bluuebunny/crossref_metadata_2025 huggingface dataset:
A minimum of two distinct heritable factors are required to explain correlation structures in proliferating lymphocytes
Authors: Markham John F. , Wellard Cameron J. , Hawkins Edwin D. , Duffy Ken R. , Hodgkin Philip D.
Published: January 2010

During the adaptive immune response, lymphocyte populations undergo a characteristic three-phase process: expansion through a series of cell divisions; cessation of expansion; and, finally, most of the accumulated lymphocytes die by apoptosis. The data used, thus far, to inform understanding of these processes, both
in vitro
and
in vivo
, are taken from flow cytometry experiments. One significant drawback of flow cytometry is that individual cells cannot be tracked, so that it is not possible to investigate interdependencies in the fate of cells within a family tree. This deficit in experimental information has recently been overcome by Hawkins
et al
. (Hawkins
et al
. 2009
Proc. Natl Acad. Sci. USA
106
, 13 457–13 462 (
doi:10.1073/pnas.0905629106
)), who reported on time-lapse microscopy experiments in which B-cells were stimulated through the TLR-9 receptor. Cells stimulated in this way do not aggregate, so that data regarding family trees can be recorded. In this article, we further investigate the Hawkins
et al
. data. Our conclusions are striking: in order to explain the familial correlation structure in division times, death times and propensity to divide, a minimum of two distinct heritable factors are necessary. As the data show that two distinct factors are necessary, we develop a stochastic model that has two heritable factors and demonstrate that it can reproduce the key features of the data. This model shows that two heritable factors are sufficient. These deductions have a clear impact upon biological understanding of the adaptive immune response. They also necessitate changes to the fundamental premises behind the tools developed by statisticians to draw deductions from flow cytometry data. Finally, they affect the mathematical modelling paradigms that are used to study these systems, as these are widely developed based on assumptions of cellular independence that are not accurate.
Systemic factors dominate mammal protein evolution
Authors: Vinogradov Alexander E.
Published: January 2010

Proteins encoded by highly expressed genes evolve more slowly. This correlation is thought to arise owing to purifying selection against toxicity of misfolded proteins (that should be more crucial for highly expressed genes). It is now widely accepted that this individual (by-gene) effect is a dominant cause in protein evolution. Here, I show that in mammals, the evolutionary rate of a protein is much more strongly related to the evolutionary rate of coexpressed proteins (and proteins of the same biological pathway) than to the expression level of its encoding gene. The complexity of gene regulation (estimated by the numbers of transcription factor targets and regulatory microRNA targets in the encoding gene) is another important cause, which is much stronger than gene expression level. Proteins encoded by complexly regulated genes evolve more slowly. The intronic length and the ratio of intronic to coding sequence lengths also correlate negatively with protein evolutionary rate (which contradicts the expectation from the negative link between expression level and evolutionary rate). One more important factor, which is much stronger than gene expression level, is evolutionary age. More recent proteins evolve faster, and expression level of an encoding gene becomes quite a minor cause in the evolution of mammal proteins of metazoan origin. These data suggest that, in contrast to a widespread opinion, systemic factors dominate mammal protein evolution.
Behavioural consequences of sensory plasticity in guppies
Authors: Chapman Ben B. , Morrell Lesley J. , Tosh Colin R. , Krause Jens
Published: January 2010

Sensory plasticity, whereby individuals compensate for sensory deprivation in one sense by an improvement in the performance of an alternative sense, is a well-documented phenomenon in nature. Despite this, the behavioural and ecological consequences of sensory plasticity have not been addressed. Here we show experimentally that some components (vision and chemoreception) of the sensory system of guppies are developmentally plastic, and that this plasticity has important consequences for foraging behaviour. Guppies reared under low light conditions had a significantly stronger response to chemical food cues encountered in isolation than fish reared at higher light levels. Conversely, they exhibited a weaker response to visual-only cues. When visual and olfactory/gustatory cues were presented together, no difference between the strength of response for fish reared at different light intensities was evident. Our data suggest that guppies can compensate for experience of a visually poor, low light environment via a sensory switch from vision to olfaction/gustation. This switch from sight to chemoreception may allow individuals to carry out the foraging behaviour that is essential to their survival in a visually poor environment. These considerations are especially important given the increasing frequency of anthropogenic changes to ecosystems. Compensatory phenotypic plasticity as demonstrated by our study may provide a hitherto unconsidered buffer that could allow animals to perform fundamental behaviours in the face of considerable change to the sensory environment.
A high-resolution association mapping panel for the dissection of complex traits in mice
Authors: Bennett Brian J. , Farber Charles R. , Orozco Luz , Min Kang Hyun , Ghazalpour Anatole , Siemers Nathan , Neubauer Michael , Neuhaus Isaac , Yordanova Roumyana , Guan Bo , Truong Amy , Yang Wen-pin , He Aiqing , Kayne Paul , Gargalovic Peter , Kirchgessner Todd , Pan Calvin , Castellani Lawrence W. , Kostem Emrah , Furlotte Nicholas , Drake Thomas A. , Eskin Eleazar , Lusis Aldons J.
Published: January 2010

Systems genetics relies on common genetic variants to elucidate biologic networks contributing to complex disease-related phenotypes. Mice are ideal model organisms for such approaches, but linkage analysis has been only modestly successful due to low mapping resolution. Association analysis in mice has the potential of much better resolution, but it is confounded by population structure and inadequate power to map traits that explain less than 10% of the variance, typical of mouse quantitative trait loci (QTL). We report a novel strategy for association mapping that combines classic inbred strains for mapping resolution and recombinant inbred strains for mapping power. Using a mixed model algorithm to correct for population structure, we validate the approach by mapping over 2500 cis-expression QTL with a resolution an order of magnitude narrower than traditional QTL analysis. We also report the fine mapping of metabolic traits such as plasma lipids. This resource, termed the Hybrid Mouse Diversity Panel, makes possible the integration of multiple data sets and should prove useful for systems-based approaches to complex traits and studies of gene-by-environment interactions.
CORNET: A User-Friendly Tool for Data Mining and Integration
Authors: De Bodt Stefanie , Carvajal Diana , Hollunder Jens , Van den Cruyce Joost , Movahedi Sara , Inzé Dirk
Published: January 2010

As an overwhelming amount of functional genomics data have been generated, the retrieval, integration, and interpretation of these data need to be facilitated to enable the advance of (systems) biological research. For example, gathering and processing microarray data that are related to a particular biological process is not straightforward, nor is the compilation of protein-protein interactions from numerous partially overlapping databases identified through diverse approaches. However, these tasks are inevitable to address the following questions. Does a group of differentially expressed genes show similar expression in diverse microarray experiments? Was an identified protein-protein interaction previously detected by other approaches? Are the interacting proteins encoded by genes with similar expression profiles and localization? We developed CORNET (for CORrelation NETworks) as an access point to transcriptome, protein interactome, and localization data and functional information on Arabidopsis (Arabidopsis thaliana). It consists of two flexible and versatile tools, namely the coexpression tool and the protein-protein interaction tool. The ability to browse and search microarray experiments using ontology terms and the incorporation of personal microarray data are distinctive features of the microarray repository. The coexpression tool enables either the alternate or simultaneous use of diverse expression compendia, whereas the protein-protein interaction tool searches experimentally and computationally identified protein-protein interactions. Different search options are implemented to enable the construction of coexpression and/or protein-protein interaction networks centered around multiple input genes or proteins. Moreover, networks and associated evidence are visualized in Cytoscape. Localization is visualized in pie charts, thereby allowing multiple localizations per protein. CORNET is available at http://bioinformatics.psb.ugent.be/cornet.
Channel-Like Characteristics of the Low-Affinity Barley Phosphate Transporter PHT1;6 When Expressed inXenopusOocytes
Authors: Preuss Christian P. , Huang Chun Y. , Gilliham Matthew , Tyerman Stephen D.
Published: January 2010

Remobilization of inorganic phosphate (Pi) within a plant is critical for sustaining growth and seed production under external Pi fluctuation. The barley (Hordeum vulgare) transporter HvPHT1;6 has been implicated in Pi remobilization. In this report, we expressed HvPHT1;6 in Xenopus laevis oocytes, allowing detailed characterization of voltage-dependent fluxes and currents induced by HvPHT1;6. HvPHT1;6 increased efflux of Pi near oocyte resting membrane potentials, dependent on external Pi concentration. Time-dependent inward currents were observed when membrane potentials were more negative than −160 mV, which was consistent with nH+:HPO42− (n > 2) cotransport, based on simultaneous radiotracer and oocyte voltage clamping, dependent upon Pi concentration gradient and pH. Time- and voltage-dependent inward currents through HvPHT1;6 were also observed for SO42−and to a lesser degree for NO3−Cl−but not for malate. Inward and outward currents showed linear dependence on the concentration of external HPO42−similar to low-affinity Pi transport in plant studies. The electrophysiological properties of HvPHT1;6, which locates to the plasma membrane when expressed in onion (Allium cepa) epidermal cells, are consistent with its suggested role in the remobilization of Pi in barley plants.
RETRACTED: Pyrrolo[1,2‐b][1,2,5]benzothiadiazepines (PBTDs) exert their anti‐proliferative activity by interfering with Akt–mTOR signaling and bax:bcl‐2 ratio modulation in cells from chronic myeloid leukemic patients
Authors: Di Stefano Carla , Marfe Gabriella , Trawinska Malgorzata Monika , Sinibaldi‐Salimei Paola , Silvestri Romano , Amadori Sergio , Abruzzese Elisabetta
Published: January 2010

In our study we found that pyrrolo[1,2‐b][1,2,5]benzothiadiazepines (PBTDs) mediated apoptosis in primary leukemia cells from 27 chronic myelogenous leukemia (CML) patients at onset through the activation of the caspase‐9 and ‐3, and cleavage of poly (ADP‐ribose) polymerase (PARP). The bax:bcl‐2 ratio was increased as a consequence of down‐regulation of bcl‐2 and up‐regulation of bax proteins in response to treatment with PBTDs. In addition, PBTDs were able to induce cell death in primary leukemia cells derived from 23 CML‐chemoresistant patients. Furthermore, the effects of PBTDs on the Akt–mTOR (mammalian target of rapamycin) pathway were determined by Western blot. PBTDs possessed inhibitory activity against mTOR and also impeded hyper‐phosphorylation of Akt as a feedback of inhibition of mTOR by rapamycin. The results presented in this study demonstrate that we have identified the PBTDs as restoring the apoptotic pathways both in primary leukemia cells derived from CML patients at onset and in primary leukemia cells derived from CML‐chemoresistant patients, thus showing their ability to undergo apoptosis. These compounds constitute a promising therapeutic approach for patients with leukemia. They provide the basis for new strategies for an additional anticancer drug in leukemia therapies, especially when conventional ones fail. (Cancer Sci 2010; 101: 991–1000)
Elucidating the apparent maize tolerance to weed competition in long‐term organically managed systems
Authors: RYAN M R , MORTENSEN D A , BASTIAANS L , TEASDALE J R , MIRSKY S B , CURRAN W S , SEIDEL R , WILSON D O , HEPPERLY P R
Published: January 2010

Ryan MR, Mortensen DA, Bastiaans L, Teasdale JR, Mirsky SB, Curran WS, Seidel R, Wilson DO & Hepperly PR (2010). Elucidating the apparent maize tolerance to weed competition in long‐term organically managed systems. Weed Research50, 25–36.

In a long‐term cropping systems trial comparing organically and conventionally managed systems, organic maize production sustained crop yields equal to conventional methods despite higher weed levels. In 2005 and 2006, an experiment nested within the trial was conducted to gain insight into this apparent crop tolerance to weed competition. Density of mixed weed species was experimentally manipulated to achieve a broad range of weed infestation levels. Under standard management conditions, all cropping systems produced equivalent maize yields, even though weedy plant biomass in the organic treatments was between fourfold and sevenfold greater than in the conventionally managed maize. Increased yield capacity, evidenced when plots were maintained weed‐free, and enhanced crop competitiveness, were the main pillars of this apparent crop tolerance to weed competition in the organic systems. Increased soil resource availability and a faster relative crop growth rate in the organic systems probably contributed to these factors, which play an important role in buffering crop fitness during years of less than ideal weed control. Simultaneously, the experiment illustrated the poor efficacy of mechanical weed management in the organic systems, which is the main reason organic maize did not out‐yield conventional maize under standard management conditions.
Examination of the change in Assessment of Motor and Process Skills performance in patients with acquired brain injury between the hospital and home environment
Authors: Toneman Michelle , Brayshaw Julie , Lange Bridget , Trimboli Connie
Published: January 2010

Aim:  The Assessment of Motor and Process Skills (AMPS) is a standardised, valid, reliable, observational assessment that is sensitive to change over time. This research aimed to examine the change in AMPS performance in patients discharged from a neurosurgical rehabilitation ward to a home‐based therapy programme over a four‐week time frame.

Methods:  A total of 15 individuals with acquired brain injury who were participating in rehabilitation were recruited to the study. The AMPS was conducted with each individual during the participant’s inpatient rehabilitation and again approximately four weeks later, while participating in home‐based rehabilitation. Assessment results were collated using the AMPS computer programme and entered into a statistics package from which data were analysed.

Results:  As a group, no statistically significant change in function was identified between the home and hospital environments; however, individual results did indicate a change in occupational performance for many of the participants.

Conclusions:  The AMPS was shown to reflect a change in occupational performance for many of the research participants. This research supports previous studies which indicate that some individuals’ motor and process skill abilities appear to be affected by the environment in which they perform. This suggests that occupational therapists wishing to know how an individual will perform activities of daily living should evaluate the individual’s performance in the environment in which they will be functioning.
Gene expression profiling of Dunaliella sp. acclimated to different salinities
Authors: Kim Minjung , Park Seunghye , Polle Jürgen E.W. , Jin EonSeon
Published: January 2010

To investigate which genes may be important for growth under extreme conditions such as very low or high salinities, a survey of the Dunaliella sp. transcriptome was performed with a cDNA microarray which had been generated previously representing 778 expressed sequence tags. The comparative microarray analysis indicated that 142 genes differed in expression levels by more than twofold in cells grown at extreme salinities (0.08 M and 4.5 M NaCl) when compared with cells grown at intermediate salinity (1.5 M NaCl). Of these genes, 28 had increased expression and 57 were suppressed in cells grown at low salinity. In cells grown at high salinity, 43 genes showed increased expression and 69 genes showed suppressed expression. However, we did observe a large overlap in the expression of extreme salinity‐responsive genes based on Venn diagram analysis, which found 55 genes that responded to both of the two extreme salinity conditions. Further, we found that several genes had similar expression levels under low and high salinities, including some general stress response genes that were upregulated in both extreme salinity conditions. For confirmation of the validity of the cDNA microarray analysis, expression of several genes was independently confirmed by the use of gene‐specific primers and real‐time polymerase chain reaction. The present study is the first large‐scale comparative survey of the transcriptome from the microalga Dunaliella sp. acclimated to extreme salinities, thus providing a platform for further functional investigation of differentially expressed genes in Dunaliella.
Spatial variations in nutrient supply to the red algae Eucheuma serra (J. Agardh) J. Agardh
Authors: Nishihara Gregory N. , Terada Ryuta
Published: January 2010

The nutrient supply rates within the canopy of the economically important red algal species, Eucheuma serra J. Agardh were determined experimentally in a recirculating flow‐chamber. A single individual was placed in the working section of the 2000 × 200 × 250 mm3 acrylic flow‐chamber and subjected to unidirectional water velocities from 1.0 to 9.3 cm s−1. Rates of nutrient supply were determined using 9.7 mm diameter CaSO4 (gypsum) spheres that were attached to the thallus inside and outside of the canopy. The supply rates within the canopy were 56% less than outside of the canopy. Increases in internal and external water velocity asymptotically increased the nutrient supply rates regardless of location. A model was developed to examine how changes in ammonium and nitrate supply compared with the physiologically maximum uptake rates of these nutrients. The results suggest that when the ammonium concentration in the water was 20 µmol L−1 uptake rates were limited by the supply rate especially at velocities below 5 cm s−1, whereas in the case of 20 µmol L−1 of nitrate, the supply of nitrate was more than adequate to maximize nutrient uptake.
Dutogliptin, a selective DPP4 inhibitor, improves glycaemic control in patients with type 2 diabetes: a 12‐week, double‐blind, randomized, placebo‐controlled, multicentre trial
Authors: Pattzi H. M. R. , Pitale S. , Alpizar M. , Bennett C. , O’Farrell A. M. , Li J. , Cherrington J. M. , Guler H.‐P. ,   PHX1149‐PROT202 Study Group
Published: January 2010

Aim: To determine efficacy and tolerability of dutogliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor, in patients with type 2 diabetes mellitus.

Methods: This was a 12‐week, multicentre, randomized, double‐blind, placebo‐controlled trial in 423 patients with type 2 diabetes with suboptimal metabolic control. Following a 2‐week single‐blind placebo run‐in, patients aged 18–75 years with a body mass index of 25–48 kg/m2 and baseline HbA1c of 7.3–11.0% were randomized 2:2:1 to receive once‐daily oral therapy with either dutogliptin (400 or 200 mg) or placebo on a background medication of either metformin alone, a thiazolidinedione (TZD) alone or a combination of metformin plus a TZD.

Results: Average HbA1c at baseline was 8.4%. Administration of dutogliptin 400 and 200 mg for 12 weeks decreased HbA1c by −0.52% (p < 0.001) and −0.35% (p = 0.006), respectively (placebo‐corrected values), with absolute changes in HbA1c for the 400 mg, 200 mg and placebo groups of −0.82, −0.64 and −0.3%, respectively. The proportion of patients achieving an HbA1c < 7% was 27, 21 and 12% at dutogliptin doses of 400 and 200 mg or placebo, respectively (p = 0.008 for comparison of 400 mg vs. placebo). Fasting plasma glucose (FPG) levels were significantly reduced in both active treatment groups compared to placebo: the placebo‐corrected difference was −1.00 mmol/l (p < 0.001) for the 400 mg group and −0.88 mmol/l (p = 0.003) for the 200 mg group. Dutogliptin caused significantly greater reductions in postprandial glucose AUC 0–2h in both the 400 and 200 mg groups (placebo corrected values −2.58 mmol/l/h, p < 0.001 and −1.63 mmol/l/h, p = 0.032, respectively). In general, patients tolerated the study drug well. There were minor, not clinically meaningful differences in adverse events (AEs) between dutogliptin‐treated patients and placebo controls, and 60% of all reported AEs were mild. Vital signs and body weight were stable, and routine safety laboratory parameters did not change compared with placebo. Trough ex vivo DPP4 inhibition at the end of the 12‐week treatment period was 80 and 70%, at the 400 and 200 mg doses of dutogliptin, respectively.

Conclusions: Dutogliptin treatment for 12 weeks improved glycaemic control in patients with type 2 diabetes who were on a background medication of metformin, a TZD or metformin plus a TZD. Tolerability was favourable for both doses tested. The 400 mg dose of dutogliptin resulted in larger changes of HbA1c and FPG and more subjects reached an HbA1c target of < 7% than the 200 mg dose.
Patient‐reported outcomes following treatment with the human GLP‐1 analogue liraglutide or glimepiride in monotherapy: results from a randomized controlled trial in patients with type 2 diabetes
Authors: Bode B. W. , Testa M. A. , Magwire M. , Hale P. M. , Hammer M. , Blonde L. , Garber A. ,   on behalf of the LEAD‐3 Study Group
Published: January 2010

Aim: As weight gain and hypoglycaemia associated with glimepiride therapy can negatively impact weight perceptions, psychological well‐being and overall quality of life in type 2 diabetes, we investigated whether liraglutide treatment could improve these factors.

Methods: Seven hundred and thirty‐two patients with type 2 diabetes completed a 77‐item questionnaire during a randomized, 52‐week, double‐blind study with liraglutide 1.2 mg (n = 245) or 1.8 mg (n = 242) compared with glimepiride 8 mg (n = 245).

Results: Mean (SE) decreases in glycated haemoglobin levels were greater with liraglutide 1.2 mg [−0.84 (0.08)%] and 1.8 mg [−1.14 (0.08)%] than glimepiride [−0.51 (0.08)%; p = 0.0014 and p < 0.0001, respectively]. Patients gained weight on glimepiride [mean (SE), 1.12 (0.27) kg] but lost weight on liraglutide [1.2 mg: −2.05 (0.28) kg; 1.8 mg: −2.45 (0.28) kg; both p < 0.0001]. Patient weight assessment was more favourable with liraglutide 1.8 mg [mean (SE) score: 40.0 (2.0)] than glimepiride [48.7 (2.0); p = 0.002], and liraglutide 1.8 mg patients were 52% less likely to feel overweight [odds ratio (OR) 0.48; 95% confidence interval (CI): 0.331–0.696]. Mean (SE) weight concerns were less with liraglutide [1.2 mg: 30.0 (1.2); 1.8 mg: 32.8 (1.2)] than glimepiride [38.8 (1.2); p < 0.0001 and p < 0.001, respectively], with liraglutide groups 45% less likely to report weight concern (OR 0.55, 95% CI: 0.41–0.73). Mean (SE) mental and emotional health and general perceived health improved more with liraglutide 1.8 mg [476.1 (2.8) and 444.2 (3.2), respectively] than glimepiride [466.3 (2.8) and 434.5 (3.2), respectively; p = 0.012 and p = 0.033, respectively].

Conclusions: Improved glycaemic control and decreased weight with liraglutide 1.8 mg vs. glimepiride can improve psychological and emotional well‐being and health perceptions by reducing anxiety and worry associated with weight gain.
The ethics of knowledge production – Pacific challenges
Authors: Du Plessis Rosemary , Fairbairn‐Dunlop Peggy
Published: January 2010

The impact on Pacific peoples of developments in genetic science and the actions of researchers and companies working in the life sciences have prompted increasing discussion about the politics and ethics of knowledge. People in the Pacific have also taken up recent opportunities to discuss initiatives like the UNESCO Universal Declaration on Bioethics and Human Rights. This article reviews the responses of participants in a number of different gatherings on ethics‐related issues in the Pacific. It explores the importance of Pacific ideals of collective rights and the need to recognise the value of indigenous knowledge systems, particularly the way this knowledge has been collectively produced, shared and used. What is distinctive about particular Pacific cultures, what is shared by Pacific people and the negotiated spaces between indigenous thinking and western science are highlighted in this introduction to articles that offer Pacific challenges to established thinking on the ethics of knowledge production.
Pacific health research guidelines: the cartography of an ethical relationship
Authors: Mila‐Schaaf Karlo
Published: January 2010

In 2004 the Health Research Council of New Zealand (HRC) published a set of “Guidelines on Pacific health research”. The Guidelines were an attempt to articulate the features of ethical research relationships with Pacific peoples living in Aotearoa New Zealand. This article describes the process of developing these guidelines, using Pacific knowledge paradigms and concepts as a starting point. Central to the discussion are two spatial metaphors, the Pacific concept of Va and Smith, Hudson, et al.'s (2008) contemporary concept of the negotiated space. It is asserted that via a conceptual negotiated space, traditional Pacific indigenous ethics were explored and respected in the development of the Guidelines. However, this was balanced with the desire for worldview expansion, knowledge innovation and the development of new philosophies, which required drawing from other knowledge paradigms. The process of deliberating, negotiating and, to some extent, integrating and synthesising values and ideas from different knowledge paradigms characterise the Guidelines as not only a project of restoration but also a project of transformation.
A multilocus candidate approach identifies ACE and HIF1A as susceptibility genes for cellulite
Authors: Emanuele E , Bertona M , Geroldi D
Published: January 2010

Background  Cellulite is a common complex cosmetic problem for many post‐adolescent women characterised by relief alterations of the skin surface, which give the skin an orange‐peel appearance. Although genetic factors have been suggested to play a role in the development of cellulite, the genetic background of this condition remains unclear. We therefore conducted a multi‐locus genetic study examining the potential associations of candidate gene variants in oestrogen receptors, endothelial function/adipose tissue hypoxia, lipid metabolism, extracellular matrix homeostasis, inflammation and adipose tissue biology, with the risk of cellulite.

Methods  Using a case–control study of 200 lean women with cellulite and 200 age‐ and BMI‐matched controls (grade 0 according to Nurnberger–Muller scale), we examined the association of cellulite with 25 polymorphisms in 15 candidate genes.

Results  Two of the 25 polymorphisms were significantly associated with cellulite at the P < 0.01 level. After allowance for age, body mass index, the prevalence of contraceptive use and smoking in logistic regression analysis, the multivariable‐adjusted odds ratios for cellulite were 1.19 (95% CI: 1.10–1.51; P < 0.01) for ACE rs1799752 and 0.61 (95% CI: 0.45–0.88, P < 0.01) for HIF1A rs11549465.

Conclusions  This study, which demonstrates an independent role of ACE and HIF1A in predisposing to cellulite, may provide novel information on the pathophysiology of this common cosmetic problem, and offer a topic for research for novel beautification interventions.
Functional anatomy of the lymphatics draining the skin: a detailed statistical analysis
Authors: Reynolds Hayley M. , Walker Cameron G. , Dunbar P. Rod , O’Sullivan Michael J. , Uren Roger F. , Thompson John F. , Smith Nicolas P.
Published: January 2010

Relatively little is known about the functional anatomy of the lymphatic vessels draining the skin. To address this issue, we previously created a three‐dimensional computer model of skin lymphatic drainage, using melanoma lymphoscintigraphy (LS) data from 5232 patients. In this study we sought to extend our model by performing a detailed statistical analysis of the mapped LS data to characterize the functional anatomy of the superficial lymphatics without any a‐priori spatial bias. We investigated the commonly held assumption that lymphatic drainage is symmetric between the two sides of the body. Results indicated that, with the exception of the lower anterior torso, posterior leg and a small section of the posterior torso, most skin regions with sufficient data showed symmetric drainage. LS data from each symmetric skin region were then reflected to the opposite side of the body to provide an increased LS dataset for subsequent analysis. Cluster analysis was then applied to this reflected LS dataset to group regions of skin that drained in a similar manner. Results defined nine large clusters of skin, largely draining to the dominant axillary, groin, cervical level II and preauricular node fields. Each of the four axillary and groin node fields defined large clusters of skin on the torso, dividing it into regions similar to the historical ‘Sappey’s lines’, although a fifth region of highly ambiguous drainage was also shown in the anterior and posterior center of the torso. Collectively, these results provide important new insights into skin lymphatic drainage, both improving and quantifying our understanding of functional lymphatic anatomy.
Maternal and fetal microvasculature in sheep placenta at several stages of gestation
Authors: Hafez Shireen A. , Borowicz Pawel , Reynolds Lawrence P. , Redmer Dale A.
Published: January 2010

Maternal and fetal microvasculature was studied in ewes at days 50, 90 and 130 of gestation using microvascular corrosion casting and scanning electron microscopy. Microvascular corrosion casts of caruncles at day 50 were cup‐shaped with a centrally located cavity. Branches of radial arteries entered the caruncle from its base and ramified on the maternal surface of the caruncle. Stem arteries broke into an extensive mesh of capillaries forming crypts on the fetal surface. The architecture of the caruncle at day 90 was similar to what was found at day 50 but the vascularity and the depth of the crypts increased in correspondence to increased branching of fetal villi. The substance of the caruncle was thicker at day 130 compared with day 50, with no remarkable difference compared with day 90. Capillary sinusoids of irregular form and diameter were observed on the fetal surface of the caruncle at all stages. These sinusoids may reduce blood flow resistance and subsequently increase transplacental exchange capacity. A microvascular corrosion cast of the cotyledon was cup‐shaped with wide and narrow sides. Cotyledonary vessels entered and left the cotyledon from the narrow side. A cotyledonary artery gave proximal collateral branches immediately after entering the cotyledon and then further branched to supply the remaining portion of the cotyledon. Vessel branches broke into a mesh of capillaries forming the fetal vascular villi. Fetal villi that were nearest to the center of the cotyledon were the longest. Capillaries forming villi were in the form of a web‐like mesh, were irregular in size and had sinusoidal dilations. The architecture of the cotyledon at day 90 was similar to day 50, but the vascularity increased. Branching of the fetal villi became more abundant. This extensive branching presumably allows a higher degree of invasion and surface contact to maternal tissues. At day 130, the distal portions of the fetal villi showed low ridges and troughs to increase the surface area for diffusion. Branching of fetal villi appears to influence the elaboration of maternal crypts in all stages of gestation. However, correspondence between crypts and villi is restricted to distal portions of fetal villi.
Architectural properties of the first dorsal interosseous muscle
Authors: Infantolino Benjamin W. , Challis John H.
Published: January 2010

Muscle architecture is considered to reflect the function of muscle in vivo, and is important for example to clinicians in designing tendon‐transfer and tendon‐lengthening surgeries. The purpose of this study was to quantify the architectural properties of the FDI muscle. It is hypothesized that there will be consistency, that is low variability, in the architectural parameters used to describe the first dorsal interosseous muscle because of its clear functional role in index finger motion. The important architectural parameters identified were those required to characterize a muscle adequately by modeling. Specifically the mass, cross‐sectional area, and length of the tendon and muscle were measured in cadavers along with the muscle fiber optimum length and pennation angle, and the moment arm of the first dorsal interosseous at the metacarpophalangeal joint. These parameters provide a characterization of the architecture of the first dorsal interosseous, and were used to indicate the inherent variability between samples. The results demonstrated a large amount of variability for all architectural parameters measured; leading to a rejection of the hypothesis. Ratios designed to describe the functioning of the muscles in vivo, for example the ratio of tendon to fiber optimum lengths, also demonstrated a large variability. The results suggest that function cannot be deduced from form for the first dorsal interosseous, and that subject‐specific architectural parameters may be necessary for the formulation of accurate musculoskeletal models or making clinical decisions.
Rapidly Shifting Baselines in Yangtze Fishing Communities and Local Memory of Extinct Species
Authors: TURVEY SAMUEL T. , BARRETT LEIGH A. , YUJIANG HAO , LEI ZHANG , XINQIAO ZHANG , XIANYAN WANG , YADONG HUANG , KAIYA ZHOU , HART TOM , DING WANG
Published: January 2010

Abstract: Local ecological knowledge can provide a unique source of data for conservation, especially in efforts to investigate the status of rare or possibly extinct species, but it is unlikely to remain constant over time. Loss of perspective about past ecological conditions caused by lack of communication between generations may create “shifting baseline syndrome,” in which younger generations are less aware of local species diversity or abundance in the recent past. This phenomenon has been widely discussed, but has rarely been examined quantitatively. We present new evidence of shifting baselines in local perception of regional species declines and on the duration of “community memory” of extinct species on the basis of extensive interviews with fishers in communities across the middle‐lower Yangtze basin. Many Yangtze species have experienced major declines in recent decades, and the Yangtze River dolphin or baiji (Lipotes vexillifer) and Yangtze paddlefish (Psephurus gladius) may have become extinct during the 21stcentury. Although informants across all age classes were strongly aware of the Yangtze ecosystem's escalating resource depletion and environmental degradation, older informants were more likely to recognize declines in two commercially important fish species, Reeves’ shad (Tenualosa reevesii) and Yangtze pufferfish (Takifugu fasciatus), and to have encountered baiji and paddlefish in the past. Age was also a strong predictor of whether informants had even heard of baiji or paddlefish, with younger informants being substantially less likely to recognize either species. A marked decrease in local knowledge about the Yangtze freshwater megafauna matched the time of major population declines of these species from the 1970s onwards, and paddlefish were already unknown to over 70% of all informants below the age of 40 and to those who first started fishing after 1995. This rapid rate of cultural baseline shift suggests that once even megafaunal species cease to be encountered on a fairly regular basis, they are rapidly forgotten by local communities.
Use of Abundance of One Species as a Surrogate for Abundance of Others
Authors: CUSHMAN SAMUEL A. , McKELVEY KEVIN S. , NOON BARRY R. , McGARIGAL KEVIN
Published: January 2010

Abstract:  Indicator species concepts have a long history in conservation biology. Arguments in favor of these approaches generally stress expediency and assume efficacy. We tested the premise that the abundance patterns of one species can be used to infer those of other species. Our data consisted of 72,495 bird observations on 55 species across 1046 plots distributed across 30 sub basins. We analyzed abundance patterns at two spatial scales (plot and sub basin) and for empirical and a priori grouping. There were few significant indicator relationships at either scale or under either grouping rule, and those few we found did not explain a substantial portion of the abundance of other species. Coupled with the lack of proven efficacy for species surrogacy in the literature, our results indicate the utility of indicators and similar types of surrogate approaches must be demonstrated rather than assumed.
Spontaneous recurrent seizures after status epilepticus induced by soman in Sprague‐Dawley rats
Authors: De Araujo Furtado Marcio , Lumley Lucille A. , Robison Christopher , Tong Lawrence C. , Lichtenstein Spencer , Yourick Debra L.
Published: January 2010

Purpose:  Exposure to toxic levels of organophosphorus (OP) nerve agents can lead to seizures, respiratory failure, and, if untreated, death. The cholinesterase inhibitor soman belongs to the class of OP nerve agents and can cause status epilepticus (SE) and brain damage due to neuroexcitotoxicity. In the present study, electroencephalographic seizures are characterized through telemetry implants in rats exposed to soman, followed by treatment with therapeutics similar to those administered after nerve agent exposure.

Methods:  Cortical electroencephalography (EEG), motor activity and body temperature were recorded continuously for 2 days preexposure and 15 days postexposure to verify the occurrence of spontaneous recurrent seizures (SRS) after soman exposure.

Results:  Behavioral seizures were monitored and the latency to SE was 7.8 ± 4.0 min after exposure. Among the rats that showed SE, approximately 90% had prolonged seizures within the initial 3 days after soman exposure. Five percent of the rats developed stage 1 seizures, 16% stage 2, 23% stage 3, 18% stage 4, and 38% stage 5. Seventy‐nine percent of the rats presented SE and epileptiform‐like discharges several days after SE, and 28.9% of those with SE experienced electrographic SRS. The latency to the appearance of SRS ranged from 5–10 days. Fiber degeneration evaluated through silver staining revealed damage in cortical and subcortical areas directly correlated with SE.

Discussion:  The presence of SRS after seizures induced by soman highlights the importance of quantifying SRS in studies where the objective is to find new therapeutics against soman‐induced seizures.
Potentiation of the anticonvulsant efficacy of sodium channel inhibitors by an NK1‐receptor antagonist in the rat
Authors: Kalinichev Mikhail , Bradford Andrea , Bison Silvia , Lucas Adam , Sartori Ilaria , Garbati Nicoletta , Andreetta Filippo , Bate Simon , Austin Nigel E. , Jones Declan N. C. , Read Kevin D. , Alvaro Giuseppe , Large Charles H.
Published: January 2010

Purpose: Many patients with epilepsy are refractory to anticonvulsant drugs or do not tolerate side effects associated with the high doses required to fully prevent seizures. Antagonists of neurokinin‐1 (NK1) receptors have the potential to reduce seizure severity, although this potential has not been fully explored in animals or humans. The present study was designed to evaluate the efficacy of the NK1‐receptor antagonist, vofopitant, alone and in combination with different anticonvulsant drugs.

Methods: Studies were conducted in rats using a model of generalized seizure induced by electroshock. Drug concentrations in blood and brain were determined in parallel to distinguish pharmacodynamic from pharmacokinetic interactions.

Results: The NK1‐receptor antagonist,GR205171(vofopitant) had no anticonvulsant efficacy by itself, but could potentiate the anticonvulsant efficacy of lamotrigine and other sodium channel blockers. However,GR205171had no effect on the anticonvulsant potency of either valproate or gabapentin.GR205171did not produce central nervous system (CNS) side effects at the doses tested, and it did not potentiate side effects induced by high doses of lamotrigine. The NK1‐receptor inactive enantiomer ofGR205171,GR226206did not potentiate the efficacy of lamotrigine, suggesting that effects observed withGR205171were mediated by NK1 receptors. Analysis of the dose–effect relationship forGR205171indicated that a high (>99%) occupancy of NK1 receptors is required for effect, consistent with previous behavioral and human clinical studies with this pharmacologic class.

Discussion: These results suggest that there may be benefit in adding treatment with a suitable NK1‐receptor antagonist to treatment with a sodium channel blocker in patients with refractory epilepsy.
Effect of sildenafil on the anticonvulsant action of classical and second‐generation antiepileptic drugs in maximal electroshock‐induced seizures in mice
Authors: Nieoczym Dorota , Łuszczki Jarogniew J. , Czuczwar Stanisław J. , Wlaź Piotr
Published: January 2010

Purpose: The goal of the present study was to evaluate the effects of sildenafil on the threshold for electrically induced seizures in mice. In addition, interactions between sildenafil and classical and second‐generation antiepileptic drugs (AEDs), that is, carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), valproate (VPA), lamotrigine (LTG), topiramate (TPM), and oxcarbazepine (OXC) were evaluated.

Methods: Two electroconvulsive tests were used: maximal electroshock seizure threshold (MEST) and maximal electroshock seizure (MES) tests in mice. Acute adverse effects of the studied combinations were investigated in the chimney test, step‐through passive avoidance task, and grip‐strength test. Total brain and free plasma concentrations of AEDs were also determined.

Results: Sildenafil raised the threshold for electroconvulsions in a dose‐dependent manner. It also increased the anticonvulsant activity of CBZ, VPA, and TPM in the MES test, whereas the activity of the remaining AEDs was not significantly changed. Sildenafil increased total brain and free (protein unbound) plasma CBZ concentrations and total brain VPA concentration. Neither sildenafil nor its coadministration with the studied AEDs affected motor coordination and long‐term memory in mice. Interestingly, sildenafil dose‐dependently enhanced the skeletal muscle strength in mice, although combinations of sildenafil with AEDs were ineffective in this respect.

Conclusions: Sildenafil significantly raised the threshold for electroconvulsions in mice without any impairment of motor performance and long‐term memory, but it enhanced muscle strength. Treatment of patients on CBZ or VPA with sildenafil may not be recommended due to pharmacokinetic interactions. Coadministration of sildenafil with other AEDs, especially with TPM, seems to be a reasonable choice.
How common is ictal hypoxemia and bradycardia in children with partial complex and generalized convulsive seizures?
Authors: Moseley Brian D. , Nickels Katherine , Britton Jeffrey , Wirrell Elaine
Published: January 2010

Purpose:  Autonomic effects of seizures, including cardiorespiratory abnormalities, may be involved in sudden unexpected death in epilepsy (SUDEP). The purpose of this study was to determine the prevalence and risk factors for ictal hypoxemia (oxygen saturation <90%) and ictal bradycardia (heart rate < second percentile for age) in children during recorded seizures.

Methods:  The medical records of children admitted to our Epilepsy Monitoring Unit (EMU) between November 1, 2007 and March 13, 2009 were reviewed. Children selected for this study had at least one partial complex or generalized convulsive seizure with recorded oximetry and/or heart rate data.

Results:  Forty‐nine children were identified and 225 seizures were analyzed. Ictal hypoxemia was observed in 48.9% of children and 26.8% of seizures. Ictal hypoxemia was significantly more likely to occur during generalized versus nongeneralized seizures (43.9% vs. 18.9%) and when tapering antiepileptic drugs (AEDs) (75% vs. 35.5%). For partial complex seizures, there was an association between ictal hypoxemia and prolonged seizure duration. There was no correlation between ictal hypoxemia and partial seizure onset localization or lateralization.

Ictal bradycardia occurred in 8.2% of children and 3.7% of seizures. Ictal bradycardia was observed solely with partial complex seizures of extratemporal onset. Due to the low prevalence of ictal bradycardia, these findings were not statistically significant.

Discussion:  Ictal hypoxemia is common, particularly in the setting of generalized tonic–clonic seizures, prolonged partial complex seizures, and when AEDs are tapered. In contrast to previous ictal bradycardia studies, ictal bradycardia occurred exclusively in extratemporal partial complex seizures in this cohort.
What comes first, agricultural growth or democracy?
Authors: Fulginiti Lilyan E.
Published: January 2010

Today, the international community faces two major development challenges: how to ignite growth and how to establish democracy. Economic research has identified two plausible hypotheses regarding this association. The first hypothesis emphasizes the need to start with democracy and institutions that secure property rights. The second hypothesis emphasizes the need to start with physical and human capital accumulation. In this article, we discuss some of the econometric evidence on the relationship between institutions, human capital, and agricultural productivity growth across developed and developing countries with the objective of finding support for one or the other hypothesis. We find that most variables used in the literature to capture the effect of institutions are not independent of the process of growth. While no evidence of causation from political institutions to agricultural productivity growth is found, human capital accumulation emerges as an important source of growth.
Price transmission in the Spanish bovine sector: the BSE effect
Authors: Hassouneh Islam , Serra Teresa , Gil José M.
Published: January 2010

A regime‐switching vector error correction model is applied to monthly price data to assess the impact of Bovine Spongiform Encephalopathy (BSE) outbreaks on price relationships and patterns of transmission among farm and retail markets for bovines in Spain. To evaluate the degree to which price transmission is affected by BSE food scares, a BSE food scare index is developed and used to determine regime switching. Results suggest that BSE scares affect beef producers and retailers differently. Consumer prices are found to be weakly exogenous and not found to react to BSE scares, while producer prices are conversely adjusted. The magnitude of the adjustment is found to depend on the magnitude of the BSE scare.