bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting macrophages in the tumour environment to enhance the efficacy of αOX40 therapy
Authors: Gough Michael J. , Killeen N. , Weinberg Andrew D.
Published: May 2012

The treatment of high‐grade tumours must consider a tumour environment dominated by cells that support cancer growth. In addition to directing angiogenesis and invasion, alternatively activated macrophages in the tumour provide protection from adaptive immunity and permit tumour growth. Agonist antibodies to the tumour necrosis factor receptor family member OX40 are an effective therapy for cancer in a range of murine models; however, as with many immune therapies, αOX40 therapy is less effective as the tumour grows and develops an immune suppressive environment. We demonstrate that αOX40 directly activates T cells and that this T‐cell activation alters macrophage differentiation in the tumour environment. We demonstrate that macrophages in the tumour limit the efficacy of αOX40 therapy, and that combining αOX40 therapy with inhibitors of arginase significantly enhances survival of tumour‐bearing mice. These data demonstrate that macrophages in the tumour environment limit the effectiveness of OX40‐based immunotherapy, and combination therapies that target both the cell‐mediated immune response and the suppressive tumour environment will be required for translation of effective immunotherapies to patients with established tumours.
Aromatase Knockout Mice Show Normal Steroid‐Induced Activation of Gonadotrophin‐Releasing Hormone Neurones and Luteinising Hormone Surges With a Reduced Population of Kisspeptin Neurones in the Rostral Hypothalamus
Authors: Szymanski L. , Bakker J.
Published: May 2012

We recently reported that female aromatase knockout (ArKO) mice show deficits in sexual behaviour and a decreased population of kisspeptin‐immunoreactive neurones in the rostral periventricular area of the third ventricle (RP3V), resurrecting the question of whether oestradiol actively contributes to female‐typical sexual differentiation. To further address this question, we assessed the capacity of ArKO mice to generate a steroid‐induced luteinising hormone (LH) surge. Adult, gonadectomised wild‐type (WT) and ArKO mice were given silastic oestradiol implants s.c. and, 1 week later, received s.c. injections of either oestradiol benzoate (EB) followed by progesterone, EB alone, or no additional steroids to activate gonadotrophin‐releasing hormone (GnRH) neurones and generate an LH surge. Treatment with EB and progesterone induced significant Fos/GnRH double‐labelling and, consequently, an LH surge in female WT and in ArKO mice of both sexes but not in male WT mice. ArKO mice of both sexes had fewer cells expressing Kiss‐1 mRNA in the RP3V compared to female WT mice but had more Kiss‐1 mRNA‐expressing cells compared to WT males, reflecting an incomplete sexual differentiation of this system. To determine the number of cells expressing kisspeptin, the same experimental design was repeated in Experiment 2 with the addition of groups of WT and ArKO mice that were given EB + progesterone and sacrificed 2 h before the expected LH surge. No differences were observed in the number of kisspeptin‐immunoreactive cells 2 h before and at the time of the LH surge. The finding that ArKO mice of both sexes have a competent LH surge system suggests that oestradiol has predominantly defeminising actions on the GnRH/LH surge system in males and that the steroid‐induced LH surge can occur in females even with a greatly reduced population of kisspeptin neurones in the RP3V.
Paired‐Related Homeodomain Proteins Prx1 and Prx2 are Expressed in Embryonic Pituitary Stem/Progenitor Cells and May Be Involved in the Early Stage of Pituitary Differentiation
Authors: Susa T. , Kato T. , Yoshida S. , Yako H. , Higuchi M. , Kato Y.
Published: May 2012

We recently cloned a paired‐related homeodomain protein Prx2 as a novel factor in the pituitary. In the present study, we investigated the ontogenic profiles of Prx2 and another cognate Prx1 in the rat embryonic pituitary. Quantitative real‐time polymerase chain reaction showed low expression of Prx2 and a marked increase of Prx1 on rat embryonic day (E)20.5. Immunohistochemical analyses using an antibody that recognises both proteins, with the aim of investigating their roles in pituitary organogenesis, demonstrated that PRXs first appear in the Rathke’s pouch on E13.5 in the pituitary stem/progenitor cells expressing Prop1 and Sox2. After E16.5, the number of Prx‐expressing cells was increased in both anterior and intermediate lobes. SOX2+ stem/progenitor cells in the intermediate lobe started to produce PRXs, and PRX+/SOX2+/PROP1+‐cells were present on the anterior side of the marginal cell layer and were scattered in the parenchyma of the anterior lobe. On the other hand, PRX+‐cells negative for PROP1 and SOX2 were located in the anterior lobe. Analysis of the relationship with pituitary endocrine cells revealed that a part of PRX+/PROP1−/SOX2−‐cells in the anterior lobe co‐expressed all types of hormones. The proportion of co‐localisation of PRXs and hormones was highest on the day each hormone first appeared. These data indicate that PRXs are produced in the pituitary progenitor cells and may play roles in the process of terminal differentiation during early pituitary organogenesis. An in vitro small interfering RNA‐knockdown experiment in the pituitary‐derived cell line, TtT/GF, revealed that PRX1 and PRX2 play roles in proliferation by different mechanisms because knockdown of Prx2, but not Prx1, induced the p21 expression. Furthermore, immunohistochemical analysis demonstrated that 76% of PRXs+ cells were positive for a cell proliferation marker Ki67 in the E18.5 pituitary. This is the first report of the involvement of PRX1 and PRX2 in organogenesis of tissue originating from the ectoderm other than the mesoderm.
Characterisation of Human Oestrogen Receptor beta (ERβ) Splice Variants in Neuronal Cells
Authors: Mott N. N. , Pak T. R.
Published: May 2012

Oestrogen receptor (ER)α and ERβ are members of the ligand‐activated superfamily of nuclear receptors and mediate most facets of oestrogen signalling. Several naturally occurring splice variants of each ER have been identified in the human brain, yet the biological significance of these splice variants in the brain remains unknown. In the present study, we exploit the unique structural differences of the human ERβ splice variants to determine the functional significance of individual ER domains in the brain. We previously established that full‐length rodent ERβ (i.e. rERβ1) has constitutive transcriptional activity in neuronal cells in the absence of ligand. By contrast to the rodent splice variants, the human ERβ splice variants used in the present study contain varying length truncations of exon 8, which encodes for the E/F domains. Our results reveal that, in neuronal cells, each human‐specific ERβ splice variant constitutively activated promoters mediated by a canonical oestrogen response element and repressed promoters mediated by activator protein‐1 sites via p38 activity. From these data, we conclude that the C‐terminus, encoding the AF‐2 region and F domain, is not essential for the constitutive properties of human ERβ. Taken together, these studies show that human‐specific ERβ variants are constitutively active and also provide novel insight into the contributions of the functional domains of ERβ towards mediating constitutive transcription at various promoters in neuronal cells.
Morphological and molecular diversity of Colletotrichum spp. causing pepper spot and anthracnose of lychee (Litchi chinensis) in Australia
Authors: Anderson J. M. , Aitken E. A. B. , Dann E. K. , Coates L. M.
Published: May 2012

Since the 1980s a new disease has been affecting Australian lychee. Pepper spot appears as small, black superficial lesions on fruit, leaves, petioles and pedicels and is caused by Colletotrichum gloeosporioides, the same fungus that causes postharvest anthracnose of lychee fruit. The aim of this study was to determine if a new genotype of C. gloeosporioides is responsible for the pepper spot symptom. Morphological assessments, arbitrarily‐primed PCR (ap‐PCR) and DNA sequencing studies did not differentiate isolates of C. gloeosporioides from anthracnose and pepper spot lesions. The ap‐PCR identified 21 different genotypes of C. gloeosporioides, three of which were predominant. A specific genotype identified using ap‐PCR was associated with the production of the teleomorph in culture. Analysis of sequence data of ITS and β‐tubulin regions of representative isolates did not group the lychee isolates into a monophyletic clade; however, given the majority of the isolates were from one of three genotypes found using ap‐PCR, the possibility of a lychee specific group of C. gloeosporioides is discussed.
Non‐random distribution of weed species abundance in arable fields
Authors: BORGY B , GABA S , PETIT S , REBOUD X
Published: May 2012

Borgy B, Gaba S, Petit S & Reboud X (2012) Non‐random distribution of weed species abundance in arable fields. Weed Research52, 383–389.

Many decisions for pest control in agriculture are based on densities, rather than species presence only. Little is known about the distribution of pest abundance and even less when several species present in a field may interact. With the aim of developing an ecologically based approach to weed management, we compared observed co‐occurrence patterns with a null model, to test whether the abundances of weed species were randomly assembled. The data set covered the pattern of co‐occurrence of abundances of weeds within 200‐m2 plots located in 1143 arable fields scattered across France. Our results pinpointed a highly significant ‘similar attraction–dissimilar repulsion’ rule, as species reaching similar abundance levels co‐occurred significantly more often than expected under the hypothesis of a random distribution of abundance. A similar analysis applied to the 25% plots that had the highest weed densities indicated that the ‘similar attraction–dissimilar repulsion’ rule held true for low‐abundance classes, but not in situations where at least one species was observed at densities above 20 individuals m−2. Our analysis extends the analysis of community beyond the sole species richness index by accounting for their abundance. Overall, weed species interfered or responded similarly to an external biotic or abiotic factor, with resulting adjustment of densities at the scale of the agricultural field.
The sensitivity of predicted financial and genetic gains in Holsteins to changes in the economic value of traits
Authors: Cottle D.J. , Coffey M.P.
Published: May 2012

The objective of this study was to assess the impact of using different relative economic values (REVs) in selection indices on predicted financial and trait gains from selection of sires of cows and on the choice of leading Holstein bulls available in the UK dairy industry. Breeding objective traits were milk yield, fat yield, protein yield, lifespan, mastitis, non‐return rate, calving interval and lameness. Relative importance of a trait, as estimated by a.h2, was only moderately related to the rate of financial loss or total economic merit (ΔTEM) per percentage under‐ or overestimation of REV (r = 0.38 and 0.29, respectively) as a result of the variance–covariance structure of traits. The effects on TEM of under‐ or overestimating trait REVs were non‐symmetrical. TEM was most sensitive to incorrect REVs for protein, fat, milk and lifespan and least sensitive to incorrect calving interval, lameness, non‐return and mastitis REVs. A guide to deciding which dairy traits require the most rigorous analysis in the calculation of their REVs is given. Varying the REVs within a fairly wide range resulted in different bulls being selected by index and their differing predicted transmitting abilities would result in the herds moving in different directions in the long term (20 years). It is suggested that customized indices, where the farmer creates rankings of bulls tailored to their specific farm circumstances, can be worthwhile.
Optimal contribution selection applied to the Norwegian and the North‐Swedish cold‐blooded trotter – a feasibility study
Authors: Olsen H. F. , Meuwissen T. , Klemetsdal G.
Published: May 2012

The aim of this study was to examine how to apply optimal contribution selection (OCS) in the Norwegian and the North‐Swedish cold‐blooded trotter and give practical recommendations for the future. OCS was implemented using the software Gencont with overlapping generations and selected a few, but young sires, as these turn over the generations faster and thus is less related to the mare candidates. In addition, a number of Swedish sires were selected as they were less related to the selection candidates. We concluded that implementing OCS is feasible to select sires (there is no selection on mares), and we recommend the number of available sire candidates to be continuously updated because of amongst others deaths and geldings. In addition, only considering sire candidates with phenotype above average within a year class would allow selection candidates from many year classes to be included and circumvent current limitation on number of selection candidates in Gencont (approx. 3000). The results showed that mare candidates can well be those being mated the previous year. OCS will, dynamically, recruit young stallions and manage the culling or renewal of annual breeding permits for stallions that had been previously approved. For the annual mating proportion per sire, a constraint in accordance with the maximum that a sire can mate naturally is recommended.
MACROPRUDENTIAL POLICY – A LITERATURE REVIEW
Authors: Galati Gabriele , Moessner Richhild
Published: May 2012

The recent financial crisis has highlighted the need to go beyond a purely micro approach to financial regulation and supervision. As a consequence, the number of policy speeches, research papers and conferences that discuss a macro perspective on financial regulation has grown considerably. The policy debate is focusing in particular on macroprudential tools and their usage, their relationship with monetary policy, their implementation and their effectiveness. Macroprudential policy has recently also attracted considerable attention among researchers. This paper provides an overview of research on this topic. We also identify important future research questions that emerge from both the literature and the current policy debate.
Low serum uric acid concentration in Parkinson's disease in southern Spain
Authors: Jesús S. , Pérez I. , Cáceres‐Redondo M. T. , Carrillo F. , Carballo M. , Gómez‐Garre P. , Mir P.
Published: May 2012

Background and purpose

Uric acid (UA) is thought to have an antioxidant effect on the central nervous system and may also prevent cerebral damage induced by oxidative stress. Our study aimed to investigate whether patients with Parkinson's disease (PD) had lower serum UA concentrations than controls and whether UA concentration was related to clinical parameters of the disease.

Methods

We included 161 patients with PD and 178 controls from southern Spain. UA concentration was compared between these two groups. Clinical parameters including severity of the disease were related to serum UA.

Results

Patients with PD showed statistically significant lower serum UA concentrations than controls. Serum UA concentration was lower in patients with PD in severe stages (4 and 5) than in those in moderate stage (2) according to the modified Hoehn and Yahr scale. Other clinical parameters were not related to serum UA concentration, except for levodopa equivalent daily dose that was associated with lower serum UA concentration in men.

Conclusions

Our study produced consistent findings that UA might have a protective effect against PD and could influence its clinical progression.
ATXN8 −62 G/A promoter polymorphism and risk of Taiwanese Parkinson's disease
Authors: Chen I.‐C. , Wu Y.‐R. , Yang S.‐J. , Kao S.‐H. , Chen Y.‐C. , Chang K.‐H. , Lee C.‐M. , Lee‐Chen G.‐J. , Chen C.‐M.
Published: May 2012

Background and purpose

We recently reported a novel −62 G/A polymorphism within ataxin 8 (ATXN8) gene promoter region, with −62 G displaying significantly higher luciferase activity compared with −62 A. Phenotypic variability in spinocerebellar ataxia type 8 (SCA8) has been suggested, and large SCA8 repeats were found in patients with Parkinson's disease (PD). We aimed to investigate the association of ATXN8 −62 G/A polymorphism with the risk of Taiwanese PD, and identify the trans‐acting factor modulating the ATXN8 promoter activity.

Methods

A case–control study in a cohort of 569 PD cases and 547 ethnically matched controls was conducted by polymerase chain reaction (PCR) and restriction enzyme analysis. The trans‐acting factor binding to the ATXN8 promoter was examined by chromatin immunoprecipitation (ChIP)‐PCR assay, cDNA co‐transfection and luciferase reporter assay.

Results

When genotype distribution was calculated by comparing the rare AA genotype with the GG + GA genotypes (recessive model), a significant difference was found (P = 0.035, 1 df). Individuals carrying AA genotype exhibited a decreased risk of developing PD (odds ratio: 0.73; 95% CI: 0.55–0.98, P = 0.035). After stratification by age, individuals over 60 years of age carrying AA genotype demonstrated a further decrease in the risk of developing PD (odds ratio: 0.64; 95% CI: 0.43–0.96, P = 0.030). ChIP‐PCR and cDNA over‐expression revealed that CCAAT/enhancer‐binding protein alpha binds to the ATXN8 proximal promoter to upregulate ATXN8 expression in neuroblastoma SK‐N‐SH cells.

Conclusions

Our data suggest that ATXN8 −62 G/A polymorphism plays a role in Taiwanese PD susceptibility.
Interrater reliability and convergent validity of the American Academy for Cerebral Palsy and Developmental Medicine methodology for conducting systematic reviews
Authors: WIART LESLEY , KOLASKI KAT , BUTLER CHARLENE , VOGTLE LAURA , LOGAN LYNNE ROMEISER , HICKMAN ROBBIN , ROMEISER JAMIE , SAMSON‐FANG LISA , MATSUBA CAREY A , BAIRD MICAH W , ROXBOROUGH LORI , MAYSON TANJA , DINU IRINA
Published: May 2012

Aim  The aim of this study was to evaluate the interrater reliability and convergent validity of the American Academy for Cerebral Palsy and Developmental Medicine’s (AACPDM) methodology for conducting systematic reviews (group design studies).

Method  Four clinicians independently rated 24 articles for the level of evidence and conduct using AACPDM methodology. Study conduct was also assessed using the Effective Public Health Practice Project scale. Raters were randomly assigned to one of two pairs to resolve discrepancies. The level of agreement between individual raters and pairs was calculated using kappa (α=0.05) and intraclass correlations (ICCs; α=0.05). Spearman’s rank correlation coefficient was calculated to evaluate the relationship between raters’ categorization of quality categories using the two tools.

Results  There was acceptable agreement between raters (κ=0.77; p<0.001; ICC=0.90) and between assigned pairs (κ=0.83; p<0.001; ICC=0.96) for the level of evidence ratings. There was acceptable agreement between pairs for four of the seven conduct questions (κ=0.53–0.87). ICCs (all raters) for conduct category ratings (weak, moderate, and strong) also indicated good agreement (ICC=0.76). Spearman’s rho indicated a significant positive correlation for the overall quality category comparisons of the two tools (0.52; p<0.001).

Conclusions  The AACPDM rating system has acceptable interrater reliability. Evaluation of its study quality ratings demonstrated reasonable agreement when compared with a similar tool.
Congenital non‐central nervous system malformations in cerebral palsy: a distinct subset?
Authors: SELF LAUREN , DAGENAIS LYNN , SHEVELL MICHAEL
Published: May 2012

Aim  The aim of this article was to identify and contrast the subset of children with cerebral palsy (CP) and non‐central nervous system (CNS) congenital malformations with children with CP but no coexisting non‐CNS congenital malformations.

Method  A population‐based regional comprehensive CP registry was used to identify children with CP who had non‐CNS congenital malformations (n=34; 19 males, 15 females; 22 classified as Gross Motor Function Classification System [GMFCS] levels I–III, 12 as GMFCS level IV or V). Their clinical features were then compared with other children with CP without non‐CNS congenital malformations (n=207; 115 males, 92 females; 138 classified as GMFCS levels I–III, 69 as GMFCS level IV or V).

Results  Children with CP and non‐CNS congenital malformations did not differ from those without in terms of neurological subtype distribution or functional severity, as measured by the GMFCS. Also, there was no association with previous maternal infections (i.e. toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus 2 [TORCH]), maternal fever, use of illicit substances, asphyxia, neonatal encephalopathy, intraventricular haemorrhage, or septicaemia. The incidence of comorbidities such as convulsions, communication difficulties, gavage feeding, cortical blindness, and auditory impairment was not higher in this subgroup.

Interpretation  The incidence of congenital non‐CNS malformations among children with CP is appreciable. Children with these non‐CNS malformations do not appear to differ from other children with CP regarding neurological subtype, functional severity, and comorbidities, or maternal or obstetrical factors. Thus, the specific presence of a non‐CNS congenital malformation does not appear to assist the practitioner in the management or understanding of a child’s CP.
Cerebral palsy and birth defects: what is the frame of reference?
Authors: KIRBY RUSSELL S
Published: May 2012

This commentary is on the original article by Self et al. on pages http://dx.doi.org/10.1111/j.1469‐8749.2012.04309.x">748‐752 of this issue
Performance and biomass kinetics of activated sludge system treating dairy wastewater
Authors: EMERALD FRANKLIN MAGDALINE ELJEEVA , PRASAD DATTATREYA S A , RAVINDRA MENON REKHA , PUSHPADASS HEARTWIN A
Published: May 2012

The performance and bio‐kinetic coefficients of the activated sludge process (ASP) treating synthesised dairy wastewater were evaluated in a lab‐scale setup. The step‐loading experiment showed that the chemical oxygen demand (COD) removal efficiency, in general, increased with increasing influent wastewater COD concentration from 180 to 1200 mg/L (correlation coefficient was 0.80). The COD removal efficiency ranged from almost 80–88.4% depending on the COD concentration of the influent wastewater. Also, it could be stated that the ASP was probably underfed with organics at COD concentrations <725 mg/L. Monod, Moser, Contois and Chen & Hashimoto substrate utilisation models, relating the growth of micro‐organisms to substrate utilisation, were employed to describe the bio‐kinetics of the ASP at an organic loading rate of 1200 mg/L. Amongst them, the Contois and Monod models predicted the bio‐kinetic reactions of the ASP very well with coefficient of determination (R2) values of 0.95 and 0.93, respectively. The estimated bio‐kinetic coefficients of the Contois model (on COD basis) were as follows: half‐velocity constant (0.20 mg/L), maximum substrate utilisation rate (3.13 per day), biomass yield coefficient (0.68), endogenous decay coefficient (0.07 per day) and maximum specific growth rate (2.13 per day).
Abcg2 deficiency augments oxidative stress and cognitive deficits in Tg‐SwDI transgenic mice
Authors: Zeng Yu , Callaghan Debbie , Xiong Huaqi , Yang Ze , Huang Peilin , Zhang Wandong
Published: May 2012

J. Neurochem. (2012) 122, 456–469.

Oxidative stress and neuroinflammation play important roles in Alzheimer’s disease (AD). ABCG2 is a transporter protein expressed in the brain and involved in GSH transport. To study the roles of Abcg2 in oxidative stress and AD, we cross‐bred Tg‐SwDI and Abcg2‐KO mice and generated Tg‐SwDI/Abcg2‐KO (double‐tg) mice. Brain tissues from double‐tg, Tg‐SwDI, wild‐type, and Abcg2‐KO mice at various ages were analyzed. Aβ40 and Aβ42 were detected in Tg‐SwDI and double‐tg mice. Total brain GSH was decreased and levels of lipid/DNA oxidation were increased in 3‐month double‐tg compared to Tg‐SwDI mice. Low brain GSH was still detected in 9‐month double‐tg mice. Increased HMOX‐1 and MCP‐5 expression was observed in 9‐month double‐tg mice but not in Tg‐SwDI mice compared to WT and Abcg2‐KO mice. Increased HMOX‐1 and decreased ICAM‐1 expression were observed in 12‐month double‐tg mice compared to Tg‐SwDI mice. The levels of Nrf‐2 expression and activity were decreased in 6‐month double‐tg mice. Behavioral tests show impaired cognitive/memory performance of 9‐month double‐tg compared to Tg‐SwDI mice as well as WT and Abcg2‐KO mice. These results suggest that Abcg2 deficiency increases oxidative stress and alters inflammatory response in the brain and exacerbates cognitive/memory deficit in double‐tg mice at different developmental stages.
An allosteric modulator of metabotropic glutamate receptors (mGluR2), (+)‐TFMPIP, inhibits restraint stress‐induced phasic glutamate release in rat prefrontal cortex
Authors: Hascup Erin R. , Hascup Kevin N. , Pomerleau Francois , Huettl Peter , Hajos‐Korcsok Eva , Kehr Jan , Gerhardt Greg A.
Published: May 2012

J. Neurochem. (2012) 122, 619–627.

The potential anxiolytic effects of a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor subgroup 2 (mGluR2) were investigated using a self‐referencing recording technique with enzyme‐based microelectrode arrays (MEAs) that reliably measures tonic and phasic changes in extracellular glutamate levels in awake rats. Studies involved glutamate measures in the rat prefrontal cortex during subcutaneous injections of the following: vehicle, a mGluR2/3 agonist, LY354740 (10 mg/kg), or a mGluR2 PAM, 1‐Methyl‐2‐((cis‐(R,R)‐3‐methyl‐4‐(4‐trifluoromethoxy‐2‐fluoro)phenyl)piperidin‐1‐yl)methyl)‐1H‐imidazo[4,5‐b]pyridine ((+)‐TFMPIP; 1.0 or 17.8 mg/kg). Studies assessed changes in tonic glutamate levels and the glutamatergic responses to a 5‐min restraint stress. Subcutaneous injection of (+)‐TFMPIP at a dose of 1.0 mg/kg (day 3: ‐7.1 ± 15.1 net AUC; day 5: ‐24.8 ± 24.9 net AUC) and 17.8 mg/kg (day 3: ‐46.5 ± 33.0 net AUC; day 5: 34.6 ± 36.8 net AUC) significantly attenuated the stress‐evoked glutamate release compared to vehicle controls (day 3: 134.7 ± 50.6 net AUC; day 5: 286.6 ± 104.5 net AUC), whereas the mGluR2/3 agonist LY354740 had no effect. None of the compounds significantly affected resting glutamate levels, which we have recently shown to be extensively derived from neurons. Taken together, these data support that systemic administration of (+)‐TFMPIP produces phasic rather than tonic release of glutamate that may play a major role in the effects of stress on glutamate neuronal systems in the prefrontal cortex.
Nicotine modulates multiple regions in the limbic stress network regulating activation of hypophysiotrophic neurons in hypothalamic paraventricular nucleus
Authors: Yu Guoliang , Sharp Burt M.
Published: May 2012

J. Neurochem. (2012) 122, 628–640.

Nicotine intake affects CNS responses to stressors. We reported that nicotine self‐administration (SA) augmented the hypothalamo‐pituitary‐adrenal (HPA) stress response, in part because of the altered neurotransmission and neuropeptide expression within hypothalamic paraventricular nucleus (PVN). Limbic‐PVN interactions involving medial prefrontal cortex, amygdala, and bed nucleus of the stria terminalis (BST) greatly impact the HPA stress response. Therefore, we investigated the effects of nicotine SA on stress‐induced neuronal activation in limbic‐PVN network, using c‐Fos protein immunohistochemistry and retrograde tracing. Nicotine decreased stress‐induced c‐Fos in prelimbic cortex (PrL), anteroventral BST (avBST), and peri‐PVN, but increased c‐Fos induction in medial amygdala (MeA), locus coeruleus, and PVN. Fluoro‐gold (FG) was injected into avBST or PVN, as GABAergic neurons in avBST projecting to PVN corticotrophin‐releasing factor neurons relay information from both PrL glutamatergic and MeA GABAergic neurons. The stress‐induced c‐Fos expression in retrograde‐labeled FG+ neurons was decreased in PrL by nicotine, but increased in MeA, and also reduced in avBST. Therefore, within limbic‐PVN network, nicotine SA exerts selective regional effects on neuronal activation by stress. These findings expand the mechanistic framework by demonstrating altered limbic‐BST‐PVN interactions underlying the disinhibition of PVN corticotrophin‐releasing factor neurons, an essential component of the amplified HPA response to stress by nicotine.
Molecular mechanism of Jmjd3‐mediated interleukin‐6 gene regulation in endothelial cells underlying spinal cord injury
Authors: Lee Kwanghyun , Na Wonho , Lee Jee Youn , Na Jungtae , Cho Heejung , Wu Hongjin , Yune Tae Young , Kim Won‐Sun , Ju Bong‐Gun
Published: May 2012

J. Neurochem. (2012) 122, 272–282.

The inflammatory response contributes substantially to secondary injury cascades after spinal cord injury, with both neurotoxic and protective effects. However, epigenetic regulations of inflammatory genes following spinal cord injury have yet to be characterized thoroughly. In this study, we found that histone H3K27me3 demethylase Jmjd3 expression is acutely up‐regulated in blood vessels of the injured spinal cord. We also observed up‐regulation of Jmjd3 gene expression in bEnd.3 endothelial cells that were subjected to oxygen‐glucose deprivation/reperfusion injury. When Jmjd3 was depleted by siRNA, oxygen‐glucose deprivation/reperfusion injury‐induced up‐regulation of IL‐6 was significantly inhibited. In addition, Jmjd3 associated with NF‐κB (p65/p50) and CCAAT‐enhancer‐binding protein β at the IL‐6 gene promoter. The recruitment of Jmjd3 coincided with decreased levels of tri‐methylated H3K27 as well as increased levels of mono‐methylated H3K27 at the IL‐6 gene promoter. Furthermore, Jmjd3 depletion did not result in significant changes of methylation level of H3K27 at the IL‐6 gene promoter. Collectively, our findings imply that Jmjd3‐mediated H3K27me3 demethylation is crucial for IL‐6 gene activation in endothelial cells, and this molecular event may regulate acute inflammatory response and integrity of the blood‐spinal cord barrier following spinal cord injury.
Data uncertainty and the selectivity of extinction risk in freshwater invertebrates
Authors: Bland Lucie M. , Collen Ben , Orme C. David L. , Bielby Jon
Published: May 2012

Aim

To investigate the impact of different treatments of the IUCN Data Deficient (DD) category on taxonomic and geographical patterns of extinction risk in crayfish, freshwater crabs and dragonflies.

Location

Global.

Methods

We used contingency tables to evaluate taxonomic and geographical selectivity of data deficiency and extinction risk for three invertebrate taxonomic groups (crayfish, dragonflies and damselflies, and freshwater crabs) based on their IUCN Red List status. We investigated differences in patterns of data deficiency and extinction risk among taxonomic families, geographical realms and taxonomic families within geographical realms for each of the three groups. At each level, we evaluated the impact of uncertainty conferred by the conservation status of DD species on extinction risk patterns exhibited by that group. We evaluated three scenarios: excluding DD species, treating all DD species as non‐threatened and treating all DD species as threatened.

Results

At the global scale, DD species were taxonomically non‐randomly distributed in freshwater crabs and dragonflies, and geographically non‐randomly distributed in all three taxonomic groups. Although the presence of under‐ or over‐threatened families and biogeographical realms was generally unchanging across scenarios, the strength of taxonomic and geographical selectivity of extinction risk varied. There was little consistent evidence for taxonomic selectivity of extinction risk at sub‐global scales in freshwater crabs and dragonflies, either among biogeographical realms or among scenarios.

Main conclusions

Global patterns of taxonomic selectivity and geographical selectivity were generally consistent with one another and robust to different treatments of DD species. However, sub‐global scale conservation prioritization from these types of data sets will require increased investment to make accurate decisions. Given the current levels of data uncertainty, the relative importance of biological characteristics and threatening processes in driving extinctions in freshwater invertebrates cannot be easily determined. We recommend that DD species should be given high research priority to determine their true status.
Individual migratory patterns of two threatened seabirds revealed using stable isotope and geolocation analyses
Authors: Militão Teresa , Bourgeois Karen , Roscales Jose L. , González‐Solís Jacob
Published: May 2012

Aim

Intraspecific variability in the migratory movements of seabirds is being revealed far more complex than hitherto recognized, and our lack of understanding undermines their effective protection. Our aim is to test whether the isotopic values of a single feather of two threatened seabirds, the Mediterranean (Puffinus yelkouan) and the Balearic (Puffinus mauretanicus) shearwaters allow the geographic assignment of birds to their non‐breeding areas.

Location

These two species are known to use three main non‐breeding areas: the NE Atlantic Ocean, the W Mediterranean and the Aegean‐Black seas.

Methods

We clustered in three groups the δ13C and δ15N values of the first primary feather (P1), inferred to be grown during the non‐breeding period, of 34 Mediterranean and 56 Balearic shearwaters accidentally caught by longliners. To link the isotopic values of P1 to its corresponding non‐breeding area, we performed a discriminant function analysis (DFA) based on the three clusters and applied this function to feathers of known origin: P1 from seven Mediterranean shearwaters from Hyères Archipelago (France) tracked with geolocators and body feathers from six chicks from Balearic shearwaters. To link the moulting patterns to the areas where the feathers were grown, we applied the DFA to a sequence of primary feathers of eight Balearic and five Mediterranean shearwaters (caught by longliners).

Results

Isotopic and tracking data indicate that none of the Mediterranean shearwaters migrated to the Atlantic. The cluster and discriminant function analyses revealed that 8% of Balearic and 54% of Mediterranean shearwater moulted P1 in the Mediterranean Sea. Migratory movements were reflected in the changing isotopic values of the primary sequences.

Main conclusions

Stable isotope analyses (SIA) are a powerful approach to reveal the intraspecific variability in the migratory patterns of seabirds that use distinct isotopic areas over their annual cycle. The assignment of birds to their non‐breeding areas by means of SIA is a simple and effective tool that can help to evaluate the impact of human activities in remote areas not only at population but also at individual level, which is an essential knowledge for the management and conservation of threatened species.
Fibroblasts from long‐lived mutant mice exhibit increased autophagy and lower TOR activity after nutrient deprivation or oxidative stress
Authors: Wang Min , Miller Richard A.
Published: May 2012

Previous work has shown that primary skin‐derived fibroblasts from long‐lived pituitary dwarf mutants resist the lethal effects of many forms of oxidative and nonoxidative stress. We hypothesized that increased autophagy may protect fibroblasts of Pit‐1dw/dw (Snell dwarf) mice from multiple forms of stress. We found that dwarf‐derived fibroblasts had higher levels of autophagy, using LC3 and p62 as markers, in response to amino acid deprivation, hydrogen peroxide, and paraquat. Fibroblasts from dwarf mice also showed diminished phosphorylation of mTOR, S6K, and 4EBP1, consistent with the higher levels of autophagy in these cells after stress. Similar results were also observed in fibroblasts from mutant mice lacking growth hormone receptor (GHRKO mice) after amino acid withdrawal. Our results suggested that increased autophagy, regulated by TOR‐dependent processes, may contribute to stress resistance in fibroblasts from long‐lived mutant mice.
Distinct effects of inflammation on gliosis, osmohomeostasis, and vascular integrity during amyloid beta‐induced retinal degeneration
Authors: Dinet Virginie , Bruban Julien , Chalour Naima , Maoui Agathe , An Na , Jonet Laurent , Buret Alain , Behar‐Cohen Francine , Klein Christophe , Tréton Jacques , Mascarelli Frédéric
Published: May 2012

In normal retinas, amyloid‐β (Aβ) accumulates in the subretinal space, at the interface of the retinal pigment epithelium, and the photoreceptor outer segments. However, the molecular and cellular effects of subretinal Aβ remain inadequately elucidated. We previously showed that subretinal injection of Aβ(1–42) induces retinal inflammation, followed by photoreceptor cell death. The retinal Müller glial (RMG) cells, which are the principal retinal glial cells, are metabolically coupled to photoreceptors. Their role in the maintenance of retinal water/potassium and glutamate homeostasis makes them important players in photoreceptor survival. This study investigated the effects of subretinal Aβ(1–42) on RMG cells and of Aβ(1–42)‐induced inflammation on retinal homeostasis. RMG cell gliosis (upregulation of GFAP, vimentin, and nestin) on day 1 postinjection and a proinflammatory phenotype were the first signs of retinal alteration induced by Aβ(1–42). On day 3, we detected modifications in the protein expression patterns of cyclooxygenase 2 (COX‐2), glutamine synthetase (GS), Kir4.1 [the inwardly rectifying potassium (Kir) channel], and aquaporin (AQP)‐4 water channels in RMG cells and of the photoreceptor‐associated AQP‐1. The integrity of the blood‐retina barrier was compromised and retinal edema developed. Aβ(1–42) induced endoplasmic reticulum stress associated with sustained upregulation of the proapoptotic factors of the unfolded protein response and persistent photoreceptor apoptosis. Indomethacin treatment decreased inflammation and reversed the Aβ(1–42)‐induced gliosis and modifications in the expression patterns of COX‐2, Kir4.1, and AQP‐1, but not of AQP‐4 or GS. Nor did it improve edema. Our study pinpoints the adaptive response to Aβ of specific RMG cell functions.
Peripheral refraction in myopia corrected with spectacles versus contact lenses
Authors: Backhouse Simon , Fox Stephanie , Ibrahim Basma , Phillips John R
Published: May 2012

Citation information: Backhouse S, Fox S, Ibrahim B & Phillips JR. Peripheral refraction in myopia corrected with spectacles versus contact lenses. Ophthalmic Physiol Opt 2012, 32, 294–303. doi: 10.1111/j.1475‐1313.2012.00912.x

Purpose:  Previous studies suggest that the refractive status of the peripheral retina can influence the development and progression of myopia. Our aim was to compare peripheral refractions in the same cohort of human eyes corrected with spectacle lenses vs soft contact lenses.

Methods:  Ten young adults with moderate to high myopia (−5.00 D to −8.00 D) were investigated. Open‐field autorefraction was used to measure on‐ and off‐axis refractions with the eyes in primary gaze, when uncorrected, and when corrected with spectacles and contact lenses. Measures were made every 5° out to 30° horizontally in nasal and temporal retina and analysed as power vectors (M, J0, and J45). Partial coherence interferometry measures of eye size were also made on‐axis and off‐axis at 10º and 20º in nasal and temporal retina.

Results:  Subjects (mean age 24; range 19–29 years) had an average on‐axis mean‐sphere refraction of −6.33 ± 0.31 D (mean ± 1 S.E.) and an average axial eye length of 25.99 ± 0.20 mm. The average relative peripheral refraction (RPR) for all subjects across all eccentricities was hyperopic when uncorrected (+0.90 ± 0.14 D) and also when corrected with spectacles (+1.01 ± 0.13 D) but changed to a myopic RPR when corrected with contact lenses (−1.84 ± 0.61 D). There was a highly significant effect of correction on peripheral refraction (p < 0.0001). Peripheral J0 astigmatism also became significantly more negative (less with‐the‐rule) on correction with contact lenses (p = 0.015), whereas J45 astigmatism remained unchanged. On‐ and off‐ axis eye length measures indicated a relatively prolate eye shape.

Conclusions:  Correcting the on‐axis refractive error in moderate to high myopia with conventional spherical spectacle lenses results in hyperopic defocus in the peripheral retina. Correcting the same eyes with conventional spherical soft contact lenses results in significant myopic defocus in the peripheral retina. These results corroborate the general findings of earlier studies and the predictions of optical modelling by others. If the refractive status of the peripheral retina does influence myopia progression, then these results suggest that myopia progression should be slower with conventional contact lens wear than with conventional spectacle wear. However, previous studies comparing myopia progression with conventional spectacles and conventional contact lenses have reported no such difference.
REGULATION OF GEOGRAPHIC VARIABILITY IN HAPLOID:DIPLOD RATIOS OF BIPHASIC SEAWEED LIFE CYCLES1
Authors: da Silva Vieira Vasco Manuel Nobre de Carvalho , Santos Rui Orlando Pimenta
Published: May 2012

The relative abundance of haploid and diploid individuals (H:D) in isomorphic marine algal biphasic cycles varies spatially, but only if vital rates of haploid and diploid phases vary differently with environmental conditions (i.e. conditional differentiation between phases). Vital rates of isomorphic phases in particular environments may be determined by subtle morphological or physiological differences. Herein, we test numerically how geographic variability in H:D is regulated by conditional differentiation between isomorphic life phases and the type of life strategy of populations (i.e. life cycles dominated by reproduction, survival or growth). Simulation conditions were selected using available data on H:D spatial variability in seaweeds. Conditional differentiation between ploidy phases had a small effect on the H:D variability for species with life strategies that invest either in fertility or in growth. Conversely, species with life strategies that invest mainly in survival, exhibited high variability in H:D through a conditional differentiation in stasis (the probability of staying in the same size class), breakage (the probability of changing to a smaller size class) or growth (the probability of changing to a bigger size class). These results were consistent with observed geographic variability in H:D of natural marine algae populations.
Modulation of Pre‐Capillary Arteriolar Pressure with Drag‐Reducing Polymers: A Novel Method for Enhancing Microvascular Perfusion
Authors: PACELLA JOHN J. , KAMENEVA MARINA V. , BRANDS JUDITH , LIPOWSKY HERBERT H. , VINK HANS , LAVERY LINDA L. , VILLANUEVA FLORDELIZA S.
Published: May 2012

Please cite this paper as: Pacella JJ, Kameneva MV, Brands J, Lipowsky HH, Vink H, Lavery LL, Villanueva FS. Modulation of pre‐capillary arteriolar pressure with drag‐reducing polymers: a novel method for enhancing microvascular perfusion. Microcirculation 19: 580–585, 2012.

Objective:  We have shown that drag‐reducing polymers (DRP) enhance capillary perfusion during severe coronary stenosis and increase red blood cell velocity in capillaries, through uncertain mechanisms. We hypothesize that DRP decreases pressure loss from the aorta to the arteriolar compartment.

Methods:  Intravital microscopy of the rat cremaster muscle and measurement of pressure in arterioles (diameters 20–132 μm) was performed in 24 rats. DRP (polyethylene oxide, 1 ppm) was infused i.v. and measurements were made at baseline and 20 minutes after completion of DRP infusion. In a 10‐rat subset, additional measurements were made three minutes after the start, and one to five and 10 minutes after completion of DRP.

Results:  Twenty minutes after the completion of DRP, mean arteriolar pressure was 22% higher than baseline (from 42 ± 3 to 49 ± 3 mmHg, p < 0.005, n = 24). DRP decreased the pressure loss from the aorta to the arterioles by 24% (from 35 ± 6 to 27 ± 5 mmHg, p = 0.001, n = 10). In addition, there was a strong trend toward an increase in pressure at 10 minutes after the completion of DRP (n = 10).

Conclusions:  Drag‐reducing polymers diminish pressure loss between the aorta and the arterioles. This results in a higher pre‐capillary pressure and probably explains the observed DRP enhancement in capillary perfusion.
Pharmacological Profiling of Store‐Operated Ca2+ Entry in Retinal Arteriolar Smooth Muscle
Authors: MCGAHON MARY K. , MCKEE JONATHAN , DASH DURGA P. , BROWN EOIN , SIMPSON DAVID A. , CURTIS TIMOTHY M. , McGEOWN JAMES G. , SCHOLFIELD CHARLES N.
Published: May 2012

Please cite this paper as: McGahon MK, McKee J, Dash DP, Brown E, Simpson DA, Curtis TM, McGeown JG, Scholfield CN. Pharmacological profiling of store‐operated Ca2+ entry in retinal arteriolar smooth muscle. Microcirculation 19: 586–597, 2012.

Objective:  Pharmacological profiling of SOCE and molecular profiling of ORAI and TRPC expression in arterioles.

Methods:  Fura‐2‐based microfluorimetry was used to assess CPA‐induced SOCE in rat retinal arteriolar myocytes. Arteriolar ORAI and TRP transcript expression was screened using RT‐PCR.

Results:  The SKF96365 and LOE908 blocked SOCE (IC50s of 1.2 and 1.4 μm, respectively). Gd3+ and La3+ potently inhibited SOCE (IC50s of 21 and 42 nm, respectively), but Ni2+ showed lower potency (IC50 = 11.6 μm). 2APB inhibited SOCE (IC50 = 3.7 μm) but enhanced basal influx (>100 μm). Verapamil and nifedipine had no effect at concentrations that inhibit L‐type Ca2+ channels, but diltiazem inhibited SOCE by approximately 40% (≥0.1 μm). The RT‐PCR demonstrated transcript expression for ORAI 1, 2, and 3, and TRPC1, 3, 4, and 7. Transcripts for TRPV1 and 2, which are activated by 2APB, were also expressed.

Conclusions:  The pharmacological profile of SOCE in retinal arteriolar smooth muscle appears unique when compared with other vascular tissues. This suggests that the molecular mechanisms underlying SOCE can differ, even in closely related tissues. Taken together, the pharmacological and molecular data are most consistent with involvement of TRPC1 in SOCE, although involvement of ORAI or other TRPC channels cannot be excluded.
Concurrent sensitization to metals and occupation
Authors: Rui Francesca , Bovenzi Massimo , Prodi Andrea , Fortina Anna Belloni , Romano Ilaria , Corradin Maria Teresa , Filon Francesca Larese
Published: May 2012

Background. Cosensitization to nickel, cobalt and chromium occurs in the general population and in some occupational groups.

Objectives. To estimate the isolated and concurrent occurrence of nickel, cobalt and chromium contact sensitization and their association with individual and occupational risk factors.

Patients/methods. Twelve thousand four hundred and ninety‐two patients were patch tested with the European baseline series between 1997 and 2004 in north‐eastern Italy. The associations between patch test results and patient characteristics and occupations were investigated by means of multinomial logistic regression analysis.

Results. Of the patients, 34.7% (4334 patients) had one or more positive patch test reactions to metals. As compared with those with negative reactions to all three metals, nickel sensitization was significantly higher in females than in males, not only as monosensitization, but also as cosensitization with cobalt, with chromium, or with both metals. Building and related trades workers showed positive reactions to chromium + nickel [odds ratio (OR) 1.99; 95% confidence interval (CI) 1.05–3.76) and chromium + cobalt (OR 2.61; 95% CI 1.46–4.67]. Cleaning workers showed a high prevalence of nickel, chromium, nickel + chromium and nickel + cobalt + chromium cosensitization (ORs 1.29, 1.66, 2.11, and 1.79, respectively). An excess risk for cosensitization to all three metals was found in textile and leather workers (OR 2.19; 95% CI 1.10–4.33), and in bartenders (OR 2.10; 95% CI 1.03–4.26).

Conclusions. Some occupational groups are more likely to develop nickel, cobalt and chromium cosensitization.