bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo
Authors: Yadav Mahesh , Louvet Cedric , Davini Dan , Gardner James M. , Martinez-Llordella Marc , Bailey-Bucktrout Samantha , Anthony Bryan A. , Sverdrup Francis M. , Head Richard , Kuster Daniel J. , Ruminski Peter , Weiss David , Von Schack David , Bluestone Jeffrey A.
Published: September 2012

Foxp3+ CD4+ T helper cells called regulatory T (T reg) cells play a key role in controlling reactivity to self-antigens and onset of autoimmunity. T reg cells either arise in thymus and are called natural T reg (nT reg) cells or are generated in the periphery through induction of Foxp3 and are called inducible T reg (iT reg) cells. The relative contributions of iT reg cells and nT reg cells in peripheral tolerance remain unclear as a result of an inability to separate these two subsets of T reg cells. Using a combination of novel TCR transgenic mice with a defined self-antigen specificity and conventional mouse models, we demonstrate that a cell surface molecule, neuropilin-1 (Nrp-1), is expressed at high levels on nT reg cells and can be used to separate nT reg versus iT reg cells in certain physiological settings. In addition, iT reg cells generated through antigen delivery or converted under homeostatic conditions lack Nrp-1 expression. Nrp-1lo iT reg cells show similar suppressive activity to nT reg cells in controlling ongoing autoimmune responses under homeostatic conditions. In contrast, their activity might be compromised in certain lymphopenic settings. Collectively, our data show that Nrp-1 provides an excellent marker to distinguish distinct T reg subsets and will be useful in studying the role of nT reg versus iT reg cells in different disease settings.
Plasmin and chymotrypsin have distinct preferences for channel activating cleavage sites in the γ subunit of the human epithelial sodium channel
Authors: Haerteis Silke , Krappitz Matteus , Diakov Alexei , Krappitz Annabel , Rauh Robert , Korbmacher Christoph
Published: September 2012

Proteolytic activation of the epithelial sodium channel (ENaC) involves cleavage of its γ subunit in a critical region targeted by several proteases. Our aim was to identify cleavage sites in this region that are functionally important for activation of human ENaC by plasmin and chymotrypsin. Sequence alignment revealed a putative plasmin cleavage site in human γENaC (K189) that corresponds to a plasmin cleavage site (K194) in mouse γENaC. We mutated this site to alanine (K189A) and expressed human wild-type (wt) αβγENaC and αβγK189AENaC in Xenopus laevis oocytes. The γK189A mutation reduced but did not abolish activation of ENaC whole cell currents by plasmin. Mutating a putative prostasin site (γRKRK178AAAA) had no effect on the stimulatory response to plasmin. In contrast, a double mutation (γRKRK178AAAA;K189A) prevented the stimulatory effect of plasmin. We conclude that in addition to the preferential plasmin cleavage site K189, the putative prostasin cleavage site RKRK178 may serve as an alternative site for proteolytic channel activation by plasmin. Interestingly, the double mutation delayed but did not abolish ENaC activation by chymotrypsin. The time-dependent appearance of cleavage products at the cell surface nicely correlated with the stimulatory effect of chymotrypsin on ENaC currents in oocytes expressing wt or double mutant ENaC. Delayed proteolytic activation of the double mutant channel with a stepwise recruitment of so-called near-silent channels was confirmed in single-channel recordings from outside-out patches. Mutating two phenylalanines (FF174) in the vicinity of the prostasin cleavage site prevented proteolytic activation by chymotrypsin. This indicates that chymotrypsin preferentially cleaves at FF174. The close proximity of FF174 to the prostasin site may explain why mutating the prostasin site impedes channel activation by chymotrypsin. In conclusion, this study supports the concept that different proteases have distinct preferences for certain cleavage sites in γENaC, which may be relevant for tissue-specific proteolytic ENaC activation.
Enhancement of plasma burn-through simulation and validation in JET
Authors: Kim Hyun-Tae , Fundamenski W. , Sips A.C.C.
Published: September 2012

In this paper, new models for a plasma burn-through simulation using the DYON code are introduced in detail, and the quantitative validation of the simulation results against JET data is presented for the first time. In order to calculate the particle confinement time, a dynamic effective connection length model including an eddy current effect is used assuming ambipolar transonic transport and the Bohm diffusion model for parallel and perpendicular particle losses, respectively. Plasma–surface interaction effects are treated with an impurity sputtering yield and an exponential saturation model of the deuterium recycling coefficient. The rate and power coefficients in the Atomic Data and Analysis Structure (ADAS) package are adopted to solve energy and particle balance. The neutral screening effects are taken into account according to particle species, and the sophisticated energy and particle balances are presented. The new burn-through simulation shows good agreement against carbon-wall JET data. This indicates that the burn-through simulation can be applied to investigate the key aspect of physics in plasma burn-through and to perform a predictive simulation for ITER start-up.
Escape from Equilibrium: Thinking Historically about Firm Responses to Competition
Authors: Levenstein Margaret C.
Published: September 2012

Firms use a variety of strategies to limit competition that would otherwise erode profits. Firms innovate, creating new technologies, new markets, and new firms. Innovations allow them to distinguish their products or lower their costs and thus maintain profits. Their ability to innovate depends on the existence of social institutions that allow them to amass the resources—labor, capital, and information—necessary to compete successfully. Firms also maintain profits by manipulating the political process to maintain preferred access to markets, technology and resources. Finally, firms take actions to limit competition directly. Waves of consolidation, justified by an assumption of the inevitability of increasing firm size, have limited competition and entrepreneurship. Cartels and other forms of collusion, sometimes thought to have disappeared from US markets after the adoption of the Sherman Antitrust Act in 1890, are still active in a wide variety of national and international markets.
Ensuring America's Health: Publicly Constructing the Private Health Insurance Industry, 1945–1970
Authors: Chapin Christy Ford
Published: September 2012

“Ensuring America's Health” demonstrates how public and private power intermingled to embed a specific organizational model—the insurance company model—into the health care system. The dissertation draws on government documents, trade association papers, company archives, and interviews with policymakers, insurance industry leaders, and physicians. In addition to exploring health care politics, it presents a detailed study of major trade associations and ground-level organizations, such as individual insurance companies and physician offices. This history reveals the degree to which policy debates and private sector organization have informed one another; exposes the factors driving US health care costs; and details the origins of the system's pseudo-corporate structure, which places insurance companies in a supervisory role over physicians and hospitals.
Modeling of epigenome dynamics identifies transcription factors that mediate Polycomb targeting
Authors: Arnold Phil , Schöler Anne , Pachkov Mikhail , Balwierz Piotr J. , Jørgensen Helle , Stadler Michael B. , van Nimwegen Erik , Schübeler Dirk
Published: September 2012

Although changes in chromatin are integral to transcriptional reprogramming during cellular differentiation, it is currently unclear how chromatin modifications are targeted to specific loci. To systematically identify transcription factors (TFs) that can direct chromatin changes during cell fate decisions, we model the relationship between genome-wide dynamics of chromatin marks and the local occurrence of computationally predicted TF binding sites. By applying this computational approach to a time course of Polycomb-mediated H3K27me3 marks during neuronal differentiation of murine stem cells, we identify several motifs that likely regulate the dynamics of this chromatin mark. Among these, the sites bound by REST and by the SNAIL family of TFs are predicted to transiently recruit H3K27me3 in neuronal progenitors. We validate these predictions experimentally and show that absence of REST indeed causes loss of H3K27me3 at target promoters in trans, specifically at the neuronal progenitor state. Moreover, using targeted transgenic insertion, we show that promoter fragments containing REST or SNAIL binding sites are sufficient to recruit H3K27me3 in cis, while deletion of these sites results in loss of H3K27me3. These findings illustrate that the occurrence of TF binding sites can determine chromatin dynamics. Local determination of Polycomb activity by REST and SNAIL motifs exemplifies such TF based regulation of chromatin. Furthermore, our results show that key TFs can be identified ab initio through computational modeling of epigenome data sets using a modeling approach that we make readily accessible.
Lactate dehydrogenase as an indicator of severe illness in neonatal intensive care patients: a longitudinal cohort study
Authors: Karlsson Mathias , Dung Khu T K , Thi Truong L , Borgström Erik , Jonstam Karin , Kasström Lovisa , Winbladh Birger
Published: September 2012

Aim:  Lactate dehydrogenase (LDH) increases in several critical conditions that cause cell damage and could potentially be used for early detection of serious illness in the newborn. Our aim was to investigate the relationship between the early clinical course of NICU infants and LDH in plasma at admission.

Methods:  LDH was measured in a cohort of patients consecutively admitted to a major NICU in Hanoi. The infants were classified as ‘obviously needing intensive care during the first week’ (n = 83) or ‘not receiving intensive care measures during the first week’ (n = 260) by a senior neonatologist blinded to the LDH and lactate activity.

Results:  LDH differed significantly between the groups in infants born after 32 gestational weeks. LDH differed with the vitality of the patient (F = 26.25, p < 0.0001) at admittance and correlated with lactate (R = 0.496, p < 0.0001). Also, the predictive value for obvious need of intensive care was higher for LDH than for lactate assessed by area under the curve calculated with ROC‐curves [0.82 (0.77–0.88) vs. 0.67 (0.60–0.75)].

Conclusion:  There is a strong relationship between bad clinical condition of infants during first week of life and elevated plasma LDH. The results suggest that LDH might be a valuable support in decision making in the neonatal period.
Relationship between serum adiponectin levels and age in healthy subjects and patients with type 2 diabetes
Authors: Obata Yoshinari , Yamada Yuya , Takahi Yasumitsu , Baden Megu Y. , Saisho Kenji , Tamba Sachiko , Yamamoto Koji , Umeda Miyuki , Furubayashi Aiko , Matsuzawa Yuji
Published: September 2012

Objective

Serum adiponectin levels are affected by gender, body fat mass, several pathological factors or therapeutic interventions and it might be also affected by age. This study aimed to investigate the relationship between serum adiponectin levels and age in several physiological states.

Design, Patients and Measurements

The study was carried out in 21 100 healthy subjects (12 363 men and 8737 women) and 1833 patients with type 2 diabetes (1233 men and 600 women). Physical and demographic characteristics were recorded, and blood samples were collected to measure serum adiponectin levels. Using these data, we determined the relationships between serum adiponectin levels and various parameters, including age.

Results

Serum adiponectin levels increased with increasing age of healthy subjects and in patients with diabetes, in both men and women. Serum adiponectin levels were positively correlated with age in healthy subjects and patients with diabetes, in both men and women. In stepwise multiple regression analysis with serum adiponectin levels as the dependent variable and physiological characteristics as explanatory variables, age was significantly and independently associated with serum adiponectin levels in each of these groups of subjects.

Conclusions

Serum adiponectin levels are significantly and positively associated with age in healthy subjects and in patients with diabetes. This association is independent of renal function, body fat status, glucose metabolism and lipid profiles.
Relatively high frequency of non‐synonymous GLI2 variants in patients with congenital hypopituitarism without holoprosencephaly
Authors: França Marcela M. , Jorge Alexander A. L. , Carvalho Luciani R. S. , Costalonga Everlayny F. , Otto Aline P. , Correa Fernanda A. , Mendonca Berenice B. , Arnhold Ivo J. P.
Published: September 2012

Objective

GLI2 is a downstream transcription factor in Sonic Hedgehog signalling, acting early in ventral forebrain and pituitary development. Heterozygous nonsense GLI2 mutations have been reported in patients with isolated or combined pituitary hormone deficiency (CPHD), with or without holoprosencephaly. The aim of this study was to screen for GLI2 mutations in a large cohort of patients with congenital GH deficiency.

Design and Patients

The GLI2 coding region of 41 patients with severe isolated GH deficiency (IGHD) and 136 patients with CPHD was amplified by PCR using intronic primers and sequenced. The frequency of GLI2 variants was verified in up to 155 Brazilian controls and in the 1000 Genomes database. The consequences of allelic variants were analysed by the Polyphen, SIFT, Mutationtaster and SNAP prediction sites.

Results

Eighteen different heterozygous non‐synonymous GLI2 variants were identified in 24 patients. Twenty‐three patients had CPHD and one had IGHD. Two patients had additional diabetes insipidus, indicating deficiencies of anterior and posterior pituitary lobes. The posterior pituitary lobe on MRI was ectopic in 16, not visible in 4, normally placed in 2 and imaging was not available in two patients, but there were no signs of holoprosencephaly. Sixteen GLI2 variants were considered deleterious in at least one of the prediction sites.

Conclusions

A relatively high frequency of non‐synonymous GLI2 variants was identified in patients with congenital GH deficiency without other brain defects, and most of these patients presented with CPHD and an ectopic posterior pituitary lobe. In vitro functional assays may contribute to ascertain the deleterious consequences of these variants.
Long‐term impacts of invasive species on a native top predator in a large lake system
Authors: RUSH SCOTT A. , PATERSON GORDON , JOHNSON TIM B. , DROUILLARD KEN G. , HAFFNER GORDON D. , HEBERT CRAIG E. , ARTS MICHAEL T. , McGOLDRICK DARYL J. , BACKUS SEAN M. , LANTRY BRIAN F. , LANTRY JANA R. , SCHANER TED , FISK AARON T.
Published: September 2012

1. Declining abundances of forage fish and the introduction and establishment of non‐indigenous species have the potential to substantially alter resource and habitat exploitation by top predators in large lakes.

2. We measured stable isotopes of carbon (δ13C) and nitrogen (δ15N) in field‐collected and archived samples of Lake Ontario lake trout (Salvelinus namaycush) and five species of prey fish and compared current trophic relationships of this top predator with historical samples.

3. Relationships between δ15N and lake trout age were temporally consistent throughout Lake Ontario and confirmed the role of lake trout as a top predator in this food web. However, δ13C values for age classes of lake trout collected in 2008 ranged from 1.0 to 3.9‰ higher than those reported for the population sampled in 1992.

4. Isotope mixing models predicted that these changes in resource assimilation were owing to the replacement of rainbow smelt (Osmerus mordax) by round goby (Neogobius melanostomus) in lake trout diet and increased reliance on carbon resources derived from nearshore production. This contrasts with the historical situation in Lake Ontario where δ13C values of the lake trout population were dominated by a reliance on offshore carbon production.

5. These results indicate a reduced capacity of the Lake Ontario offshore food web to support the energetic requirements of lake trout and that this top predator has become increasingly reliant on prey resources that are derived from nearshore carbon pathways.
Evaluation of photoacoustic infrared spectroscopy for simultaneous measurement of N2O and CO2 gas concentrations and fluxes at the soil surface
Authors: Iqbal Javed , Castellano Michael J. , Parkin Timothy B.
Published: September 2012

Simultaneous measurement of N2O and CO2 flux at the soil surface with photoacoustic infrared spectroscopy (PAS) is gaining popularity due to portability, low maintenance, and ease‐of‐operation. However, the ability of PAS to measure N2O with accuracy and precision similar to gas chromatography (GC) is uncertain due to overlap in N2O, CO2, and H2O absorbance spectra combined with the large range in analyte concentrations. We tested the ability of six PAS units to simultaneously measure N2O and CO2 gas concentrations and fluxes with accuracy and precision similar to two GC units. We also evaluated H2O vapor and CO2 interferences with N2O measurement. The accuracy and precision of standard gas concentration measurements with PAS and GC were similar. High water vapor (~26 600 ppm) and CO2 concentrations (~4500 ppm) did not interfere with N2O measurement across the concentration range typically observed in static flux chambers at the soil surface (~0.5–3.0 ppm N2O). On average, N2O fluxes measured with the six PAS were 4.7% higher than one GC and 9.9% lower than the second GC.
Two Japanese cases of dermatitis herpetiformis associated each with lung cancer and autoimmune pancreatitis but showing no intestinal symptom or circulating immunoglobulin A antibodies to any known antigens
Authors: Shigeta Mika , Saiki Minoru , Tsuruta Daisuke , Ohata Chika , Ishii Norito , Ono Fumitake , Hamada Takahiro , Dainichi Teruki , Furumura Minao , Zone John J. , Karpati Sarolta , Sitaru Cassian , Hashimoto Takashi
Published: September 2012

Dermatitis herpetiformis (DH) is common in some Caucasian populations but extremely rare in Japanese, probably because of different immunogenetic backgrounds. We report two Japanese DH cases with typical clinical, histological and direct immunofluorescence features. However, no symptom of gluten‐sensitive enteropathy was shown. The diagnosis was confirmed by eliminating other autoimmune blistering diseases by indirect immunofluorescence, enzyme‐linked immunosorbent assays and immunoblotting. However, circulating immunoglobulin (Ig)A anti‐endomysium, reticulin and gliadin antibodies were not detected. IgA antibodies to tissue and epidermal transglutaminases were also negative. One case was associated with lung cancer and the other one with autoimmune pancreatitis. On review of 17 cases of DH reported in Japan over the previous 10 years, including our cases, one case was associated with gluten‐sensitive enteropathy, four with malignant neoplasms, two with autoimmune systemic disorders and one with psoriasis. Although our cases were typical of DH in clinical, histopathological and IgA deposit features, they showed different human leukocyte antigen haplotypes, no gluten‐sensitive enteropathy and no DH‐specific IgA antibodies, including those to epidermal and tissue transglutaminases. These results suggest that studies of unique characteristics in Japanese DH patients should facilitate further understanding of pathogenesis in DH.
Novel treatment using thioglycolic acid for pincer nails
Authors: Okada Kikuzo , Okada Eijiro
Published: September 2012

The authors developed a novel treatment using thioglycolic acid (TGA) to chemically soften pincer nails. The objective was to describe a new treatment method for pincer nails by applying TGA to soften the nail and then fix it in the correct position. A total of 104 patients (nine men and 95 women; mean age, 56 years) with 106 pincer nails underwent our treatment. A small hole was made on the markedly incurvated side of the pincer nail, and a super‐elastic wire was inserted into the hole and bent backwards; 5% TGA was then applied for 6–7 h prior to reduction. Favorable reduction was achieved in 66% of patients within 1 day of the procedure, in 30% within 2–4 days and in 4% 5 days or more later. No patient required surgery. No post‐procedure infection, rash, continuous pain or nail cut out was evident. In eight cases, recurrences of nail deformity were observed within the 1‐year follow‐up period. Our novel method, which consists of administrating TGA via a hole in the nail plate, is a useful treatment for pincer nails.
The dominant exploiters of the fig/pollinator mutualism vary across continents, but their costs fall consistently on the male reproductive function of figs
Authors: SEGAR SIMON T. , COOK JAMES M.
Published: September 2012

1. Fig trees (Moraceae: Ficus) are keystone species, whose ecosystem function relies on an obligate mutualism with wasps (Chalcidoidea: Agaonidae) that enter fig syconia to pollinate. Each female flower produces one seed (fig female reproductive function), unless it also receives a wasp egg, in which case it supports a wasp. Fig male reproductive function requires both male flowers and pollinator offspring, which are the only vectors of fig pollen.

2. The mutualism is exploited by other wasps that lay eggs but provide no pollination service. Most of these non‐pollinating fig wasps (NPFWs) do not enter syconia, but lay eggs through the wall with long ovipositors. Some are gall‐makers, while others are parasitoids or lethal inquilines of other wasps.

3. Ficus is pan‐tropical and contains >750 fig species. However, NPFW communities vary across fig lineages and continents and their effects on the mutualism may also vary. This provides a series of natural experiments to investigate how the costs to a keystone mutualism vary geographically.

4. We made the first detailed study of the costs of NPFWs in a fig (Ficus obliqua G. Forst) from the endemic Australasian section Malvanthera. In contrast to the communities associated with section Americana in the New World, wasps from the subfamily Sycoryctinae (Chalcidoidea: Pteromalidae) dominated this community.

5. These sycoryctine wasps have a negative impact on pollinator offspring numbers, but not on seed production. Consequently, while the NPFW fauna varies greatly at high taxonomic levels across continents, we show that the consistent main effect of locally dominant exploiters of the mutualism is to reduce fig male reproductive function.
Sodium‐specific foraging by leafcutter ant workers (Atta cephalotes, Hymenoptera: Formicidae)
Authors: CHAVARRIA PIZARRO LAURA , MCCREERY HELEN F. , LAWSON SARAH P. , WINSTON MAX E. , O’DONNELL SEAN
Published: September 2012

1. Sodium is often a limiting nutrient for terrestrial animals, and may be especially sought by herbivores. Leafcutter ants are dominant herbivores in the Neotropics, and leafcutter foraging may be affected by nutritional demands of the colony and/or the demands of their symbiotic fungal mutualists. We hypothesized that leafcutter colonies are sodium limited, and that leafcutter ants will therefore forage specifically for sodium.

2. Previous studies demonstrated that leafcutter Atta cephalotes Linnaeus workers preferentially cut and remove paper baits treated with NaCl relative to water control baits. Atta cephalotes colonies in this study were presented with baits offering NaCl, Na2SO4, and KCl to test whether leafcutters forage specifically for sodium. Sucrose and water were used as positive and negative controls, respectively.

3. Atta foragers removed significantly more of the baits treated with NaCl and Na2SO4 than the KCl treatment, which did not differ from water. The NaCl and Na2SO4 treatments were collected at similar rates. We conclude A. cephalotes forage specifically for sodium rather than for anions (chloride) or solutes in general. This study supports the hypothesis that leafcutter ants are limited by, and preferentially forage for, sodium.
Higher gregarine parasitism often in sibling species of host damselflies with smaller geographical distributions
Authors: MLYNAREK JULIA J. , HASSALL CHRISTOPHER , FORBES MARK R.
Published: September 2012

1. This study investigated inter‐specific variation in parasitism by gregarines (Eugregarinorida: Actinocephalidae), among sibling species of damselflies (Odonata: Zygoptera), in relation to relative size of geographical ranges of host species.

2. Gregarines are considered generalist parasites, particularly for taxonomically related host species collected at the same sites or area. Prevalence and median intensity of gregarine parasitism was obtained for 1338 adult damselflies, representing 14 species (7 sibling species pairs) across 3 families within the suborder Zygoptera. Damselflies were collected at three local sites in Southeastern Ontario, during the same periods over the season.

3. Five out of seven species pairs had significant differences in parasitism between sibling species. The less widespread host species was the more parasitised for three species pairs with significant differences in gregarine prevalence, and for two species pairs with differences in median intensity. The more widespread host had a higher intensity of infection as expected, in two species pairs.

4. Future studies on ecological determinants of parasitism among related species should examine robust measures of abundance of species and representation of species regionally.
Habitat overlap between predatory benthic fish and their invertebrate prey in streams: the relative influence of spatial and temporal factors on predation risk
Authors: WORISCHKA SUSANNE , KOEBSCH CHRISTOPH , HELLMANN CLAUDIA , WINKELMANN CAROLA
Published: September 2012

1. The spatial heterogeneity of ecosystems as well as temporal activity patterns of organisms can have far‐reaching effects on predator–prey relationships. We hypothesised that spatiotemporal constraints in mesohabitat use by benthic fish predators would reduce habitat overlap with benthic invertebrates and lead to mesohabitat‐specific predation risks.

2. We analysed the spatiotemporal activity patterns of two small‐bodied benthivorous fishes, gudgeon (Gobio gobio) and stone loach (Barbatula barbatula), and of benthic invertebrates in a small temperate stream during three 24‐h field experiments. By applying a novel method of field video observation, we monitored the spatiotemporal foraging behaviour of the fish in their natural environment. A parallel analysis of invertebrate mesohabitat use by means of small area Hess sampling allowed a direct estimation of habitat overlap at a pool–riffle scale.

3. Gudgeon showed a dominant spatial activity pattern preferring pools at all times of day, whereas stone loach used both mesohabitats but with a distinct temporal (nocturnal) activity pattern. The patterns of residence were not identical with those of active foraging. Invertebrate community composition differed significantly between mesohabitats but not between times of day. More than half of the total dissimilarity between pools and riffles was accounted for by six invertebrate taxa. Five of these were subject to higher fish predation in pools than in riffles. The total prey consumption of the two fish species together in pools was about three times as high as in riffles. Trophic niche breadth of stone loach and thus its predation range was broader than that of gudgeon.

4. These results indicate that the potential predation risk for stream invertebrates depends on the combination of spatial and temporal patterns of both predator and prey. Given the distinct differences in predation risk found between pools and riffles, we conclude that spatial heterogeneity at the mesohabitat scale can influence mechanisms and consequences of selective predation. We also suggest that the analysis of spatiotemporal predator–prey relationships should not be based on the premise that the main residence habitat and active foraging habitat of a predator are identical.
Mice Heterozygous for the Oxytocin Receptor Gene (Oxtr+/−) Show Impaired Social Behaviour but not Increased Aggression or Cognitive Inflexibility: Evidence of a Selective Haploinsufficiency Gene Effect
Authors: Sala M. , Braida D. , Donzelli A. , Martucci R. , Busnelli M. , Bulgheroni E. , Rubino T. , Parolaro D. , Nishimori K. , Chini B.
Published: September 2012

We characterised the behavioural phenotype of mice heterozygous (Oxtr+/−) for the oxytocin receptor gene (Oxtr) and compared it with that of Oxtr null mice (Oxtr−/−), which display autistic‐like behaviours, including impaired sociability and preference for social novelty, impaired cognitive flexibility, and increased aggression. Similar to Oxtr−/− mice, the Oxtr+/− showed impaired sociability and preference for social novelty but, unlike the null genotype, their cognitive flexibility and aggression were normal. By autoradiography, Oxtr+/− mice were found to have approximately 50% fewer oxytocin receptors (OXTRs) in all of the examined brain regions. Thus, because a partial reduction in Oxtr gene expression is sufficient to compromise social behaviour, the Oxtr acts as a haploinsufficient gene. Furthermore, the inactivation of the Oxtr gene affects specific behaviours in a dose‐dependent manner: social behaviour is sensitive to even a partial reduction in Oxtr gene expression, whereas defects in aggression and cognitive flexibility require the complete inactivation of the Oxtr gene to emerge. We then investigated the rescue of the Oxtr+/− social deficits by oxytocin (OT) and Thr4Gly7OT (TGOT) administered i.c.v. at different doses. TGOT was more potent than OT in rescuing sociability and social novelty in both genotypes. Furthermore, the TGOT doses that reverted impaired sociability and preference for social novelty in Oxtr+/− were lower than those required in Oxtr−/−, thus suggesting that the rescue effect is mediated by OXTR in Oxtr+/− and by other receptors (presumably vasopressin V1a receptors) in Oxtr−/−. In line with this, a low dose of the selective oxytocin antagonist desGlyDTyrOVT blocks the rescue effect of TGOT only in the Oxtr+/− genotype, whereas the less selective antagonist SR49059 blocks rescue in both genotypes. In conclusion, the Oxtr+/− mouse is a unique animal model for investigating how partial loss of the Oxtr gene impair social interactions, and for designing pharmacological rescue strategies.
Quantifying the cost of laparoscopic inguinal hernia repair
Authors: Smart Philip , Castles Lindsay
Published: September 2012

Background

Laparoscopic inguinal hernia repair has been widely adopted. While the clinical advantages and disadvantages are well‐quantified, the economic cost is less well‐studied.

Methods

A retrospective audit and case review of a single‐centre public hospital consecutive case series was performed using data captured from real‐time stock usage tracking technology and review of electronic medical records.

Results

Laparoscopic inguinal hernia repair requires 11‐min (21%) extra theatre time and costs $1268 (370%) more for single‐use disposable equipment and prostheses.

Conclusions

Laparoscopic inguinal hernia repair does not require significantly more theatre time, but has a higher short‐term in‐hospital cost. Repair technique should be tailored according to patient factors.
Evaluation of a Japanese “Prevention of Long‐term Care” project for the improvement in oral function in the high‐risk elderly
Authors: Sakayori Takaharu , Maki Yoshinobu , Hirata SoIchiro , Okada Mahito , Ishii Takuo
Published: September 2012

Aim:  The purpose of this study was to analyze the improvement in oral function and environment in high‐risk elderly persons participating in a program to improve oral function organized by their local government.

Methods:  Participants comprised 36 high‐risk elderly and the mean age was 77.11 ± 7.24 years. The program involved training sessions carried out five or six times every 2–3 weeks for 3 months. Oral function and environment was evaluated before and after the program. The research period extended from 2008 to 2010.

Results:  The effects of intervention were clearly observed in oral diadochokinesis score in the high‐risk elderly. Persons with a lower repetitive saliva swallowing test (RSST) and oral diadochokinesis score before intervention showed a tendency toward even greater improvement. No significant changes were observed in saliva secretion or total amounts of Streptococcus mutans, Lactobacilli, Candida or total microorganisms.

Conclusions:  The effects of intervention were clearly recognized in regards to oral diadochokinesis. Improvement in RSST and oral diadochokinesis scores was marked in those persons showing a lower number of articulations before intervention. Geriatr Gerontol Int 2013; 13: 451–457.
Intensified rehabilitation therapy and transitions to skilled nursing facilities in community‐living seniors with acute medical illnesses
Authors: Yoo Ji Won , Kim Sulgi , Choi Jai Hyun , Ryu Woo Sang
Published: September 2012

Aim:  To examine whether rehabilitation therapy type would be associated with transitions to skilled nursing facilities (SNF) in community‐living seniors with acute medical illnesses.

Methods:  Using administrative and clinical data, multivariate regression analysis examined the relationship between the extent of rehabilitation therapy and transitions to SNF in all participants, as well as participants by physical function at admission.

Results:  In all participants (n = 929), the intensified rehabilitation therapy was associated with a lower probability of transitions to SNF (14% vs 21%; odds ratio [OR] 0.59; 95% confidence intervals [CI] 0.22–0.96; P = 0.02). In participants with mild physical limitations (n = 270), less frequent transitions to SNF occurred when patients received intensified rehabilitation therapy [16% vs 23%; OR 0.46; 95% CI 0.17–0.94; P = 0.01]. In participants with moderate to severe physical limitations (n = 265), the decreased frequency of transitions to SNF associated with rehabilitation therapy became more pronounced (18% vs 28%; OR 0.34; 95% CI 0.07–0.89; P = 0.004). By contrast, in participants without physical limitation (n = 394), the number of transitions to SNF did not change significantly when they received intensified rehabilitation therapy (P = 0.53).

Conclusions:  We found a significant relationship between intensified rehabilitation therapy and the decrease of transitions to SNF in community‐living seniors with acute medical illness. The magnitude of this relationship increased in participants with more physical limitations, but not in participants without physical limitations at admission. Geriatr Gerontol Int 2013; 13: 547–554.
Rate of progression of Alzheimer's disease in younger versus older patients: A longitudinal single photon emission computed tomography study
Authors: Sakai Minoru , Hanyu Haruo , Kume Kazumasa , Sato Tomohiko , Hirao Kentaro , Kanetaka Hidekazu , Abe Shine , Kanaya Kiyoshi , Sakurai Hirofumi , Iwamoto Toshihiko
Published: September 2012

Aim:  Although several researchers have examined the effect of age on disease progression in patients with Alzheimer's disease (AD), the results are controversial. We investigated the effect of age on the rate of progression of cognitive impairment and on regional cerebral blood flow (rCBF) deficits using longitudinal single photon emission computed tomography (SPECT) studies.

Methods:  We divided 75 patients with AD who were followed up for 24–90 months into the younger AD group (n = 32, age at initial examination ≤75 years) and the older AD group (n = 43, age at initial examination >75 years). We assessed changes in Mini‐Mental State Examination (MMSE) scores and rCBF between initial and final examinations.

Results:  The change in the annual MMSE score was greater in the younger AD group than in the older AD group. The mean annual MMSE score changes correlated significantly with age at the initial examination. The initial and follow‐up SPECT studies showed more severe and extensive rCBF deficits in the younger AD group than in the older AD group.

Conclusion:  Our longitudinal SPECT study showed that the rate of progression of cognitive impairment and the rCBF deficits were higher in younger patients with AD than in older patients with AD. Therefore, age is an important factor to consider, not only in the diagnosis, but also in the treatment and prognosis of patients with AD. Geriatr Gerontol Int 2013; 13: 555–562.
Wzx flippase‐mediated membrane translocation of sugar polymer precursors in bacteria
Authors: Islam Salim T. , Lam Joseph S.
Published: September 2012

Bacterial cell surface polysaccharides confer resistance to external stress and promote survival in biotic and abiotic environments. Glycan assembly often occurs at the periplasmic leaflet of the inner membrane (IM) from undecaprenyl pyrophosphate (UndPP)‐linked polysaccharide units via the Wzx/Wzy‐dependent pathway. Wzx is an integral IM protein found in Gram‐negative and Gram‐positive bacteria that mediates IM translocation of UndPP‐linked sugar repeats from the cytoplasmic to the periplasmic leaflet; interaction of Wzx with other assembly proteins is indirectly supported by genetic evidence. Topological mapping has indicated 12 α‐helical transmembrane segments (TMS), with the number of charged TMS residues fluctuating based on the mapping method used. A novel Wzx tertiary structure model has been built, allowing for substrate‐binding or energy‐coupling roles to be proposed for functionally important charged and aromatic TMS residues. It has also led to a proposed antiport‐like mechanism of Wzx function. Exquisite substrate specificity of Wzx proteins was recently revealed in distinguishing between UndPP‐linked substrates with identical main‐chain sugar repeats, but differing in the chemical composition of a terminal sugar side‐branch cap. The objective of this review is to synthesize the most up‐to‐date knowledge concerning Wzx flippases and to provide perspective for future investigations in this burgeoning field.
Oxygen minimum zones harbour novel viral communities with low diversity
Authors: Cassman Noriko , Prieto‐Davó Alejandra , Walsh Kevin , Silva Genivaldo G. Z. , Angly Florent , Akhter Sajia , Barott Katie , Busch Julia , McDole Tracey , Haggerty J. Matthew , Willner Dana , Alarcón Gadiel , Ulloa Osvaldo , DeLong Edward F. , Dutilh Bas E. , Rohwer Forest , Dinsdale Elizabeth A.
Published: September 2012

Oxygen minimum zones (OMZs) are oceanographic features that affect ocean productivity and biodiversity, and contribute to ocean nitrogen loss and greenhouse gas emissions. Here we describe the viral communities associated with the Eastern Tropical South Pacific (ETSP) OMZ off Iquique, Chile for the first time through abundance estimates and viral metagenomic analysis. The viral‐to‐microbial ratio (VMR) in the ETSP OMZ fluctuated in the oxycline and declined in the anoxic core to below one on several occasions. The number of viral genotypes (unique genomes as defined by sequence assembly) ranged from 2040 at the surface to 98 in the oxycline, which is the lowest viral diversity recorded to date in the ocean. Within the ETSP OMZ viromes, only 4.95% of genotypes were shared between surface and anoxic core viromes using reciprocal BLASTn sequence comparison. ETSP virome comparison with surface marine viromes (Sargasso Sea, Gulf of Mexico, Kingman Reef, Chesapeake Bay) revealed a dissimilarity of ETSP OMZ viruses to those from other oceanic regions. From the 1.4 million non‐redundant DNA sequences sampled within the altered oxygen conditions of the ETSP OMZ, more than 97.8% were novel. Of the average 3.2% of sequences that showed similarity to the SEED non‐redundant database, phage sequences dominated the surface viromes, eukaryotic virus sequences dominated the oxycline viromes, and phage sequences dominated the anoxic core viromes. The viral community of the ETSP OMZ was characterized by fluctuations in abundance, taxa and diversity across the oxygen gradient. The ecological significance of these changes was difficult to predict; however, it appears that the reduction in oxygen coincides with an increased shedding of eukaryotic viruses in the oxycline, and a shift to unique viral genotypes in the anoxic core.
Multigroup Confirmatory Factor Analysis of the Cognitive Dysfunction Questionnaire: Instrument refinement and measurement invariance across age and sex
Authors: VESTERGREN PETER , RÖNNLUND MICHAEL , NYBERG LARS , NILSSON LARS‐GÖRAN
Published: September 2012

Vestergren, P., Rönnlund, M., Nyberg, L. & Nilsson, L.‐G. (2012). Multigroup confirmatory factor analysis of the Cognitive Dysfunction Questionnaire: Instrument refinement and measurement invariance across age and sex. Scandinavian Journal of Psychology 53, 390–400.

The study adopted Confirmatory Factor Analysis (CFA) to investigate the factorial structure and reduce the number of items of the Cognitive Dysfunction Questionnaire (CDQ). The analyses were based on data for a total of 1,115 participants from population based samples (mean age: 63.0 ± 14.5 years, range: 25–95) randomly split into a refinement (N = 569) and a cross‐validation (N = 546) sample. Equivalence of the measurement and structural portions of the refined model was demonstrated across the refinement and cross‐validation samples. Among competing models the best fitting and parsimonious model had a hierarchical factor structure with five first‐order and one second‐order general factor. For the final version of the CDQ, 20 items within five domains were selected (Procedural actions, Semantic word knowledge, Face recognition, Temporal orientation, and Spatial navigation). Internal consistency reliabilities were adequate for the total scale and for the subscales. Multigroup CFAs indicated measurement invariance across age and sex up to the scalar level. Finally, higher levels of cognitive dysfunction as reflected by CDQ scores were predicted by advancing age, fewer years of education, and with deficits in general cognitive functioning as reflected by scores on the Mini‐Mental State Examination. In conclusion, the CDQ appears to be psychometrically sound and shows the expected relationships with variables known to be associated with cognitive dysfunction and dementia. Future studies should apply it among clinical groups to further test its usefulness.
Resampling with TinkerPlots
Authors: Watson Jane M.
Published: September 2012

The constructivist data handling software TinkerPlots is used to carry out resampling in a manner that illustrates the stages of the process without the need for programming skills.
Using context to classify variables
Authors: Lesser Lawrence M.
Published: September 2012

Asking clarifying questions and utilizing context can help students classify variables.
High‐tech Clusters, Innovation Capabilities and Technological Entrepreneurship: Evidence from Ireland
Authors: Ryan Paul , Giblin Majella
Published: September 2012

Underpinned theoretically by the capabilities perspective, the purpose of this study is to identify capabilities in high‐technology activity within the Irish economy. A deeper understanding of the capabilities that underscore the economy at present is needed to determine the strengths to build on and how they can be cultivated for future economic growth. In particular, this study focuses on the evolution of capabilities, both technological and those that are more intangible, such as managerial expertise and their source of development. The argument underpinning this study is that analysing industrial dynamics using aggregate data on employment, trade and numbers of firms in distinct sectors provides an incomplete picture. Such an approach fails to capture evolving technologies that may cross sectoral boundaries. Therefore, in this study, a unique methodological approach that uses an analysis of highly specified products and services produced in the economy is employed to identify high‐tech capabilities. More specifically, the approach is applied to the case of medical technology activity in Ireland. The evolution and nature of capabilities is examined using an exploratory analysis of the medical technology cluster in the West of Ireland in particular.
Maker of Heaven and Earth
Authors: Wood Donald
Published: September 2012

The first article of the Nicene creed forms Christian teaching about creation in two ways. It exhibits a particular order of Christian confession and instruction, and it recommends to the church the importance of properly distinguishing three relations: the relation between God the Father and God the Son; the relation between God and the world; and the relation between heaven and earth. This dogmatic commentary on the creed attends to the first two relations and introduces the third.
The Urban Question under Planetary Urbanization
Authors: Merrifield Andy
Published: September 2012

In Le Droit à la Ville (1968), Lefebvre projects the urban trajectory of his day into the sci‐fi imaginary of Isaac Asimov's remarkable Foundation series, recognizing the germ of ‘Trantor’ in our midst, the planet of 40 billion inhabitants where urbanization has reached its absolute maximum; all 75 million square miles of Trantor's land surface are a single city. In La Révolution Urbaine (1970), Lefebvre had already begun hinting at a new reality, not only an urban society, but of planetary urbanization. Today, four decades on, Asimov's extraterrestrial universe seems closer to home than ever, and closer to Lefebvre's own terrestrial prognostications: planetary urbanization is creating a whole new spatial world (dis)order. But how shall we reclaim the shapeless, formless and boundless metropolis as a theoretical object and political object of the progressive struggle? If the arena of politics has no discernible form, what would be the form of these politics? What, exactly, are urban politics? This article tries to rethink theoretically the urban question and the question of urban politics in our era of planetary urbanization, working through the political role of the urban in the light of recent ‘Occupy’ mobilizations.