bluuebunny/crossref_metadata_2025 huggingface dataset:
A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts
Authors: Blüthgen Nils , Legewie Stefan , Kielbasa Szymon M. , Schramme Anja , Tchernitsa Oleg , Keil Jana , Solf Andrea , Vingron Martin , Schäfer Reinhold , Herzel Hanspeter , Sers Christine
Published: January 2009

Mitogen‐activated protein kinase (MAPK) signaling determines crucial cell fate decisions in most cell types, and mediates cellular transformation in many types of cancer. The activity of MAPK is controlled by reversible phosphorylation, and the quantitative characteristics of MAPK activation determine the cellular response. Many systems biological studies have analyzed the activation kinetics and the dose–response behavior of the MAPK signaling pathway. Here we investigate how the pathway activity is controlled by transcriptional feedback loops. Initially, we predict that MAPK signaling regulates phosphatases, by integrating promoter sequence data and ontology‐based classification of gene function. From this, we deduce that MAPK signaling might be controlled by transcriptional negative feedback regulation via dual‐specificity phosphatases (DUSPs), and implement a mathematical model to further test this hypothesis. Using time‐resolved measurements of pathway activity and gene expression, we employ a model selection approach, and select DUSP6 as a highly likely candidate for shaping the activity of the MAPK pathway during cellular transformation caused by oncogenic RAS. Two predictions from the model were confirmed: first, feedback regulation requires that DUSP6 mRNA and protein are unstable; and second, the activation kinetics of MAPK are ultrasensitive. Taken together, an integrated systems biological approach reveals that transcriptional negative feedback controls the kinetics and the extent of MAPK activation under both physiological and pathological conditions.
Interlaboratory evaluation of two Reverse‐transcriptase Polymeric Chain Reaction‐based methods for detection of four fruit tree viruses
Authors: Massart S. , Brostaux Y. , Barbarossa L. , Batlle A. , Cesar V. , Dutrecq O. , Fonseca F. , Guillem R. , Komorowska B. , Olmos A. , Steyer S. , Wetzel T. , Kummert J. , Jijakli M.H.
Published: January 2009

Recent technological development of molecular methods has led to the proliferation of new rapid PCR or reverse‐transcriptase (RT)‐PCR‐derived diagnostic tests for plant viruses. Nevertheless, for routine use, the reliability of all these new methods is not widely established and there is still an apprehension to adopt them in official diagnostic for certification of plant material. This is partly because of the lack of confidence in the obtained results and the poor knowledge on the reproducibility and limits of the RT‐PCR protocols. There is a lack of information on the adequate risk assessment in the use of this new technology. An interlaboratory evaluation of two RT‐PCR duplex protocols for the detection of four different fruit tree viruses was performed to address these questions. Identical samples were sent as crude extract preparation to each of the participant laboratories. Samples were coded to ensure a double‐blind test. General principles of result analysis are described, for example calculation of parameters such as specificity, sensitivity, repeatability, reproducibility, likelihood ratios and post‐test probabilities. These parameters and the integration of the protocols within official certification scheme are discussed. Finally, guidelines for researchers desirous of validating their new plant virus diagnostic protocols through interlaboratory evaluation are suggested.
Phosphorylation of Microtubule‐associated Protein SB401 from Solanum berthaultii Regulates Its Effect on Microtubules
Authors: Liu Bao‐Quan , Jin Lifeng , Zhu Lei , Li Jiejie , Huang Shuli , Yuan Ming
Published: January 2009

We reported previously that the protein SB401 from Solanum berthaultii binds to and bundles both microtubules and F‐actin. In the current study, we investigated the regulation of SB401 activity by its phosphorylation. Our experimental results showed that the phosphorylation of SB401 by casein kinase II (CKII) downregulates the activities of SB401, namely the bundling of microtubules and enhancement of the polymerization of tubulin. However, phosphorylation of SB401 had no observable effect on its bundling of F‐actin. Further investigation using extract of potato pollen indicated that a CKII‐like kinase may exist in potato pollen. Antibodies against CKII alpha recognized specifically a major band from the pollen extract and the pollen extract was able to phosphorylate the SB401 protein in vitro. The CKII‐like kinase showed a similar ability to downregulate the bundling of microtubules. Our experiments demonstrated that phosphorylation plays an important role in the regulation of SB401 activity. We propose that this phosphorylation may regulate the effects of SB401 on microtubules and the actin cytoskeleton.
From alert commander to passive spectator: older male carers’ experience of receiving formal support
Authors: Sandberg Jonas , Eriksson Henrik
Published: January 2009

Aim.  The aim was to describe older male carers’ experience of receiving formal support.

Background.  To older male carers, creating new roles seems to be important. Their need for support in their caregiving is poorly understood.

Design.  A qualitative approach with a critical perspective on men and masculinities was used.

Participants.  Focus groups comprising a total of 11 men were used.

Methods.  Qualitative content analysis was adopted.

Results.  Three categories of response were found: ‘using ad hoc solutions for maintaining a protective environment’, ‘coping but being left behind’ and ‘recapturing the caregiving role’.

Discussion.  Not only the quantity of support services offered to older male carers but also their quality dimension, based on a genuine understanding of the men’s support needs, must be addressed.

Conclusions.  Professional caregivers attempt to relieve the men of their care obligations entirely. A reciprocal arrangement involving the men as partners, instead, may help them to regard their caring experience as valuable, which is important to their self‐image.

Relevance to clinical practice.  These men’s socially based networks need to be recognized by professional caregivers as important, to reframe the men’s identity and notion of masculinity.
Cerebral extension of steroid‐responsive meningitis arteritis in a boxer
Authors: Wrzosek M. , Konar M. , Vandevelde M. , Oevermann A.
Published: January 2009

A comatose 30‐month‐old, entire male boxer was presented because of an acute history of a cluster of three to four seizures. Neurological examination suggested a diffuse to multifocal intracranial lesion. Magnetic resonance tomography revealed symmetrical multifocal to diffuse changes of the cerebral grey matter and ependymal lining with sediment in the lateral ventricles. Haematological examination revealed leucocytosis with neutrophilia. Cerebrospinal fluid examination revealed high protein concentration and polymorphonuclear pleocytosis. Despite antiepileptic treatment, therapy against increased intracranial pressure and antibiosis, the dog’s condition continued to deteriorate and he was euthanased. Pathological examination revealed fibrinosuppurative meningo‐ependymitis and necrotising arteritis throughout the brain. In addition, chronic inflammation and arterial stenosis was found in the spinal meninges. No infectious agent was found. A diagnosis of steroid‐responsive meningitis arteritis was made. The massive extension into the meninges and ventricular system of the forebrain has not been described previously in dogs with steroid‐responsive meningitis arteritis and should be considered in the differential diagnosis when an intracranial suppurative infection is suspected.
Effect of weather factors on populations of Helicoverpa armigera moths at cotton‐based agro‐ecological sites
Authors: AHEER Ghulam Mustafa , ALI Amjad , AKRAM Muhammad
Published: January 2009

Pheromone trapping was used to monitor populations of the moth Helicoverpa armigera at five cotton‐based agro‐ecological sites – river, vegetable, orchard, forest and clean cultivation (areas under only cotton cultivation) – in the Bahawalpur district, Pakistan. Three locations at each site were chosen and three pheromone traps at each location were installed in cotton fields. Moth catches were recorded at 15–20 day intervals from 24 October 2004 to 19 December 2006. In 2004, the river sites showed the maximum trapped population of H. armigera (0.22/trap) followed by 0.165 per trap at the vegetable sites. Orchard, clean cultivation and forest sites had zero moth catches. In 2005, the river sites again showed the highest trapped population (0.57/trap), followed by clean cultivation (0.45/trap), vegetable (0.44/trap), orchard (0.40/trap) and forest (0.29/trap). The moths appeared during July to December and March to May. In 2006, sites showed non‐significant difference, with a population range of 0.47 to 0.97 moths per trap. On average, river sites peaked at 0.49 per trap, followed by vegetable (0.38), clean cultivation (0.47), orchard (0.35) and forest (0.25) sites. The peak was observed on 3 April 2006, and moths appeared during February to July and October to December. The minimum temperature in river, forest and clean cultivation sites; the maximum temperature in orchard sites; and the average temperature in river, orchard, forest and clean cultivation sites showed significant positive correlations with trapped moth populations. Relative humidity showed significant negative correlation with population at the orchard sites in 2005. All weather factors during 2004 and 2006 showed non‐significant correlations with the moth populations. No model was found to be best fit by multiple linear regression analysis; however, relative humidity, minimum temperature, maximum temperature, minimum temperature and maximum temperature contributed 8.40, 10.23, 2.43, 4.53 and 2.53% to the population fluctuation of the moth at river, vegetable, orchard, forest and clean cultivation sites, respectively.
Male and female genitalia in some Libyan species of Acrididae (Orthoptera: Acridoidea)
Authors: USMANI Mohammad Kamil
Published: January 2009

A comparative study of male and female genitalia was carried out in thirty‐seven Libyan species representing twenty genera of the family Acrididae. An attempt has been made to describe and illustrate the different structures, namely, epiphallus, aedeagus, subgenital plate, supra‐anal plate and cerci of the male, and spermatheca, ovipositor, subgenital plate, supra‐anal plate and cerci of the female, in Acridids, with an aim to discover their significance in order to make the identification of genera and species, together with other generic characters, more perfect and convenient. Distinct family characters are shield or bridge‐shaped condition of epiphallus; presence or absence of dorso‐lateral appendices, oval sclerites and lophi on epiphallus; divided, undivided or flexured condition of aedeagus; presence or absence of gonopore process on aedeagus; condition of apical and pre‐apical diverticula of spermatheca; presence or absence of glandular pouches of Cornstock and Kellog on female subgenital plate; and rudimentary or well developed condition of egg‐guide. Stable characters for separating the subfamilies are taken to be presence or absence of ancorae on epiphallus, long or short condition of aedeagal sclerites; elongate, slender or short and broad condition of ovipositor valves: presence or absence of Jannone's organs and setae on posterior margin of female subgenital plate; and shape of diverticula of spermatheca. Useful generic characters are shape of male subgenital plate, supra‐anal plate and cerci, broad or narrow condition of bridge, presence or absence of branch of bridge connecting lophi with bridge of epiphallus; mono‐, bi‐ or tri‐lobate condition of lophi of epiphallus, length and upcurved or downcurved condition of apical valve of aedeagus, shape of posterior margin of female subgenital plate, presence of setae on the whole posterior margin or confined to lateral margins only; and toothed, tuberculate or smooth condition of ovipositor valves, length of the lateral apodeme in relation to the dorsal valves. Specific characters are shape of egg‐guide of female subgenital plate, shape of ovipositor valves and apical tips, shape of male supra‐anal plate and cerci, size of anterior and posterior lobes of lophi of epiphallus, size and shape of ancorae, shape of apical valves of aedeagus; and size of apical and pre‐apical diverticula and presence of protuberance on pre‐apical diverticulum.
Larvicidal and smoke repellency effect of Toddalia asiatica and Aegle marmelos against the dengue vector, Aedes aegypti (Insecta: Diptera: Culicidae)
Authors: VINEETHA Arunachalam , MURUGAN Kadarkarai
Published: January 2009

Investigations were made to evaluate the larvicidal activity and smoke repellent potential of Toddalia asiatica (L.) and Aegle marmelos at different concentrations (20, 40, 60, 80 and 100 p.p.m.) against first to fourth instar larvae and pupae of Aedes aegypti (L.). The LC50 of A. marmelos and T. asiatica against first instars was 50.960 and 47.893 p.p.m., respectively; against second instars, 52.979 and 50.922; third instars, 56.653 and 54.461; and fourth instars, 60.778 and 61.278. The LC50 and LC90 for A. marmelos and T. asiatica against pupae were 56.634 and 112.992, and 53.64 and 116.22 p.p.m., respectively. The smoke toxicity of T. asiatica against Ae. aegypti was greater than that of A. marmelos. Smoke‐exposed gravid females oviposited fewer eggs when compared to those that were not exposed to smoke. Smoke‐exposed females hatched a lower percentage of eggs compared to unexposed females.
Seasonal prevalence of mosquitoes collected from light traps in the Republic of Korea, 2005
Authors: KIM Heung Chul , CHONG Sung Tae , COLLIER Brett W. , KLEIN Terry A.
Published: January 2009

Adult mosquito surveillance was conducted during 2005 at 22 US military installations and two training sites located in six provinces in the Republic of Korea. Adult mosquitoes were collected in New Jersey light traps from 1 May to 15 October to determine threshold levels to initiate pesticide applications based on trap indices. A total of 27 363 adult mosquitoes (22 368 [81.7%] females and 4995 [18.3%] males) comprising 15 species (including five members of the Anopheles sinensis group) belonging to seven genera were collected. The most common species collected were members of the Anopheles sinensis Wiedemann group (50.2%), followed by Culex tritaeniorhynchus Giles (30.6%), Aedes vexans nipponii (Theobald) (11.8%), and Culex pipiens Coquillett (6.3%) females. Trap indices varied widely for species over their range, due in part to geographical distribution and degree of association with urban or rural communities.
New record of Orthotylus pallen (Matsumura) (Hemiptera: Miridae) from Korea, with a key to and checklist of Korean species
Authors: KWON Yong Jung , CHO Young Jae , SUH Sang Jae
Published: January 2009

Orthotylus pallen (Mastumura, 1911) is recorded for the first time from Korea and is diagnosed. An image of its dorsal habitus as well as illustrations of the male and female genitalia are provided. A key to and checklist of Korean Orthotylus species are given.
BmNPV chitinase gene deletion enhances foreign gene expression in a BmN cell system
Authors: WANG Fang , ZHANG Chuan‐Xi
Published: January 2009

Bombyx mori nucleopolyhedrovirus (BmNPV) is extensively being studied as an expression vector for heterologous gene expression in silkworm‐derived cells as well as in the host larvae or pupae. BmNPV chitinase is necessary for liquefaction of the virus‐infected host insect. The influence of chitinase on the efficiency of foreign gene expression was studied to provide a scientific basis for improving the BmNPV expression system. The BmNPV chitinase gene (chiA) was deleted and the expression level of the polyhedrin promoter controlling the lacZ gene in BmN cells was determined. Sodium dodecylsulfate (SDS)–polyacrylamide gel electrophoresis (PAGE) showed that β‐galactosidase accounted for approximately 6.9 and 7.7% of the total protein in BmN cells infected with the chiA deficient BmlacZ+chiA− at 3 and 4 days post infection, while the total protein was 3.2 and 4.2% in cells infected with BmlacZ+. The relative β‐galactosidase activities in BmlacZ+chiA−‐infected cells improved 2.33‐ and 1.56‐fold compared to those of BmlacZ+‐infected cells at 3 and 4 days post infection. The results of the present study suggest that chitinase deletion could improve the lacZ expression level in the BmNPV‐BmN cell expression system.
Seasonal and geographical toxicity of Indoxacarb against Helicoverpa armigera and influence of different host plants against Indoxacarb in India, 2005–2007
Authors: GHODKI Basweshwar S. , THAKARE Shivcharan M. , MOHARIL Mangesh P. , RAO Nagarjuna G. V.
Published: January 2009

Indoxacarb, an oxadiazine insecticide, was evaluated for its effectiveness against Helicoverpa armigera collected from selected locations in India. Determination of Indoxacarb efficacy was done using a log‐dose probit (LDP) bioassay against third instars collected from cotton (Gossypium arborium) fields near Akola, India. Monthly levels of toxicity of Indoxacarb were determined from July 2005 to March 2007. The maximum tolerance level of Indoxacarb was reported for the Amaravati strain (5.09 p.p.m.) and the minimum tolerance level for the Fatehbad strain (0.22 p.p.m.). Seasonal monitoring of Indoxacarb toxicity revealed an increased trend in tolerance from July 2005 to February 2006, which decreased from March 2006. The LC50 of Indoxacarb was 2.71 p.p.m. in July 2005 and 17.14 p.p.m. in February 2006. During 2006–2007, the LC50 was 3.84 p.p.m. at the start of the season and in March 2007 it was 13.51 p.p.m. The minimum LC50 of Indoxacarb was reported for H. armigera larvae fed on Legasca spp. (1.62 p.p.m.) and the maximum LC50 was reported for H. armigera reared on chickpea (Cicer arietium) (8.45 p.p.m.). LC50 of 2.73 and 4.56 p.p.m. were reported for H. armigera fed on cotton (Gossypium arborium) and pigeonpea (Cajanus cajan), respectively.
Larvicidal and insect growth regulator effect of α‐amyrin acetate from Catharanthus Roseus Linn against the malaria vector Anopheles Stephensi Liston (Diptera: Culicidae)
Authors: KUPPUSAMY Chenniappan , MURUGAN Kadarkarai , ARUL Narayanasamy , YASODHA Perumal
Published: January 2009

Vector control is a serious concern in developing countries. Over the past two decades, phytochemicals have received progressively more attention as insecticide alternatives, and they have recently become the focus in the concept of integrated vector control. α‐Amyrin acetate, the n‐hexane fraction of acetone extract from the leaves of Catharanthus roseus, was evaluated for its larvicidal, pupicidal and fecundity effects as well as insect growth regulator activity against the malaria vector Anopheles stephensi Liston. The highest concentration of 1 p.p.m. produced 100% mortality in first to second instars and 94% mortality in third and fourth instars. In addition, the duration of larval instars and the total developmental time were prolonged, while female longevity and fecundity were markedly decreased. The suppression of pupation and adult emergence was probably due to its action similar to juvenile hormone analogs in combination with growth regulator activity and toxicity, which reduced the overall performance of the malaria vector An. stephensi.
Quantification ofWolbachiacopy number inTrichogrammaeggs (Hymenoptera: Trichogrammatidae): Lysozyme treatment significantly improves total gene yield from the Gram‐negative bacterium
Authors: JEONG Gilsang , STOUTHAMER Richard
Published: January 2009

TheWolbachiabacterium is one of the most prevalent endosymbionts of arthropods. The bacterium is known to induce four distinct reproductive manipulations in its various hosts; namely, cytoplasmic incompatibility, feminization, male killing and parthenogenesis induction. The bacterial titer has been thought to have an important role in expression of these phenotypes. Although host eggs of the bacterium are the place where all of the manipulations take place, in most cases, they are not big enough to be subjected to mechanical disruption to extract genetic materials from them. Furthermore, DNA extraction protocols generally involve washing steps in which part of the DNA is lost. With the simple three step digestion protocol we developed, we were able to preserve the whole genome and measure the titer ofWolbachiain individualTrichogrammaeggs by real‐time quantitative polymerase chain reaction (PCR), which was comparable to the titer by visual observation.
Death, Burial, and the Study of Contemporary Japanese Buddhism
Authors: Rowe Mark
Published: January 2009

This article approaches mortuary practices as a window into the current state of Japanese Buddhism. Despite widespread scholarly awareness of the intimate connection between Buddhism and death throughout much of Japanese history, to date little work has been done to explore the profound significance of changing burial practices on all of the major sects today. Making the argument that ‘funerary Buddhism’ (sōshiki Bukkyō) is important to both think about and think with, this article provides an overview of funerary culture in Japan and reflects upon what contemporary changes to that culture tell us about Japanese Buddhism.
Microbial degradation of lignin: how a bulky recalcitrant polymer is efficiently recycled in nature and how we can take advantage of this
Authors: Ruiz‐Dueñas Francisco J. , Martínez Ángel T.
Published: January 2009

Lignin is the second most abundant constituent of the cell wall of vascular plants, where it protects cellulose towards hydrolytic attack by saprophytic and pathogenic microbes. Its removal represents a key step for carbon recycling in land ecosystems, as well as a central issue for industrial utilization of plant biomass. The lignin polymer is highly recalcitrant towards chemical and biological degradation due to its molecular architecture, where different non‐phenolic phenylpropanoid units form a complex three‐dimensional network linked by a variety of ether and carbon–carbon bonds. Ligninolytic microbes have developed a unique strategy to handle lignin degradation based on unspecific one‐electron oxidation of the benzenic rings in the different lignin substructures by extracellular haemperoxidases acting synergistically with peroxide‐generating oxidases. These peroxidases posses two outstanding characteristics: (i) they have unusually high redox potential due to haem pocket architecture that enables oxidation of non‐phenolic aromatic rings, and (ii) they are able to generate a protein oxidizer by electron transfer to the haem cofactor forming a catalytic tryptophanyl‐free radical at the protein surface, where it can interact with the bulky lignin polymer. The structure–function information currently available is being used to build tailor‐made peroxidases and other oxidoreductases as industrial biocatalysts.
Chitosan and its antimicrobial potential – a critical literature survey
Authors: Raafat Dina , Sahl Hans‐Georg
Published: January 2009

Chitosan, an aminopolysaccharide biopolymer, has a unique chemical structure as a linear polycation with a high charge density, reactive hydroxyl and amino groups as well as extensive hydrogen bonding. It displays excellent biocompatibility, physical stability and processability. The term ‘chitosan’ describes a heterogenous group of polymers combining a group of physicochemical and biological characteristics, which allow for a wide scope of applications that are both fascinating and as yet uncharted. The increased awareness of the potentials and industrial value of this biopolymer lead to its utilization in many applications of technical interest, and increasingly in the biomedical arena. Although not primarily used as an antimicrobial agent, its utility as an ingredient in both food and pharmaceutical formulations lately gained more interest, when a scientific understanding of at least some of the pharmacological activities of this versatile carbohydrate began to evolve. However, understanding the various factors that affect its antimicrobial activity has become a key issue for a better usage and a more efficient optimization of chitosan formulations. Moreover, the use of chitosan in antimicrobial systems should be based on sufficient knowledge of the complex mechanisms of its antimicrobial mode of action, which in turn would help to arrive at an appreciation of its entire antimicrobial potential.
Anomalous secondary structures in stem and root of two typical halophytes
Authors: Kong Lingan , Li Fazeng
Published: January 2009

Limonium sinense (Girard) O. Kuntze (Plumbaginaceae) and Suaeda salsa (L.) Pal. (Chenopodiaceae), both typical halophytes, have been used to investigate the peculiar structural features adapted to saline conditions, with a special emphasis on the anomalous secondary structure of stem and root. The results showed that in saline environments, L. sinense developed tripartite vascular cylinders in the root and cortical bundles in the scape. Suaeda salsa developed concentric rings of vascular tissue and interxylary phloem in the root and stem. Based on these findings, we discuss the adaptive significance of these anomalous secondary structures for plants living in saline environments.
Karyotype variation and evolution in populations of the Chinese endemicOrychophragmusviolaceuscomplex (Brassicaceae)
Authors: Zhou Lirong , Liu Zhibin , Wu Jun , Wang Jianmei , Yang Yi , Li Xufeng
Published: January 2009

The karyological variation and cytogeography of theOrychophragmusviolaceuscomplex from 15 locations across China has been studied to elucidate the evolutionary relationships amongst several chromosomal cytotypes. The results show that chromosomal variation within the complex is larger than previously thought, with three base numbers being identified: x=10 (Orychophragmusdiffuses), 11 (Orychophragmushupehensis) and 12 (OrychophragmustaibaiensisandOrychophragmus violaceus). For the first time, a tetraploid population ofO.taibaiensisbased on x=12 has been found. Two base numbers x=10 and x=12 may represent the ancestral condition of theO. violaceuscomplex. A progressive increase in chromosome number, decrease in intra‐chromosomal asymmetry, and appearance of tetraploidy is shown to be some of the most significant karyological changes associated with an increase in altitude of habitat. It is hypothesized that a center of differentiation is situated between the upper to mid Chang Jiang River and the Qin Mountain, where several biogeographic events involving recent evolutionary radiation have taken place.
Recurrence of primary biliary cirrhosis and development of autoimmune hepatitis after liver transplant: A blind histologic study
Authors: Hytiroglou Prodromos , Gutierrez Julio A. , Freni Maria , Odin Joseph A. , Stanca Carmen M. , Merati Sukma , Schiano Thomas D. , Branch Andrea D. , Thung Swan N.
Published: January 2009

Aim:  This long‐term study aimed to evaluate recurrence and evolution of primary biliary cirrhosis (PBC) after orthotopic liver transplantation (OLT).

Methods:  We reviewed “blindly” allograft biopsy specimens of women who underwent transplantation for PBC (n = 84), and women who received a transplant for chronic hepatitis C virus infection (CHCV ) (n = 108). All needle liver biopsy specimens obtained more than 6 months post‐OLT were examined, including 83 specimens from 44 PBC patients and 152 specimens from 58 CHCV patients.

Results:  Granulomatous destructive cholangitis was found in five biopsies from four PBC patients (P = 0.0048). Non‐necrotizing epithelioid cell granulomas were present in four biopsies from four PBC patients, and in two biopsies from one CHCV patient. Piecemeal necrosis (P = 0.0002), lobular necroinflammatory activity (P < 0.0001), steatosis (P < 0.0001) and fibrosis (P < 0.0001) were more prevalent in CHCV patients than PBC patients. Four PBC patients developed histologic evidence of autoimmune hepatitis (AIH), at a mean time of 3.66 years post‐OLT. One of these patients had histologic features of AIH/PBC overlap syndrome. All four patients developed bridging fibrosis (n = 2) or cirrhosis (n = 2). No other PBC patient had evidence of cirrhosis after OLT.

Conclusions:  Histologic findings indicative of recurrent PBC were present in 15.9% of the PBC patients undergoing biopsy in this series. However, this group of patients did not suffer significant bile duct loss or fibrosis, as compared to the control group, suggesting that recurrent PBC is a mild or slowly progressive disease. Histologic evidence of AIH was observed in allograft biopsies of some PBC patients.
The guanine nucleotide binding protein β polypeptide 3 gene C825T polymorphism is associated with elite endurance athletes
Authors: Eynon Nir , Oliveira José , Meckel Yoav , Sagiv Moran , Yamin Chen , Sagiv Michael , Amir Ruthie , Duarte José Alberto
Published: January 2009

A functional C825T polymorphism in the human guanine nucleotide binding protein β polypeptide 3 (GNB3) gene has been associated with enhanced G protein activation. Since reports regarding the interaction between physical activity and the GNB3 C825T polymorphism are limited and inconsistent, the aim of this study was to determine the frequency of C825T alleles among 155 elite Israeli athletes (endurance athletes and sprinters) and 234 healthy control subjects. Genotyping for GNB3 C825T was performed using polymerase chain reaction on DNA from leucocytes. Results showed that there was a significant difference in GNB3 C825T polymorphism genotype frequencies between endurance athletes and sprinters (P= 0.045) as well as between endurance athletes and control subjects (P= 0.046). We also observed a significantly higher proportion of the GNB3 TT genotype in the group of endurance athletes (19%) compared with the sprinters (5%, P= 0.014) and the control subjects (8.5%, P= 0.026). In the group of athletes, the odds ratio of GNB3 TT genotype being an endurance athlete was 4.49 (95% confidence interval 1.4–14.3) and of GNB3 CC genotype was 0.91 (95% confidence interval 0.47–1.77). These results were even more pronounced when we compared between the subgroups of 20 top‐level endurance athletes and 24 top‐level sprinters. We conclude that in Israeli athletes the GNB3 TT genotype is higher in elite endurance athletes than it is in sprinters, and within the endurance group it is higher in top‐level athletes, suggesting a positive association between the TT genotype and the likelihood of being an elite endurance athlete.
The lactate paradox revisited in lowlanders during acclimatization to 4100 m and in high‐altitude natives
Authors: Van Hall G. , Lundby C. , Araoz M. , Calbet J. A. L. , Sander M. , Saltin B.
Published: January 2009

Chronic hypoxia has been proposed to induce a closer coupling in human skeletal muscle between ATP utilization and production in both lowlanders (LN) acclimatizing to high altitude and high‐altitude natives (HAN), linked with an improved match between pyruvate availability and its use in mitochondrial respiration. This should result in less lactate being formed during exercise in spite of the hypoxaemia. To test this hypothesis six LN (22–31 years old) were studied during 15 min warm up followed by an incremental bicycle exercise to exhaustion at sea level, during acute hypoxia and after 2 and 8 weeks at 4100 m above sea level (El Alto, Bolivia). In addition, eight HAN (26–37 years old) were studied with a similar exercise protocol at altitude. The leg net lactate release, and the arterial and muscle lactate concentrations were elevated during the exercise in LN in acute hypoxia and remained at this higher level during the acclimatization period. HAN had similar high values; however, at the moment of exhaustion their muscle lactate, ADP and IMP content and Cr/PCr ratio were higher than in LN. In conclusion, sea‐level residents in the course of acclimatization to high altitude did not exhibit a reduced capacity for the active muscle to produce lactate. Thus, the lactate paradox concept could not be demonstrated. High‐altitude natives from the Andes actually exhibit a higher anaerobic energy production than lowlanders after 8 weeks of acclimatization reflected by an increased muscle lactate accumulation and enhanced adenine nucleotide breakdown.
Intracellular traffic of the K+ channels TASK‐1 and TASK‐3: role of N‐ and C‐terminal sorting signals and interaction with 14‐3‐3 proteins
Authors: Zuzarte Marylou , Heusser Katja , Renigunta Vijay , Schlichthörl Günter , Rinné Susanne , Wischmeyer Erhard , Daut Jürgen , Schwappach Blanche , Preisig‐Müller Regina
Published: January 2009

The two‐pore‐domain potassium channels TASK‐1 (KCNK3) and TASK‐3 (KCNK9) modulate the electrical activity of neurons and many other cell types. We expressed TASK‐1, TASK‐3 and related reporter constructs in Xenopus oocytes, mammalian cell lines and various yeast strains to study the mechanisms controlling their transport to the surface membrane and the role of 14‐3‐3 proteins. We measured potassium currents with the voltage‐clamp technique and fused N‐ and C‐terminal fragments of the channels to various reporter proteins to study changes in subcellular localisation and surface expression. Mutational analysis showed that binding of 14‐3‐3 proteins to the extreme C‐terminus of TASK‐1 and TASK‐3 masks a tri‐basic motif, KRR, which differs in several important aspects from canonical arginine‐based (RxR) or lysine‐based (KKxx) retention signals. Pulldown experiments with GST fusion proteins showed that the KRR motif in the C‐terminus of TASK‐3 channels was able to bind to COPI coatomer. Disabling the binding of 14‐3‐3, which exposes the KRR motif, caused localisation of the GFP‐tagged channel protein mainly to the Golgi complex. TASK‐1 and TASK‐3 also possess a di‐basic N‐terminal retention signal, KR, whose function was found to be independent of the binding of 14‐3‐3. Suppression of channel surface expression with dominant‐negative channel mutants revealed that interaction with 14‐3‐3 has no significant effect on the dimeric assembly of the channels. Our results give a comprehensive description of the mechanisms by which 14‐3‐3 proteins, together with N‐ and C‐terminal sorting signals, control the intracellular traffic of TASK‐1 and TASK‐3.
Modulation of primary motor cortex outputs from ventral premotor cortex during visually guided grasp in the macaque monkey
Authors: Prabhu Gita , Shimazu Hideki , Cerri Gabriella , Brochier Thomas , Spinks Rachel L. , Maier Marc A. , Lemon Roger N.
Published: January 2009

Area F5, in the ventral premotor cortex of the macaque monkey, plays a critical role in determining the hand shape appropriate for grasp of a visible object. F5 neurones show increased firing for particular types of grasp, and inactivation of F5 produces deficits in visually guided grasp. But how is F5 activity transformed into the appropriate pattern of hand muscle activity for efficient grasp? Here we investigate the pathways that may be involved by testing the effect of single stimuli delivered through microwires chronically implanted in area F5 and in primary motor cortex (M1) of two macaque monkeys. The EMG responses from M1 test (T) stimulation were recorded from 4–11 contralateral hand, digit and arm muscles during reach‐to‐grasp of visually presented objects. Conditioning (C) stimulation of F5, at intensities subthreshold for motor effects, caused strong modulation (over twofold) of M1 test (T) responses. The pattern of facilitation was specific. First, facilitation of the T response was particularly evident at short C–T intervals of −1 to 1 ms. Second, this facilitation was only present in some muscles and during reach‐to‐grasp of a subset of objects; it did not appear to be simply related to the level of EMG activity in the muscles at the moment of cortical stimulation or indeed to the upcoming contribution of that muscle during grasp. At later C–T intervals (1–6 ms), F5 stimulation caused significant suppression of the test M1 response. The results are in keeping with the concept that during visually guided grasp, F5 modulates corticospinal outputs from M1 in a muscle‐ and grasp‐specific manner.
The development of cortical columns: role of Fragile X mental retardation protein
Authors: Bureau Ingrid
Published: January 2009

Neuronal circuits in the brain are complex and precise. Here, I review aspects of the development of cortical columns in the rodent barrel cortex, focusing on the anatomical and functional data describing the maturation of ascending glutamatergic circuits. Projections from layer 4 to layer 3 develop into cortical columns with little macroscopic refinement. Depriving animals of normal sensory experience induces long‐term synaptic depression but does not perturb this pattern of development. Mouse models of mental retardation can help us understand the mechanisms of development of cortical columns. Fmr1 knock‐out (ko) mice, a model for Fragile X syndrome, lack Fragile X mental retardation protein (FMRP), a suppressor of translation present in synapses. Because FMRP expression is stimulated by neuronal activity, Fmr1‐ko mice provide a model to survey the role of sensory input in brain development. Layer 4 to layer 3 projections are altered in multiple ways in the young mutant mice: connection rate is low and layer 4 cell axons are spatially diffuse. Sensory deprivation rescues the connection rate phenotype. The interaction of FMRP and neuronal activity in the development of cortical circuits is discussed.
Feedback inhibition of action potential discharge by endogenous adenosine enhancement of the medium afterhyperpolarization
Authors: Ruan Ming , Brown Colin H.
Published: January 2009

Phasic activity in supraoptic nucleus vasopressin neurones is characterized by alternating periods of activity (bursts) and silence. During bursts, activation of a medium afterhyperpolarization induces spike frequency adaptation. Antagonism of A1 adenosine receptors within the supraoptic nucleus decreases spike frequency adaptation and prolongs phasic burstsin vivo, indicating that endogenous adenosine contributes to spike frequency adaptation. Here we used sharp electrode intracellular recordings from supraoptic nucleus neurones in hypothalamic explants to show that endogenous adenosine increases medium afterhyperpolarization amplitude to enhance spike frequency adaptation during phasic bursts. Superfusion of the A1 receptor antagonist 8‐cyclopentyl‐1,3‐dimethylxanthine (CPT, 10 μm) increased intraburst firing rate of phasic neurones (by 2.0 ± 0.7 spikes s−1,P= 0.03) and burst duration (by 141 ± 113 s,P= 0.03). The CPT‐induced increase in intraburst firing rate developed over the first few seconds of firing and persisted thereafter. In a separate series of experiments, CPT reduced the amplitude of the medium afterhyperpolarization evoked by a 1 s 20 Hz spike train (by 0.8 ± 0.3 mV,P< 0.001) in supraoptic nucleus neurones; this inhibition was not prevented by 3 mmCsCl (0.8 ± 0.1 mV decrease,P< 0.01) to block the afterdepolarization (which overlaps temporally with the medium afterhyperpolarization). In the presence of apamin to block the medium afterhyperpolarization, CPT did not alter afterdepolarization amplitude. Taken together, these data show that endogenous adenosine enhances medium afterhyperpolarization amplitude to contribute to spike frequency adaptation in phasic supraoptic nucleus neurones.
Ablation of a Ca2+‐activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation
Authors: Li Ning , Timofeyev Valeriy , Tuteja Dipika , Xu Danyan , Lu Ling , Zhang Qian , Zhang Zhao , Singapuri Anil , Albert Trevine R. , Rajagopal Amutha V. , Bond Chris T. , Periasamy Muthu , Adelman John , Chiamvimonvat Nipavan
Published: January 2009

Small conductance Ca2+‐activated K+ channels (SK channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca2+(Ca2+i) with membrane potential. We have recently reported the functional existence of SK2 channels in human and mouse cardiac myocytes. Moreover, we have found that the channel is predominantly expressed in atria compared to the ventricular myocytes. We hypothesize that knockout of SK2 channels may be sufficient to disrupt the intricate balance of the inward and outward currents during repolarization in atrial myocytes. We further predict that knockout of SK2 channels may predispose the atria to tachy‐arrhythmias due to the fact that the late phase of the cardiac action potential is highly susceptible to aberrant excitation. We take advantage of a mouse model with genetic knockout of the SK2 channel gene. In vivo and in vitro electrophysiological studies were performed to probe the functional roles of SK2 channels in the heart. Whole‐cell patch‐clamp techniques show a significant prolongation of the action potential duration prominently in late cardiac repolarization in atrial myocytes from the heterozygous and homozygous null mutant animals. Morover, in vivo electrophysiological recordings show inducible atrial fibrillation in the null mutant mice but not wild‐type animals. No ventricular arrhythmias are detected in the null mutant mice or wild‐type animals. In summary, our data support the important functional roles of SK2 channels in cardiac repolarization in atrial myocytes. Genetic knockout of the SK2 channels results in the delay in cardiac repolarization and atrial arrhythmias.
Time reversal of parametrical driving and the stability of the parametrically excited pendulum
Authors: Stannarius Ralf
Published: January 2009

It is well known that the periodic driving of a parametrically excited pendulum can stabilize or destabilize its stationary states, depending upon the frequency, wave form, and amplitude of the parameter modulations. We discuss the effect of time reversal of the periodic driving function for the parametric pendulum at small elongations. Such a time reversal usually leads to different solutions of the equations of motion and to different stability properties of the system. Two interesting exceptions are discussed, and two conditions are formulated for which the character of the solutions of the system is not influenced by a time reversal of the driving function, even though the trajectories of the dynamic variables are different.
Is a box model effective for understanding the carbon cycle?
Authors: Tomizuka Akira
Published: January 2009

A seven-box carbon cycle model is used to show the time dependence of atmospheric CO2 for the past 250years and the current flux between individual reservoirs. The model also yields results for future levels of atmospheric CO2 based on various scenarios.
A Physics Road Rally
Authors: Ilyes Mark A. , Ortman-Link Whitney
Published: January 2009

Our school recently acquired1 Vernier's Wireless Dynamics Sensor System (WDSS). The WDSS consists of a three-axis accelerometer, altimeter, and force sensor that has the ability to remotely collect data for later transfer to a computer.2 While our primary purpose for acquiring the WDSS was to enhance our amusement park physics experiments, we decided to test one of the WDSS units by using it to collect data during the drive home from school one day, since measuring the acceleration of a car is one of the experiments suggested in the Vernier Wireless Dynamics Sensor System User Manual. We taped the device to the floor of the car with its +x-axis pointed forward and its +y-axis pointed to the left. The WDSS was configured to take five samples per second for a total time period of 10 minutes.
An Analysis of a Video Game
Authors: Allain Rhett , Williams Richard
Published: January 2009

Suppose we had a brand new world to study—a world that possibly works with a different set of principles, a non-Newtonian world. Maybe this world is Newtonian, maybe it isn't. This world exists in video games, and it is open for exploration. Most video games try to incorporate realistic physics, but sometimes this does not happen. The obvious approach is to look at the source code for the game, but this would not allow students to apply analysis techniques.
Finding Method in Madness
Authors: Conlin Luke D.
Published: January 2009

Editor's note: Luke Conlin taught high school physics in Massachusetts for five years. Currently he is working toward a PhD in Science Education at the University of Maryland, College Park, where he supervises intern teachers and conducts research on student reasoning.
Activity of Anidulafungin in a Murine Model of
Candida krusei
Infection: Evaluation of Mortality and Disease Burden by Quantitative Tissue Cultures and Measurement of Serum (1,3)-β-
d
-Glucan Levels
Authors: Ostrosky-Zeichner Luis , Paetznick Victor L. , Rodriguez Jose , Chen Enuo , Sheehan Daniel J.
Published: January 2009

Experience with anidulafungin against
Candida krusei
is limited. Immunosuppressed mice were injected with 1.3 × 10
7
to 1.5 × 10
7
CFU of
C. krusei
. Animals were treated with saline, 40 mg/kg fluconazole, 1 mg/kg amphotericin B, or 10 and 20 mg/kg anidulafungin for 5 days. Anidulafungin improved survival and significantly reduced the number of CFU/g in kidneys and serum β-glucan levels.
Tigecycline Therapy Significantly Reduces the Concentrations of Inflammatory Pulmonary Cytokines and Chemokines in a Murine Model of
Mycoplasma pneumoniae
Pneumonia
Authors: Salvatore C. M. , Techasaensiri C. , Tagliabue C. , Katz K. , Leos N. , Gomez A. M. , McCracken G. H. , Hardy R. D.
Published: January 2009

Mycoplasma pneumoniae
is one of the causative agents of atypical community-acquired pneumonia. Tigecycline belongs to a new class of glycylcycline antimicrobials that have activity against a wide range of microorganisms, including in vitro activity against
M. pneumoniae
. We investigated the effect of tigecycline on microbiologic, histologic, and immunologic indices in a murine model of
M. pneumoniae
pneumonia. BALB/c mice were inoculated intranasally with
M. pneumoniae
and treated subcutaneously with tigecycline or placebo for 6 days. Outcome variables included quantitative bronchoalveolar lavage (BAL)
M. pneumoniae
culture, lung histopathologic score (HPS), BAL cytokine and chemokine concentrations (tumor necrosis factor alpha [TNF-α], gamma interferon [IFN-γ], interleukin 1β [IL-1β], IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 [p40/p70], granulocyte-macrophage colony-stimulating factor, MIP-1α, MIG, KC, MCP-1, and IP-10). BAL
M. pneumoniae
concentrations in mice treated with tigecycline (MpTige) tended to be reduced compared with mice treated with placebo (MpPl); however this did not reach statistical significance. The lung HPS was significantly lower, as well as the parenchymal-pneumonia subscore, in the MpTige mice than in the MpPl mice. MpTige mice had significantly lower BAL cytokine concentrations of IL-1β, IL-12 (p40/p70), IFN-γ, and TNF-α; of the chemokines, MIG, MIP-1α, and IP-10 were statistically lower in MpTige mice. While tigecycline treatment demonstrated a modest microbiologic effect, it significantly improved lung histologic inflammation and reduced pulmonary cytokines and chemokines.
Voriconazole Use for Endemic Fungal Infections
Authors: Freifeld Alison , Proia Laurie , Andes David , Baddour Larry M. , Blair Janis , Spellberg Brad , Arnold Sandra , Lentnek Arnold , Wheat L. Joseph
Published: January 2009

In a retrospective review of 24 patients with histoplasmosis, blastomycosis, or coccidioidomycosis treated with voriconazole (most for salvage therapy), the outcome was favorable (improved or stable) for 22 (95.8%) within 2 months of starting voriconazole and for 20 (83.3%) at the last follow-up. Prospective studies are required to determine its role in the treatment of endemic mycoses.