bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of neuropathic-pain-related behaviour by the spinal endocannabinoid/endovanilloid system
Authors: Starowicz Katarzyna , Przewlocka Barbara
Published: October 2012

Neuropathic pain refers to chronic pain that results from injury to the nervous system. The mechanisms involved in neuropathic pain are complex and involve both peripheral and central phenomena. Although numerous pharmacological agents are available for the treatment of neuropathic pain, definitive drug therapy has remained elusive. Recent drug discovery efforts have identified an original neurobiological approach to the pathophysiology of neuropathic pain. The development of innovative pharmacological strategies has led to the identification of new promising pharmacological targets, including glutamate antagonists, microglia inhibitors and, interestingly, endogenous ligands of cannabinoids and the transient receptor potential vanilloid type 1 (TRPV1). Endocannabinoids (ECs), endovanilloids and the enzymes that regulate their metabolism represent promising pharmacological targets for the development of a successful pain treatment. This review is an update of the relationship between cannabinoid receptors (CB1) and TRPV1 channels and their possible implications for neuropathic pain. The data are focused on endogenous spinal mechanisms of pain control by anandamide, and the current and emerging pharmacotherapeutic approaches that benefit from the pharmacological modulation of spinal EC and/or endovanilloid systems under chronic pain conditions will be discussed.
The evolution and comparative neurobiology of endocannabinoid signalling
Authors: Elphick Maurice R.
Published: October 2012

CB1- and CB2-type cannabinoid receptors mediate effects of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide in mammals. In canonical endocannabinoid-mediated synaptic plasticity, 2-AG is generated postsynaptically by diacylglycerol lipase alpha and acts via presynaptic CB1-type cannabinoid receptors to inhibit neurotransmitter release. Electrophysiological studies on lampreys indicate that this retrograde signalling mechanism occurs throughout the vertebrates, whereas system-level studies point to conserved roles for endocannabinoid signalling in neural mechanisms of learning and control of locomotor activity and feeding. CB1/CB2-type receptors originated in a common ancestor of extant chordates, and in the sea squirtCiona intestinalisa CB1/CB2-type receptor is targeted to axons, indicative of an ancient role for cannabinoid receptors as axonal regulators of neuronal signalling. Although CB1/CB2-type receptors are unique to chordates, enzymes involved in biosynthesis/inactivation of endocannabinoids occur throughout the animal kingdom. Accordingly, non-CB1/CB2-mediated mechanisms of endocannabinoid signalling have been postulated. For example, there is evidence that 2-AG mediates retrograde signalling at synapses in the nervous system of the leechHirudo medicinalisby activating presynaptic transient receptor potential vanilloid-type ion channels. Thus, postsynaptic synthesis of 2-AG or anandamide may be a phylogenetically widespread phenomenon, and a variety of proteins may have evolved as presynaptic (or postsynaptic) receptors for endocannabinoids.
Endocannabinoids in nervous system health and disease: the big picture in a nutshell
Authors: Skaper Stephen D. , Di Marzo Vincenzo
Published: October 2012

The psychoactive component of the cannabis resin and flowers, delta9-tetrahydrocannabinol (THC), was first isolated in 1964, and at least 70 other structurally related ‘phytocannabinoid’ compounds have since been identified. The serendipitous identification of a G-protein-coupled cannabinoid receptor at which THC is active in the brain heralded an explosion in cannabinoid research. Elements of the endocannabinoid system (ECS) comprise the cannabinoid receptors, a family of nascent lipid ligands, the ‘endocannabinoids’ and the machinery for their biosynthesis and metabolism. The function of the ECS is thus defined by modulation of these receptors, in particular, by two of the best-described ligands, 2-arachidonoyl glycerol and anandamide (arachidonylethanolamide). Research on the ECS has recently aroused enormous interest not only for the physiological functions, but also for the promising therapeutic potentials of drugs interfering with the activity of cannabinoid receptors. Many of the former relate to stress-recovery systems and to the maintenance of homeostatic balance. Among other functions, the ECS is involved in neuroprotection, modulation of nociception, regulation of motor activity, neurogenesis, synaptic plasticity and the control of certain phases of memory processing. In addition, the ECS acts to modulate the immune and inflammatory responses and to maintain a positive energy balance. This theme issue aims to provide the reader with an overview of ECS pharmacology, followed by discussions on the pivotal role of this system in the modulation of neurogenesis in the developing and adult organism, memory processes and synaptic plasticity, as well as in pathological pain and brain ageing. The volume will conclude with discussions that address the proposed therapeutic applications of targeting the ECS for the treatment of neurodegeneration, pain and mental illness.
Sinobacterium caligoides gen. nov., sp. nov., a new member of the family

Oceanospirillaceae

isolated from the South China Sea, and emended description of

Amphritea japonica
Authors: Su Jianqiang , Zhou Yanyan , Lai Qiliang , Li Xinyi , Dong Peiyan , Yang Xiaoru , Zhang Bangzhou , Zhang Jinlong , Zheng Xiaowei , Tian Yun , Zheng Tianling
Published: October 2012

A taxonomic study was carried out on strain SCSWE24T, isolated from a seawater sample collected from the South China Sea. Cells of strain SCSWE24T were Gram-negative, rod-shaped, non-motile, moderately halophilic and capable of reducing nitrate to nitrite. Growth was observed at salinities from 1.5 to 4.5 % and at 4–37 °C; it was unable to degrade gelatin. The dominant fatty acids (>15 %) were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c; 50.4 %) and C16 : 0 (21.1 %). The G+C content of the chromosomal DNA was 58.8 mol%. 16S rRNA gene sequence comparisons showed that strain SCSWE24T was most closely related to an uncultured bacterium clone Tun3b.F5 (98 %; GenBank accession no. FJ169216), and showed 92 % similarity to an endosymbiont bacterium from the bone-eating worm Osedax mucofloris (clone Omu 9 c4791; FN773233). Levels of similarity between strain SCSWE24T and type strains of recognized species in the family

Oceanospirillaceae

were less than 93 %; the highest similarity was 92 %, to both

Amphritea japonica

JAMM 1866T and ‘Oceanicoccus sagamiensis’ PZ-5. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain SCSWE24T formed a distinct evolutionary lineage within the family

Oceanospirillaceae

. Strain SCSWE24T was distinguishable from members of phylogenetically related genera by differences in several phenotypic properties. On the basis of the phenotypic and phylogenetic data, strain SCSWE24T represents a novel species of a new genus, for which the name Sinobacterium caligoides gen. nov., sp. nov. is proposed. The type strain of Sinobacterium caligoides is SCSWE24T ( = CCTCC AB 209289T  = LMG 25705T  = MCCC 1F01088T). An emended description of

Amphritea japonica

is also provided.
Sagittula marina sp. nov., isolated from seawater and emended description of the genus

Sagittula
Authors: Lee Dong-Heon , Cho Sun Ja , Kim Suk Min , Lee Sun Bok
Published: October 2012

A novel bacterium, designated strain F028-2T, was isolated from seawater at Damupo beach in Pohang, Korea, and investigated in a taxonomic study using a polyphasic approach. This novel strain was strictly aerobic, non-motile, Gram-stain-negative and rod-shaped, and occasionally formed aggregates. The temperature, pH and NaCl ranges for growth were 4–30 °C, pH 6.5–9.0 and 1–7 % (w/v), respectively. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain F028-2T formed a lineage within the family

Rhodobacteraceae

of the class

Alphaproteobacteria

, and was closely related to members of the genera

Sagittula

and

Antarctobacter

with 96.3–96.4 % sequence similarities. The polar lipid profile of strain F028-2T comprised diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminolipids, one unidentified phospholipid and six unidentified lipids. The predominant cellular fatty acids were C18 : 1ω7c and C12 : 1 3-OH. The genomic DNA G+C content of strain F028-2T was 61.6 mol% and the major respiratory quinone was Q-10. Based on phenotypic, phylogenetic and genotypic data, strain F028-2T is considered to represent a novel species in the genus

Sagittula

, for which the name Sagittula marina sp. nov. is proposed. The type strain is F028-2T ( = KCTC 23543T = JCM 17627T). An emended description of the genus Sagittula is also proposed.
Litorisediminicola beolgyonensis gen. nov., sp. nov., isolated from a coastal sediment
Authors: Yoon Jung-Hoon , Lee Soo-Young , Jung Yong-Taek , Lee Jung-Sook , Lee Keun-Chul
Published: October 2012

A Gram-negative, non-spore-forming, aerobic, non-flagellated and rod- or oval-shaped bacterial strain, BB-MW24T, was isolated from a coastal sediment in South Korea. Strain BB-MW24T grew optimally at 30–37 °C, at pH 7.0–7.5 and in the presence of 2.0–3.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences revealed that strain BB-MW24T clustered with

Ponticoccus litoralis

CL-GR66T and

Roseivivax lentus

S5-5T, with which it exhibited 96.0 and 96.2 % 16S rRNA gene sequence similarity, respectively. Strain BB-MW24T exhibited 85.2 % gyrB sequence similarity with

Sagittula stellata

DSM 11524T and 83.3 and 83.2 % gyrB sequence similarity with

P. litoralis

DSM 18986T and

R. lentus

S5-5T, respectively. Strain BB-MW24T contained Q-10 as the predominant ubiquinone and C18 : 1ω7c as the predominant fatty acid. The polar lipid profile in strain BB-MW24T was similar to those of members of the genera

Ponticoccus

and

Roseivivax

, but one unidentified phospholipid was found as a major polar lipid only in strain BB-MW24T. The DNA G+C content was 68.9 mol%. The phylogenetic data and differential chemotaxonomic and phenotypic properties revealed that strain BB-MW24T represents a novel species in a new genus within the class

Alphaproteobacteria

, for which the name Litorisediminicola beolgyonensis gen. nov., sp. nov. is proposed; the type strain of Litorisediminicola beolgyonensis is BB-MW24T ( = KCTC 32139T  = CCUG 62953T).
Parvularcula dongshanensis sp. nov., isolated from soft coral
Authors: Yu Zhiwei , Lai Qiliang , Li Guizhen , Shao Zongze
Published: October 2012

A taxonomic study was carried out on strain SH25T, which was isolated from soft coral collected from Dongshan Island, China. The isolate was a heterotrophic organism to the soft coral, and was a Gram-reaction-negative, short rod that was motile by a polar flagellum. Growth was observed at salinities from 0 to 12 % and at temperatures from 10 to 41 °C. It was unable to reduce nitrate to nitrite. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SH25T belonged to the genus

Parvularcula

, with highest sequence similarity to

Parvularcula lutaonensis

CC-MMS-1T (96.1 %) and

Parvularcula bermudensis

HTCC2503T (94.3 %); 16S rRNA gene sequence similarities to other taxa were below 90.0 %. The dominant fatty acids were C16 : 0 and summed feature 8 (C18 : 1ω7c/ω6c,). The G+C content of the chromosomal DNA was 61.8 mol%. The major quinone was Q10. These combined genotypic and phenotypic data show that strain SH25T represents a novel species of the genus

Parvularcula

, for which the name Parvularcula dongshanensis sp. nov. is proposed. The type strain is SH25T ( = CCTCC AB 2010355T = LMG 26158T = MCCC 1A06534T).
The Relationship of Orthodontic Treatment Need with Periodontal Status, Dental Caries, and Sociodemographic Factors
Authors: Nalcaci Ruhi , Demirer Serhat , Ozturk Firat , Altan Burcu A. , Sokucu Oral , Bostanci Vildan
Published: October 2012

The aim of this study was to determine the relationship of orthodontic malocclusion with periodontal status, dental caries, and sociodemographic status. Our study population consisted of a sample of 836 school children (384 male and 452 female, aged 11–14 years). Four experienced orthodontists and two experienced periodontists performed the clinical examinations. The Treatment Priority Index (TPI), Community Periodontal Index of Treatment Needs (CPITN), decayed, missing, filled teeth (DMFT) scores, and a questionnaire that surveyed socio-demographic status of students were used. Spearman’s rank correlation coefficients were used to measure the association between variables. TPI scores showed that 36.4% of the students had normal occlusion, while 41.2% had slight, 15.7% had definite, 4% had severe, and 2.7% had very severe malocclusion. TPI values did not show any significant differences between pupils in different age, gender, socioeconomic status groups, and CPITN scores, whereas there was a significant relationship between TPI and DMFT scores. The orthodontic treatment need was not significantly correlated with CPITN or socio-demographic status; however, the correlation coefficient showed a significant relationship between TPI and DMFT scores.
Complementation contributes to transcriptome complexity in maize (Zea mays L.) hybrids relative to their inbred parents
Authors: Paschold Anja , Jia Yi , Marcon Caroline , Lund Steve , Larson Nick B. , Yeh Cheng-Ting , Ossowski Stephan , Lanz Christa , Nettleton Dan , Schnable Patrick S. , Hochholdinger Frank
Published: October 2012

Typically, F1-hybrids are more vigorous than their homozygous, genetically distinct parents, a phenomenon known as heterosis. In the present study, the transcriptomes of the reciprocal maize (Zea mays L.) hybrids B73×Mo17 and Mo17×B73 and their parental inbred lines B73 and Mo17 were surveyed in primary roots, early in the developmental manifestation of heterotic root traits. The application of statistical methods and a suitable experimental design established that 34,233 (i.e., 86%) of all high-confidence maize genes were expressed in at least one genotype. Nearly 70% of all expressed genes were differentially expressed between the two parents and 42%–55% of expressed genes were differentially expressed between one of the parents and one of the hybrids. In both hybrids, ∼10% of expressed genes exhibited nonadditive gene expression. Consistent with the dominance model (i.e., complementation) for heterosis, 1124 genes that were expressed in the hybrids were expressed in only one of the two parents. For 65 genes, it could be shown that this was a consequence of complementation of genomic presence/absence variation. For dozens of other genes, alleles from the inactive inbred were activated in the hybrid, presumably via interactions with regulatory factors from the active inbred. As a consequence of these types of complementation, both hybrids expressed more genes than did either parental inbred. Finally, in hybrids, ∼14% of expressed genes exhibited allele-specific expression (ASE) levels that differed significantly from the parental-inbred expression ratios, providing further evidence for interactions of regulatory factors from one parental genome with target genes from the other parental genome.
LCAA, a Novel Factor Required for Magnesium Protoporphyrin Monomethylester Cyclase Accumulation and Feedback Control of Aminolevulinic Acid Biosynthesis in Tobacco
Authors: Albus Christin Anne , Salinas Annabel , Czarnecki Olaf , Kahlau Sabine , Rothbart Maxi , Thiele Wolfram , Lein Wolfgang , Bock Ralph , Grimm Bernhard , Schöttler Mark Aurel
Published: October 2012

Low Chlorophyll Accumulation A (LCAA) antisense plants were obtained from a screen for genes whose partial down-regulation results in a strong chlorophyll deficiency in tobacco (Nicotiana tabacum). The LCAA mutants are affected in a plastid-localized protein of unknown function, which is conserved in cyanobacteria and all photosynthetic eukaryotes. They suffer from drastically reduced light-harvesting complex (LHC) contents, while the accumulation of all other photosynthetic complexes per leaf area is less affected. As the disturbed accumulation of LHC proteins could be either attributable to a defect in LHC biogenesis itself or to a bottleneck in chlorophyll biosynthesis, chlorophyll synthesis rates and chlorophyll synthesis intermediates were measured. LCAA antisense plants accumulate magnesium (Mg) protoporphyrin monomethylester and contain reduced protochlorophyllide levels and a reduced content of CHL27, a subunit of the Mg protoporphyrin monomethylester cyclase. Bimolecular fluorescence complementation assays confirm a direct interaction between LCAA and CHL27. 5-Aminolevulinic acid synthesis rates are increased and correlate with an increased content of glutamyl-transfer RNA reductase. We suggest that LCAA encodes an additional subunit of the Mg protoporphyrin monomethylester cyclase, is required for the stability of CHL27, and contributes to feedback-control of 5-aminolevulinic acid biosynthesis, the rate-limiting step of chlorophyll biosynthesis.
Poly[di-μ-aqua-[μ6-N-(4-bromophenylsulfonyl)dithiocarbimato]dipotassium] and poly[di-μ-aqua-[μ4-N-(4-iodophenylsulfonyl)dithiocarbimato]dipotassium]
Authors: Janczak Jan , Rubinger Mayura M. M. , Alves Leandro C. , Oliveira Marcelo R. L.
Published: October 2012

The rigid organic linkersN-(4-bromophenylsulfonyl)dithiocarbimate(2−) andN-(4-iodophenylsulfonyl)dithiocarbimate(2−) crystallize with two potassium cations and two water molecules in their asymmetric units, forming the title coordination polymers, [K2(C7H4BrNO2S3)(H2O)2]nand [K2(C7H4INO2S3)(H2O)2]n. The anions and the water molecules link the potassium cations into broad two-dimensional networks, which are further linked by K...halide interactions.
Obstructive sleep apnoea and cardiovascular complications: perception versus knowledge
Authors: Thomas Joi J , Ren Jun
Published: October 2012

Epidemiological evidence has confirmed that obstructive sleep apnoea (OSA) significantly promotes cardiovascular risk, independent of age, sex, race and other common risk factors for cardiovascular diseases, such as smoking, drinking, obesity, diabetes mellitus, dyslipidaemia and hypertension.

Patients with severe OSA exhibit a higher prevalence of coronary artery disease, heart failure and stroke. Despite the tight correlation between sleep apnoea and these comorbidities, the mechanisms behind increased cardiovascular risk in OSA remain elusive. Several theories have been postulated, including sympathetic activation, endothelial dysfunction, oxidative stress and inflammation.

The association between OSA and cardiovascular diseases may be rather complicated and compounded by the presence of components of metabolic syndrome, such as obesity, hypertension, diabetes mellitus and dyslipidaemia. The present minireview updates current knowledge with regard to the cardiovascular sequelae of OSA and the mechanisms involved.
Review and synthesis of the effects of climate change on amphibians
Authors: LI Yiming , COHEN Jeremy M. , ROHR Jason R.
Published: October 2012

Considerable progress has been made in understanding the responses of amphibians to climate change, with successful research carried out on climate change‐associated shifts in amphibian phenology, elevational distributions and amphibian–parasite interactions. We review and synthesize the literature on this topic, emphasizing acutely lethal, sublethal, indirect and positive effects of climate change on amphibians, and major research gaps. For instance, evidence is lacking on poleward shifts in amphibian distributions and on changes in body sizes and morphologies of amphibians in response to climate change. We have limited information on amphibian thermal tolerances, thermal preferences, dehydration breaths, opportunity costs of water conserving behaviors and actual temperature and moisture ranges amphibians experience. Even when much of this information is available, there remains little evidence that climate change is acutely lethal to amphibians. This suggests that if climate change is contributing to declines, it might be through effects that are not acutely lethal, indirect, or both, but evidence in support of this suggestion is necessary. In fact, evidence that climate change is directly contributing to amphibian declines is weak, partly because researchers have not often ruled out alternative hypotheses, such as chytrid fungus or climate–fungus interactions. Consequently, we recommend that amphibian–climate research shift from primarily inductive, correlational approach as to studies that evaluate alternative hypotheses for declines. This additional rigor will require interdisciplinary collaborations, estimates of costs and benefits of climate change to amphibian fitness and populations, and the integration of correlative field studies, experiments on ‘model’ amphibian species, and mathematical and functional, physiological models.
A preliminary assessment of the effectiveness of the Mesoamerican Biological Corridor for protecting potential Baird's tapir (Tapirus bairdii) habitat in southern Mexico
Authors: MENDOZA Eduardo , FULLER Trevon L. , THOMASSEN Henri A. , BUERMANN Wolfgang , RAMÍREZ‐MEJÍA Diana , SMITH Thomas B.
Published: October 2012

Baird's tapir (Tapirus bairdii) is one of the most emblematic mammals of Mesoamerica, but like other large‐bodied animals, it is facing an increasing risk of extinction due primarily to habitat loss. Mexico's ‘ortion of the Mesoamerican Biological Corridor (MBC‐M) is located in one of the main strongholds for Bairds tapir. To assess the MBC‐M's effectiveness for tapir conservation, we estimated the distribution of the species’ potential habitat by applying 2 modelling approaches (random forest and Maxent) to a set of uncorrelated environmental variables and a 157‐point presence dataset. We calculated the extent of tapir habitat in within the MBC‐M and modelled new corridors and conservation areas, which we compared to the MBC‐M. Moreover, we assessed deforestation patterns in the region. Twenty‐seven percent of highly suitable tapir habitat occurred in protected areas, 15% in corridors and 58.3% was outside the MBC‐M and associated reserves. The spatial configuration of the MBC‐M was partially concordant with the modelled set of conservation areas and corridors. The main dissimilarity was that the modelled corridors traversed forests in Belize and Guatemala to connect conservation areas. Analyses of deforestation since 1993 and human population density in the vicinity of the MBC‐M indicated that future conservation efforts should give particular attention to the Montes Azules‐El Triunfo Corridor due to greater habitat threat. The MBC‐M has a great potential to play a prominent role in the conservation of tapir habitat but there is an urgent need to implement management plans that reinforce and complement this conservation initiative.
Updating the Relationship between Hyperhomocysteinemia Lowering Therapy and Cardiovascular Events
Authors: Cheng Xiaoshu
Published: October 2012

Hyperhomocysteinemia (Hhcy) was defined as an independent risk factor for cardiovascular events. A number of clinical trials had investigated the relationship between Hhcy lowering treatment and cardiovascular diseases, however, the results of these studies remain controversial. This review article gave an over view of the homocysteine metabolisms and updated the recently published results in the role of Hhcy lowering therapy on cardiovascular events.
Androgen receptor genetic variants in male patients with ankylosing spondylitis in Taiwan
Authors: Yu Shan‐Fu , Hsu Yi‐Hsiang , Cheng Tien‐Tsai , Lai Han‐Ming , Chen Chung‐Jen , Kang Hong‐Yo
Published: October 2012

Aim

Ankylosing spondylitis (AS) is a chronic rheumatic disorder with gender differences. The aim of study was to investigate the association between polymorphisms of the androgen receptor (AR) gene and the susceptibility to AS in Taiwanese men of Han Chinese descent.

Methods

We conducted a case‐control study with 92 male AS patients and 108 healthy controls. Trinucleotide (CAG and GGC) repeats and seven single nucleotide polymorphisms (SNPs) rs962458, rs6152, rs1204038, rs5918757, rs2361634, rs6624304 and rs1337080 in the AR gene were genotyped.

Results

We found that only one patient had polymorphic SNPs of the AR gene. None of the genotyped SNPs in the AR gene, originally found in Caucasians, was polymorphic in the Taiwanese men. Neither CAG nor GGC repeat lengths in the AR gene had a significant relationship with human leukocyte antigen (HLA)‐B27 positivity or disease severity in AS.

Conclusion

There were no differences in CAG and GGC lengths in the AR gene between AS and the controls. None of the genotyped SNPs in AR gene are detected to be polymorphic in male Taiwanese, which indicates that the effect of AR gene on AS may be ethnic‐specific and may be conserved in East Asians compared to Caucasian populations. Still, additional studies using large sets of subjects deserve further attention, since our sample size was small with limited statistical power and supporting evidence for association between the AR gene and AS risk in the Japanese population exists.
Adult onset Still's disease: experience from a tertiary care rheumatology unit
Authors: Reddy Munagala Vishnu V. , Misra Ramnath , Agarwal Vikas , Lawrence Able , Aggarwal Amita
Published: October 2012

Background

Adult‐onset Still's disease (AOSD) is a rare chronic inflammatory disorder presenting with prolonged fever and polyarthritis.

Methods

Retrospective study of patients with AOSD, seen between 1992 and 2009 at a large tertiary care hospital.

Results

Twenty‐nine patients (18 female) with median age at onset of 28 (17–58) years were seen. The clinical features included fever in 29, inflammatory polyarthritis in 26, sore throat in eight and typical rash in 13. Lymphadenopathy was present in 15, hepatomegaly in 15, splenomegaly in 13 and serositis in five patients. Anemia was present in 22, neutrophilic leukocytosis in 28 and thrombocytosis in 13 patients. Acute phase reactants were elevated in all. Fifteen patients had transaminitis. Low titer antinuclear antibodies were present in 6/28 patients. On median follow‐up (25 patients) of 23.7 months (range: 3–84) one patient had self‐limited or monocyclic pattern, eight had polycyclic and 16 had chronic articular pattern. All patients received non‐steroidal anti‐inflammatory drugs and 25 received methotrexate and/or prednisolone. During the course 14 patients had remission and of these six were in remission on drugs at last follow‐up. One patient received tociliziumab and was in clinical remission. One patient developed macrophage activation syndrome and one had atlanto‐axial dislocation. Three patients developed tuberculosis and two died of infection associated with immunosuppression.

Conclusion

AOSD is an uncommon disorder with 1–2 patients seen at a large tertiary care rheumatology unit. Overall AOSD has a fair outcome with significant morbidity and most needing long‐term therapy with steroids and methotrexate.
Continuous use of oral contraceptives: an overview of effects and side‐effects
Authors: HEE LENE , KETTNER LAURA OZER , VEJTORP MOGENS
Published: October 2012

Objective. To describe the effects and side‐effects of the continuous use of oral contraceptives. Design. A review of articles concerning oral contraceptives taken continuously or in cycles with hormones taken for more than 21 days per cycle. Methods. We searched publications in PubMed and Embase. Randomized controlled trials were selected if possible, otherwise case–control studies or cohort studies with controls were chosen. A level of evidence as described by the Centre for Evidence Based Medicine (Oxford University, Oxford, UK) was assigned to all selected studies. Main outcome measures. Clinical and paraclinical effects and side‐effects of oral contraceptives administered continuously. Results. The studies suggest that the endometrium is inactive during continuous use of oral contraceptives and the risk of endometrial hyperplasia is not increased. Numbers of bleeding days are halved with continuous use; however, spotting and irregular bleeding are more often seen in the beginning of use, decreasing with time. Hemostatic parameters and serum lipid and carbohydrate profiles in continuous and conventional users do not differ. Menstrual cycle‐related symptoms are relieved better by continuous treatment. After surgery for endometriosis, the effect of continuously used oral contraceptives on the risk of recurrence of pain has been found to be less than that of gonadotropin‐releasing hormone (GnRH) analogues, but better than the rate seen during conventional cyclic use. Conclusion. Oral contraceptives taken continuously or in long cycles seem to offer benefits with regard to menstrual symptoms and the recurrence of symptoms related to endometriosis. Long‐term studies, comprising large groups of women, are lacking.
Intestinal microbial profiles in extremely preterm infants with and without necrotizing enterocolitis
Authors: Normann Erik , Fahlén Annika , Engstrand Lars , Lilja Helene Engstrand
Published: October 2012

Aim

Necrotizing enterocolitis (NEC) represents one of the gravest complications in premature infants. The suggested role of intestinal microbiota in the development of NEC needs to be elucidated.

Methods

This prospective single‐centre case–control study applied barcoded pyrosequencing to map the bacterial composition of faecal samples from extremely preterm infants. Ten patients were diagnosed with NEC and matched to healthy controls with regard to sex, gestational age and mode of delivery prior to analysis of the samples.

Results

Enterococcus, Bacillales and Enterobacteriaceae dominated the flora. Although not statistically significant, a high relative abundance of Bacillales and Enterobacteriaceae was detected at early time points in patients developing NEC, while healthy controls had a microbiota more dominated by Enterococcus. A low diversity of intestinal microbial flora was found without any differences between NEC patients and controls. In 16 healthy controls, Firmicutes (Enterococcus and Bacillales) dominated the faecal flora during the first weeks after birth and were then succeeded by Enterobacteriaceae.

Conclusion

No significant differences in the composition of intestinal microbiota of patients developing NEC were detected; however, some findings need to be scrutinized in subsequent studies.
Association of HLA locus variant in Parkinson's disease
Authors: Zhao Y , Gopalai AA , Ahmad‐Annuar A , Teng EWL , Prakash KM , Tan LCS , Au W‐L , Li H‐H , Lim S‐Y , Lim SK , Chong YB , Tan LP , Ibrahim NM , Tan E‐K
Published: October 2012

A variant (rs3129882) in the genome‐wide association study (GWAS)‐linked variant [in the human leukocyte antigen (HLA) gene region] has been reported to associate with an increased risk of Parkinson's disease (PD) in Caucasian population. Studies among Chinese are limited. To address this, we analysed rs3129882 in a total of 1312 subjects of Chinese ethnicity from independent Asian centers comprising of 675 controls and 637 PD cases. The rs3129882 variant was associated with a decreased risk in our ethnic Chinese PD patients. Logistic regression analysis taking into consideration variables of age, gender and race showed that allele A reduced the risk of PD via a dominant model [odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.62, 0.96, p = 0.018]. As HLA is a highly polymorphic region, it is possible that ethnic‐specific effect or environmental agents may modulate the effect of this GWAS‐linked locus in influencing the risk of PD.
Exogenous Basic Fibroblast Growth Factor Inhibits ER Stress–Induced Apoptosis and Improves Recovery from Spinal Cord Injury
Authors: Zhang Hong‐Yu , Zhang Xie , Wang Zhou‐Guang , Shi Hong‐Xue , Wu Fen‐Zan , Lin Bei‐Bei , Xu Xin‐Long , Wang Xiao‐Jie , Fu Xiao‐Bing , Li Zhao‐Yu , Shen Chen‐Jie , Li Xiao‐Kun , Xiao Jian
Published: October 2012

Aim

To investigate the mechanism of endoplasmic reticulum (ER) stress–induced apoptosis as well as the protective action of basic fibroblast growth factor (bFGF) both in vivo and in vitro.

Methods and Results

ER stress–induced apoptosis was involved in the injuries of spinal cord injury (SCI) model rat. bFGF administration improved the recovery and increased the survival of neurons in spinal cord lesions in model rat. The protective effect of bFGF is related to the inhibition of CHOP, GRP78 and caspase‐12, which are ER stress–induced apoptosis response proteins. bFGF administration also increased the survival of neurons and the expression of growth‐associated protein 43 (GAP43), which is related to neural regeneration. The protective effect of bFGF is related to the activation of downstream signals, PI3K/Akt/GSK‐3β and ERK1/2, especially in the ER stress cell model.

Conclusions

This is the first study to illustrate that the role of bFGF in SCI recovery is related to the inhibition of ER stress–induced cell death via the activation of downstream signals. Our work also suggested a new trend for bFGF drug development in central neural system injuries, which are involved in chronic ER stress–induced apoptosis.
Endoscopic mucosal resection vs endoscopic submucosal dissection for rectal carcinoid tumours: a systematic review and meta‐analysis
Authors: Zhong D.‐D. , Shao L.‐M. , Cai J.‐T.
Published: October 2012

Aim

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are used for the removal of rectal carcinoid tumours. There are no current guidelines or consensus on the optimal treatment strategy for these lesions. A systematic review was conducted to compare the efficacy and safety of ESD and EMR.

Method

The generation of inclusion criteria and analysis of data were based on Preferred Reporting Items for Systematic Reviews and Meta‐Analyses recommendations. A systematic literature review was conducted using the following databases: Medline, Embase, SpringerLink, Elsevier ScienceDirect, Science Citation Index and the Cochrane Library. Only papers comparing treatment of rectal carcinoid tumours by EMR and by ESD were selected. The data collected included the patients' demographic information, interventions made, observed outcome and sources of bias.

Results

Four papers were included in this systematic review and meta‐analysis. ESD was more effective than EMR in complete resection (OR 0.29; 95% CI 0.14–0.58; P = 0.000). ESD was as safe as EMR [rate difference (RD) −0.01; 95% CI −0.07 to 0.05; P = 0.675]. Recurrence rates did not differ significantly between the EMR and ESD groups (RD 0.04; 95% CI −0.01 to 0.09; P = 0.150). The duration of ESD was longer than EMR (standardized mean difference −1.73; 95% CI −2.73 to −0.74; P = 0.001).

Conclusion

The study indicates that ESD is the better treatment for rectal carcinoid tumours.
Molecular genetic analysis of 16 XP‐C patients from Germany: environmental factors predominately contribute to phenotype variations
Authors: Schäfer Annika , Hofmann Lars , Gratchev Alexei , Laspe Petra , Schubert Steffen , Schürer Anke , Ohlenbusch Andreas , Tzvetkov Mladen , Hallermann Christian , Reichrath Jörg , Schön Michael P. , Emmert Steffen
Published: October 2012

Patients belonging to xeroderma pigmentosum (XP) complementation group C comprise one‐third of all XP patients. Only four major reports compiled larger groups of XP‐C patients from southern Europe (12 pts), North America (16 pts) and Africa (14 and 56 pts) as well as their genetic background (46 XPC mutations). We identified 16 XP‐C patients from Germany. Interestingly, only five patients exhibited severe sun sensitivity. The mean age of XP diagnosis was 9.4 years, and the median age of the first skin cancer was 7 years. Neurological symptoms were absent in all but two patients. Primary fibroblasts from all 16 patients showed reduced post‐UV cell survival (mean: 50% vs 93% in normal cells) and reduced reactivation of an UV‐treated luciferase reporter gene (mean: 6.4% vs 30.7% in normal cells). XPC mRNA expression was also greatly reduced compared with normal cells (mean: 14.3%; range 8.3–25.7%) except in XP47MA (274.1%). All patients carried homozygous XPC mutations. Four mutations have been described previously: c.1747_1748delTG (found in 4/16), c.567 C>T (4/16), c.1839 C>T (1/16) and a complex insertion/deletion mutation in exon 9 (1/16). The novel frameshift mutations c.446_447delAG (2/16), c.1525insA (1/16) and c.2271delC (1/16) lead to truncated XPC proteins as does the novel nonsense mutation c.843C>T (1/16). XP47MA carries an interesting mutation (c.2538_2540delATC; p.Ile812del) resulting in an in‐frame single amino acid deletion. This mutation results in a classical XP phenotype, a non‐functional XPC protein, but elevated XPC mRNA expression. Our study indicates that extrinsic factors may contribute to XP‐C symptom severity due to nonsense‐mediated message decay.
Non‐invasive assessment of tryptophan fluorescence and confocal microscopy provide information on skin barrier repair dynamics beyond TEWL
Authors: Bargo Paulo R. , Walston Steven T. , Chu Melissa , Seo Inseok , Kollias Nikiforos
Published: October 2012

The stratum corneum (SC) serves a primary function of skin barrier and understanding the kinetics of SC formation may provide great insight for skin diagnosis and evaluation of therapies. Besides trans‐epidermal water loss (TEWL), few methods have been characterized to assess skin barrier non‐invasively in vivo, particularly for dynamic measurements on the same specimen over time. The objective of this study was to characterize alternative non‐invasive methods to evaluate the dynamic processes involved in the recovery of normal human SC after total removal. TEWL, tryptophan fluorescence and reflectance confocal microscopy (RCM) were used to determine skin barrier function, cell turnover and epidermal morphology over a period of 10 days after total removal of the SC by tape stripping. The results show a biphasic recovery of TEWL over time, which contrasted with a linear increase of 2.3 μm/day in SC thickness. Tryptophan assessment of cell turnover also demonstrated a biphasic pattern attaining a maximum three to four times the levels of the control site 3 days after injury that slowly returned to baseline and displayed great correlation (R2 > 0.95) to viable epidermis thickness that also achieved a maximum about 3 days after injury with an approximate increase of 55%. When plotting the change of TEWL versus SC thickness, a single exponential function is observed [Δ‐TEWL = 55 exp (−0.157×)] which contrasts with other proposed models. These methods were able to present rates for SC recovery processes beyond skin barrier (TEWL) that may provide new insights on kinetics of barrier formation for evaluation of skin conditions and treatments.
Structural basis of peptide recognition by the angiotensin‐1 converting enzyme homologue AnCE from Drosophila melanogaster
Authors: Akif Mohd , Masuyer Geoffrey , Bingham Richard J. , Sturrock Edward D. , Isaac R. Elwyn , Acharya K. Ravi
Published: October 2012

Human somatic angiotensin‐1 converting enzyme (ACE) is a zinc‐dependent exopeptidase, that catalyses the conversion of the decapeptide angiotensin I to the octapeptide angiotensin II, by removing a C‐terminal dipeptide. It is the principal component of the renin‐angiotensin–aldosterone system that regulates blood pressure. Hence it is an important therapeutic target for the treatment of hypertension and cardiovascular disorders. Here, we report the structures of an ACE homologue from Drosophila melanogaster (AnCE; a proven structural model for the more complex human ACE) co‐crystallized with mammalian peptide substrates (bradykinin, Thr6–bradykinin, angiotensin I and a snake venom peptide inhibitor, bradykinin‐potentiating peptide‐b). The structures determined at 2‐Å resolution illustrate that both angiotensin II (the cleaved product of angiotensin I by AnCE) and bradykinin‐potentiating peptide‐b bind in an analogous fashion at the active site of AnCE, but also exhibit significant differences. In addition, the binding of Arg–Pro–Pro, the cleavage product of bradykinin and Thr6– bradykinin, provides additional detail of the general peptide binding in AnCE. Thus the new structures of AnCE complexes presented here improves our understanding of the binding of peptides and the mechanism by which peptides inhibit this family of enzymes.

Database

The atomic coordinates and structure factors for AnCE–Ang II (code 4AA1), AnCE–BPPb (code 4AA2), AnCE–BK (code 4ASQ) and AnCE–Thr6–BK (code 4ASR) complexes have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/)

Structured digital abstract

• AnCE cleaves Ang I by enzymatic study (View interaction)

• Bradykinin and AnCE bind by x-ray crystallography (View interaction)

• BPP and AnCE bind by x-ray crystallography (View interaction)

• AnCE cleaves Bradykinin by enzymatic study (View interaction)

• Ang II and AnCE bind by x-ray crystallography (View interaction)
Plant functional traits mediate reproductive phenology and success in response to experimental warming and snow addition in Tibet
Authors: Dorji Tsechoe , Totland Ørjan , Moe Stein R. , Hopping Kelly A. , Pan Jianbin , Klein Julia A.
Published: October 2012

Global climate change is predicted to have large impacts on the phenology and reproduction of alpine plants, which will have important implications for plant demography and community interactions, trophic dynamics, ecosystem energy balance, and human livelihoods. In this article we report results of a 3‐year, fully factorial experimental study exploring how warming, snow addition, and their combination affect reproductive phenology, effort, and success of four alpine plant species belonging to three different life forms in a semiarid, alpine meadow ecosystem on the central Tibetan Plateau. Our results indicate that warming and snow addition change reproductive phenology and success, but responses are not uniform across species. Moreover, traits associated with resource acquisition, such as rooting depth and life history (early vs. late flowering), mediate plant phenology, and reproductive responses to changing climatic conditions. Specifically, we found that warming delayed the reproductive phenology and decreased number of inflorescences of Kobresia pygmaea C. B. Clarke, a shallow‐rooted, early‐flowering plant, which may be mainly constrained by upper‐soil moisture availability. Because K. pygmaea is the dominant species in the alpine meadow ecosystem, these results may have important implications for ecosystem dynamics and for pastoralists and wildlife in the region.
The imprint of humans on landscape patterns and vegetation functioning in the dry subtropics
Authors: Baldi Germán , Verón Santiago R. , Jobbágy Esteban G.
Published: October 2012

Dry subtropical regions (DST), originally hosting woodlands and savannas, are subject to contrasting human pressures and land uses and different degrees of water limitation. We quantified how this variable context influences landscape pattern and vegetation functioning, by exploring the associations between three groups of variables describing (i) human pressures (population density, poverty, and market isolation) and climate (water availability), (ii) landscape pattern (woody cover, infrastructure, paddock size, etc.), and (iii) vegetation functioning (magnitude and stability of primary productivity), in regions of Asia, Africa, Australia, and America. We collected data from global socioeconomic databases and remote sensing products for 4525 samples (representing uncultivated and cultivated conditions), located along 35 transects spanning semiarid to subhumid conditions. A Reciprocal Averaging ordination of uncultivated samples revealed a dominant gradient of declining woody cover accompanied by lower and less stable productivity. This gradient, likely capturing increasing vegetation degradation, had a negative relationship with poverty (characterized by infant mortality) and with market isolation (measured by travel time to large cities). With partial overlaps, regions displayed an increasing degradation ranking from Africa to South America, to Australia, to North America, and to Asia. A similar analysis of cultivated samples, showed a dominant gradient of increasing paddock size accompanied by decreasing primary productivity stability, which included all regions except Asia. This gradient was negatively associated with poverty and population density. A unique combination of small paddocks and high infrastructure differentiated Asian cultivated samples. While water availability gradients were related to productivity trends, they were unrelated to landscape pattern. Our comparative approach suggests that, in DST, human pressures have an overwhelming role driving landscape patterns and one shared with water availability shaping vegetation functioning.
Environmental context determines multi‐trophic effects of consumer species loss
Authors: O'Connor Nessa E. , Donohue IAN
Published: October 2012

Loss of biodiversity and nutrient enrichment are two of the main human impacts on ecosystems globally, yet we understand very little about the interactive effects of multiple stressors on natural communities and how this relates to biodiversity and ecosystem functioning. Advancing our understanding requires the following: (1) incorporation of processes occurring within and among trophic levels in natural ecosystems and (2) tests of context‐dependency of species loss effects. We examined the effects of loss of a key predator and two groups of its prey on algal assemblages at both ambient and enriched nutrient conditions in a marine benthic system and tested for interactions between the loss of functional diversity and nutrient enrichment on ecosystem functioning. We found that enrichment interacted with food web structure to alter the effects of species loss in natural communities. At ambient conditions, the loss of primary consumers led to an increase in biomass of algae, whereas predator loss caused a reduction in algal biomass (i.e. a trophic cascade). However, contrary to expectations, we found that nutrient enrichment negated the cascading effect of predators on algae. Moreover, algal assemblage structure varied in distinct ways in response to mussel loss, grazer loss, predator loss and with nutrient enrichment, with compensatory shifts in algal abundance driven by variation in responses of different algal species to different environmental conditions and the presence of different consumers. We identified and characterized several context‐dependent mechanisms driving direct and indirect effects of consumers. Our findings highlight the need to consider environmental context when examining potential species redundancies in particular with regard to changing environmental conditions. Furthermore, non‐trophic interactions based on empirical evidence must be incorporated into food web‐based ecological models to improve understanding of community responses to global change.