bluuebunny/crossref_metadata_2025 huggingface dataset:
The phylogenetic construction of sociocultural phenomena
Authors: Chapais Bernard
Published: November 2013

In this paper I argue that many sociocultural phenomena are best explained by the comparative (phylogenetic) method, which consists of using information on other species, notably our closest relatives, the nonhuman primates, as a means to understand the evolutionary history and biological underpinnings of human traits. The social phenomena considered here embody theunitary social configuration of humankind, the set of traits common to all human societies. Those traits could not be explained by sociocultural anthropology, or the other social sciences, because even though they have a highly variable cultural content, they are not cultural creations but rather the products of human nature, or natural categories. I argue that some of those traits resulted from the cognitive enhancement of specific primate traits in the course of human evolution and others evolved as by-products of the coalescence of several primate traits, and I illustrate each process with a number of examples. I also show that even though many of those traits are crossculturally universal, they need not be: culture may modulate the expression of primate legacies and produce various sociocultural patterns from the same set of universal biological underpinnings, or biological constants. Finally, I discuss the importance for the social sciences of integrating biological constants in their models and theories even when they seek to explain culturaldifferences.
Sex‐specific acute heart failure phenotypes and outcomes from PROTECT
Authors: Meyer Sven , van der Meer Peter , Massie Barry M. , O'Connor Christopher M. , Metra Marco , Ponikowski Piotr , Teerlink John R. , Cotter Gad , Davison Beth A. , Cleland John G.F. , Givertz Michael M. , Bloomfield Daniel M. , Fiuzat Mona , Dittrich Howard C. , Hillege Hans L. , Voors Adriaan A.
Published: November 2013

Aims

Differences in manifestation, treatment, and outcomes of acute heart failure between men and women have not been well studied. The objective of this analysis was to characterize differences in clinical presentation, and in‐hospital and post‐discharge outcomes between sexes in acute heart failure patients.

Methods and results

Clinical profiles, treatment characteristics, and outcomes were compared between sexes in 2033 patients hospitalized for acute heart failure and impaired renal function. Women comprised 33% of the study population and were older, had higher body mass index, LVEF, and systolic blood pressure, and a greater prevalence of diabetes. At baseline, women showed signs and symptoms of congestion comparable with men, but more often had rales, orthopnoea, and worse renal function. Women were less intensively diuresed, as indicated by lower oral and intravenous diuretic doses used, fewer dose increases, and less total weight loss during hospitalization. Furthermore, hospitalization was slightly but significantly prolonged in women (11.04 ± 7.8 vs. 10.65 ± 8.86 days; P = 0.024). Age‐adjusted 180‐day mortality was lower in women (15.8% vs. 18.5%, hazard ratio 0.74; 95% confidence interval 0.59–0.93, P = 0.010), but multivariable risk‐adjusted mortality was similar in both sexes, mainly attributable to lower blood urea nitrogen, higher LVEF, and higher systolic blood pressure in women compared with men.

Conclusions

Women with acute heart failure present with a clinical profile different from that of men, with more hypertension, diabetes, and depression, and a preserved LVEF. During hospitalization, they were less intensively diuresed. Nevertheless, risk‐adjusted 180‐day outcome was similar between sexes.
Meta‐analysis of symptomatic response attributable to the pacing component of cardiac resynchronization therapy
Authors: Sohaib S.M. Afzal , Chen Zhongbo , Whinnett Zachary I. , Bouri Sonia , Dickstein Kenneth , Linde Cecilia , Hayes David L. , Manisty Charlotte H. , Francis Darrel P.
Published: November 2013

Aims

Prognostic benefit from CRT compared with controls is well established. Symptomatic response rates, however, are controversial and have never been systematically evaluated with standard subtraction of control rates to establish the incremental symptomatic response effect of CRT pacing.

Methods and results

First, we identified 150 consecutive CRT papers and assessed researchers' perceptions of the symptomatic response to CRT. The mean quoted response rate was 66%. Only 26 studies acknowledged the existence of response without the device. Secondly, we examined actual symptomatic response rates in the randomized trials (CARE‐HF, COMPANION, CONTAK‐CD, MIRACLE, MIRACLE‐ICD, MIRACLE‐ICD II, MUSTIC, and REVERSE) totalling 3904 patients. The NYHA status improved in 51% of those randomized to CRT vs. 35% of controls (incremental effect 16%). This incremental improvement was significantly greater in open studies (with no device for controls) than in blinded studies (control arm receiving a device but no CRT, such as a defibrillator or a CRT programmed off), 20% vs. 13%, P < 0.001.

Conclusions

Quoting CRT responder rates in isolation without recognizing spontaneous ‘response’ is common but unwise. The incremental symptomatic response rate from CRT pacing is ∼16%, much lower than widely reported. This value is similar to that for drugs in heart failure and should not be considered disappointing: they both exert powerful prognostic benefits. For scientific purposes, e.g. to explore potential improvements, symptomatic benefit from CRT should be quantified, like all other effects, by comparison with a control.
One-step zero-background IgG reformatting of phage-displayed antibody fragments enabling rapid and high-throughput lead identification
Authors: Chen Chao-Guang , Fabri Louis J. , Wilson Michael J. , Panousis Con
Published: November 2013

We describe a novel cloning method, referred to as insert-tagged (InTag) positive selection, for the rapid one-step reformatting of phage-displayed antibody fragments to full-length immunoglobulin Gs (IgGs). InTag positive selection enables recombinant clones of interest to be directly selected without cloning background, bypassing the laborious process of plating out cultures and colony screening and enabling the cloning procedure to be automated and performed in a high-throughput format. This removes a significant bottleneck in the functional screening of phage-derived antibody candidates and enables a large number of clones to be directly reformatted into IgG without the intermediate step of Escherichia coli expression and testing of soluble antibody fragments. The use of InTag positive selection with the Dyax Fab-on-phage antibody library is demonstrated, and optimized methods for the small-scale transient expression of IgGs at high levels are described. InTag positive selection cloning has the potential for wide application in high-throughput DNA cloning involving multiple inserts, markedly improving the speed and quality of selections from protein libraries.
Pain in 1,000 Women Treated for Breast Cancer
Authors: Kaunisto Mari A. , Jokela Ritva , Tallgren Minna , Kambur Oleg , Tikkanen Emmi , Tasmuth Tiina , Sipilä Reetta , Palotie Aarno , Estlander Ann-Mari , Leidenius Marjut , Ripatti Samuli , Kalso Eija A.
Published: November 2013

Background:

This article describes the methods and results of the early part (experimental pain tests and postoperative analgesia) of a study that assesses genetic and other factors related to acute pain and persistent pain after treatment of breast cancer in a prospective cohort of 1,000 women.

Methods:

One thousand consenting patients were recruited to the study. Before surgery (breast resection or mastectomy with axillary surgery), the patients filled in questionnaires about health, life style, depression (Beck Depression Inventory), and anxiety (State-Trait Anxiety Inventory). They were also exposed to experimental tests measuring heat (43° and 48°C, 5 s) and cold (2-4°C) pain intensity and tolerance. Anesthesia was standardized with propofol and remifentanil, and postoperative analgesia was optimized with i.v. oxycodone.

Results:

The patients showed significant interindividual variation in heat and cold pain sensitivity and cold pain tolerance. There was a strong correlation between the experimental pain measures across the tests. Presence of chronic pain, the number of previous operations, and particularly state anxiety were related to increased pain sensitivity. Previous smoking correlated with decreased heat pain sensitivity. These factors explained 4–5% of the total variance in pain sensitivity in these tests. Oxycodone consumption during 20 h was significantly higher in patients who had axillary clearance. Oxycodone consumption had only a weak correlation with the experimental pain measures.

Conclusions:

Contact heat and cold pressure tests identify variability in pain sensitivity which is modified by factors such as anxiety, chronic pain, previous surgery, and smoking. High levels of anxiety are connected to increased pain sensitivity in experimental and acute postoperative pain.

In a study of 1,000 women undergoing breast surgery for cancer, a small portion of the variance in preoperative response to noxious heat and cold testing could be explained by anxiety, the presence of chronic pain, and the number of previous operations. There was a weak correlation between response to experimental pain testing and acute postoperative pain, with largely similar predictive factors across both.
Plastid-bearing sea slugs fix CO2in the light but do not require photosynthesis to survive
Authors: Christa Gregor , Zimorski Verena , Woehle Christian , Tielens Aloysius G. M. , Wägele Heike , Martin William F. , Gould Sven B.
Published: November 2013

Several sacoglossan sea slugs (Plakobranchoidea) feed upon plastids of large unicellular algae. Four species—called long-term retention (LtR) species—are known to sequester ingested plastids within specialized cells of the digestive gland. There, the stolen plastids (kleptoplasts) remain photosynthetically active for several months, during which time LtR species can survive without additional food uptake. Kleptoplast longevity has long been puzzling, because the slugs do not sequester algal nuclei that could support photosystem maintenance. It is widely assumed that the slugs survive starvation by means of kleptoplast photosynthesis, yet direct evidence to support that view is lacking. We show that two LtR plakobranchids,Elysia timidaandPlakobranchus ocellatus, incorporate14CO2into acid-stable products 60- and 64-fold more rapidly in the light than in the dark, respectively. Despite this light-dependent CO2fixation ability, light is, surprisingly, not essential for the slugs to survive starvation. LtR animals survived several months of starvation (i) in complete darkness and (ii) in the light in the presence of the photosynthesis inhibitor monolinuron, all while not losing weight faster than the control animals. Contrary to current views, sacoglossan kleptoplasts seem to be slowly digested food reserves, not a source of solar power.
Anatomical and functional analysis of domestication effects on the olfactory system of the silkmoth
Bombyx mori
Authors: Bisch-Knaden Sonja , Daimon Takaaki , Shimada Toru , Hansson Bill S. , Sachse Silke
Published: November 2013

The silkmoth
Bombyx mori
is the main producer of silk worldwide and has furthermore become a model organism in biological research, especially concerning chemical communication. However, the impact domestication might have had on the silkmoth's olfactory sense has not yet been investigated. Here, we show that the pheromone detection system in
B. mori
males when compared with their wild ancestors
Bombyx mandarina
seems to have been preserved, while the perception of environmental odorants in both sexes of domesticated silkmoths has been degraded. In females, this physiological impairment was mirrored by a clear reduction in olfactory sensillum numbers. Neurophysiological experiments with hybrids between wild and domesticated silkmoths suggest that the female W sex chromosome, so far known to have the sole function of determining femaleness, might be involved in the detection of environmental odorants. Moreover, the coding of odorants in the brain, which is usually similar among closely related moths, differs strikingly between
B. mori
and
B. mandarina
females. These results indicate that domestication has had a strong impact on odour detection and processing in the olfactory model species
B. mori
.
Time course of cerebrovascular autoregulation during extreme Trendelenburg position for robotic‐assisted prostatic surgery
Authors: Schramm P. , Treiber A.‐H. , Berres M. , Pestel G. , Engelhard K. , Werner C. , Closhen D.
Published: November 2013

Trendelenburg positioning in combination with pneumoperitoneum during robotic‐assisted prostatic surgery possibly impairs cerebrovascular autoregulation. If cerebrovascular autoregulation is disturbed, arterial hypertension might induce cerebral hyperaemia and brain oedema, while low arterial blood pressure can induce cerebral ischaemia. The time course of cerebrovascular autoregulation was investigated during use of the Trendelenburg position and a pneumoperitoneum for robotic‐assisted prostatic surgery using transcranial Doppler ultrasound. Cerebral blood flow velocity was correlated with arterial blood pressure and the autoregulation index (Mx) was calculated. In 23 male patients, Mx was assessed at baseline, after induction of general anaesthesia, during the Trendelenburg position (40–45°), and after repositioning. During the Trendelenburg position, Mx increased over time, indicating an impairment of cerebrovascular autoregulation. After repositioning, Mx recovered to baseline levels. It can be concluded that with longer durations of Trendelenburg position and pneumoperitoneum, cerebrovascular autoregulation deteriorates, and, therefore, blood pressure management should be adapted to avoid cerebral oedema and the duration of Trendelenburg position should be as short as possible.
A Novel Method for Real‐Time Atrial Fibrillation Detection in Electrocardiograms Using Multiple Parameters
Authors: Du Xiaochuan , Rao Nini , Qian Mengyao , Liu Dingyu , Li Jie , Feng Wei , Yin Lixue , Chen Xu
Published: November 2013

Background

Automatic detection of atrial fibrillation (AF) in electrocardiograms (ECGs) is beneficial for AF diagnosis, therapy, and management. In this article, a novel method of AF detection is introduced. Most current methods only utilize the RR interval as a critical parameter to detect AF; thus, these methods commonly confuse AF with other arrhythmias.

Methods

We used the average number of f waves in a TQ interval as a characteristic parameter in our robust, real‐time AF detection method. Three types of clinical ECG data, including ECGs from normal, AF, and non‐AF arrhythmia subjects, were downloaded from multiple open access databases to validate the proposed method.

Results

The experimental results suggested that the method could distinguish between AF and normal ECGs with accuracy, sensitivity, and positive predictive values (PPVs) of 93.67%, 94.13%, and 98.69%, respectively. These values are comparable to those of related methods. The method was also able to distinguish between AF and non‐AF arrhythmias and had performance indexes (accuracy 94.62%, sensitivity 94.13%, and PPVs 97.67%) that were considerably better than those of other methods.

Conclusions

Our proposed method has prospects as a practical tool enabling clinical diagnosis, treatment, and monitoring of AF.
Sudden Cardiac Arrest in Hemodialysis Patients with Wearable Cardioverter Defibrillator
Authors: Wan Chingping , Herzog Charles A. , Zareba Wojciech , Szymkiewicz Steven J.
Published: November 2013

Background

The survival outcome following a sudden cardiac arrest (SCA) in hemodialysis (HD) patients is poor regardless of whether an event takes place in or out of a dialysis center. The characteristics of SCA and post‐SCA survival with HD patients using a wearable cardioverter defibrillator (WCD) are unknown.

Methods

All HD patients who were prescribed a WCD between 2004 and 2011 and experienced at least one SCA event were included in this study. Demographics, clinical background, characteristics of SCA events were identified from the manufacturer's database. An SCA event was defined as all sustained ventricular tachycardia/fibrillation (VT/VF) or asystole occurring within 24 hours of the index arrhythmia episode. The social security death index was used to determine mortality after WCD use.

Results

A total of 75 HD patients (mean age = 62.9 ± 11.7 years, female = 37.3%) experienced 84 SCA events (119 arrhythmia episodes) while wearing the WCD. Sixty six (78.6%) SCA events were due to VT/VF and 18 (21.4%) were due to asystole. Most SCA episodes occurred between 09:00 and 10:00 (RR = 2.82, 95% CI [1.05, 7.62], P < 0.0001), followed by the 13:00–14:00 time interval (RR = 2.22, 95% CI [0.79, 6.21], P = 0.006). Acute 24‐hour survival was 70.7% for all SCA events; 30‐day and 1‐year survival were 50.7% and 31.4%, respectively. Women had a better post‐SCA survival than men (HR = 2.41, 95% CI [1.09, 5.36], P = 0.03).

Conclusions

The use of WCD in HD patients was associated with improved post‐SCA survival when compared to historical data.
In Vivo Evaluation of Centrifugal Blood Pump for Cardiopulmonary Bypass—Spiral Pump
Authors: da Silva Cibele , da Silva Bruno Utiyama , Leme Juliana , Uebelhart Beatriz , Dinkhuysen Jarbas , Biscegli José F. , Andrade Aron , Zavaglia Cecília
Published: November 2013

The Spiral Pump (SP), a centrifugal blood pump for cardiopulmonary bypass (CPB), has been developed at the Dante Pazzanese Institute of Cardiology/Adib Jatene Foundation laboratories, with support from Sintegra Company (Pompeia, Brazil). The SP is a disposable pump with an internal rotor—a conically shaped fuse with double entrance threads. This rotor is supported by two ball bearings, attached to a stainless steel shaft fixed to the housing base. Worm gears provide axial motion to the blood column, and the rotational motion of the conically shaped impeller generates a centrifugal pumping effect, improving pump efficiency without increasing hemolysis. In vitro tests were performed to evaluate the SP's hydrodynamic performance, and in vivo experiments were performed to evaluate hemodynamic impact during usual CPB. A commercially available centrifugal blood pump was used as reference. In vivo experiments were conducted in six male pigs weighing between 60 and 90 kg, placed on CPB for 6 h each. Blood samples were collected just before CPB (T0) and after every hour of CPB (T1–T6) for hemolysis determination and laboratory tests (hematological and biochemical). Values of blood pressure, mean flow, pump rotational speed, and corporeal temperature were recorded. Also, ergonomic conditions were recorded: presence of noise, difficulty in removing air bubbles, trouble in installing the pump in the drive module (console), and difficulties in mounting the CPB circuit. Comparing the laboratory and hemolysis results for the SP with those of the reference pump, we can conclude that there is no significant difference between the two devices. In addition, reports made by medical staff and perfusionists described a close similarity between the two devices. During in vivo experiments, the SP maintained blood flow and pressure at physiological levels, consistent with those applied in cardiac surgery with CPB, without presenting any malfunction. Also, the SP needed lower rotational speed to obtain average blood flow and pressure, compared with the reference pump.
Quantifying Foreign Direct Investment Productivity Spillovers in China: A Computable General Equilibrium Model
Authors: Deng Ziliang , Falvey Rod , Blake Adam
Published: November 2013

For the purposes of this study, we will construct a static monopolistically‐competitive computable general equilibrium model to quantify the endogenous productivity spillovers from foreign and domestic firms, using the Chinese economy as a case study. Our simulation results indicate: (i) that the net spillover effects are positive in terms of national total output, GDP and welfare; (ii) that both state‐owned and privately‐owned firms benefit, but that private firms benefit more; (iii) that industries with large volumes of foreign direct investment (FDI) do not necessarily observe the largest spillover effects; and (iv) that the spillover effects become more prominent when the initial market structure is more concentrated.
Role of Information on Consumers’ Willingness‐to‐pay for Genetically‐modified Rice with Health Benefits: An Application to China
Authors: De Steur Hans , Buysse Jeroen , Feng Shuyi , Gellynck Xavier
Published: November 2013

Despite their potential health benefits, the controversial nature surrounding the use of GM technology in biofortified crops remains a subject of discussion. This paper investigates the role of information on willingness‐to‐pay for folate‐biofortified rice in a Chinese folate‐deficient region. We conducted second price auctions with 252 women of childbearing age, split up into two target groups based on street (n = 132, non‐student sample) or school auctions (n = 120, student sample). Notwithstanding a general positive effect of folate‐related information (i.e. content, benefits and regional situation), evidence reveals that the non‐student sample is less concerned about GM technology. The results also provide insight into serial position effects in conflicting GM information. Whereas participants in the non‐student sample are more prone to a primacy bias when receiving both positive and negative information, an alarmist reaction is observed in the student sample. This study highlights the need for segmented, targeted communication strategies on biofortification.
Laparoscopic adrenalectomy for metastatic adrenal tumor
Authors: Hirayama Takahiro , Fujita Tetsuo , Koguchi Dai , Nishi Morihiro , Kurosaka Shinji , Tsumura Hideyasu , Tabata Ken‐ichi , Iwamura Masatsugu
Published: November 2013

Introduction

Treating adrenal metastases from primary malignancies with laparoscopic adrenalectomy (LA) remains controversial. The aim of this study was to evaluate the feasibility, effectiveness and efficiency of LA for solitary adrenal metastasis.

Methods

From November 2003 to September 2012, eight consecutive patients with adrenal metastasis were treated with LA. A retrospective study was conducted, and clinical and histological data were analyzed.

Results

All LA were successfully performed. There were no major complications, blood transfusions or conversions to open adrenalectomy. The patients included seven men and one woman with a median age of 59 years at the time of operation. Adrenal metastases were most commonly noted to be from non‐small‐cell lung cancer (four patients) and renal cell carcinoma (four patients). The majority of adrenal metastases were unilateral (right: one patient; left: seven patients). One patient had bilateral metastases. The median overall survival was 14 months. Four patients (two with non‐small‐cell lung cancer; two with renal cell carcinoma) were alive with no evidence of metastatic disease as of October 2013.

Conclusion

LA is a safe and effective procedure for patients with isolated metastases. Surgical resection with LA for a solitary adrenal metastasis from primary malignancy can achieve a good prognosis.
A quantitative model of amphetamine action on the 5‐HT transporter
Authors: Sandtner Walter , Schmid Diethart , Schicker Klaus , Gerstbrein Klaus , Koenig Xaver , Mayer Felix P , Boehm Stefan , Freissmuth Michael , Sitte Harald H
Published: November 2013

Background and Purpose

Amphetamines bind to the plasmalemmal transporters for the monoamines dopamine (DAT), noradrenaline (NET) and 5‐HT (SERT); influx of amphetamine leads to efflux of substrates. Various models have been proposed to account for this amphetamine‐induced reverse transport in mechanistic terms. A most notable example is the molecular stent hypothesis, which posits a special amphetamine‐induced conformation that is not likely in alternative access models of transport. The current study was designed to evaluate the explanatory power of these models and the molecular stent hypothesis.

Experimental Approach

Xenopus laevis oocytes and HEK293 cells expressing human (h) SERT were voltage‐clamped and exposed to 5‐HT, p‐chloroamphetamine (pCA) or methylenedioxyamphetamine (MDMA).

Key Results

In contrast to the currents induced by 5‐HT, pCA‐triggered currents through SERT decayed slowly in Xenopus laevis oocytes once the agonist was removed (consistent with the molecular stent hypothesis). However, when SERT was expressed in HEK293 cells, currents induced by 3 or 100 μM pCA decayed 10 or 100 times faster, respectively, after pCA removal.

Conclusions and Implications

This discrepancy in decay rates is inconsistent with the molecular stent hypothesis. In contrast, a multistate version of the alternative access model accounts for all the observations and reproduces the kinetic parameters extracted from the electrophysiological recordings. A crucial feature that explains the action of amphetamines is their lipophilic nature, which allows for rapid diffusion through the membrane.
Unilateral segmentally arranged basaloid follicular hamartomas with osteoma cutis and hypodontia: a case of Happle–Tinschert syndrome
Authors: Lo C.-S. , Wu Y.-F. , Hsiao Y.-W. , Chung W.-H. , Yang C.-H.
Published: November 2013

Happle–Tinschert syndrome (HTS) is a rare syndrome characterized by segmentally arranged basaloid follicular hamartomas (BFH) associated with ipsilateral osseous, dental and cerebral abnormalities. Happle and Tinschert first reported this disorder in 2008, and three cases with similar presentations have since been reported. We report another case, that of a 40-year-old man, presenting with the characteristic clinical features of HTS.
Recovery‐oriented policy and care systems in the UK and USA
Authors: Humphreys Keith , Lembke Anna
Published: November 2013

The concept of recovery has been an influence on addicted individuals for many decades. But only in the past 15 years has the concept had a purchase in the world of public policy. In the USA, federal and state officials have promulgated policies intended to foster ‘recovery‐oriented systems of care’ and have ratified recovery‐supportive laws and regulations. Though of more recent vintage and therefore less developed, recovery policy initiatives are also being implemented in the UK. The present paper describes recovery‐oriented policy in both countries and highlights key evaluations of the recovery‐oriented interventions. [Humphreys K, Lembke A. Recovery‐oriented policy and care systems in the UK and USA. Drug Alcohol Rev 2014;33:13–18]
Combined antidiabetic benefits of exenatide and dapagliflozin in diabetic mice
Authors: Tatarkiewicz K. , Polizzi C. , Villescaz C. , D'Souza L. J. , Wang Y. , Janssen S. , Parkes D. G.
Published: November 2013

The combined glucose‐lowering effect of exenatide and dapagliflozin has not yet been studied. We investigated this combination (single‐dose or 4‐week dosing) in diabetic ob/ob mice. Vehicle‐corrected basal glucose showed greater reduction 1 h following exenatide + dapagliflozin than with exenatide or dapagliflozin alone, and stayed significantly lower for all groups versus vehicle over 3 h. During an oral glucose tolerance test, glucose excursion (30 min post‐dose) was significantly lower for exenatide + dapagliflozin versus exenatide or dapagliflozin, or vehicle. Exenatide + dapagliflozin and exenatide, but not dapagliflozin alone, reduced glucose excretion over 24 h versus vehicle. After dosing for 4 weeks, exenatide, dapagliflozin and exenatide + dapagliflozin similarly decreased haemoglobin A1c (HbA1c). Body weight was reduced only with exenatide or exenatide + dapagliflozin. The glomerular filtration rate was similar with exenatide, dapagliflozin and vehicle, and increased with exenatide + dapagliflozin. Optimized combinatorial dosing of these antidiabetic agents may provide additive glucose lowering in type 2 diabetes mellitus.
Changes in adiponectin level and fat distribution in patients with type 2 diabetes
Authors: Miazgowski Tomasz , Dziwura‐Ogonowska Joanna , Safranow Krzysztof , Iskierska Katarzyna , Widecka Krystyna
Published: November 2013

Background

The aim of this study was to assess the impact of standard hypoglycaemic treatment strategies on adiponectin levels and fat distribution in patients with newly diagnosed type 2 diabetes mellitus (T2DM).

Material and methods

This was a prospective observational study of 50 women with newly diagnosed T2DM, aged 64·6 ± 7·9 years and treated for 12 months with lifestyle modification alone (n = 24) or in combination with metformin (n = 26), according to current standards of diabetic care and clinical practice guidelines. None of the patients required insulin therapy during the entire study period. Total (BF), abdominal (android) and hip (gynoid) fat were measured by dual‐energy X‐ray absorptiometry at the baseline and after 12 months of treatment. Total adiponectin, glycated haemoglobin (HbA1c) and fasting glucose were measured in 3‐month intervals.

Results

Baseline adiponectin level was low (9·37 ± 2·81 μg/mL). Lifestyle modifications and metformin produced comparable changes in adiponectin levels, which were not associated with changes in BF, HbA1c, glucose and regional fat depots. Baseline adiponectin was inversely correlated with triglycerides (R = −0·441; P = 0·0007) and the android/gynoid ratio (R = −0·272; P = 0·042). Treatment with metformin was associated with a significant weight reduction (P = 0·033), which resulted from a decrease in BF% (P = 0·044) but was not associated with changes in android and gynoid depots.

Conclusions

In postmenopausal women with newly diagnosed T2DM, lifestyle modifications alone or combined with metformin produced comparable changes in adiponectin levels. Weight reduction in patients treated with metformin was associated with significant decrease in %BF but not in regional fat depots.
Responses of a native beetle to novel exotic plant species with varying invasion history
Authors: DAI HONGJUN , LU XINMIN , ZHANG JIALIANG , DING JIANQING
Published: November 2013

The impact of plant invaders on the fitness of native insects has received increasing attention, but it remains unclear how native insects that have a taxonomic conservatism in host–plant use respond to novel hosts.

In this study, an experimental approach was taken to this issue by comparing the preference and performance of a native beetle, Cassida piperata Hope, on native hosts Chenopodium album and Alternanthera sessilis, and non‐coevolved exotic hosts Alternanthera spinosus and Alternanthera philoxeroides of varying invasion history with choice and cross‐rearing experiments.

In host choice experiments, adult beetles preferred to oviposit on the older invader A. spinosus to the same degree as it did the native hosts, but generally avoided the newer invader A. philoxeroides. However, in rearing experiments, larval beetles developed more slowly on the two exotic hosts than on the native hosts.

The varying responses of adult beetles to invaders might be explained by their differing invasive history, and suggest that the beetle has adapted to the older invader behaviourally. However, the slower development of the beetle on the two invaders suggests that the beetle has failed to adapt physiologically to either species of invasive plant.

These results offer insights into the temporal dynamics of a native insect adapting to plant invaders, and suggest that when testing the impact of exotic plant invasion on native insect fitness, it is necessary to consider the duration of novel association between the insect and the novel plant species.
Novel Disabled‐1‐expressing neurons identified in adult brain and spinal cord
Authors: Abadesco Autumn D. , Cilluffo Marianne , Yvone Griselda M. , Carpenter Ellen M. , Howell Brian W. , Phelps Patricia E.
Published: November 2013

Components of the Reelin‐signaling pathway are highly expressed in embryos and regulate neuronal positioning, whereas these molecules are expressed at low levels in adults and modulate synaptic plasticity. Reelin binds to Apolipoprotein E receptor 2 and Very‐low‐density lipoprotein receptors, triggers the phosphorylation of Disabled‐1 (Dab1), and initiates downstream signaling. The expression of Dab1 marks neurons that potentially respond to Reelin, yet phosphorylated Dab1 is difficult to detect due to its rapid ubiquitination and degradation. Here we used adult mice with a lacZ gene inserted into the dab1 locus to first verify the coexpression of β‐galactosidase (β‐gal) in established Dab1‐immunoreactive neurons and then identify novel Dab1‐expressing neurons. Both cerebellar Purkinje cells and spinal sympathetic preganglionic neurons have coincident Dab1 protein and β‐gal expression in dab1lacZ/+ mice. Adult pyramidal neurons in cortical layers II–III and V are labeled with Dab1 and/or β‐gal and are inverted in the dab1lacZ/lacZ neocortex, but not in the somatosensory barrel fields. Novel Dab1 expression was identified in GABAergic medial septum/diagonal band projection neurons, cerebellar Golgi interneurons, and small neurons in the deep cerebellar nuclei. Adult somatic motor neurons also express Dab1 and show ventromedial positioning errors in dab1‐null mice. These findings suggest that: (i) Reelin regulates the somatosensory barrel cortex differently than other neocortical areas, (ii) most Dab1 medial septum/diagonal band neurons are probably GABAergic projection neurons, and (iii) positioning errors in adult mutant Dab1‐labeled neurons vary from subtle to extensive.
Spatiotemporal flow of information in the early visual pathway
Authors: Moore Bartlett D. , Rathbun Daniel L. , Usrey W. Martin , Freeman Ralph D.
Published: November 2013

The spatial components of a visual scene are processed neurally in a sequence of coarse features followed by fine features. This coarse‐to‐fine temporal stream was initially considered to be a cortical function, but has recently been demonstrated in the dorsal lateral geniculate nucleus. The goal of this study was to test the hypothesis that coarse‐to‐fine processing is present at earlier stages of visual processing in the retinal ganglion cells that supply lateral geniculate nucleus (LGN) neurons. To compare coarse‐to‐fine processing in the cat's visual system, we measured the visual responses of connected neuronal pairs from the retina and LGN, and separate populations of cells from each region. We found that coarse‐to‐fine processing was clearly present at the ganglion cell layer of the retina. Interestingly, peak and high‐spatial‐frequency cutoff responses were higher in the LGN than in the retina, indicating that there was a progressive cascade of coarse‐to‐fine information from the retina to the LGN to the visual cortex. The analysis of early visual pathway receptive field characteristics showed that the physiological response interplay between the center and surround regions was consistent with coarse‐to‐fine features and may provide a primary role in the underlying mechanism. Taken together, the results from this study provided a framework for understanding the emergence and refinement of coarse‐to‐fine processing in the visual system.
Noise‐rearing disrupts the maturation of multisensory integration
Authors: Xu Jinghong , Yu Liping , Rowland Benjamin A. , Stanford Terrence R. , Stein Barry E.
Published: November 2013

It is commonly believed that the ability to integrate information from different senses develops according to associative learning principles as neurons acquire experience with co‐active cross‐modal inputs. However, previous studies have not distinguished between requirements for co‐activation versus co‐variation. To determine whether cross‐modal co‐activation is sufficient for this purpose in visual–auditory superior colliculus (SC) neurons, animals were reared in constant omnidirectional noise. By masking most spatiotemporally discrete auditory experiences, the noise created a sensory landscape that decoupled stimulus co‐activation and co‐variance. Although a near‐normal complement of visual–auditory SC neurons developed, the vast majority could not engage in multisensory integration, revealing that visual–auditory co‐activation was insufficient for this purpose. That experience with co‐varying stimuli is required for multisensory maturation is consistent with the role of the SC in detecting and locating biologically significant events, but it also seems likely that this is a general requirement for multisensory maturation throughout the brain.
Historical contingency in species interactions: towards niche‐based predictions
Authors: Vannette Rachel L. , Fukami Tadashi
Published: November 2013

The way species affect one another in ecological communities often depends on the order of species arrival. The magnitude of such historical contingency, known as priority effects, varies across species and environments, but this variation has proven difficult to predict, presenting a major challenge in understanding species interactions and consequences for community structure and function. Here, we argue that improved predictions can be achieved by decomposing species' niches into three components: overlap, impact and requirement. Based on classic theories of community assembly, three hypotheses that emphasise related, but distinct influences of the niche components are proposed: priority effects are stronger among species with higher resource use overlap; species that impact the environment to a greater extent exert stronger priority effects; and species whose growth rate is more sensitive to changes in the environment experience stronger priority effects. Using nectar‐inhabiting microorganisms as a model system, we present evidence that these hypotheses complement the conventional hypothesis that focuses on the role of environmental harshness, and show that niches can be twice as predictive when separated into components. Taken together, our hypotheses provide a basis for developing a general framework within which the magnitude of historical contingency in species interactions can be predicted.
Repeated clenching causes plasticity in corticomotor control of jaw muscles
Authors: Iida Takashi , Komiyama Osamu , Obara Ryoko , Baad‐Hansen Lene , Kawara Misao , Svensson Peter
Published: November 2013

This study tested the effect of short‐term tooth‐clenching on corticomotor excitability of the masseter muscle using transcranial magnetic stimulation (TMS). Fifteen subjects with normal stomatognathic function participated. All subjects performed a tooth‐clenching task (TCT) on five consecutive days. The TCT consisted of 10, 20, and 40% of maximum voluntary contraction in a randomized order within 1 h. All subjects underwent TMS in four sessions: pretask day 1 (baseline), post‐task day 1, pretask day 5, and post‐task day 5. Motor‐evoked potentials (MEPs) from the masseter and the first dorsal interosseous (FDI) muscles were obtained using TMS in four sessions. Motor thresholds decreased, after the TCT, for the masseter muscle MEPs. Masseter muscle MEPs were dependent on stimulus intensity and on session, whereas FDI muscle MEPs were only dependent on stimulus intensity. Post‐hoc Tukey tests demonstrated significantly higher masseter muscle MEPs post‐task on day 5 with 80 and 90% stimulus intensity and above when compared with pre‐ and post‐task day 1 values. Our results suggest that the performance of repeated TCTs can trigger neuroplastic changes in the corticomotor control of the jaw‐closing muscles and that such neuroplastic changes may contribute to the mechanism underlying the clinical manifestations of tooth clenching.
Injury of the origin of the gastrocnemius and superficial digital flexor muscles in aThoroughbred racehorse: An atypical presentation of reciprocal apparatus failure
Authors: McLellan J. , Denoix J.‐M.
Published: November 2013

Damage to the origin of the gastrocnemius and superficial digital flexor muscles has been previously reported as an acute injury in both foals and adult horses. This case report describes, for the first time, the clinical onset of caudal reciprocal apparatus failure in a 2‐year‐oldThoroughbred. These signs were due to injury of the gastrocnemius and superficial digital flexor muscle origins sustained prior to the onset of lameness. This condition should be considered in cases demonstrating similar clinical signs, even in the absence of known trauma or acute injury to the region.
Insights into the suppressor of T‐cell receptor (TCR) signaling‐1 (Sts‐1)‐mediated regulation of TCR signaling through the use of novel substrate‐trapping Sts‐1 phosphatase variants
Authors: Luis Boris S. , Carpino Nick
Published: November 2013

High affinity substrate‐trapping protein tyrosine phosphatases have been widely used both to investigate the endogenous targets of many phosphatases and to address questions of substrate specificity. Herein, we extend the concept of a substrate‐trapping phosphatase to include an enzyme of the histidine phosphatase superfamily. This is the first description of substrate‐trapping technology applied to a member of the histidine phosphatase family. The phosphatase suppressor of T‐cell receptor signaling (Sts)‐1 has recently been reported to negatively regulate signaling downstream of the T‐cell receptor. We generated high‐affinity substrate‐trapping variants of Sts‐1 by mutagenesis of key active site residues within the phosphatase catalytic domain. Mutation of both the nucleophilic His380 and the general acid Glu490 yielded Sts‐1 enzymes that were catalytically inactive but showed high affinity for an important tyrosine kinase in T cells that Sts‐1 is known to regulate, Zap‐70. Sts‐1 substrate‐trapping mutants isolated tyrosine‐phosphorylated Zap‐70 from lysates of activated T cells, validating Zap‐70 as a possible substrate for Sts‐1 and highlighting the efficacy of the mutants as substrate‐trapping agents. Inhibition of the Zap‐70 interaction by vanadate suggests that the substrate‐trapping effect occurred via the Sts‐1 phosphatase active site. Finally, overexpression of Sts‐1 substrate‐trapping mutants in T cells blocked T‐cell receptor signaling, confirming the inhibitory effect of Sts‐1 on Zap‐70.

Structured digital abstract

Sts-1 physically interacts with Zap-70 by anti tag coimmunoprecipitation (1, 2, 3)

Zap-70 physically interacts with Sts-1 by anti bait coimmunoprecipitation (1, 2)

Zap-70 physically interacts with Sts-1 by pull down (1, 2, 3, 4, 5)
Direct interaction of natural and synthetic catechins with signal transducer activator of transcription 1 affects both its phosphorylation and activity
Authors: Menegazzi Marta , Mariotto Sofia , Dal Bosco Martina , Darra Elena , Vaiana Nadia , Shoji Kazuo , Safwat Abdel‐Azeim , Marechal Jean Didier , Perahia David , Suzuki Hisanori , Romeo Sergio
Published: November 2013

Our previous studies showed that (−)‐epigallocatechin‐3‐gallate (EGCG) inhibits signal transducer activator of transcription 1 (STAT1) activation. Since EGCG may be a promising lead compound for new anti‐STAT1 drug design, 15 synthetic catechins, characterized by the (−)‐gallocatechin‐3‐gallate stereochemistry, were studied in the human mammary MDA‐MB‐231 cell line to identify the minimal structural features that preserve the anti‐STAT1 activity. We demonstrate that the presence of three hydroxyl groups of B ring and one hydroxyl group in D ring is essential to preserve their inhibitory action. Moreover, a possible molecular target of these compounds in the STAT1 pathway was investigated. Our results demonstrate a direct interaction between STAT1 protein and catechins displaying anti‐STAT1 activity. In particular, surface plasmon resonance (SPR) analysis and molecular modeling indicate the presence of two putative binding sites (a and b) with different affinity. Based on docking data, site‐directed mutagenesis was performed, and interaction of the most active catechins with STAT1 was studied with SPR to test whether Gln518 on site a and His568 on site b could be important for the catechin–STAT1 interaction. Data indicate that site b has higher affinity for catechins than site a as the highest affinity constant disappears in the H568A‐STAT1 mutant. Furthermore, Janus kinase 2 (JAK2) kinase assay data suggest that the contemporary presence in vitro of STAT1 and catechins inhibits JAK2‐elicited STAT1 phosphorylation. The very tight catechin–STAT1 interaction prevents STAT1 phosphorylation and represents a novel, specific and efficient molecular mechanism for the inhibition of STAT1 activation.

Structured digital abstract

Jak2 phosphorylates STAT1 by protein kinase assay (View interaction)
Pharmacokinetic analysis of anti‐hemophilic factor in the obese patient
Authors: Graham A. , Jaworski K.
Published: November 2013

Standard dosing for individuals with hemophilia A is based on body weight such that 50 IU kg−1 is defined as a 100% dose, or one attaining 1.00 IU mL−1 factor VIII (FVIII) clotting activity. No guidelines exist, however, for individuals with hemophilia who are obese, body mass index (BMI) ≥ 30, who may actually be ‘over’‐treated based on higher in vivo recovery based on higher weight. Alternative treatment guidelines are needed for such patients. To determine FVIII pharmacokinetics we retrospectively collected data during ideal‐body‐weight dosing from six obese (BMI ≥ 30) hemophilia A patients cared for at the Hemophilia Center of Western PA, for prophylaxis or surgery. The pharmacokinetic data from six subjects undergoing ideal‐body‐weight dosing with recombinant FVIII indicate peak levels and half‐life comparable to standard 50 IU kg−1 dosing. The mean peak FVIII:C was 1.00 IU dL−1 and the mean FVIII:C half‐life was 10.14 h. IBW‐dosing resulted in an average 48.9% reduction in factor use per patient over a 3‐month period, for an annualized savings of $133 000 per patient. Ideal‐body‐weight dosing of recombinant FVIII in obese patients with hemophilia A results in comparable pharmacokinetics, including peak and half‐life, with comparable hemostatic efficacy for prophylaxis and surgical treatment, at a significant reduction in factor use and cost. Future studies are needed to confirm these findings in individuals with other congenital bleeding disorders and in children.
Combating plagiarism: the role of the health librarian
Authors: Spring Hannah , Adams Rachel
Published: November 2013

This feature looks at the issue of plagiarism in health care students and the role of the health librarian in combating the problem. In particular, consideration is given to how plagiarism can occur and provides some examples from two UK universities of approaches health librarians can take in supporting students to avoid these common pitfalls.

H.S.