vitro OVCA cisplatin resistance was associated with BAD-pathway expression (P < 0.001). In OVCA cell lines and primary specimens, BAD protein phosphorylation was associated with platinum resistance (n = 147, P < 0.0001) and also with overall patient survival (n = 134, P = 0.0007). Targeted modulation of BAD-phosphorylation levels influenced cisplatin sensitivity. A 47-gene BAD-pathway score was associated with in vitro phosphorylated BAD levels and with survival in 142 patients with advanced-stage (III/IV) serous OVCA. Integration of BAD-phosphorylation or BAD-pathway score with OVCA surgical cytoreductive status was significantly associated with overall survival by log-rank test (P = 0.004 and P < 0.0001, respectively).

Conclusion: The BAD apoptosis pathway influences OVCA chemosensitivity and overall survival, likely via modulation of BAD phosphorylation. The pathway has clinical relevance as a biomarker of therapeutic response, patient survival, and as a promising therapeutic target. Clin Cancer Res; 17(19); 6356–66. ©2011 AACR.
Oxidative Stress and Prostate Cancer Progression Are Elicited by Membrane-Type 1 Matrix Metalloproteinase
Authors: Nguyen Hoang-Lan , Zucker Stanley , Zarrabi Kevin , Kadam Pournima , Schmidt Cathleen , Cao Jian
Published: August 2011

Oxidative stress caused by high levels of reactive oxygen species (ROS) has been correlated with prostate cancer aggressiveness. Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP), which has been implicated in cancer invasion and metastasis, is associated with advanced prostate cancer. We show here that MT1-MMP plays a key role in eliciting oxidative stress in prostate cancer cells. Stable MT1-MMP expression in less invasive LNCaP prostate cancer cells with low endogenous MT1-MMP increased activity of ROS, whereas MT1-MMP knockdown in DU145 cells with high endogenous MT1-MMP decreased activity of ROS. Expression of MT1-MMP increased oxidative DNA damage in LNCaP and in DU145 cells, indicating that MT1-MMP–mediated induction of ROS caused oxidative stress. MT1-MMP expression promoted a more aggressive phenotype in LNCaP cells that was dependent on elaboration of ROS. Blocking ROS activity using the ROS scavenger N-acetylcysteine abrogated MT1-MMP–mediated increase in cell migration and invasion. MT1-MMP–expressing LNCaP cells displayed an enhanced ability to grow in soft agar that required increased ROS. Using cells expressing MT1-MMP mutant cDNAs, we showed that ROS activation entails cell surface MT1-MMP proteolytic activity. Induction of ROS in prostate cancer cells expressing MT1-MMP required adhesion to extracellular matrix proteins and was impeded by anti-β1 integrin antibodies. These results highlight a novel mechanism of malignant progression in prostate cancer cells that involves β1 integrin–mediated adhesion, in concert with MT1-MMP proteolytic activity, to elicit oxidative stress and induction of a more invasive phenotype. Mol Cancer Res; 9(10); 1305–18. ©2011 AACR.
Causal Link between Microsatellite Instability and hMRE11 Dysfunction in Human Cancers
Authors: Wu Xiling , Xu Yang , Chai Weihang , Her Chengtao
Published: August 2011

Maintenance of genomic integrity is essential for cell survival, and genomic instability is a commonly recognized intrinsic property of all cancers. Microsatellite instability (MSI) represents a frequently occurring and easily traceable simple form of sequence variation, signified by the contraction or expansion of specific DNA sequences containing short tandem repeats. MSI is frequently detected in tumor cells with DNA mismatch repair (MMR) deficiency. It is commonly conceived that instability at individual microsatellite loci can arise spontaneously in cells independent of MMR status, and different microsatellite loci are generally not affected uniformly by MMR deficiency. It is well recognized that MMR deficiency per se is not sufficient to initiate tumorigenesis; rather, the biological effects have to be exerted by mutations in genes controlling cell survival, DNA damage response, and apoptosis. Recently, shortening of an intronic hMRE11 poly(T)11 tract has been associated with MMR deficiency, raising the possibility that hMRE11 may be inactivated by defective MMR. However, the molecular nature underlying this association is presently unknown, and review of the current literature suggests that hMRE11 is most likely involved with the MMR pathway in a more complex fashion than simply being a MMR target gene. An alternative scenario is proposed to better reconcile the differences among various studies. The potential role of hMRE11 in telomere repeats stability is also discussed. Mol Cancer Res; 9(11); 1443–8. ©2011 AACR.
Traditional and Nontraditional Cardiovascular Risk Factors and Estimated Risk for Coronary Artery Disease in Renal Transplant Recipients: A Single-Center Experience
Authors: Banas Miriam C. , Banas Bernhard , Orth Stephan R. , Langer Veronika , Reinhold Stephan W. , Weingart Christian , Jung Bettina , Krüger Bernd , Krämer Bernhard K.
Published: August 2011

Background/Aims: The prevalence of cardiovascular disease in renal transplant recipients is markedly higher than in the general population due to the high prevalence of traditional cardiovascular risk factors, renal transplant function impairment and treatment with immunosuppressive drugs that affect blood pressure, cholesterol and blood glucose levels. Methods: Cross-sectional analysis using our renal transplant clinic cohort investigating (1) the cardiovascular risk factors present in this cohort, and (2) estimating their impact on the risk of coronary artery disease (CAD) by using the Framingham algorithm. Results: Control of modifiable cardiovascular risk factors in 231 renal transplant recipients is suboptimal, i.e. 47.2% of patients are hypertensive, 10.3% actively smoke, 39.4% have serum cholesterol concentrations >200 mg/dl, and 19.7% have diabetes mellitus. Blood pressure, age, hyperlipidemia, smoking and diabetes modulate the estimated CAD risk in males and females. Furthermore, a short time period (less than 1 year) since transplantation and increased serum creatinine levels negatively influenced the CAD risk in this patient population. Conclusion: According to current guidelines, the control of modifiable cardiovascular risk factors in renal transplant recipients is suboptimal. The decreasing CAD risk over time after transplantation may be due to the reduction of immunosuppressive drugs with time and survival bias.
Anti-Inflammatory Effects of Electroacupuncture in the Respiratory System of a Symptomatic Amyotrophic Lateral Sclerosis Animal Model
Authors: Jiang Jing Hua , Yang Eun Jin , Baek Myung Gi , Kim Seon Hwy , Lee Sang Min , Choi Sun-Mi
Published: August 2011

Background: Because amyotrophic lateral sclerosis (ALS) is a progressive inflammatory disease, treatment of the pulmonary system plays a key role in ALS patients’ care. Previous studies have mainly examined the pathological mechanism of ALS in the central nervous system; however, there has been relatively little research regarding the pulmonary system in ALS animal models. In inflammatory diseases, including asthma and arthritis, electroacupuncture (EA) is commonly used for its anti-inflammatory effects. The goal of this study was to determine whether EA treatment affects inflammation in the pulmonary system in an ALS animal model. Methods: EA treatment at ST36 (Zusanli) acupoint was performed with 14-week-old hSOD1G93A transgenic mice. Immunohistochemical analysis was performed using anti-ionized calcium binding adaptor molecule 1 (Iba-1) and anti-tumor necrosis factor alpha (TNF-α) antibodies. To investigate the expression level of inflammatory proteins, Western blot analyses were performed using anti-Iba-1, anti-TNF-α, anti-nuclear factor kappa B (NF-ĸB), and anti-interleukin 6 (IL-6) antibodies. The activation of Ser435-phospho-specific RAC-alpha serine/threonine-protein kinase 1 (pAKT) and the increase of phosphorylated extracellular-signal-regulated kinases (pERK) protein in lung tissues of EA-treated and untreated hSOD1G93A mice were also evaluated by Western blot. Results: EA treatment decreased the expression of the proinflammatory proteins such as TNF-α and IL-6, pNF-ĸB, and Iba-1 and increased the level of activated pAKT and pERK compared to control hSOD1G93A mice. Conclusions: Our findings suggest that EA could be an effective anti-inflammatory treatment for the respiratory impairment that occurs in ALS animal models.
Assessment of Hippocampal Adeno-Associated Viral Vector Gene Delivery via Frameless Stereotaxis in a Nonhuman Primate
Authors: Leung Cary H. , Kliem Michele A. , Heeke Brenten L. , McPhee Scott W.J. , Federici Thais , Snyder Brooke R. , Boulis Nicholas M.
Published: August 2011

Background/Aims: Expression of the neuropeptide galanin in hippocampal neurons reduces seizures in the kainic acid rodent model of epilepsy. In order to translate these findings into a human clinical trial, the safety and feasibility of hippocampal adeno-associated viral (AAV) vector expression must be demonstrated in a nonhuman primate model. Methods: The Stealth Frameless Stereotactic System and Navigus Biopsy Appliance (Medtronic) were used to inject self-complementary AAV2 carrying the gene for green fluorescent protein (GFP) into monkey hippocampi. Using a single occipital trajectory per side (n = 8 trajectories), multiple injections spaced by 5 mm were delivered to each hippocampus. Results: GFP was expressed in both neuronal and glial cells. Injections led to nonhomogeneous gene expression, suggesting closer spacing of injections may lead to more gene expression. Increasing injection volumes entailed a general increase in volume of expression, but there was no overlap of expression within the 5-mm injection interval. Efforts to avoid the occipital horn failed to prevent leaking of vector into the ventricle, and resulted in deviation of the trajectory at proximal points from the hippocampus. Conclusion: Using the occipital approach, adequate cannulation of the monkey hippocampus will require transventricular trajectories.
Reproducibility of Heart Rate Variability during Rest, Paced Breathing and Light-to-Moderate Intense Exercise in Patients One Month after Stroke
Authors: Ginsburg P. , Bartur G. , Peleg S. , Vatine J.J. , Katz-Leurer M.
Published: August 2011

Aim: To examine test-retest reliability of time and frequency domain heart rate variability (HRV) in patients 1 month after stroke during rest, paced breathing and light-to-moderate physical activity. Methods: Fifteen patients up to 1 month after stroke underwent two measurements of HRV, with the measurements 4 days apart. Measurements took place under three conditions while sitting: (1) at rest with self-select breathing frequency, (2) paced breathing and (3) cycling while sitting. Reliability was assessed statistically by calculating intraclass correlation coefficients (ICC), standard error of measurement and coefficient of variance (CV). Results: The relative reliability was found to be good-to-excellent for SDNN (ICC: 0.86–0.91), RMSSD (ICC: 0.81–0.87) and HF (ICC: 0.91–0.94) in all three conditions and poor for LF at rest and paced breathing (ICC: 0.43–0.47). The absolute reliability for all measures was found to be poor (CV >15%). Conclusions: HRV can be reliably assessed at rest, paced breathing and light-to-moderate physical activity for identifying differences between patients, while individual changes in autonomic functioning exhibited large random variations between test-retest measurements.
Familial Autosomal Recessive Renal Tubular Acidosis: Importance of Early Diagnosis
Authors: Vivante Asaf , Lotan Danny , Pode-Shakked Naomi , Landau Daniel , Svec Peter , Nampoothiri Sheela , Verma Ishwar , Abu-Libdeh Abdulsalam , Bockenhauer Detlef , Dekel Benjamin , Anikster Yair
Published: August 2011

Background and Aims: Untreated renal tubular acidosis (RTA) can result in severe complications. We reviewed the clinical features of patients with mutations in two genes causing RTA and evaluated their developmental expression assuming that timing, symptom severity and complications may be related to its occurrence. Methods: Clinical data from 16 patients with RTA due to mutations in either ATP6V1B1 or CAII were retrospectively reviewed. Both genes’ localization and expression pattern in the developing human kidney were analyzed by real-time polymerase chain reaction and immunostaining. Results: RTA-presenting symptoms were non-specific. Patients with mutations in ATP6V1B1 had earlier presentation (4.9 vs. 11 months, p < 0.041) and longer time to diagnosis than patients with CAII mutations (5.8 vs. 57 months, p < 0.01). Patients with ATP6V1B1 mutations were more likely to develop chronic kidney disease than those with CAII mutations (follow-up GFR values: 89 vs. 110 ml/min/1.73 m2, respectively, p < 0.017), probably secondary to nephrocalcinosis. Both ATP6V1B1 and CAII were expressed early during human nephrogenesis, with relatively higher transcript levels of ATP6V1B1. Conclusions: There is considerable delay in establishing a diagnosis of both types of RTA, supporting the need for earlier biochemical investigation. RTA due to ATP6V1B1 mutations is associated with mild progressive loss of kidney function.
EX-HOM (EXome HOMozygosity): A Proof of Principle
Authors: Pippucci Tommaso , Benelli Matteo , Magi Alberto , Martelli Pier Luigi , Magini Pamela , Torricelli Francesca , Casadio Rita , Seri Marco , Romeo Giovanni
Published: August 2011

Objective: We provide the proof of principle that exome sequencing of only two affected siblings born to first-cousin parents is capable of directly identifying a single candidate gene for an autosomal recessive disorder. This strategy, which we call EX-HOM (EXome HOMozygosity), combines in a single step the capacity of exome sequencing to identify all the coding variants present in a genome with the property of homozygosity mapping to limit the search for candidate genes to specific chromosomal regions. Methods: We sequenced the exomes of two siblings born to first-cousin parents affected with dysmyelinating leukodystrophy and spastic paraparesis caused by a mutation in FA2H. We used exome sequencing data to identify homozygous regions shared by the two affected siblings (EX-HOM regions), compared them with the regions of maximum LOD score obtained with SNP genotyping, and selected the candidate variants within. Results: We identified regions of shared homozygosity (>1 Mb) accounting for about 290 Mb, containing only 3 candidate variants. Among these, the FA2H mutation remained the only plausible one. Conclusion: In single consanguineous pedigrees with a few affected sibs, EX-HOM can be a one-step approach to identify the candidate genetic defect, bypassing obstacles such as genetic heterogeneity and the need for large pedigrees.
Methylaminolaevulinic Acid Photodynamic Therapy in the Treatment of Erythroplasia of Queyrat
Authors: Feldmeyer Laurence , Krausz-Enderlin Valérie , Töndury Bettina , Hafner Jürg , French Lars E. , Hofbauer Günther F.L.
Published: August 2011

Background: Erythroplasia of Queyrat (EQ) is an intra-epithelial carcinoma of the penis. Progression to invasive carcinoma may occur. Its cause is unknown but some evidence suggests infection with human papillomavirus in the pathogenesis of EQ; however, recent data do not confirm this. Therapy is difficult and associated with important recurrence rates. Photodynamic therapy (PDT) employs a photosensitizer excited by visible light. The resulting photodynamic reaction selectively destroys atypical cells. Only few reports exist on the use of topical PDT in the treatment of EQ. Objective: We report 11 cases of EQ treated by topical methylaminolaevulinic acid (MAL) PDT. Results: Out of 11 male patients withEQ treated by topical MAL-PDT, 3 achieved complete remission sustained for 24 and 51 months and 4 a partial remission sustained for 2–45 months with a follow-up period of 4–45 months (1 patient lost to follow-up); surprisingly, 2 of the 4 patients with partial remission presented a complete remission after 20 and 45 months of follow-up, respectively, without further therapy. Four patients showed progression of the disease. Conclusion: Whereas topical MAL-PDT offers the advantages of tumour specificity, preservation of function and a good cosmetic result, side effects may cause treatment discontinuation in some cases. Treatment of EQ with PDT may represent a valuable option in selected cases, but our data do not allow considering it as a first-line therapeutic option.
Vertebral Artery Involvement by Tympanojugular Paragangliomas: Management and Outcomes with a Proposed Addition to the Fisch Classification
Authors: Shin Seung-Ho , Sivalingam Shailendra , De Donato Giuseppe , Falcioni Maurizio , Piazza Paolo , Sanna Mario
Published: August 2011

Objectives: To present the management and outcomes of cases of tympanojugular paraganglioma (TJP) with vertebral artery (VA) involvement, and to propose the addition of the new ‘V’ category to the Fisch classification. Materials and Methods: Retrospective analysis of data from a quaternary neuro-otologic and skull base referral center. We studied 230 TJP patients to identify the cases with VA involvement and present their management, surgical findings and outcome. Results: Out of 230 patients, 8 patients were found to have VA involvement by TJP. The extradural artery was involved in 1 patient and the intradural VA was involved in 6 patients. The intradural and extradural VA were simultaneously involved in 1 patient. Seven of the 8 patients underwent surgery. In 2 patients, preoperative occlusion was performed (1 with balloon, 1 with coils). In 5 of these 7 patients, the tumor was successfully separated from the VA by microdissection with or without endovascular intervention. In another patient, the tumor together with the involved VA was removed. Of 7 patients who had surgery, 1 patient did not undergo endovascular intervention and had subtotal tumor removal from the VA. There were no serious complications in removing the tumor from around the VA. Conclusion: Although uncommon, the intradural or extradural VA can be involved by TJP. To avoid vascular accidents, the VA should be thoroughly evaluated at the planning stage. We advocate that the addition of a ‘V’ category would help to identify patients who need individualized VA management as part of a complete surgical evaluation.
Elevated White Blood Cell Count Worsens Proteinuria but Not Estimated Glomerular Filtration Rate: The Kansai Healthcare Study
Authors: Sato Kyoko Kogawa , Hayashi Tomoshige , Harita Nobuko , Koh Hideo , Maeda Isseki , Endo Ginji , Nakamura Yoshiko , Kambe Hiroshi , Fukuda Kanji
Published: August 2011

Background/Aims: No prospective studies have estimated the association between white blood cell (WBC) count and the risk of proteinuria. We prospectively examined the relationships of WBC count, as a marker of inflammation, with two outcomes: proteinuria and low estimated glomerular filtration rate (eGFR). Methods: We enrolled 10,008 Japanese men aged 40–55 years who had neither proteinuria nor low eGFR and were not taking antihypertensive medications at entry. Proteinuria was defined as 1+ or higher on urine dipstick. Low eGFR was defined if eGFR was <60 ml/min/1.73 m2. Results: During the 49,644 person-years of follow-up, 1,557 cases of proteinuria were confirmed. After adjusting for age, body mass index, fasting plasma glucose, systolic blood pressure, diastolic blood pressure, antidiabetic medications, alcohol consumption, smoking, regular leisure-time physical activity and eGFR, the highest quintile (≧7.51 × 103/µl) of WBC count was independently associated with an increased risk of incidence of proteinuria [HR: 1.45 (95% CI: 1.23–1.73)] compared with the lowest quintile (≤4.80 × 103/µl). On the other hand, during 52,833 person-years, we confirmed 439 cases of low eGFR. In multivariate models, there was no association between WBC count and low eGFR. Conclusion: Elevated WBC count was independently associated with an increased risk of proteinuria, but not low eGFR.
Microparticles, Vascular Function, and Atherothrombosis
Authors: Rautou Pierre-Emmanuel , Vion Anne-Clémence , Amabile Nicolas , Chironi Gilles , Simon Alain , Tedgui Alain , Boulanger Chantal M.
Published: August 2011

Membrane-shed submicron microparticles (MPs) are released after cell activation or apoptosis. High levels of MPs circulate in the blood of patients with atherothrombotic diseases, where they could serve as a useful biomarker of vascular injury and a potential predictor of cardiovascular mortality and major adverse cardiovascular events. Atherosclerotic lesions also accumulate large numbers of MPs of leukocyte, smooth muscle cell, endothelial, and erythrocyte origin. A large body of evidence supports the role of MPs at different steps of atherosclerosis development, progression, and complications. Circulating MPs impair the atheroprotective function of the vascular endothelium, at least partly, by decreased nitric oxide synthesis. Plaque MPs favor local inflammation by augmenting the expression of adhesion molecule, such as intercellular adhesion molecule -1 at the surface of endothelial cell, and monocyte recruitment within the lesion. In addition, plaque MPs stimulate angiogenesis, a key event in the transition from stable to unstable lesions. MPs also may promote local cell apoptosis, leading to the release and accumulation of new MPs, and thus creating a vicious circle. Furthermore, highly thrombogenic plaque MPs could increase thrombus formation at the time of rupture, together with circulating MPs released in this context by activated platelets and leukocytes. Finally, MPs also could participate in repairing the consequences of arterial occlusion and tissue ischemia by promoting postischemic neovascularization.
Respectability, Middle-Class Material Culture, and Economic Crisis: The Case of Lier in Brabant, 1690–1770
Authors: Poukens Johan , Provoost Nele
Published: August 2011

Poll-tax lists and probate inventories from the small town of Lier reveal an expanding middle class with an enduring investment in objects and activities that signaled prudence and trustworthiness. The middle class created a self-image of respectability by consuming hot drinks in tastefully decorated dining rooms and parlors. Rather than curbing the desire for novelty, the adverse economic conditions of the 1720s sharpened the relative importance of participation in activities that signified credibility.
History's Changing Climate: Climate Science, Genomics, and the Emerging Consilient Approach to Interdisciplinary History
Authors: McCormick Michael
Published: August 2011

Consilience refers to the quality of investigations that draw conclusions from forms of evidence that are epistemologically distinct. The term seems particularly apt for conclusions produced by natural-scientific investigations on the one hand and by historical and archaeological studies on the other. Consilience points to areas of underlying unity of humanistic and scientific investigation— a unity arising from that of reality itself; it represents a convergence in parallel but independent investigations that results in deductions that are much more robust than any investigation would be able to produce on its own.
A Continental-Scale Classification of Rainfall Seasonality Regimes in Africa Based on Gridded Precipitation and Land Surface Temperature Products
Authors: Herrmann Stefanie M. , Mohr Karen I.
Published: August 2011

A classification of rainfall seasonality regimes in Africa was derived from gridded rainfall and land surface temperature products. By adapting a method that goes back to Walter and Lieth’s approach of presenting climatic diagrams, relationships between estimated rainfall and temperature were used to determine the presence and pattern of humid, arid, and dry months. The temporal sequence of humid, arid, and dry months defined nonseasonal as well as single-, dual-, and multiple-wet-season regimes with one or more rainfall peaks per wet season. The use of gridded products resulted in a detailed, spatially continuous classification for the entire African continent at two different spatial resolutions, which compared well to local-scale studies based on station data. With its focus on rainfall patterns at fine spatial scales, this classification is complementary to coarser and more genetic classifications based on atmospheric driving forces. An analysis of the stability of the resulting seasonality regimes shows areas of relatively high year-to-year stability in the single-wet-season regimes and areas of lower year-to-year stability in the dual- and multiple-wet-season regimes as well as in transition zones.
A Systematic Study of Longwave Radiative Heating and Cooling within Valleys and Basins Using a Three-Dimensional Radiative Transfer Model
Authors: Hoch Sebastian W. , Whiteman C. David , Mayer Bernhard
Published: August 2011

The Monte Carlo code for the physically correct tracing of photons in cloudy atmospheres (MYSTIC) three-dimensional radiative transfer model was used in a parametric study to determine the strength of longwave radiative heating and cooling in atmospheres enclosed in idealized valleys and basins. The parameters investigated included valley or basin shape, width, and near-surface temperature contrasts. These parameters were varied for three different representative atmospheric temperature profiles for different times of day. As a result of counterradiation from surrounding terrain, nighttime longwave radiative cooling in topographic depressions was generally weaker than over flat terrain. In the center of basins or valleys with widths exceeding 2 km, cooling rates quickly approached those over flat terrain, whereas the cooling averaged over the entire depression volume was still greatly reduced. Valley or basin shape had less influence on cooling rates than did valley width. Strong temperature gradients near the surface associated with nighttime inversion and daytime superadiabatic layers over the slopes significantly increased longwave radiative cooling and heating rates. Local rates of longwave radiative heating ranged between −30 (i.e., cooling) and 90 K day−1. The effects of the near-surface temperature gradients extended tens of meters into the overlying atmospheres. In small basins, the strong influence of nocturnal near-surface temperature inversions could lead to cooling rates exceeding those over flat plains. To investigate the relative role of longwave radiative cooling on total nighttime cooling in a basin, simulations were conducted for Arizona’s Meteor Crater using observed atmospheric profiles and realistic topography. Longwave radiative cooling accounted for nearly 30% of the total nighttime cooling observed in the Meteor Crater during a calm October night.