bluuebunny/crossref_metadata_2025 huggingface dataset:
Topologies of Climate Change: Actor-Network Theory, Relational-Scalar Analytics, and Carbon-Market Overflows
Authors: Blok Anders
Published: September 2010

Climate change is quickly becoming a ubiquitous socionatural reality, mediating extremes of sociospatial scale from the bodily to the planetary. Although environmentalism invites us to ‘think globally and act locally’, the meaning of these scalar designations remains ambiguous. This paper explores the topological presuppositions of social theory in the context of global climate change, asking how carbon emissions ‘translate’ into various sociomaterial forms. Staging a meeting between Tim Ingold's phenomenology of globes and spheres and the social topologies of actor-network theory (ANT), the paper advances a ‘relational-scalar’ analytics of spatial practices, technoscience, and power. As technoscience gradually constructs a networked global climate, this ‘grey box’ comes to circulate within fluid social spaces, taking on new shades as it hybridizes knowledges, symbols, and practices. Global climates thus come in multiple interfering versions, and we need to pay attention to both continuities and overflows, as illustrated in the paper by controversies surrounding transnational carbon markets. The relational-scalar analytics of ANT, I contend, are well suited to navigating such shifting terrains, a task central to the intellectual as well as practical challenges raised by the climate crisis.
Conflict and Contact: The ‘Humane’ City, Agonistic Politics, and the Phenomenological Body
Authors: Collins Matthew
Published: September 2010

This paper puts forward a retheorisation of urban agonistic politics, using the phenomenology of Maurice Merleau-Ponty to reground Ernesto Laclau and Chantal Mouffe's theories of agonism in a more explicitly spatial register. The author theorises the city, in terms of its potential, in a utopian or ‘humane’ fashion. Social scientists and philosophers both explore how the ontological and the political are coconstitutive. An ontopolitical perspective can be found in the works of many of the poststructuralists, and this paper forwards another such approach to the ontology of the political by taking together the agonistic politics of Laclau and Mouffe with the intersubjective and intercorporeal framework of Merleau-Ponty to create a novel perspective on the functioning of democracy and the democratic city. The city is conceived of both literally and figuratively as a system for the proliferation of multiple publics, or multiple spaces and modes of appearance, in the Arendtian sense. By taking agonism and intersubjectivity together, the paper attempts to resist some of the individualising tendencies within liberal democracy whilst retaining its commitment to freedom.
I am Also of the Opinion That Materialism Must Be Destroyed
Authors: Harman Graham
Published: September 2010

This paper criticizes two forms of philosophical materialism that adopt opposite strategies but end up in the same place. Both hold that individual entities must be banished from philosophy. The first kind is ground floor materialism, which attempts to dissolve all objects into some deeper underlying basis; here, objects are seen as too shallow to be the truth. The second kind is first floor materialism, which treats objects as naive fictions gullibly posited behind the direct accessibility of appearances or relations; here, objects are portrayed as too deep to be the truth. One major thesis of this paper is that these two forms of materialism are parasitical on one another and need each other's resources to make sense of the world. The second major thesis is that both forms of materialism thereby stand condemned, and that philosophy must be rebuilt from the individual objects that the two forms of materialism disdain. These points are made through a detailed consideration of the book Every Thing Must Go by the analytic structural realists James Ladyman and Don Ross, which has gained a surprising following among some speculative realists in continental philosophy. Ladyman and Ross claim to preserve objects by treating them as “real patterns”, but they do so at the price of destroying their autonomous reality. Furthermore, they are unable to tell us whether the mathematical structures they see as the basis of human knowledge are also the basis of reality itself. In short, their ontology is scientism for scientism's sake (or ‘Bunsen burner realism’) and must be eliminated in favor of a genuine realist metaphysics of objects.
Producing Spaces for Representation: Racist Marches, Counterdemonstrations, and Public-Order Policing
Authors: Wahlström Mattias
Published: September 2010

This paper analyzes how space is produced in the interaction between political demonstrations and protest policing during a series of racist and antiracist actions in Sweden. A model is proposed for a spatial analysis of both police and protesters based on the concepts of territorialization and deterritorialization. The spatial practices of police and protesters unfold on different scales in conflicts of territorial border control and order control within territories. As indicated by Lefebvre's spatial triad, this process is also influenced by authorities' representations of space and the representational spaces of the actors involved. When spaces are claimed for representation, symbolic meanings of protest spaces are used and modified, occasionally as ‘truth-spots’ for demonstrating movement knowledge claims. The paper contributes to a more systematic theoretical understanding of the spatial interaction between police and protesters, while indicating the importance of considering cases with multiple stakeholders in order to avoid an all too dichotomous understanding of conflicts over public space.
Unsettling the Imperial Sciences
Authors: Okihiro Gary Y
Published: September 2010

Latitudes of climates and constitutions, like the allied myth of continents and races, have a deep and persistent past within European and US imperial discourses both as language and ideology. Taxonomies that name, classify, and attribute natures to lands, waters, climates, plants, animals, and peoples discipline, interpellate, and exert dominion over them. Those sciences create subjects, and in their imposition of order and hierarchies, they constitute the imperial project. Conversely, reconstituting space by deconstructing the racialized, gendered, and sexualized attributions of islands and continents, the tropical and temperate zones can unsettle the imperial order and endanger the privileges and poverties they sustain. Toward that end, this essay suggests a remapping of our Earth according to tectonic geographies, in their plenitude inclusive of both lands and waters and their biotic communities and their ceaseless movements and engagements.
Re-educating natural killer cells
Authors: Sun Joseph C.
Published: September 2010

The development and function of natural killer (NK) cells is dictated by signals received through activating and inhibitory receptors expressed on the cell surface. During their maturation in the bone marrow, NK cells undergo an education process that ensures they are tolerant to healthy peripheral tissues. Several recent studies advance our understanding of self-tolerance mechanisms at work in NK cells. These studies demonstrate that the developmental programming in NK cells is not fixed, and that perturbations to the peripheral environment (via transplantation or viral infection, for example) greatly influence the ability of mature NK cells to mount an effector response. This newfound ability of mature NK cells to be “re-educated” may be clinically applicable in the immunotherapeutic use of NK cells against infection and cancer.
p53 connects tumorigenesis and reprogramming to pluripotency
Authors: Tapia Natalia , Schöler Hans R.
Published: September 2010

The tumor suppressor gene p53 prevents the initiation of tumor formation by inducing cell cycle arrest, senescence, DNA repair, and apoptosis. Recently, the absence or mutation of p53 was described to facilitate nuclear reprogramming. These findings suggest an influence of p53 on the de-differentiation process, and highlight the similarities between induction of pluripotency and tumor formation.
Activation of the KATP channel by Mg-nucleotide interaction with SUR1
Authors: Proks Peter , de Wet Heidi , Ashcroft Frances M.
Published: September 2010

The mechanism of adenosine triphosphate (ATP)-sensitive potassium (KATP) channel activation by Mg-nucleotides was studied using a mutation (G334D) in the Kir6.2 subunit of the channel that renders KATP channels insensitive to nucleotide inhibition and has no apparent effect on their gating. KATP channels carrying this mutation (Kir6.2-G334D/SUR1 channels) were activated by MgATP and MgADP with an EC50 of 112 and 8 µM, respectively. This activation was largely suppressed by mutation of the Walker A lysines in the nucleotide-binding domains of SUR1: the remaining small (∼10%), slowly developing component of MgATP activation was fully inhibited by the lipid kinase inhibitor LY294002. The EC50 for activation of Kir6.2-G334D/SUR1 currents by MgADP was lower than that for MgATP, and the time course of activation was faster. The poorly hydrolyzable analogue MgATPγS also activated Kir6.2-G334D/SUR1. AMPPCP both failed to activate Kir6.2-G334D/SUR1 and to prevent its activation by MgATP. Maximal stimulatory concentrations of MgATP (10 mM) and MgADP (1 mM) exerted identical effects on the single-channel kinetics: they dramatically elevated the open probability (PO > 0.8), increased the mean open time and the mean burst duration, reduced the frequency and number of interburst closed states, and eliminated the short burst states. By comparing our results with those obtained for wild-type KATP channels, we conclude that the MgADP sensitivity of the wild-type KATP channel can be described quantitatively by a combination of inhibition at Kir6.2 (measured for wild-type channels in the absence of Mg2+) and activation via SUR1 (determined for Kir6.2-G334D/SUR1 channels). However, this is not the case for the effects of MgATP.
Neuroglial ATP release through innexin channels controls microglial cell movement to a nerve injury
Authors: Samuels Stuart E. , Lipitz Jeffrey B. , Dahl Gerhard , Muller Kenneth J.
Published: September 2010

Microglia, the immune cells of the central nervous system, are attracted to sites of injury. The injury releases adenosine triphosphate (ATP) into the extracellular space, activating the microglia, but the full mechanism of release is not known. In glial cells, a family of physiologically regulated unpaired gap junction channels called innexons (invertebrates) or pannexons (vertebrates) located in the cell membrane is permeable to ATP. Innexons, but not pannexons, also pair to make gap junctions. Glial calcium waves, triggered by injury or mechanical stimulation, open pannexon/innexon channels and cause the release of ATP. It has been hypothesized that a glial calcium wave that triggers the release of ATP causes rapid microglial migration to distant lesions. In the present study in the leech, in which a single giant glial cell ensheathes each connective, hydrolysis of ATP with 10 U/ml apyrase or block of innexons with 10 µM carbenoxolone (CBX), which decreased injury-induced ATP release, reduced both movement of microglia and their accumulation at lesions. Directed movement and accumulation were restored in CBX by adding ATP, consistent with separate actions of ATP and nitric oxide, which is required for directed movement but does not activate glia. Injection of glia with innexin2 (Hminx2) RNAi inhibited release of carboxyfluorescein dye and microglial migration, whereas injection of innexin1 (Hminx1) RNAi did not when measured 2 days after injection, indicating that glial cells’ ATP release through innexons was required for microglial migration after nerve injury. Focal stimulation either mechanically or with ATP generated a calcium wave in the glial cell; injury caused a large, persistent intracellular calcium response. Neither the calcium wave nor the persistent response required ATP or its release. Thus, in the leech, innexin membrane channels releasing ATP from glia are required for migration and accumulation of microglia after nerve injury.
The effects of lysosomal and proteasomal inhibitors on abnormal forms of prion protein degradation in murine macrophages
Authors: Sassa Yukiko , Yamasaki Takeshi , Horiuchi Motohiro , Inoshima Yasuo , Ishiguro Naotaka
Published: September 2010

It has been reported that macrophages degrade infectious forms of prion protein (PrPSc). In order to investigate the mechanisms underlying PrPSc degradation in macrophages, the effects of lysosomal and proteasomal inhibitors on macrophage cell lines which were incubated with scrapie‐affected brain homogenate were studied. PrPSc degradation was inhibited in the presence of both proteasomal and lysosomal inhibitors. Indirect fluorescence assays to determine the cellular localization of PrPSc were undertaken. PrPSc colocalized with the lysosomal membrane protein Lamp‐1 and ubiquitin, a protein that is related to the proteasome. The present data indicate that macrophages might degrade PrPSc via the lysosomal and proteasomal pathways.
Treatment of paediatric hyperthyroidism but not hypothyroidism has a significant effect on weight
Authors: Crocker Melissa K. , Kaplowitz Paul
Published: September 2010

Objective  Thyroid hormones are involved in metabolic regulation, but the degree to which they affect body weight and body mass index (BMI) in children is unclear. We examined the effect of hypo‐ and hyperthyroidism on weight and BMI at the time of diagnosis and after appropriate treatment.

Design  Prospective and retrospective case series.

Patients  Children referred for thyroid dysfunction were enrolled prospectively if their total or free T4 was elevated with TSH <0·05 mIU/ml (N = 57) or if they had a subnormal total or free T4 and TSH >20 (N = 29).

Results  Almost all patients had at least 2 classic signs or symptoms including goitre, but hyperthyroid patients had more symptoms. Mean BMI z scores at the time of diagnosis did not significantly differ between the two groups. Males with hyperthyroidism complained of weight loss more frequently and had a lower pretreatment BMI z score than hyperthyroid females. Hypothyroid patients lost a minimal amount of weight by the first follow‐up (mean of 0·3 kg) and on average gained weight by the second follow‐up visit. In contrast hyperthyroid patients gained a mean of 3·4 kg at the first follow‐up visit and a mean of 7·1 kg by the second.

Conclusions  Correction of hypothyroidism resulted in minimal weight loss, suggesting that hypothyroidism does not cause significant weight gain in children. In contrast, correction of the hyperthyroid state had a somewhat greater impact on weight status. These results are consistent with prior reports but surprising given the opposite metabolic effects of hypo‐ and hyperthyroidism.
Clinical features of nonpituitary sellar lesions in a large surgical series
Authors: Valassi Elena , Biller Beverly M. K. , Klibanski Anne , Swearingen Brooke
Published: September 2010

Context  Pituitary adenomas are the most common lesions in the sellar region, but other pathologies need to be considered in the differential diagnosis.

Objective  To assess the prevalence of unusual sellar masses in a large series of patients and identify clinicopathological factors that may aid the pre‐operative diagnosis.

Design  Retrospective case series.

Patients  We analysed the records of 1469 transsphenoidal procedures performed between 1998 and 2009. One hundred sixteen cases (7·9%) were not pituitary adenomas.

Measurements  Final pathological diagnosis.

Results  One hundred sixteen patients (45 men, 71 women; mean age (±SD): 45 ± 17 years) with nonadenomatous lesions were divided into four major aetiological groups: cystic lesions (CYS) (53%); benign neoplasms (BEN) (22%); malignancies (MAL) (16%) and inflammatory lesions (INF) (9%). Rathke’s cysts, the most common lesions, represented 42% of all cases. Twenty‐five per cent of malignant lesions were metastases, and some of the MAL (e.g., fibrosarcoma, lung metastasis) had a radiographical appearance suggestive of a pituitary adenoma. The most common presenting symptoms were visual field impairment (51%) and headache (34%). Pre‐operative pituitary dysfunction was present in 58% of cases, with hyperprolactinaemia (35%), hypogonadism (23%) and hypocortisolism (23%) found most frequently. Postoperative resolution of headache and visual symptoms occurred in 63% and 65% of patients, respectively. Hyperprolactinaemia resolved in 77% of cases.

Conclusions  A substantial minority of sellar masses are not pituitary adenomas. While they frequently present with the symptoms, hormone abnormalities and radiographical appearance typical of pituitary tumours, the possibility of a nonadenomatous lesion needs to be considered in the differential diagnosis.
Subclinical hyperthyroidism is not associated with progression of cardiac mass and development of left ventricular hypertrophy in middle‐aged and older subjects: results from a 5‐year follow‐up
Authors: Dörr Marcus , Ittermann Till , Aumann Nicole , Obst Anne , Reffelmann Thorsten , Nauck Matthias , Wallaschofski Henri , Felix Stephan B. , Völzke Henry
Published: September 2010

Background  Decreased serum TSH levels are associated with increased cardiovascular mortality in elderly, and subclinical hyperthyroidism (SCH) was associated with left ventricular hypertrophy (LVH) as a predictor of cardiovascular mortality in some cross‐sectional and case‐control studies. The aim was to assess whether SCH independently impacts development of LVH over time.

Methods  Of 3300 participants of the population‐based Study of Health in Pomerania those with overt hyperthyroidism, hypothyroidism, possible thyroid disease or missing echocardiographic baseline data or follow‐up were excluded, resulting in a study population of 1112 individuals (556 women) aged 45–81 years. Echocardiographic left ventricular mass divided by height2·7 (LVMIht), and LVHht (LVMIht >44 g/m2·7 in women and >48 g/m2·7 in men) was measured at baseline and after 5‐year follow‐up (median 5·00; range 4·92; 5·08). Comparison of subjects with (n = 107) and without (n = 1005) SCH were made by linear and logistic regression models adjusted for age, gender, smoking status, hypertension, and waist circumference.

Results  At follow‐up, LVMIht did not differ between subjects with and without SCH (50·2 g/m2·7, interquartile range (IQR) 41·2; 59·5 vs 47·8 g/m2·7, IQR 39·3; 56·9; P = 0·29). LVHht was present in 66 (61·7%) subjects with and 543 (54·0%) persons without SCH (P = 0·13). Analyses revealed no association between SCH and progression of LVMIht (β = −0·18; 95%‐confidence interval (CI) −2·34; −1·99; P = 0·873), and development of LVHht (relative risk 0·86, 95%‐CI 0·60; 1·26; P = 0·462), respectively.

Conclusions  In this population‐based sample, SCH had no impact on progression of LVMI and development of LVH during 5‐year follow‐up in subjects aged 45 years or older.
Depot‐ and ethnic‐specific differences in the relationship between adipose tissue inflammation and insulin sensitivity
Authors: Evans Juliet , Goedecke Julia H. , Söderström Ingegerd , Burén Jonas , Alvehus Malin , Blomquist Caroline , Jonsson Fredrik , Hayes Philip M. , Adams Kevin , Dave Joel A. , Levitt Naomi S. , Lambert Estelle V. , Olsson Tommy
Published: September 2010

Objective  It is unclear whether there are differences in inflammatory gene expression between abdominal and gluteal subcutaneous adipose tissue (SAT), and between black and white women. We therefore tested the hypotheses that SAT inflammatory gene expression is greater in the abdominal compared to the gluteal depot, and SAT inflammatory gene expression is associated with differential insulin sensitivity (SI) in black and white women.

Design and methods  SI (frequently sampled intravenous glucose tolerance test) and abdominal SAT and gluteal SAT gene expression levels of 13 inflammatory genes were measured in normal‐weight (BMI 18–25 kg/m2) and obese (BMI >30 kg/m2) black (n = 30) and white (n = 26) South African women.

Results  Black women had higher abdominal and gluteal SAT expression of CCL2, CD68, TNF‐α and CSF‐1 compared to white women (P < 0·01). Multivariate analysis showed that inflammatory gene expression in the white women explained 56·8% of the variance in SI (P < 0·005), compared to 20·9% in black women (P = 0·30). Gluteal SAT had lower expression of adiponectin, but higher expression of inflammatory cytokines, macrophage markers and leptin than abdominal SAT depots (P < 0·05).

Conclusions  Black South African women had higher inflammatory gene expression levels than white women; however, the relationship between AT inflammation and SI was stronger in white compared to black women. Further research is required to explore other factors affecting SI in black populations. Contrary to our original hypothesis, gluteal SAT had a greater inflammatory gene expression profile than abdominal SAT depots. The protective nature of gluteo‐femoral fat therefore requires further investigation.
Behavioural and chemical mechanisms behind a Mediterranean ant–ant association
Authors: MENZEL FLORIAN , WOYWOD MARTIN , BLÜTHGEN NICO , SCHMITT THOMAS
Published: September 2010

1. Interspecific competition among ants is common, and so is competitive exclusion among dominant ant species. In contrast, specific associations between non‐parasitic ant species are rare, especially in the temperate zones. As an exception, the subordinate ant Camponotus lateralis frequently co‐occurs with the dominant Crematogaster scutellaris but rarely with other dominant ants.

2. This association is one of various associations between Camponotus and Crematogaster species across the world. However, the mechanisms behind these co‐occurences are largely unknown.

3. In the present study, we therefore investigated the association of Ca. lateralis and Cr. scutellaris. We studied the spatial association of the nests, interspecific aggression, both species' cuticular hydrocarbon profiles, and their propensity to follow the other species' pheromone trails.

4. Crematogaster scutellaris usually attacked and displaced the generally submissive Ca. lateralis, but was significantly less aggressive at jointly used trails. Camponotus nests were always in close proximity to Crematogaster nests.

5. The cuticular hydrocarbons of both species consisted of alkanes with chain lengths between C21 and C35. The two species had 25 hydrocarbons in common, including mono‐, di‐, and tetramethyl alkanes. Despite this qualitative similarity, however, the quantitative hydrocarbon composition differed between the two species.

6. Camponotus lateralis followed artificial trails containing trail pheromones of Cr. scutellaris, but the latter did not follow Ca. lateralis trail pheromones. Interspecific trail‐following by Camponotus, but not vice versa, has been observed in another Camponotus–Crematogaster association and may be a more general mechanism that facilitates associations between the two ant genera.
Factors affecting parasite prevalence among wild bumblebees
Authors: GILLESPIE SANDRA
Published: September 2010

1. Bumblebees are important pollinators in North America and are attacked by a range of parasites that impact their fitness; however, few studies have investigated the extent or causes of parasitism in North America.

2. This study used a 2‐year multi‐site survey of bumblebee parasitism to ask: (i) how common are parasitoid conopid flies and the internal parasites Crithidia bombi and Nosema bombi in Massachusetts; and (ii) what factors are correlated with parasitism?

3. Infection rates by all three parasites were higher in this study than previously documented in North America. Overall, conopids infected 0–73% of bees in each sample, C. bombi infected 0–82% of bees, and N. bombi infected 0–32%.

4. Conopid flies infected female bees more than males and intermediate‐sized bees more than large or small bees. Crithidia bombi infection rates were higher in certain bee species and sites, and exhibited a unimodal pattern of prevalence over time. Nosema bombi parasitism was higher in male than female bees.

5. Infection by N. bombi in two rare bumblebee species was higher than expected based on parasitism rates of common bee species but C. bombi infection was lower.

If high prevalence of N. bombi in these bumblebee species is common, parasitism may be a potential cause of their decline.

6. Given the documented effects of these parasites, the high levels of infection may affect bee populations in Massachusetts and threaten the stability of their valuable ecosystem services.
Elevated TGF‐β1 levels might protect HCV/ HIV‐coinfected patients from liver fibrosis
Authors: Rallón Norma I. , Barreiro Pablo , Soriano Vincent , García‐Samaniego Javier , López Mariola , Benito José M.
Published: September 2010

Eur J Clin Invest 2010; 41 (1): 70–76

Background  HIV accelerates hepatitis C virus (HCV)‐induced liver fibrosis by mechanisms not well understood. As HIV dysregulates transforming growth factor‐β1 (TGF‐β1) and T regulatory (Treg) cells, both of which are involved in hepatic fibrogenesis, herein we describe their influence on liver fibrosis staging in patients with chronic hepatitis C with and without HIV coinfection.

Methods  Eighty‐eight subjects (42 HIV/HCV co‐infected patients, 20 HCV‐monoinfected patients, and 26 healthy controls) were examined. Treg cells (CD4+Foxp3+) were measured in peripheral blood using flow cytometry. An enzyme immunoassay was used to measure TGF‐β1 in plasma. Liver fibrosis staging was estimated using elastometry and advanced liver fibrosis was considered for ≥ 9·5 kPa (F3–F4 Metavir estimates).

Results  Treg cells were increased in HIV/HCV‐coinfected patients compared with HCV‐monoinfected patients (P = 0·004), whereas TGF‐β1 levels were similar in both groups of patients. While Treg cells levels were similar in both null‐mild and advanced liver fibrosis patients, a high level of TGF‐β1 was found in patients with low levels of liver fibrosis compared with those with advanced liver fibrosis [14·9 ng mL−1 (5·6–37·9) vs. 5·5 ng mL−1 (1·9–7·9) respectively P = 0·007]. In a multivariate logistic regression model, elevated TGF‐β1 levels were significantly associated with not having advanced liver fibrosis [OR: 0·13 (95% CI: 0·02–0·71), P = 0·019].

Conclusions  While Treg cells do not influence liver fibrosis staging, elevated TGF‐β1, probably through its anti‐inflammatory effects, might protect HCV/HIV‐coinfected patients from liver fibrosis.
A comprehensive approach to soil‐atmosphere trace‐gas flux estimation with static chambers
Authors: Pedersen A. R. , Petersen S. O. , Schelde K.
Published: September 2010

A new procedure (HMR) for soil‐atmosphere trace‐gas flux estimation with static chambers is presented. It classifies data series into three categories according to criteria based on the application of a particular non‐linear model and provides statistical data analyses for all categories. The two main categories are non‐linear and linear concentration data, for which data are analysed by, respectively, the non‐linear model and linear regression. The third category is represented by concentration data within the range of experimental error, or noise, from sites with no significant flux. Data in this category may be analysed by linear regression or simply classified as no flux. The particular non‐linear model has been selected among alternatives because its exponential curvature generally fits non‐linear static chamber concentration data well, and because it can be proven, mathematically, to be robust against horizontal gas transport through the soil or leaks in the chamber. The application of the HMR procedure is demonstrated on 244 data series of nitrous oxide accumulation over time. On average, 47% of these data were non‐linear, with an average flux increase over linear regression of 52%. The classification and analysis of data with a small signal‐to‐noise ratio requires special attention, and it is demonstrated how diagnostic graphical plots may be used to select the appropriate data analysis. The HMR procedure has been implemented as a free add‐on package for the free software R and is available for download through CRAN (http://www.r‐project.org).
The anti‐oestrogen fulvestrant (ICI 182,780) reduces the androgen receptor expression, ERK1/2 phosphorylation and cell proliferation in the rat ventral prostate
Authors: Fernandes S. A. F. , Gomes G. R. O. , Siu E. R. , Damas‐Souza D. M. , Bruni‐Cardoso A. , Augusto T. M. , Lazari M. F. M. , Carvalho H. F. , Porto C. S.
Published: September 2010

This study proposed to investigate further the role of oestrogens during pubertal growth of rat ventral prostate, by analysing the effect of anti‐oestrogen fulvestrant (ICI 182,780) on the expression of androgen (AR) and oestrogen receptors (ESR1 and ESR2), mitogen‐activated protein kinase (ERK1/2) phosphorylation, and expression of Ki‐67, a biomarker for cell proliferation. Ventral prostates were obtained from 90‐day‐old rats treated once a week for 2 months with vehicle (control) or ICI 182,780 (10 mg/rat, s.c.). Transcripts for AR, ESR1 and ESR2 were evaluated by quantitative real‐time polymerase chain reaction. Expression of AR, ESR1, ESR2, total and phospho‐ERK1/2 was analysed by Western blot or immunofluorescence. Ki‐67‐positive cells and myosin heavy chain were detected by immunohistochemistry. Cylindrical epithelial cells slightly taller, epithelial dysplasia and an increase in smooth muscle layer were observed in the ventral prostate from ICI 182,780‐treated rats. ICI 182,780 did not change the mRNA, but decreased the protein levels for AR in the ventral prostate. The expression of ESR1 (mRNA and protein) was upregulated by ICI 182,780, but no changes were observed on ESR2 expression (mRNA and protein). ICI 182,780 decreased the phosphorylation state of ERK1/2, with no changes in total ERK1/2 levels. Ki‐67‐positive cells in the ventral prostate were also decreased by ICI 182,780. In conclusion, ICI 182,780 induces downregulation of AR expression and may block the translocation of ESR1 and ESR2 from the nucleus to the plasma membrane, decreasing ERK1/2 phosphorylation and prostatic epithelial cell proliferation. These findings provide a basis for physiological roles of oestrogen in the ventral prostate. Further studies with fulvestrant are necessary in benign prostate hyperplasia and prostatic cancer models.
Zaditen (Ketotifen), as mast cell blocker, improves sperm quality, chromatin integrity and pregnancy rate after varicocelectomy
Authors: Azadi L. , Abbasi H. , Deemeh M. R. , Tavalaee M. , Arbabian M. , Pilevarian A. A. , Nasr‐Esfahani M. H.
Published: September 2010

Surgery is considered the most common choice for the treatment of male infertility with clinical varicocele. Increased numbers of mast cells (MCs) have been associated with different types of infertility, including varicocele. Despite there being different reports on improved fertility following administration of MC blockers, there is no report on the effect of a MC blocker on varicocele or after varicocelectomy. Therefore, the aim of this study was to evaluate the effect of Zaditen on semen quality, protamine content, DNA damage and fertility post‐surgery. The study included 103 infertile men who were referred to Isfahan Fertility and Infertility Center for varicocelectomy. Varicocele individuals were randomly divided into control (52) and treatment groups (51). Semen parameters, WBC/mL, protamine content (chromomycin A3 staining) and DNA integrity (sperm chromatin dispersion test) were assessed before and 3 months after surgery. Comparison of the aforesaid parameters between the two groups revealed significant improvement in the treatment group compared with the control group, with the exception of DNA integrity. In addition, the cumulative pregnancy significantly improved by 9 months post‐surgery in the treatment group (41.17%) compared with the control group (21.15%). The results of this study, for the first time, reveal that MC blockers such as Zaditen improve semen parameters, chromatin integrity and pregnancy rates when administered as adjunct therapy post‐varicocelectomy.
Biological Flora of the British Isles*:Stachys sylvaticaL.
Authors: Taylor Kenneth , Rowland Philip
Published: September 2010

1.This account presents information on all aspects of the biology ofStachys sylvaticathat are relevant to understanding its ecological characteristics and behaviour. The main topics are presented within the standard framework of theBiological Flora of the British Isles: distribution, habitat, communities, responses to biotic factors, responses to environment, structure and physiology, phenology, floral and seed characters, herbivores and disease, history, and conservation.

2.A rhizomatous perennial herb, with strong far‐creeping stolons,Stachys sylvaticais a polymorphic native herb of open woodlands, hedgerows, banks of rivers and streams, widespread throughout most of the British Isles.

3.Stachys sylvaticaoccurs in light to moderate shade. It is suggested that the red/far red ratio is more critical than reduced irradiance in the plant’s response to shading.

4.Stachys sylvaticaoccurs on moist or damp but not wet, weakly acid to weakly basic soils, and has been described as a nitrate indicator on base‐rich soils.

5.Stachys sylvaticadepends on seedlings established close to the parent plant for maintaining population density. Stolons are probably effective in extending the area of clones.

6.The hybrid betweenStachys sylvaticaandStachys palustris,Stachys×ambigua, is most frequent in northern and western Britain, and occurs as an introduction outside the native range ofStachys sylvatica.
Estimating population structure from AFLP amplification intensity
Authors: FOLL MATTHIEU , FISCHER MARTIN C. , HECKEL GERALD , EXCOFFIER LAURENT
Published: September 2010

In the last decade, amplified fragment length polymorphisms (AFLPs) have become one of the most widely used molecular markers to study the genetic structure of natural populations. Most of the statistical methods available to study the genetic structure of populations using AFLPs consider these markers as dominant and are thus unable to distinguish between individuals being heterozygous or homozygous for the dominant allele. Some attempts have been made to treat AFLPs as codominant markers by using AFLP band intensities to infer the most likely genotype of each individual. These two approaches have some drawbacks, the former discarding potentially valuable information and the latter being sometimes unable to correctly assign genotypes to individuals. In this study, we propose an alternative likelihood‐based approach, which does not attempt at inferring the genotype of each individual, but rather incorporate the uncertainty about genotypes into a Bayesian framework leading to the estimation of population‐specificFISandFSTcoefficients. We show with simulations that the accuracy of our method is much higher than one using AFLP as dominant markers and is generally close to what would be obtained by using the same number of Single‐Nucleotide Polymorphism (SNP) markers. The method is applied to a data set of four populations of the common vole (Microtus arvalis) from Grisons in Switzerland, for which we obtained 562 polymorphic AFLP markers. Our approach is very general and has the potential to make AFLP markers as useful as SNP data for nonmodel species.
Ancient DNA sequences point to a large loss of mitochondrial genetic diversity in the saiga antelope (Saiga tatarica) since the Pleistocene
Authors: CAMPOS PAULA F. , KRISTENSEN TOMMY , ORLANDO LUDOVIC , SHER ANDREI , KHOLODOVA MARINA V. , GÖTHERSTRÖM ANDERS , HOFREITER MICHAEL , DRUCKER DOROTHÉE G. , KOSINTSEV PAVEL , TIKHONOV ALEXEI , BARYSHNIKOV GENNADY. F. , WILLERSLEV ESKE , GILBERT M. THOMAS P.
Published: September 2010

Prior to the Holocene, the range of the saiga antelope (Saiga tatarica) spanned from France to the Northwest Territories of Canada. Although its distribution subsequently contracted to the steppes of Central Asia, historical records indicate that it remained extremely abundant until the end of the Soviet Union, after which its populations were reduced by over 95%. We have analysed the mitochondrial control region sequence variation of 27 ancient and 38 modern specimens, to assay how the species’ genetic diversity has changed since the Pleistocene. Phylogenetic analyses reveal the existence of two well‐supported, and clearly distinct, clades of saiga. The first, spanning a time range from >49 500 14C ybp to the present, comprises all the modern specimens and ancient samples from the Northern Urals, Middle Urals and Northeast Yakutia. The second clade is exclusive to the Northern Urals and includes samples dating from between 40 400 to 10 250 14C ybp. Current genetic diversity is much lower than that present during the Pleistocene, an observation that data modelling using serial coalescent indicates cannot be explained by genetic drift in a population of constant size. Approximate Bayesian Computation analyses show the observed data is more compatible with a drastic population size reduction (c. 66–77%) following either a demographic bottleneck in the course of the Holocene or late Pleistocene, or a geographic fragmentation (followed by local extinction of one subpopulation) at the Holocene/Pleistocene transition.
Comparative transcriptomics implicates mechanisms of evolved pollution tolerance in a killifish population
Authors: WHITEHEAD A. , TRIANT D. A. , CHAMPLIN D. , NACCI D.
Published: September 2010

Wild populations of the killifishFundulus heteroclitusresident in heavily contaminated North American Atlantic coast estuaries have recently and independently evolved dramatic, heritable, and adaptive pollution tolerance. We compared physiological and transcriptome responses to embryonic polychlorinated biphenyl (PCB) exposures between one tolerant population and a nearby sensitive population to gain insight into genomic, physiological and biochemical mechanisms of evolved tolerance in killifish, which are currently unknown. The PCB exposure concentrations at which developmental toxicity emerged, the range of developmental abnormalities exhibited, and global as well as specific gene expression patterns were profoundly different between populations. In the sensitive population, PCB exposures produced dramatic, dose‐dependent toxic effects, concurrent with the alterations in the expression of many genes. For example, PCB‐mediated cardiovascular system failure was associated with the altered expression of cardiomyocyte genes, consistent with sarcomere mis‐assembly. In contrast, genome‐wide expression was comparatively refractory to PCB induction in the tolerant population. Tolerance was associated with the global blockade of the aryl hydrocarbon receptor (AHR) signalling pathway, the key mediator of PCB toxicity, in contrast to the strong dose‐dependent up‐regulation of AHR pathway elements observed in the sensitive population. Altered regulation of signalling pathways that cross‐talk with AHR was implicated as one candidate mechanism for the adaptive AHR signalling repression and the pollution tolerance that it affords. In addition to revealing mechanisms of PCB toxicity and tolerance, this study demonstrates the value of comparative transcriptomics to explore molecular mechanisms of stress response and evolved adaptive differences among wild populations.
Ancient lakes revisited: from the ecology to the genetics of speciation
Authors: CRISTESCU MELANIA E. , ADAMOWICZ SARAH J. , VAILLANT JAMES J. , HAFFNER DOUGLAS G.
Published: September 2010

Explosive speciation in ancient lakes has fascinated biologists for centuries and has inspired classical work on the tempo and modes of speciation. Considerable attention has been directed towards the extrinsic forces of speciation—the geological, geographical and ecological peculiarities of ancient lakes. Recently, there has been a resurgence of interest in the intrinsic nature of these radiations, the biological characteristics conducive to speciation. While new species are thought to arise mainly by the gradual enhancement of reproductive isolation among geographically isolated populations, ancient lakes provide little evidence for a predominant role of geography in speciation. Recent phylogenetic work provides strong evidence that multiple colonization waves were followed by parallel intralacustrine radiations that proceeded at relatively rapid rates despite long‐term gene flow through hybridization and introgression. Several studies suggest that hybridization itself might act as a key evolutionary mechanism by triggering major genomic reorganization/revolution and enabling the colonization of new ecological niches in ancient lakes. These studies propose that hybridization is not only of little impediment to diversification but could act as an important force in facilitating habitat transitions, promoting postcolonization adaptations and accelerating diversification. Emerging ecological genomic approaches are beginning to shed light on the long‐standing evolutionary dilemma of speciation in the face of gene flow. We propose an integrative programme for future studies on speciation in ancient lakes.
Next‐generation sequencing as a tool to study microbial evolution
Authors: BROCKHURST MICHAEL A. , COLEGRAVE NICK , ROZEN DANIEL E.
Published: September 2010

Thanks to their short generation times and large population sizes, microbes evolve rapidly. Evolutionary biologists have exploited this to observe evolution in real time. The falling costs of whole‐genome sequencing using next‐generation technologies now mean that it is realistic to use this as a tool to study this rapid microbial evolution both in the laboratory and in the wild. Such experiments are being used to accurately estimate the rates of mutation, reveal the genetic targets and dynamics of natural selection, uncover the correlation (or lack thereof) between genetic and phenotypic change, and provide data to test long‐standing evolutionary hypotheses. These advances have important implications for our understanding of the within‐ and between‐host evolution of microbial pathogens.
DNA topology of highly transcribed operons in Salmonella enterica serovar Typhimurium
Authors: Booker Betty M. , Deng Shuang , Higgins N. Patrick
Published: September 2010

Bacteria differ from eukaryotes by having the enzyme DNA gyrase, which catalyses the ATP‐dependent negative supercoiling of DNA. Negative supercoils are essential for condensing chromosomes into an interwound (plectonemic) and branched structure known as the nucleoid. Topo‐1 removes excess supercoiling in an ATP‐independent reaction and works with gyrase to establish a topological equilibrium where supercoils move within 10 kb domains bounded by stochastic barriers along the sequence. However, transcription changes the stochastic pattern by generating supercoil diffusion barriers near the sites of gene expression. Using supercoil‐dependent Tn3 and γδ resolution assays, we studied DNA topology upstream, downstream and across highly transcribed operons. Whenever two Res sites flanked efficiently transcribed genes, resolution was inhibited and the loss in recombination efficiency was proportional to transcription level. Ribosomal RNA operons have the highest transcription rates, and resolution assays at the rrnG and rrnH operons showed inhibitory levels 40–100 times those measured in low‐transcription zones. Yet, immediately upstream and downstream of RNA polymerase (RNAP) initiation and termination sites, supercoiling characteristics were similar to poorly transcribed zones. We present a model that explains why RNAP blocks plectonemic supercoil movement in the transcribed track and suggests how gyrase and TopA control upstream and downstream transcription‐driven supercoiling.
Non‐stop mRNA decay initiates at the ribosome
Authors: Ge Zhiyun , Mehta Preeti , Richards Jamie , Karzai A. Wali
Published: September 2010

The translation machinery deciphers genetic information encoded within mRNAs to synthesize proteins needed for various cellular functions. Defective mRNAs that lack in‐frame stop codons trigger non‐productive stalling of ribosomes. We investigated how cells deal with such defective mRNAs, and present evidence to demonstrate that RNase R, a processive 3′‐to‐5′ exoribonuclease, is recruited to stalled ribosomes for the specific task of degrading defective mRNAs. The recruitment process is selective for non‐stop mRNAs and is dependent on the activities of SmpB protein and tmRNA. Most intriguingly, our analysis reveals that a unique structural feature of RNase R, the C‐terminal lysine‐rich (K‐rich) domain, is required both for productive ribosome engagement and targeted non‐stop mRNA decay activities of the enzyme. These findings provide new insights into how a general RNase is recruited to the translation machinery and highlight a novel role for the ribosome as a platform for initiating non‐stop mRNA decay.
Partitioning of P1 plasmids by gradual distribution of the ATPase ParA
Authors: Hatano Toshiyuki , Niki Hironori
Published: September 2010

Recently, it has been reported that prokaryotes also have a mitotic‐like apparatus in which polymerized fibres govern the bipolar movement of chromosomes and plasmids. Here, we show evidence that a non‐mitotic‐like apparatus that does not form polymerized filaments carries out plasmid partitioning. P1 ParA, which is a DNA‐binding ATPase protein, was found to be distributed through the whole nucleoid and formed a dense spot at the centre of the nucleoid. The fluorescent intensity of the ParA spot blinked, and then the spot gradually migrated from the midcell to a cell quarter position. Such distribution was not observed in anucleate cells, suggesting that the nucleoid could be a matrix for gradual distribution of ParA. Plasmid DNA constantly colocalized at the spot of ParA and migrated according to spot migration and separation. Thus, the gradient distribution of ParA determines the destination of partitioning plasmids and may direct plasmids to the cell quarters.
Enteropathogenic E. coli non‐LEE encoded effectors NleH1 and NleH2 attenuate NF‐κB activation
Authors: Royan Sandhya V. , Jones Rheinallt M. , Koutsouris Athanasia , Roxas Jennifer L. , Falzari Kanakeshwari , Weflen Andrew W. , Kim Amy , Bellmeyer Amy , Turner Jerrold R. , Neish Andrew S. , Rhee Ki‐Jong , Viswanathan V. K. , Hecht Gail A.
Published: September 2010

Enteric bacterial pathogens have evolved sophisticated strategies to evade host immune defences. Some pathogens deliver anti‐inflammatory effector molecules into the host cell cytoplasm via a type III secretion system (T3SS). Enteropathogenic Escherichia coli (EPEC) inhibits inflammation by an undefined, T3SS‐dependent mechanism. Two proteins encoded outside of the EPEC locus of enterocyte effacement (LEE) pathogenicity island, non‐LEE‐encoded effector H1 (NleH1) and H2 (NleH2), display sequence similarity to Shigella flexneri OspG, which inhibits activation of the pro‐inflammatory transcription factor NF‐κB. We hypothesized that the anti‐inflammatory effects of EPEC were mediated by NleH1 and NleH2. In this study, we examined the effect of NleH1/H2 on the NF‐κB pathway. We show that NleH1/H2 are secreted via the T3SS and that transfection of cells with plasmids harbouring nleH1 or nleH2 decreased IKK‐β‐induced NF‐κB activity and attenuated TNF‐α‐induced degradation of phospho‐IκBα by preventing ubiquitination. Serum KC levels were higher in mice infected with ΔnleH1H2 than those infected with WT EPEC, indicating that NleH1/H2 dampen pro‐inflammatory cytokine expression. ΔnleH1H2 was cleared more rapidly than WT EPEC while complementation of ΔnleH1H2 with either NleH1 or NleH2 prolonged colonization. Together, these data show that NleH1 and NleH2 function to dampen host inflammation and facilitate EPEC colonization during pathogenesis.