bluuebunny/crossref_metadata_2025 huggingface dataset:
Human T-lymphotropic type 1 virus p30 inhibits homologous recombination and favors unfaithful DNA repair
Authors: Baydoun Hicham H. , Pancewicz Joanna , Nicot Christophe
Published: March 2011

Whereas oncogenic retroviruses are common in animals, human T-lymphotropic virus 1 (HTLV-1) is the only transmissible retrovirus associated with cancer in humans and is etiologically linked to adult T-cell leukemia. The leukemogenesis process is still largely unknown, but relies on extended survival and clonal expansion of infected cells, which in turn accumulate genetic defects. A common feature of human tumor viruses is their ability to stimulate proliferation and survival of infected pretumoral cells and then hide by establishing latency in cells that have acquired a transformed phenotype. Whereas disruption of the DNA repair is one of the major processes responsible for the accumulation of genomic abnormalities and carcinogenesis, the absence of DNA repair also poses the threat of cell-cycle arrest or apoptosis of virus-infected cells. This study describes how the HTLV-1 p30 viral protein inhibits conservative homologous recombination (HR) DNA repair by targeting the MRE11/RAD50/NBS1 complex and favors the error-prone nonhomologous-end–joining (NHEJ) DNA-repair pathway instead. As a result, HTLV-1 p30 may facilitate the accumulation of mutations in the host genome and the cumulative risk of transformation. Our results provide new insights into how human tumor viruses may manipulate cellular DNA-damage responses to promote cancer.
Mechanism for phosphatidylserine-dependent erythrophagocytosis in mouse liver
Authors: Lee Sung-Jin , Park Seung-Yoon , Jung Mi-Yeon , Bae Sang Mun , Kim In-San
Published: March 2011

Aged or damaged RBCs are effectively removed from the blood circulation by Kupffer cells in the liver, but little is known regarding the mechanism of the clearance process. Here we show that stabilin-1 and stabilin-2 in hepatic sinusoidal endothelial cells (HSECs) are critical in effectively clearing damaged RBCs in mouse liver. Damaged RBCs and phosphatidylserine (PS)–coated beads were effectively sequestered in the hepatic sinusoid regardless of the presence of Kupffer cells, suggesting a role for HSECs in PS-dependent sequestration of PS-exposed RBCs in the liver. HSECs mediate tethering of damaged RBCs in a PS-dependent manner via stabilin-1 and stabilin-2. In a sinusoid-mimicked coculture system consisting of macrophages layered over HSECs, there was significant enhancement of the phagocytic capacity of macrophages, and this was mediated by stabilin-1 and stabilin-2 in HSECs. Liver-specific knockdown of stabilin-1 and stabilin-2 inhibited the sequestration of damaged RBCs in the hepatic sinusoid and delayed the elimination of damaged cells in an in vivo animal model. Thus, the roles of stabilin-1 and stabilin-2 in hepatic sequestration of PS-exposed RBCs may represent a potential mechanism for the clearance of damaged RBCs by Kupffer cells and for the control of some pathologic conditions such as hemolytic anemia.
Thymic T-cell development in allogeneic stem cell transplantation
Authors: Krenger Werner , Blazar Bruce R. , Holländer Georg A.
Published: March 2011

Cytoreductive conditioning regimens used in the context of allogeneic hematopoietic cell transplantation (HCT) elicit deficits in innate and adaptive immunity, which predispose patients to infections. As such, transplantation outcomes depend vitally on the successful reconstruction of immune competence. Restoration of a normal peripheral T-cell pool after HCT is a slow process that requires the de novo production of naive T cells in a functionally competent thymus. However, there are several challenges to this regenerative process. Most notably, advanced age, the cytotoxic pretransplantation conditioning, and posttransplantation alloreactivity are risk factors for T-cell immune deficiency as they independently interfere with normal thymus function. Here, we discuss preclinical allogeneic HCT models and clinical observations that have contributed to a better understanding of the transplant-related thymic dysfunction. The identification of the cellular and molecular mechanisms that control regular thymopoiesis but are altered in HCT patients is expected to provide the basis for new therapies that improve the regeneration of the adaptive immune system, especially with functionally competent, naive T cells.
The Chinese version of the Pediatric Quality of Life Inventory™ (PedsQL™) Family Impact Module: cross-cultural adaptation and psychometric evaluation
Authors: Chen Ruoqing , Hao Yuantao , Feng Lifen , Zhang Yingfen , Huang Zhuoyan
Published: March 2011

Background

A pediatric chronic health condition not only influences a child's life, but also has impacts on parent health-related quality of life (HRQOL) and family functioning. To provide care and social support to these families, a psychometrically well-developed instrument for measuring these impacts is of great importance. The present study is aimed to evaluate the psychometric properties of the Chinese version of the PedsQL™ Family Impact Module.

Methods

The cross-cultural adaptation of the PedsQL™ Family Impact Module was performed following the PedsQL™ Measurement Model Translation Methodology. The Chinese version of the PedsQL™ Family Impact Module was administered to 136 parents of children with asthma and 264 parents of children with heart disease from four Triple A hospitals. The psychometric properties such as feasibility, internal consistency reliability, item-subscale correlations and construct validity were evaluated.

Results

The percentage of missing item responses was less than 0.1% for both asthma and heart disease sample groups. The Chinese version of the PedsQL™ Family Impact Module showed ceiling effects but had acceptable reliability (Cronbach's Alpha Coefficients were higher than 0.7 in all the subscales except "Daily Activities" in the asthma sample group). There were higher correlation coefficients between items and their hypothesized subscales than those with other subscales. The asthma sample group reported higher parent HRQOL and family functioning than the heart disease sample group. In the heart disease sample group, parents of outpatients reported higher parent HRQOL and family functioning than parents of inpatients. Confirmatory factor analysis showed that the instrument had marginally acceptable construct validity with some Goodness-of-Fit indices not reaching the standard indicating acceptable model fit.

Conclusions

The Chinese version of the PedsQL™ Family Impact Module has adequate psychometric properties and could be used to assess the impacts of pediatric asthma or pediatric heart disease on parent HRQOL and family functioning in China. This instrument should be field tested on parents of children with other chronic medical conditions in other areas. Construct validity tested by confirmatory factor analysis and test-retest reliability should be further assessed.
Electron cotunneling through doubly occupied quantum dots: effect of spin configuration
Authors: Lan Jian , Sheng Weidong
Published: March 2011

A microscopic theory is presented for electron cotunneling through doubly occupied quantum dots in the Coulomb blockade regime. Beyond the semiclassic framework of phenomenological models, a fully quantum mechanical solution for cotunneling of electrons through a one-dimensional quantum dot is obtained using a quantum transmitting boundary method without any fitting parameters. It is revealed that the cotunneling conductance exhibits strong dependence on the spin configuration of the electrons confined inside the dot. Especially for the triplet configuration, the conductance shows an obvious deviation from the well-known quadratic dependence on the applied bias voltage. Furthermore, it is found that the cotunneling conductance reveals more sensitive dependence on the barrier width than the height.
Phenotypic and genotypic variations within a single bacteriophage species
Authors: Ceyssens Pieter-Jan , Glonti Thea , Kropinski ndrew M , Lavigne Rob , Chanishvili Nina , Kulakov Leonid , Lashkhi Nino , Tediashvili Marina , Merabishvili Maya
Published: March 2011

Background

Although horizontal gene transfer plays a pivotal role in bacteriophage evolution, many lytic phage genomes are clearly shaped by vertical evolution. We investigated the influence of minor genomic deletions and insertions on various phage-related phenotypic and serological properties.

Findings

We collected ten different isolates of Pseudomonas aeruginosa bacteriophage ϕKMV. All sequenced genomes (42-43 kb, long direct terminal repeats) are nearly identical, which intuitively implied strongly similar infections cycles. However, their latent periods vary between 21 and 28 minutes and they are able to lyse between 5 and 58% of a collection of 107 clinical P. aeruginosa strains. We also noted that phages with identical tail structures displayed profound differences in host spectra. Moreover, point mutations in tail and spike proteins were sufficient to evade neutralization by two phage-specific antisera, isolated from rabbits.

Conclusion

Although all analyzed phages are 83-97% identical at the genome level, they display a surprisingly large variation in various phenotypic properties. The small overlap in host spectrum and their ability to readily escape immune defences against a nearly identical phage are promising elements for the application of these phages in phage therapy.
The Temporal-Spatial Encoding of Acupuncture Effects in the Brain
Authors: Qin Wei , Bai Lijun , Dai Jianping , Liu Peng , Dong Minghao , Liu Jixin , Sun Jinbo , Yuan Kai , Chen Peng , Zhao Baixiao , Gong Qiyong , Tian Jie , Liu Yijun
Published: March 2011

Background:

Functional acupoint specificity is crucial to the clinical efficacy of acupuncture treatment, such as pain relief. Whether acupuncture needling at a peripheral acupoint produces distinct patterns of brain responses remains controversial.

Results:

This fMRI study employed the complex network analysis (CNA) to test the hypothesis that acupuncture stimulation at an acupoint correspondingly induced activity changes in one or more intrinsic or resting-state brain networks. Built upon the sustained effect of acupuncture and its time-varying characteristics, we constructed a dynamic encoding system with the hub anchored at the posterior cingulate cortex and precuneus (PCC/pC). We found that needling at two visual acupoints (GB37 and BL60) and a non-visual acupoint (KI8) induced a spatially converging brain response, which overlapped at the PCC/pC. We also found distinct neural modulations during and after acupoint stimulation. During this period, the PCC/pC interacted with a visual resting-state network in different patterns. Furthermore, there was a delayed functional correspondence between the intrinsic visual network and manipulation over the visual acupoints (i.e., GB37 or BL60), but not the non-visual acupoint (KI8) via the PCC/pC, implicating a specific temporal-spatial encoding/decoding mechanism underlying the post-effect of acupuncture.

Conclusions:

This study provided an integrated view exploring the functional specificity of acupuncture in which both the needling sensation and the following neural cascades may contribute to the overall effect of acupuncture through dynamic reconfiguration of complex neural networks.
Efficient algorithms for the discovery of gapped factors
Authors: Apostolico Alberto , Pizzi Cinzia , Ukkonen Esko
Published: March 2011

Background

The discovery of surprisingly frequent patterns is of paramount interest in bioinformatics and computational biology. Among the patterns considered, those consisting of pairs of solid words that co-occur within a prescribed maximum distance -orgapped factors- emerge in a variety of contexts of DNA and protein sequence analysis. A few algorithms and tools have been developed in connection with specific formulations of the problem, however, none can handle comprehensively each of the multiple ways in which the distance between the two terms in a pair may be defined.

Results

This paper presents efficient algorithms and tools for the extraction of all pairs of words up to an arbitrarily large length that co-occur surprisingly often in close proximity within a sequence. Whereas the number of such pairs in a sequence ofncharacters can be Θ(n4), it is shown that an exhaustive discovery process can be carried out inO(n2) orO(n3), depending on the way distance is measured. This is made possible by a prudent combination of properties of pattern maximality and monotonicity of scores, which lead to reduce the number of word pairs to be weighed explicitly, while still producing also the scores attained by any of the pairs not explicitly considered. We applied our approach to the discovery of spaced dyads in DNA sequences.

Conclusions

Experiments on biological datasets prove that the method is effective and much faster than exhaustive enumeration of candidate patterns. Software is available freely by academic users via the web interface athttp://bcb.dei.unipd.it:8080/dyweb.
Multiplex genotyping system for efficient inference of matrilineal genetic ancestry with continental resolution
Authors: van Oven Mannis , Vermeulen Mark , Kayser Manfred
Published: March 2011

Background

In recent years, phylogeographic studies have produced detailed knowledge on the worldwide distribution of mitochondrial DNA (mtDNA) variants, linking specific clades of the mtDNA phylogeny with certain geographic areas. However, a multiplex genotyping system for the detection of the mtDNA haplogroups of major continental distribution that would be desirable for efficient DNA-based bio-geographic ancestry testing in various applications is still missing.

Results

Three multiplex genotyping assays, based on single-base primer extension technology, were developed targeting a total of 36 coding-region mtDNA variants that together differentiate 43 matrilineal haplo-/paragroups. These include the major diagnostic haplogroups for Africa, Western Eurasia, Eastern Eurasia and Native America. The assays show high sensitivity with respect to the amount of template DNA: successful amplification could still be obtained when using as little as 4 pg of genomic DNA and the technology is suitable for medium-throughput analyses.

Conclusions

We introduce an efficient and sensitive multiplex genotyping system for bio-geographic ancestry inference from mtDNA that provides resolution on the continental level. The method can be applied in forensics, to aid tracing unknown suspects, as well as in population studies, genealogy and personal ancestry testing. For more complete inferences of overall bio-geographic ancestry from DNA, the mtDNA system provided here can be combined with multiplex systems for suitable autosomal and, in the case of males, Y-chromosomal ancestry-sensitive DNA markers.
Metabolome in schizophrenia and other psychotic disorders: a general population-based study
Authors: Orešič Matej , Tang Jing , Seppänen-Laakso Tuulikki , Mattila Ismo , Saarni Suoma E , Saarni Samuli I , Lönnqvist Jouko , Sysi-Aho Marko , Hyötyläinen Tuulia , Perälä Jonna , Suvisaari Jaana
Published: March 2011

Background

Persons with schizophrenia and other psychotic disorders have a high prevalence of obesity, impaired glucose tolerance, and lipid abnormalities, particularly hypertriglyceridemia and low high-density lipoprotein. More detailed molecular information on the metabolic abnormalities may reveal clues about the pathophysiology of these changes, as well as about disease specificity.

Methods

We applied comprehensive metabolomics in serum samples from a general population-based study in Finland. The study included all persons with DSM-IV primary psychotic disorder (schizophrenia, n = 45; other non-affective psychosis (ONAP), n = 57; affective psychosis, n = 37) and controls matched by age, sex, and region of residence. Two analytical platforms for metabolomics were applied to all serum samples: a global lipidomics platform based on ultra-performance liquid chromatography coupled to mass spectrometry, which covers molecular lipids such as phospholipids and neutral lipids; and a platform for small polar metabolites based on two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC × GC-TOFMS).

Results

Compared with their matched controls, persons with schizophrenia had significantly higher metabolite levels in six lipid clusters containing mainly saturated triglycerides, and in two small-molecule clusters containing, among other metabolites, (1) branched chain amino acids, phenylalanine and tyrosine, and (2) proline, glutamic, lactic and pyruvic acids. Among these, serum glutamic acid was elevated in all psychoses (P = 0.0020) compared to controls, while proline upregulation (P = 0.000023) was specific to schizophrenia. After adjusting for medication and metabolic comorbidity in linear mixed models, schizophrenia remained independently associated with higher levels in seven of these eight clusters (P < 0.05 in each cluster). The metabolic abnormalities were less pronounced in persons with ONAP or affective psychosis.

Conclusions

Our findings suggest that specific metabolic abnormalities related to glucoregulatory processes and proline metabolism are specifically associated with schizophrenia and reflect two different disease-related pathways. Metabolomics, which is sensitive to both genetic and environmental variation, may become a powerful tool in psychiatric research to investigate disease susceptibility, clinical course, and treatment response.
Herpes simplex virus type I (HSV-1) replicates in mature dendritic cells but can only be transferred in a cell–cell contact-dependent manner
Authors: Goldwich Andreas , Prechtel Alexander T , Mühl-Zürbes Petra , Pangratz Nadine M , Stössel Hella , Romani Nikolaus , Steinkasserer Alexander , Kummer Mirko
Published: March 2011

HSV-1 is a very successful representative of the α-herpesvirus family, and ∼90% of the population is seropositive for this particular virus. Although the pathogen usually causes the well-known mild lesions on the lips, also, severe infections of the eye or the brain can be observed in rare cases. It is well known, that this virus can efficiently infect the most potent APCs, i.e., the DCs, in their immature and mature state. Although the infection of the iDC has been shown to be productive, infection of mMDDCs is believed to be abortive in the early phase of the viral replication cycle. In line with these findings, no virus particles can be detected in the supernatant of HSV-1-infected mMDDC. In this study, however, we show for the first time that this pathogen completes its replication cycle in mMDDCs. We detected the presence of viral gene transcripts of all three phases of the replication cycle, as well as of late viral proteins, and even the generation of small amounts of progeny virus. Although we could confirm the findings that these particles are not released into the supernatant, surprisingly, the newly generated viral particles can be passed on to Vero cells, as well as to primary keratinocytes in a cell–cell contact-dependent manner. Finally, we provide evidence that the viral gE is involved in the transfer of infectious virus from mMDDCs to other permissive cells.
Source depopulation potential and surface-wave tomography using a crosscorrelation method in a scattering medium
Authors: Gouédard Pierre , Roux Philippe , Campillo Michel , Verdel Arie , Yao Huajian , van der Hilst Robert D.
Published: March 2011

We use seismic prospecting data on a 40 × 40 regular grid of sources and receivers deployed on a 1 km × 1 km area to assess the feasibility and advantages of velocity analysis of the shallow subsurface by means of surface-wave tomography with Green’s functions estimated from crosscorrelation. In a first application we measure Rayleigh-wave dispersion curves in a 1D equivalent medium. The assumption that the medium is laterally homogeneous allows using a simple projection scheme and averaging of crosscorrelation functions over the whole network. Because averaging suppresses noise, this method yields better signal-to-noise ratio than traditional active-source approaches, and the improvement can be estimated a priori from acquisition parameters. We find that high-quality dispersion curves can be obtained even when we reduce the number of active sources used as input for the correlations. Such source depopulation can achieve significant reduction in the cost of active source acquisition. In a second application we compare Rayleigh-wave group velocity tomography from raw and reconstructed data. We can demonstrate that the crosscorrelation approach yields group velocity maps that are similar to active source maps. Scattering has an importance here as it may enhance the crosscorrelation performance. We quantify the scattering properties of the medium using mean free path measurements from coherent and incoherent parts of the signal. We conclude that for first-order velocity analysis of the shallow subsurface, the use of crosscorrelation offers a cost-effective alternative to methods that rely exclusively on active sources.
Protein Phosphatase 1 (PP-1)-Dependent Inhibition of Insulin Secretion by Leptin in INS-1 Pancreatic β-Cells and Human Pancreatic Islets
Authors: Kuehnen Peter , Laubner Katharina , Raile Klemens , Schöfl Christof , Jakob Franz , Pilz Ingo , Päth Günter , Seufert Jochen
Published: March 2011

Leptin inhibits insulin secretion from pancreatic β-cells, and in turn, insulin stimulates leptin biosynthesis and secretion from adipose tissue. Dysfunction of this adipoinsular feedback loop has been proposed to be involved in the development of hyperinsulinemia and type 2 diabetes mellitus. At the molecular level, leptin acts through various pathways, which in combination confer inhibitory effects on insulin biosynthesis and secretion. The aim of this study was to identify molecular mechanisms of leptin action on insulin secretion in pancreatic β-cells. To identify novel leptin-regulated genes, we performed subtraction PCR in INS-1 β-cells. Regulated expression of identified genes was confirmed by RT-PCR and Northern and Western blotting. Furthermore, functional impact on β-cell function was characterized by insulin-secretion assays, intracellular Ca2+ concentration measurements, and enzyme activity assays. PP-1α, the catalytic subunit of protein phosphatase 1 (PP-1), was identified as a novel gene down-regulated by leptin in INS-1 pancreatic β-cells. Expression of PP-1α was verified in human pancreatic sections. PP-1α mRNA and protein expression is down-regulated by leptin, which culminates in reduction of PP-1 enzyme activity in β-cells. In addition, glucose-induced insulin secretion was inhibited by nuclear inhibitor of PP-1 and calyculin A, which was in part mediated by a reduction of PP-1-dependent calcium influx into INS-1 β-cells. These results identify a novel molecular pathway by which leptin confers inhibitory action on insulin secretion, and impaired PP-1 inhibition by leptin may be involved in dysfunction of the adipoinsular axis during the development of hyperinsulinemia and type 2 diabetes mellitus.
Notch Signaling Is Involved in Ovarian Follicle Development by Regulating Granulosa Cell Proliferation
Authors: Zhang Chun-Ping , Yang Jun-Ling , Zhang Jun , Li Lei , Huang Lin , Ji Shao-Yang , Hu Zhao-Yuan , Gao Fei , Liu Yi-Xun
Published: March 2011

Notch signaling is an evolutionarily conserved pathway, which regulates cell proliferation, differentiation, and apoptosis. It has been reported that the members of Notch signaling are expressed in mammalian ovaries, but the exact functions of this pathway in follicle development is still unclear. In this study, primary follicles were cultured in vitro and treated with Notch signaling inhibitors, L-658,458 and N-[N-(3,5-Difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT). We found that the cultured follicles completely stopped developing after L-658,458 and DAPT treatment, most of the granulosa cells were detached, and the oocytes were also degenerated with condensed cytoplasma. Further studies demonstrated that the proliferation of granulosa cells was dependent on the Notch signaling. L-658,458 and DAPT treatment inhibited proliferation of in vitro cultured primary granulosa cells and decreased the expression of c-Myc. Lentivirus mediated overexpression of Notch intracellular domain 2, and c-Myc could promote the proliferation of granulosa cells and rescue the growth inhibition induced by L-658,458 and DAPT. In conclusion, Notch signaling is involved in follicular development by regulating granulosa cell proliferation.
Telmisartan Improves Insulin Resistance and Modulates Adipose Tissue Macrophage Polarization in High-Fat-Fed Mice
Authors: Fujisaka Shiho , Usui Isao , Kanatani Yukiko , Ikutani Masashi , Takasaki Ichiro , Tsuneyama Koichi , Tabuchi Yoshiaki , Bukhari Agussalim , Yamazaki Yu , Suzuki Hikari , Senda Satoko , Aminuddin Aminuddin , Nagai Yoshinori , Takatsu Kiyoshi , Kobayashi Masashi , Tobe Kazuyuki
Published: March 2011

Diet-induced obesity is reported to induce a phenotypic switch in adipose tissue macrophages from an antiinflammatory M2 state to a proinflammatory M1 state. Telmisartan, an angiotensin II type 1 receptor blocker and a peroxisome proliferator-activated receptor-γ agonist, reportedly has more beneficial effects on insulin sensitivity than other angiotensin II type 1 receptor blockers. In this study, we studied the effects of telmisartan on the adipose tissue macrophage phenotype in high-fat-fed mice. Telmisartan was administered for 5 wk to high-fat-fed C57BL/6 mice. Insulin sensitivity, macrophage infiltration, and the gene expressions of M1 and M2 markers in visceral adipose tissues were then examined. An insulin- or a glucose-tolerance test showed that telmisartan treatment improved insulin resistance, decreasing the body weight gain, visceral fat weight, and adipocyte size without affecting the amount of energy intake. Telmisartan reduced the mRNA expression of CD11c and TNF-α, M1 macrophage markers, and significantly increased the expressions of M2 markers, such as CD163, CD209, and macrophage galactose N-acetyl-galactosamine specific lectin (Mgl2), in a quantitative RT-PCR analysis. A flow cytometry analysis showed that telmisartan decreased the number of M1 macrophages in visceral adipose tissues. In conclusion, telmisartan improves insulin sensitivity and modulates adipose tissue macrophage polarization to an antiinflammatory M2 state in high-fat-fed mice.
Tetrahydrobiopterin Restores Diastolic Function and Attenuates Superoxide Production in Ovariectomized mRen2.Lewis Rats
Authors: Jessup Jewell A. , Zhang Lili , Presley Tennille D. , Kim-Shapiro Daniel B. , Wang Hao , Chen Alex F. , Groban Leanne
Published: March 2011

After oophorectomy, mRen2.Lewis rats exhibit diastolic dysfunction associated with elevated superoxide, increased cardiac neuronal nitric oxide synthase (nNOS) expression, and diminished myocardial tetrahydrobiopterin (BH4) content, effects that are attenuated with selective nNOS inhibition. BH4 is an essential cofactor of nNOS catalytic activity leading to nitric oxide production. Therefore, we assessed the effect of 4 wk BH4 supplementation on diastolic function and left ventricular (LV) remodeling in oophorectomized mRen2.Lewis rats compared with sham-operated controls. Female mRen2.Lewis rats underwent either bilateral ovariectomy (OVX) (n = 19) or sham operation (n = 13) at 4 wk of age. Beginning at 11 wk of age, OVX rats were randomized to receive either BH4 (10 mg/kg · d) or saline, whereas the sham rats received saline via sc mini-pumps. Loss of ovarian hormones reduced cardiac BH4 when compared with control hearts; this was associated with impaired myocardial relaxation, augmented filling pressures, increased collagen deposition, and thickened LV walls. Additionally, superoxide production increased and nitric oxide decreased in hearts from OVX compared with sham rats. Chronic BH4 supplementation after OVX improved diastolic function and attenuated LV remodeling while restoring myocardial nitric oxide release and preventing reactive oxygen species generation. These data indicate that BH4 supplementation protects against the adverse effects of ovarian hormonal loss on diastolic function and cardiac structure in mRen2.Lewis rats by restoring myocardial NO release and mitigating myocardial O2− generation. Whether BH4 supplementation is a therapeutic option for the management of diastolic dysfunction in postmenopausal women will require direct testing in humans.
Do jellyfish have central nervous systems?
Authors: Satterlie Richard A.
Published: March 2011

The traditional view of the cnidarian nervous system is of a diffuse nerve net that functions as both a conducting and an integrating system; this is considered an indicator of a primitive condition. Yet, in medusoid members, varying degrees of nerve net compression and neuronal condensation into ganglion-like structures represent more centralized integrating centers. In some jellyfish, this relegates nerve nets to motor distribution systems. The neuronal condensation follows a precept of neuronal organization of higher animals with a relatively close association with the development and elaboration of sensory structures. Nerve nets still represent an efficient system for diffuse, non-directional activation of broad, two-dimensional effector sheets, as required by the radial, non-cephalized body construction. However, in most jellyfish, an argument can be made for the presence of centralized nervous systems that interact with the more diffuse nerve nets.
Thermal effects on the dynamics and motor control of ballistic prey capture in toads: maintaining high performance at low temperature
Authors: Deban Stephen M. , Lappin A. Kristopher
Published: March 2011

Temperature has a strong influence on biological rates, including the contractile rate properties of muscle and thereby the velocity, acceleration and power of muscle-powered movements. We hypothesized that the dynamics of movements powered by elastic recoil have a lower thermal dependence than muscle-powered movements. We examined the prey capture behavior of toads (Bufo terrestris) using high speed imaging and electromyography to compare the effects of body temperature (11–35°C) on the kinematics, dynamics and motor control of two types of movement: (1) ballistic mouth opening and tongue projection, which are powered by elastic recoil, and (2) non-ballistic prey transport, including tongue retraction and mouth closing, which are powered directly by muscle contraction. Over 11–25°C, temperature coefficients of ballistic mouth opening and tongue projection dynamics (Q10 of 0.99–1.25) were not significantly different from 1.00 and were consistently lower than those of prey transport movements (Q10 of 1.77–2.26), supporting our main hypothesis. The depressor mandibulae muscle, which is responsible for ballistic mouth opening and tongue projection via the recovery of elastic strain energy stored by the muscle prior to the onset of the movement, was activated earlier and for a longer duration at lower temperatures (Q10 of 2.29–2.41), consistent with a slowing of its contractile rates. Muscle recruitment was unaffected by temperature, as revealed by the lack of thermal dependence in the intensity of activity of both the jaw depressor and jaw levator muscles (Q10 of 0.754–1.12). Over the 20–35°C range, lower thermal dependence was found for the dynamics of non-elastic movements and the motor control of both elastic and non-elastic movements, in accord with a plateau of high performance found in other systems.
Early development and molecular plasticity in the Mediterranean sea urchinParacentrotus lividusexposed to CO2-driven acidification
Authors: Martin Sophie , Richier Sophie , Pedrotti Maria-Luiza , Dupont Sam , Castejon Charlotte , Gerakis Yannis , Kerros Marie-Emmanuelle , Oberhänsli François , Teyssié Jean-Louis , Jeffree Ross , Gattuso Jean-Pierre
Published: March 2011

Ocean acidification is predicted to have significant effects on benthic calcifying invertebrates, in particular on their early developmental stages. Echinoderm larvae could be particularly vulnerable to decreased pH, with major consequences for adult populations. The objective of this study was to understand how ocean acidification would affect the initial life stages of the sea urchin Paracentrotus lividus, a common species that is widely distributed in the Mediterranean Sea and the NE Atlantic. The effects of decreased pH (elevated PCO2) were investigated through physiological and molecular analyses on both embryonic and larval stages. Eggs and larvae were reared in Mediterranean seawater at six pH levels, i.e. pHT 8.1, 7.9, 7.7, 7.5, 7.25 and 7.0. Fertilization success, survival, growth and calcification rates were monitored over a 3 day period. The expression of genes coding for key proteins involved in development and biomineralization was also monitored. Paracentrotus lividus appears to be extremely resistant to low pH, with no effect on fertilization success or larval survival. Larval growth was slowed when exposed to low pH but with no direct impact on relative larval morphology or calcification down to pHT 7.25. Consequently, at a given time, larvae exposed to low pH were present at a normal but delayed larval stage. More surprisingly, candidate genes involved in development and biomineralization were upregulated by factors of up to 26 at low pH. Our results revealed plasticity at the gene expression level that allows a normal, but delayed, development under low pH conditions.
Growth patterns and nuclear distribution in white muscle fibers from black sea bass, Centropristis striata: evidence for the influence of diffusion
Authors: Priester Carolina , Morton Lindsay C. , Kinsey Stephen T. , Watanabe Wade O. , Dillaman Richard M.
Published: March 2011

This study investigated the influence of fiber size on the distribution of nuclei and fiber growth patterns in white muscle of black sea bass, Centropristis striata, ranging in body mass from 0.45 to 4840 g. Nuclei were counted in 1 μm optical sections using confocal microscopy of DAPIand Acridine-Orange-stained muscle fibers. Mean fiber diameter increased from 36±0.87 μm in the 0.45 g fish to 280±5.47 μm in the 1885 g fish. Growth beyond 2000 g triggered the recruitment of smaller fibers, thus significantly reducing mean fiber diameter. Nuclei in the smaller fibers were exclusively subsarcolemmal (SS), whereas in larger fibers nuclei were more numerous and included intermyofibrillar (IM) nuclei. There was a significant effect of body mass on nuclear domain size (F=118.71, d.f.=3, P<0.0001), which increased to a maximum in fish of medium size (282–1885 g) and then decreased in large fish (>2000 g). Although an increase in the number of nuclei during fiber growth can help preserve the myonuclear domain, the appearance of IM nuclei during hypertrophic growth seems to be aimed at maintaining short effective diffusion distances for nuclear substrates and products. If only SS nuclei were present throughout growth, the diffusion distance would increase in proportion to the radius of the fibers. These observations are consistent with the hypothesis that changes in nuclear distribution and fiber growth patterns are mechanisms for avoiding diffusion limitation during animal growth.
Oxidative stress is transient and tissue specific during cold acclimation of threespine stickleback
Authors: Kammer Aaron R. , Orczewska Julieanna I. , O'Brien Kristin M.
Published: March 2011

Linkages between cold acclimation and oxidative stress in fishes are unclear and contradictory results have been published. We sought to determine whether oxidative stress occurs during cold acclimation of threespine stickleback (Gasterosteus aculeatus), and, if so, when it occurs and whether it varies among tissues. Fish were warm (20°C) or cold (8°C) acclimated for 9 weeks, and harvested during acclimation. Oxidative stress was assessed in oxidative and glycolytic muscles and liver by measuring levels of protein carbonyls and glutathione, and the activity and transcript levels of superoxide dismutase (SOD). Protein carbonyl levels increased in liver after 1 week at 8°C and then decreased after week 4, and remained unchanged in glycolytic and oxidative muscle. Glutathione levels increased in liver on day 3 of cold acclimation and may minimize oxidative stress later during acclimation. When measured at a common temperature, the activity of SOD increased in oxidative and glycolytic muscles on day 2 of cold acclimation, and on day 3 in liver, and remained elevated in all tissues compared with warm-acclimated animals. When measured at the acclimation temperature, the activity of SOD was significantly higher only at week 9 in oxidative muscle of cold-acclimated stickleback compared with warm-acclimated fish, and remained constant in glycolytic muscle and liver. Increased SOD activity in oxidative muscle may be required to prevent oxidative stress brought about by increased mitochondrial density. In both muscle and liver, SOD activity increased independently of an increase in transcript level, suggesting post-translational modifications regulate SOD activity.
Desert ants benefit from combining visual and olfactory landmarks
Authors: Steck Kathrin , Hansson Bill S. , Knaden Markus
Published: March 2011

The desert ant, Cataglyphis fortis, uses both visual and olfactory cues to guide its return to the nest. The ants use vision-based path integration for long-distance navigation and memorize the visual and olfactory surrounding of the nest to finally locate the entrance. In the present study we investigated how the visual and the olfactory navigation systems interact. In field experiments ants were trained to associate the nest with a visual cue, an olfactory cue or a combination of both cues. We tested ants after one, five and 15 training runs, to investigate whether the ants would make use of the training cues to pinpoint the nest. We found that they were slow to learn the location of the nest when it was specified by just an olfactory or a visual cue. However, the ants focused their nest search after the first training run with the combined cue. Equally experienced ants responded to the individually presented visual or olfactory cues with the same high accuracy as they did to the combined cue. After 15 training runs, the combined cue still evoked an accurate response in the test, whereas the individually presented cues no longer did. Apparently, C. fortis benefit from combining their visual and olfactory navigational tools, because the bimodal sensory input accelerates the acquisition of landmark information.
Prolonged fasting increases glutathione biosynthesis in postweaned northern elephant seals
Authors: Vázquez-Medina José Pablo , Zenteno-Savín Tania , Forman Henry Jay , Crocker Daniel E. , Ortiz Rudy M.
Published: March 2011

Northern elephant seals experience prolonged periods of absolute food and water deprivation (fasting) while breeding, molting or weaning. The postweaning fast in elephant seals is characterized by increases in the renin–angiotensin system, expression of the oxidant-producing protein Nox4, and NADPH oxidase activity; however, these increases are not correlated with increased oxidative damage or inflammation. Glutathione (GSH) is a potent reductant and a cofactor for glutathione peroxidases (GPx), glutathione-S transferases (GST) and 1-cys peroxiredoxin (PrxVI) and thus contributes to the removal of hydroperoxides, preventing oxidative damage. The effects of prolonged food deprivation on the GSH system are not well described in mammals. To test our hypothesis that GSH biosynthesis increases with fasting in postweaned elephant seals, we measured circulating and muscle GSH content at the early and late phases of the postweaning fast in elephant seals along with the activity/protein content of glutamate-cysteine ligase [GCL; catalytic (GCLc) and modulatory (GCLm) subunits], γ-glutamyl transpeptidase (GGT), glutathione disulphide reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), GST and PrxVI, as well as plasma changes in γ-glutamyl amino acids, glutamate and glutamine. GSH increased two- to four-fold with fasting along with a 40–50% increase in the content of GCLm and GCLc, a 75% increase in GGT activity, a two- to 2.5-fold increase in GR, G6PDH and GST activities and a 30% increase in PrxVI content. Plasma γ-glutamyl glutamine, γ-glutamyl isoleucine and γ-glutamyl methionine also increased with fasting whereas glutamate and glutamine decreased. Results indicate that GSH biosynthesis increases with fasting and that GSH contributes to counteracting hydroperoxide production, preventing oxidative damage in fasting seals.
Unusually high ferritin in a patient with obstructive jaundice
Authors: Sami S S , Penston J , Tan Hiang L , Barlow I
Published: March 2011

An 81-year-old gentleman, who had evidence of extrahepatic biliary obstruction, was found to have a serum ferritin concentration of 10,892 μg/L, which later increased to more than 40,000 μg/L when he developed sepsis. Endoscopic retrograde cholangiopancreatography was performed with stent insertion allowing drainage of the bile. The rising pattern of serum ferritin concentrations, bilirubin and alkaline phosphatase noted before the procedure was followed by a steep fall in these biochemical markers after the insertion of the stent.
The clinical utility of two renin mass methods to detect primary hyperaldosteronism compared with renin activity
Authors: Wedatilake Yehani N , Scanlon Mike J , Barnes Sophie C
Published: March 2011

Background

Primary hyperaldosteronism (PHA) is characterized by a raised plasma aldosterone concentration (PAC) with suppressed plasma renin activity (PRA). We evaluated two renin mass methods for PHA detection compared with the PAC:PRA ratio.

Methods

Samples from patients attending a specialist hypertensive clinic were analysed by Liaison automated chemiluminescent immunoassay and Diagnostic Systems Laboratories (DSL) immunoradiometric assay (IRMA) for renin mass; I−125 radioimmunoassay of angiotensin I generated from endogenous angiotensinogen for PRA; Siemens Coat-a-count radioimmunoassay for PAC. Subjects included those on β-blockers which suppress renin, causing an equivalent biochemical picture to PHA. Aldosterone/renin ratios (ARR) were calculated for PRA, DSL and Liaison methods. The first 100 subjects were used to identify cut-off ratios ensuring maximum specificity at 100% sensitivity for PHA detection. This cut-off was retested in a subsequent population ( n = 43).

Results

A Liaison renin of 5 ng/L separated PRAs of ≤0.5 from ≥0.6 pmol/mL/h. The DSL method had greater scatter. In population 1 (18 PHA), cut-off ratios of >118 pmol/ng (Liaison) and >60 pmol/ng (DSL) gave specificities of 58.5% and 61%, respectively, with 100% sensitivity. If criteria for PHA included PAC ≥350 pmol/L and excluded β-blocked subjects, specificity increased to 95.1% and 90% for Liaison and DSL, respectively. In population 2 (6 PHA), specificities for Liaison and DSL ARRs were 86.4% and 78.3%. Using the ratio with PAC and β-blocker criteria, specificities for Liaison and DSL were 97.3% and 86.5%, respectively.

Conclusions

The Liaison ARR used with PAC and β-blocker criteria provided an automatable alternative to identify the same patients as the PAC:PRA ratio.
Prolonged Neuromuscular Paralysis Following Rapid-Sequence Intubation with Succinylcholine
Authors: Kaufman Scott E , Donnell Robert W , Aiken David C , Magee Caleb
Published: March 2011

Objective:

To report a case of severely prolonged succinylcholine-induced neuromuscular paralysis in a patient with previously undiagnosed butyrylcholinesterase deficiency.

Case Summary:

A 54-year-old female was admitted for surgical drainage of a groin abscess. She was given propofol 200 mg and succinylcholine 160 mg (1 mg/kg) intravenously to induce sedation and paralysis for endotracheal intubation. Thirty minutes after the 19-minute procedure, the patient showed no evidence of spontaneous recovery of respiration. She was transferred to the intensive care unit and 11 hours later was successfully weaned from the ventilator and extubated. A butyrylcholinesterase level of 562 IU/L (refernce range 2673-6592) confirmed butyrylcholinesterase deficiency. Six months later, in compliance with institutional review board/human subjects research requirements, the patient returned for a dibucaine inhibition test and second butyrylcholinesterase assay; the butyrylcholinesterase level in the second assay was 789 IU/L The suggesting that the adverse drug effect had a phamnacogenetic basis. Use of the Naranjo probability scale indicated a probable relationship between the prolonged neuromuscular paralysis and succinylcholine therapy in this patent.

Discussion:

Succinylcholine remains the drug of choice to facilitate rapid-sequence endotracheal intubation during induction of anesthesia and in patients undergoing emergency procedures who are at risk for gastroesophageal regurgitation. Its short duration of action is due to rapid hydrolysis by the endogenous enzyme butyrylcholinesterase. Rarely, patients with butyrylcholinesterase deficiency may show marked sensitivity to succinylcholine, manifested clinically by severely prolonged neuromuscular paralysis and apnea.

Conclusions:

Butyrylcholinesterase deficiency may go undiagnosed for decades until succinylcholine is used in a surgical procedure. When it does occur, a butyrylcholinesterase level should be obtained and a dibucaine inhibition test should be conducted to test for unrecognized hereditary butyrylcholinesterase deficiency. If a pharmacogenetic basis is confirmed, the patient should receive information about the condition, implications, inheritance, and need for family testing.
Distinctive Features of Saccadic Intrusions and Microsaccades in Progressive Supranuclear Palsy
Authors: Otero-Millan Jorge , Serra Alessandro , Leigh R. John , Troncoso Xoana G. , Macknik Stephen L. , Martinez-Conde Susana
Published: March 2011

The eyes do not stay perfectly still during attempted fixation; fixational eye movements and saccadic intrusions (SIs) continuously change the position of gaze. The most common type of SI, square-wave jerks (SWJs), consists of saccade pairs that appear purely horizontal on clinical inspection: the first saccade moves the eye away from the fixation target, and after a short interval, the second saccade brings it back toward the target. SWJs are prevalent in certain neurological disorders, including progressive supranuclear palsy (PSP). Here, we developed an objective method to identify SWJs. We found that SWJs are more frequent, larger, and more markedly horizontal in PSP patients than in healthy human subjects. Furthermore, the loss of a vertical component in fixational saccades and SWJs was the eye movement feature that best distinguished PSP patients from controls. We moreover determined that, in PSP patients and controls, the larger the saccade the more likely it was part of a SWJ. Furthermore, saccades produced by PSP patients had equivalent properties whether they were part of a SWJ or not, suggesting that normal fixational saccades (microsaccades) are rare in PSP. We propose that fixational saccades and SIs are generated by the same neural circuit and that, both in PSP patients and in controls, SWJs result from a coupling mechanism that generates a second corrective saccade shortly after a large fixation saccade. Because of brainstem and/or cerebellum impairment, fixational saccades in PSP are abnormally large and thus more likely to trigger a corrective saccade, giving rise to SWJs.