bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple Antigen Peptide Vaccines againstPlasmodium falciparumMalaria
Authors: Mahajan Babita , Berzofsky Jay A. , Boykins Robert A. , Majam Victoria , Zheng Hong , Chattopadhyay Rana , de la Vega Patricia , Moch J. Kathleen , Haynes J. David , Belyakov Igor M. , Nakhasi Hira L. , Kumar Sanjai
Published: September 2010

The multiple antigen peptide (MAP) approach is an effective method to chemically synthesize and deliver multiple T-cell and B-cell epitopes as the constituents of a single immunogen. Here we report on the design, chemical synthesis, and immunogenicity of threePlasmodium falciparumMAP vaccines that incorporated antigenic epitopes from the sporozoite, liver, and blood stages of the life cycle. Antibody and cellular responses were determined in three inbred (C57BL/6, BALB/c, and A/J) strains, one congenic (HLA-A2 on the C57BL/6 background) strain, and one outbred strain (CD1) of mice. All three MAPs were immunogenic and induced both antibody and cellular responses, albeit in a somewhat genetically restricted manner. Antibodies against MAP-1, MAP-2, and MAP-3 had an antiparasite effect that was also dependent on the mouse major histocompatibility complex background. Anti-MAP-1 (CSP-based) antibodies blocked the invasion of HepG2 liver cells byP.falciparumsporozoites (highest, 95.16% in HLA-A2 C57BL/6; lowest, 11.21% in BALB/c). Furthermore, antibodies generated following immunizations with the MAP-2 (PfCSP, PfLSA-1, PfMSP-142, and PfMSP-3b) and MAP-3 (PfRAP-1, PfRAP-2, PfSERA, and PfMSP-142) vaccines were able to reduce the growth of blood stage parasites in erythrocyte cultures to various degrees. Thus, MAP-based vaccines remain a viable option to induce effective antibody and cellular responses. These results warrant further development and preclinical and clinical testing of the next generation of candidate MAP vaccines that are based on the conserved protective epitopes fromPlasmodiumantigens that are widely recognized by populations of divergent HLA types from around the world.
The Two Variants of the
Streptococcus pneumoniae
Pilus 1 RrgA Adhesin Retain the Same Function and Elicit Cross-Protection
In Vivo
Authors: Moschioni Monica , Emolo Carla , Biagini Massimiliano , Maccari Silvia , Pansegrau Werner , Donati Claudio , Hilleringmann Markus , Ferlenghi Ilaria , Ruggiero Paolo , Sinisi Antonia , Pizza Mariagrazia , Norais Nathalie , Barocchi Michèle A. , Masignani Vega
Published: September 2010

Thirty percent of
Streptococcus pneumoniae
isolates contain pilus islet 1, coding for a pilus composed of the backbone subunit RrgB and two ancillary proteins, RrgA and RrgC. RrgA is the major determinant of
in vitro
adhesion associated with pilus 1, is protective
in vivo
in mouse models, and exists in two variants (clades I and II). Mapping of the sequence variability onto the RrgA structure predicted from X-ray data showed that the diversity was restricted to the “head” of the protein, which contains the putative binding domains, whereas the elongated “stalk” was mostly conserved. To investigate whether this variability could influence the adhesive capacity of RrgA and to map the regions important for binding, two full-length protein variants and three recombinant RrgA portions were tested for adhesion to lung epithelial cells and to purified extracellular matrix (ECM) components. The two RrgA variants displayed similar binding abilities, whereas none of the recombinant fragments adhered at levels comparable to those of the full-length protein, suggesting that proper folding and structural arrangement are crucial to retain protein functionality. Furthermore, the two RrgA variants were shown to be cross-reactive
in vitro
and cross-protective
in vivo
in a murine model of passive immunization. Taken together, these data indicate that the region implicated in adhesion and the functional epitopes responsible for the protective ability of RrgA may be conserved and that the considerable level of variation found within the “head” domain of RrgA may have been generated by immunologic pressure without impairing the functional integrity of the pilus.
Mannheimia haemolyticaand Its Leukotoxin Cause Neutrophil Extracellular Trap Formation by Bovine Neutrophils
Authors: Aulik Nicole A. , Hellenbrand Katrina M. , Klos Heather , Czuprynski Charles J.
Published: September 2010

Mannheimia haemolyticais an important member of the bovine respiratory disease complex, which is characterized by abundant neutrophil infiltration into the alveoli and fibrin deposition. Recently several authors have reported that human neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of trapping and killing pathogens. Here, we demonstrate that the leukotoxin (LKT) ofM. haemolyticacauses NET formation by bovine neutrophils in a CD18-dependent manner. Using an unacylated, noncytotoxic pro-LKT produced by an ΔlktCmutant ofM. haemolytica, we show that binding of unacylated pro-LKT stimulates NET formation despite a lack of cytotoxicity. Inhibition of LKT binding to the CD18 chain of lymphocyte function-associated antigen 1 (LFA-1) on bovine neutrophils reduced NET formation in response to LKT orM. haemolyticacells. Further investigation revealed that NETs formed in response toM. haemolyticaare capable of trapping and killing a portion of the bacterial cells. NET formation was confirmed by confocal microscopy and by scanning and transmission electron microscopy. Prior exposure of bovine neutrophils to LKT enhanced subsequent trapping and killing ofM. haemolyticacells in bovine NETs. Understanding NET formation in response toM. haemolyticaand its LKT provides a new perspective on how neutrophils contribute to the pathogenesis of bovine respiratory disease.
TWO APPROXIMATE MINKOWSKI SUM ALGORITHMS
Authors: MILENKOVIC VICTOR , SACKS ELISHA
Published: September 2010

We present two approximate Minkowski sum algorithms for planar regions bounded by line and circle segments. Both algorithms form a convolution curve, construct its arrangement, and use winding numbers to identify sum cells. The first uses the kinetic convolution and the second uses our monotonic convolution. The asymptotic running times of the exact algorithms are increased by km log m with m the number of segments in the convolution and k the number of segment triples that are in cyclic vertical order due to approximate segment intersection. The approximate Minkowski sum is close to the exact sum of perturbation regions that are close to the input regions. We validate both algorithms on part packing tasks with industrial part shapes. The accuracy is near the floating point accuracy even after multiple iterated sums. The programs are 2% slower than direct floating point implementations of the exact algorithms. The monotonic algorithm is 42% faster than the kinetic algorithm.
IN VITROHEMODYNAMIC STUDY ON THE STENOTIC RIGHT CORONARY ARTERY USING EXPERIMENTAL AND NUMERICAL ANALYSIS
Authors: PARK SEUNG MAN , MIN YOUNG UK , KANG MYUNG JIN , KIM KYUNG CHUN , JI HO SEONG
Published: September 2010

To investigate the hemodynamic and hemorheological features related to circulatory diseases, in vitro experiments are carried out using a micro-particle image velocimetry (μ-PIV) technique. Numerical simulations using a commercial computational fluid dynamics (CFD) code are also performed to compare with the experimental results. Five different non-Newtonian blood models and a Newtonian water model are employed to investigate the blood flow characteristics through a stenotic right coronary artery (RCA). The in vitro model is made of two-dimensional (2D) polydimethylsiloxane (PDMS) channel based on the clinical angiogram of the RCA with stenotic lesion. The hemodynamic and hemorheologic behaviors in the control volume near the stenotic lesion are evaluated by velocity profiles. The predicted and measured velocity profiles at the center of the channel have a reasonable agreement.
Approaches to modelling saline intrusion for assessment of small island water resources
Authors: Herbert A. W. , Lloyd J. W.
Published: September 2010

The current approaches to modelling the groundwater resources of small islands are briefly reviewed and the importance of representing the variation in salinity through a transition zone between the freshwater lens and sea water is emphasized. Older approaches based on a sharp interface approximation are inappropriate. The current modelling approach is based on the advection–dispersion equation. However, key parameters in this equation are scale, density and problem specific, making the approach difficult to use predictively. The density dependence is illustrated by simple analytical results and experiments, and future consideration of this dependence is advocated. Alternative modelling approaches are identified, and investigation of their usefulness is recommended.
Groundwater rebound in the South Yorkshire coalfield: a first approximation using the GRAM model
Authors: Burke S. P. , Younger P. L.
Published: September 2010

The closures of three deep coal mines in the Rotherham area (South Yorkshire, UK), and the cessation of associated dewatering, have given rise to concerns over possible future pollution of ground‐ and/or surface‐water resources once groundwater rebound is complete. An assessment of the legitimacy of these concerns has been made by applying the recently developed, semi‐distributed computer model GRAM (Groundwater Rebound in Abandoned Mineworkings). The extent of workings and subsurface inter‐connections relating to the three principal collieries in the Rotherham area have been identified from mine plans, augmented by testimonies of former underground workers, and assessed in terms of their hydrogeological importance. GRAM was used to predict the rate of groundwater recovery in the workings, and the timing and flow‐rates of future surface discharges. The simulations predict that major surface discharges can be expected no sooner than the year 2005, and will eventually amount to around 3.9 Ml d
−1
. It is also predicted that around 0.4 Ml d
−1
of water will flow from the abandoned mine‐workings into nearby workings of Maltby Colliery. By analogy with discharges elsewhere associated with seams of similar sulphur content, it is considered that the ‘first flush’ water will contain around 200 mg/l total iron (maximum estimate 600 mg/l), declining eventually to around 20 mg/l total iron.
Transport of ammonium in aquifers: retardation and degradation
Authors: Erskine A. D.
Published: September 2010

In the assessment of the risks to groundwater posed by most landfills, the production and transport of ammonium is the key factor. Although a long list of toxic and dangerous substances can appear in the leachate from a landfill, the chemical component with the greatest impact both on the ecology and on groundwater abstractions is usually ammonium. It is therefore vital that information on the behaviour of ammonium in groundwater is compiled in order to reduce the uncertainties associated with predictions of groundwater impact.

The transport of ammonium is attenuated by two main processes: cation exchange and oxidation (often biologically enhanced). The effect of these can probably be approximated by a combination of linear retardation and exponential degradation. In principle, comparison of the breakthrough curves of ammonium and chloride at monitoring points should allow quantification of the contributions of these two processes in terms of retardation factors and decay rates.

Three case studies at different scales are compared. The results indicate that retardation factors are not higher than 3, and that degradation does contribute to reduction in concentration. While only three studies have been examined, the results seem to contrast with the typical assumptions made in risk assessments.
The Ninth Ineson Lecture
Authors: Foster S. S. D.
Published: September 2010

One of the less obvious, but most insidious, effects of the enormous changes in English agriculture over the past 50 years has been the contamination of groundwater—originally by nutrients, subsequently by pesticide residues, and most recently by the livestock parasite Cryptosporidium. The paper analyses scientific understanding of the factors determining the origin, transport and attenuation of these contaminants in groundwater systems. It focuses primarily on the British situation, but draws on experience from Europe and beyond as appropriate. Given the essentially diffuse character of the mainly agricultural activity generating the subsurface contaminant load, pollution control has (presented (and continues to present) a complex regulatory challenge in legal, technical, economic and social terms. The discussion explores this challenge, which yet again has become very topical at national and European policy levels.
Interpretation of pumping tests in the Sherwood Sandstone Group, Sellafield, Cumbria, UK
Authors: STREETLY M. , CHAKRABARTY C. , MCLEOD R.
Published: September 2010

In 1995 as part of the process to assess the suitability of a site near Sellafield, Cumbria, for a deep geological repository for solid intermediate level and some solid low level radioactive waste, United Kingdom Nirex Limited (Nirex) commissioned a series of long duration pumping tests in the various stratigraphic horizons at the site. Two of the pumping tests were conducted in vertically adjacent sections of the lower Sherwood Sandstone Group (SSG) whilst pressures were monitored at discrete intervals in surrounding monitoring boreholes. Responses were observed in over twenty monitoring zones at various levels around the pumped sections during both tests.

In order to arrive at an understanding of the hydraulic system in the SSG, a systematic methodology was adopted to analyse the data sets from the pumping tests. Preliminary analysis of the data from each responding zone used the standard 2D radial flow analytical approach. This indicated that, whilst responses conformed broadly to this model, there were important deviations. Three different analytical modifications were adopted to assess the significance of these deviations; a partial penetration model, a bounded aquifer model and a generalized radial flow model. The use of the different models allowed a conceptual model of flow processes occurring in the SSG to be developed.
Hydrogeological characterization of the onshore Quaternary sediments at Sellafield using the concept of domains
Authors: McMillan A. A. , Heathcote J. A. , Klinck B. A. , Shepley M. G. , Jackson C. P. , Degnan P. J.
Published: September 2010

As part of an assessment of the performance of a potential deep repository for intermediate- and some low-level radioactive wastes at Sellafield, numerical models of the regional scale groundwater flow were built. Quaternary sediments play an important role in the flow because they control recharge to the deeper groundwater system. This paper outlines research carried out under the Nirex Quaternary Characterization programme at Sellafield and shows how lithological and structural characterization of the sediments has enabled the development of Quaternary Hydrogeological Domains which have been used in the regional groundwater models.

The Quaternary sediments in the Sellafield area are very varied and result from more than one ice advance. Sediments include glaciogenic diamictons, coarse glaciofluvial gravels probably deposited as sandar and silts of probable glaciolacustrine origin. These sediments are locally glacitectonically deformed. Recent alluvial, marine and lacustrine sediments are also present. The lateral extent of many of the sediment bodies is expected to be small, and therefore their complete characterization by the traditional approach of interpolating between measurements in boreholes and at outcrop is likely to be difficult, without an impracticably large number of boreholes.

Thus the hydrogeology was characterized on the basis of the geology, supported by a relatively small number of boreholes and hydraulic measurements. Quaternary Geological Domains defined by distinctive landform-sediment associations and structural characteristics were mapped. Distinctive vertical profiles of sediments were identified from subsurface data (e.g. borehole data). This enabled the Geological Domains to be refined to Hydrogeological Domains.

The overall performance of the system can be confirmed by reference to detailed field scale measurements in specific areas. The behaviour varies between providing little impediment to recharge to, or discharge from, the underlying strata of the Sherwood Sandstone Group over most of the area, but with local areas where recharge or discharge is considerably impeded. Locally, the Quaternary deposits contribute a significant part of the transmissivity of the regional aquifer.

The hydraulic characteristics of individual sediment types are known from laboratory data and limited field data. These data have been integrated and upscaled using analytic calculations based on the lithological profiles recognized in the Hydrogeological Domains. This has enabled the derivation of effective properties, which were used in the regional-scale flow models. The resulting parameter values are consistent with those independently derived from regional aquifer modelling.
The influence of landsliding on the behaviour of a structurally complex clay
Authors: Fearon R.E. , Coop M.R.
Published: September 2010

The paper examines behaviour of the soils from a landslide site in the Southern Apennines, demonstrating how the structure of the soil affects their strength, and that for such a complex, heterogeneous soil normalization of the data is necessary in order to identify the underlying patterns of behaviour. The changes to the structure caused by the remoulding of the soil within the landslide are also examined, and the effects that this has on the behaviour of the soils identified. Landsliding was found to modify the macro-structure of the clays, which in this case study made them stronger, but the water contents of the soils were not altered.
A flow slide in central Italy
Authors: Clayton C.R.I. , Fiumani U. , Matthews M.C.
Published: September 2010

The paper describes a slope failure in granular colluvium, together with its geomorphological, seismic and geotechnical setting. The predictions from conventional geotechnical slope stability analyses, taking into account topography, pore pressure and seismic effects, are compared with the observed pattern of instability. It is concluded that the failure was a flow slide and resulted from a combination of factors. Geotechnical limit equilibrium stability analyses of entire slopes are rarely able to predict the smaller-scale initiation events leading to flow slides, because these are controlled by local topography, ground and groundwater conditions. Nor are they able to predict the speed and run-out of such slides.
Uncertainty in ground motion estimates for the evaluation of slope stability during earthquakes
Authors: Murphy W. , Petley D.N. , Bommer J. , Mankelow J.M.
Published: September 2010

Three examples of landslides triggered by earthquakes have been examined to consider the natural variability of the slope forming materials, and the uncertainties surrounding input ground motions. These were the landslides at Villa Del Monte, California, Tachia Gorge, Taiwan and Las Colinas, El Salvador which were triggered by the Loma Prieta, (M
W
=7.0, 1989), Chi Chi, (M
W
=7.6, 1999) and El Salvador (M
W
=7.6, 2001) earthquakes respectively. The results of these analyses show a large scatter in the calculated factors of safety for earthquake conditions, some of which indicated stability when failure actually occurred.

The models used in the calculation of seismic slope stability yield acceptable results. However, it is clear that the natural variability of slope forming materials has a strong influence on the range of results reported for the analysis of slopes subjected to strong shaking. This variability is exacerbated by limited knowledge about the interaction with seismic waves and slopes resulting in topographic amplification. Such problems are often further complicated by uncertainty and error associated with attenuation relationships.
Landslide susceptibility in the Río Aguas catchment, SE Spain
Authors: Griffiths J.S. , Mather A.E. , Hart A.B.
Published: September 2010

The definitions of hazard and risk in natural hazard studies are well established in the scientific literature. However, many examples of ‘landslide hazard assessment’ only identify the susceptibility of slopes to failure and make no statement on the frequency of occurrence that would be necessary for a complete hazard evaluation. In a research programme undertaken in SE Spain the issue of landslide susceptibility in a semi-arid, neotectonic environment was examined, with some attempt to evaluate the hazard. This work involved establishing the occurrence of landsliding within the 550 km
2
Río Aguas catchment through remote sensing interpretation and field mapping. These data were compiled in an inventory containing the records of nearly 250 landslides that was analysed to establish the nature and extent of landslide susceptible situations. Within the catchment anticipated combinations of geological materials proved to be susceptible to failure, and relationships between landslide volume and travel angle were examined in relation to standard models. The highest incidence of contemporary landsliding appeared to be related to the proximity of a major river capture site, a geomorphological event that had been dated at 100 000 
BP
. This produced localized rapid incision, a ten fold increase in sediment removal and the creation of oversteepened slopes that were only recently degrading to their long-term angle of stability. In addition to contemporary landslides, field mapping identified anomalous geological structures that proved to be degraded erosional remnants of ancient landslides. Relating these remnants to the river terrace sequence in the region provided some control on the relative ages of these ancient or ‘fossil’ landslides. It was concluded that any assessment of landslide risk in the study area would need to take into account not only geological materials and the contemporary geomorphological environment but also the geomorphological history of the region.
Profiling the Cancer Genome
Authors: Cowin Prue A. , Anglesio Michael , Etemadmoghadam Dariush , Bowtell David D.L.
Published: September 2010

Cancer profiling studies have had a profound impact on our understanding of the biology of cancers in a number of ways, including providing insights into the biological heterogeneity of specific cancer types, identification of novel oncogenes and tumor suppressors, and defining pathways that interact to drive the growth of individual cancers. Several large-scale genomic studies are underway that aim to catalog all biologically significant mutational events in each cancer type, and these findings will allow researchers to understand how mutational networks function within individual tumors. The identification of molecular predictive and prognostic tools to facilitate treatment decisions is an important step for individualized patient therapy and, ultimately, in improving patient outcomes. Whereas there are still significant challenges to implementing genomic testing and targeted therapy into routine clinical practice, rapid technological advancements provide hope for overcoming these obstacles.
Genome Evolution in Reptilia, the Sister Group of Mammals
Authors: Janes Daniel E. , Organ Christopher L. , Fujita Matthew K. , Shedlock Andrew M. , Edwards Scott V.
Published: September 2010

The genomes of birds and nonavian reptiles (Reptilia) are critical for understanding genome evolution in mammals and amniotes generally. Despite decades of study at the chromosomal and single-gene levels, and the evidence for great diversity in genome size, karyotype, and sex chromosome diversity, reptile genomes are virtually unknown in the comparative genomics era. The recent sequencing of the chicken and zebra finch genomes, in conjunction with genome scans and the online publication of the Anolis lizard genome, has begun to clarify the events leading from an ancestral amniote genome—predicted to be large and to possess a diverse repeat landscape on par with mammals and a birdlike sex chromosome system—to the small and highly streamlined genomes of birds. Reptilia exhibit a wide range of evolutionary rates of different subgenomes and, from isochores to mitochondrial DNA, provide a critical contrast to the genomic paradigms established in mammals.
The Mitochondrial Proteome and Human Disease
Authors: Calvo Sarah E. , Mootha Vamsi K.
Published: September 2010

For nearly three decades, the sequence of the human mitochondrial genome (mtDNA) has provided a molecular framework for understanding maternally inherited diseases. However, the vast majority of human mitochondrial disorders are caused by nuclear genome defects, which is not surprising since the mtDNA encodes only 13 proteins. Advances in genomics, mass spectrometry, and computation have only recently made it possible to systematically identify the complement of over 1,000 proteins that comprise the mammalian mitochondrial proteome. Here, we review recent progress in characterizing the mitochondrial proteome and highlight insights into its complexity, tissue heterogeneity, evolutionary origins, and biochemical versatility. We then discuss how this proteome is being used to discover the genetic basis of respiratory chain disorders as well as to expand our definition of mitochondrial disease. Finally, we explore future prospects and challenges for using the mitochondrial proteome as a foundation for systems analysis of the organelle.
Student perceptions regarding the usefulness of explicit discussion of “Structure of the Observed Learning Outcome” taxonomy
Authors: Prakash E. S. , Narayan K. A. , Sethuraman K. R.
Published: September 2010

One method of grading responses of the descriptive type is by using Structure of Observed Learning Outcomes (SOLO) taxonomy. The basis of this study was the expectation that if students were oriented to SOLO taxonomy, it would provide them an opportunity to understand some of the factors that teachers consider while grading descriptive responses and possibly develop strategies to improve scores. We first sampled the perceptions of 68 second-year undergraduate medical students doing the Respiratory System course regarding the usefulness of explicit discussion of SOLO taxonomy. Subsequently, in a distinct cohort of 20 second-year medical students doing the Central Nervous System course, we sought to determine whether explicit illustration of SOLO taxonomy combined with some advice on better answering descriptive test questions (to an experimental group) resulted in better student scores in a continuous assessment test compared with providing advice for better answering test questions but without any reference to SOLO taxonomy (the control group). Student ratings of the clarity of the presentation on SOLO taxonomy appeared satisfactory to the authors, as was student understanding of our presentation. The majority of participants indicated that knowledge of SOLO taxonomy would help them study and prepare better answers for questions of the descriptive type. Although scores in the experimental and control group were comparable, this experience nonetheless provided us with the motivation to orient students to SOLO taxonomy early on in the medical program and further research factors that affect students' development of strategies based on knowledge of SOLO taxonomy.
The Harvard Fatigue Laboratory: contributions to World War II
Authors: Folk G. Edgar
Published: September 2010

The war contributions of the Harvard Fatigue Laboratory in Cambridge, MA, were recorded in 169 Technical Reports, most of which were sent to the Office of the Quartermaster General. Earlier reports were sent to the National Research Council and the Office of Scientific Research and Development. Many of the reports from 1941 and later dealt with either physical fitness of soldiers or the energetic cost of military tasks in extreme heat and cold. New military emergency rations to be manufactured in large quantities were analyzed in the Fatigue Laboratory and then tested in the field. Newly designed cold weather clothing was tested in the cold chamber at −40°F, and desired improvements were made and tested in the field by staff and soldiers in tents and sleeping bags. Electrically heated clothing was designed for high-altitude flight crews and tested both in laboratory chambers and field tests before being issued. This eye witness account of the Harvard Fatigue Laboratory during World War II was recorded by Dr. G. Edgar Folk, who is likely the sole surviving member of that famous laboratory.
Process-oriented guided-inquiry learning in an introductory anatomy and physiology course with a diverse student population
Authors: Brown Patrick J. P.
Published: September 2010

Process-oriented guided-inquiry learning (POGIL), a pedagogical technique initially developed for college chemistry courses, has been implemented for 2 yr in a freshman-level anatomy and physiology course at a small private college. The course is populated with students with backgrounds ranging from no previous college-level science to junior and senior biology, biochemistry, and forensic science majors. Fifty percent of the lectures in the course were replaced with POGIL activities, performed in class by students working collaboratively in small groups. The introduction of POGIL pedagogy into the second half of a two-semester anatomy and physiology course significantly improved student performance on summative evaluations. Overall course scores increased from a mean score of 76% to 89% in the three semesters after POGIL was introduced. Performance on the same multiple-choice final exam rose from a mean of 68% to 88% over the same time period. Most significantly, the rate of students earning a D or F in the course was halved in the first two semesters after POGIL was introduced and was 0% in the third semester. Student satisfaction with the method was high, and most students perceived the value of this form of instruction.
Treatment with a CRH-R1 antagonist prevents stress-induced suppression of the central neural drive to the reproductive axis in female macaques
Authors: Herod S. M. , Pohl C. R. , Cameron J. L.
Published: September 2010

In response to everyday life stress, some individuals readily develop reproductive dysfunction (i.e., they are stress sensitive), whereas others are more stress resilient. When exposed to mild combined psychosocial plus metabolic stress (change in social environment plus reduced diet), female cynomolgus monkeys can be categorized as stress sensitive (SS; they rapidly become anovulatory in response to stress), medium stress resilient (MSR; they slowly become anovulatory in response to prolonged stress), or highly stress resilient (HSR; they maintain normal menstrual cycles in response to stress). Previously, we reported that monkeys that develop abnormal menstrual cycles following exposure to mild combined stress (MSR + SS) have increased plasma cortisol levels the day they move to a novel room and start a reduced diet compared with HSR monkeys. In this study, we examined whether there is a similar acute effect of mild combined stress on the reproductive axis specifically in the combined group of MSR + SS animals by measuring LH pulse frequency and whether treatment with a CRH-R1 antagonist can prevent a stress-induced suppression of LH pulse frequency presumably by inhibiting activity of the HPA axis. Animals that developed abnormal menstrual cycles in response to stress (MSR + SS monkeys) suppressed LH pulse frequency in response to stress exposure. Pretreatment with 10 mg/kg iv antalarmin prevented the stress-induced suppression of LH secretion in these animals without the stress-induced increase in cortisol secretion being blocked. We conclude that CRH, acting via nonneuroendocrine mechanisms to regulate neurotransmitter systems other than the HPA axis, plays a role in causing stress-induced reproductive impairment in stress-sensitive individuals.
Late-Expiratory Activity: Emergence and Interactions With the Respiratory CPG
Authors: Molkov Yaroslav I. , Abdala Ana P. L. , Bacak Bartholomew J. , Smith Jeffrey C. , Paton Julian F. R. , Rybak Ilya A.
Published: September 2010

The respiratory rhythm and motor pattern are hypothesized to be generated by a brain stem respiratory network with a rhythmogenic core consisting of neural populations interacting within and between the pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes and controlled by drives from other brain stem compartments. Our previous large-scale computational model reproduced the behavior of this network under many different conditions but did not consider neural oscillations that were proposed to emerge within the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) and drive preinspiratory (or late-expiratory, late-E) discharges in the abdominal motor output. Here we extend the analysis of our previously published data and consider new data on the generation of abdominal late-E activity as the basis for extending our computational model. The extended model incorporates an additional late-E population in RTN/pFRG, representing a source of late-E oscillatory activity. In the proposed model, under normal metabolic conditions, this RTN/pFRG oscillator is inhibited by BötC/pre-BötC circuits, and the late-E oscillations can be released by either hypercapnia-evoked activation of RTN/pFRG or by hypoxia-dependent suppression of RTN/pFRG inhibition by BötC/pre-BötC. The proposed interactions between BötC/pre-BötC and RTN/pFRG allow the model to reproduce several experimentally observed behaviors, including quantal acceleration of abdominal late-E oscillations with progressive hypercapnia and quantal slowing of phrenic activity with progressive suppression of pre-BötC excitability, as well as to predict a release of late-E oscillations by disinhibition of RTN/pFRG under normal conditions. The extended model proposes mechanistic explanations for the emergence of RTN/pFRG oscillations and their interaction with the brain stem respiratory network.
Activity in a Cortical-Basal Ganglia Circuit for Song Is Required for Social Context-Dependent Vocal Variability
Authors: Stepanek Laurie , Doupe Allison J.
Published: September 2010

Variability in adult motor output is important for enabling animals to respond to changing external conditions. Songbirds are useful for studying variability because they alter the amount of variation in their song depending on social context. When an adult zebra finch male sings to a female (“directed”), his song is highly stereotyped, but when he sings alone (“undirected”), his song varies across renditions. Lesions of the lateral magnocellular nucleus of the anterior nidopallium (LMAN), the output nucleus of a cortical-basal ganglia circuit for song, reduce song variability to that of the stereotyped “performance” state. However, such lesions not only eliminate LMAN's synaptic input to its targets, but can also cause structural or physiological changes in connected brain regions, and thus cannot assess whether the acute activity of LMAN is important for social modulation of adult song variability. To evaluate the effects of ongoing LMAN activity, we reversibly silenced LMAN in singing zebra finches by bilateral reverse microdialysis of the GABAA receptor agonist muscimol. We found that LMAN inactivation acutely reduced undirected song variability, both across and even within syllable renditions, to the level of directed song variability in all birds examined. Song variability returned to pre-muscimol inactivation levels after drug washout. However, unlike LMAN lesions, LMAN inactivation did not eliminate social context effects on song tempo in adult birds. These results indicate that the activity of LMAN neurons acutely and actively generates social context-dependent increases in adult song variability but that social regulation of tempo is more complex.
Comparison of unrestrained plethysmography and forced oscillation for identifying genetic variability of airway responsiveness in inbred mice
Authors: Berndt Annerose , Leme Adriana S. , Williams Laura K. , Smith Randy Von , Savage Holly S. , Stearns Timothy M. , Tsaih Shirng-Wern , Shapiro Steven D. , Peters Luanne L. , Paigen Beverly , Svenson Karen L.
Published: September 2010

Lung function detection in mice is currently most accurately measured by invasive techniques, which are costly, labor intensive, and terminal. This limits their use for large-scale or longitudinal studies. Noninvasive assays are often used instead, but their accuracy for measuring lung function parameters such as resistance and elastance has been questioned in studies involving small numbers of mouse strains. Here we compared parameters detected by two different methods using 29 inbred mouse strains: enhanced pause (Penh), detected by unrestrained plethysmography, and central airway resistance and lung elastance, detected by a forced oscillation technique. We further tested whether the phenotypic variations were determined by the same genomic location in genome-wide association studies using a linear mixed model algorithm. Penh, resistance, and elastance were measured in nonexposed mice or mice exposed to saline and increasing doses of aerosolized methacholine. Because Penh differed from airway resistance in several strains and because the peak genetic associations found for Penh, resistance, or elastance were located at different genomic regions, we conclude that using Penh as an indicator for lung function changes in high-throughput genetic studies (i.e., genome-wide association studies or quantitative trait locus studies) measures something fundamentally different than airway resistance and lung elastance.
How a Mycoparasite Employs G-Protein Signaling: Using the Example ofTrichoderma
Authors: Omann Markus , Zeilinger Susanne
Published: September 2010

MycoparasiticTrichodermaspp. act as potent biocontrol agents against a number of plant pathogenic fungi, whereupon the mycoparasitic attack includes host recognition followed by infection structure formation and secretion of lytic enzymes and antifungal metabolites leading to the host's death. Host-derived signals are suggested to be recognized by receptors located on the mycoparasite's cell surface eliciting an internal signal transduction cascade which results in the transcription of mycoparasitism-relevant genes. Heterotrimeric G proteins of fungi transmit signals originating from G-protein-coupled receptors mainly to the cAMP and the MAP kinase pathways resulting in regulation of downstream effectors. Components of the G-protein signaling machinery such as G subunits and G-protein-coupled receptors were recently shown to play crucial roles inTrichodermamycoparasitism as they govern processes such as the production of extracellular cell wall lytic enzymes, the secretion of antifungal metabolites, and the formation of infection structures.
PPARG: Gene Expression Regulation and Next-Generation Sequencing for Unsolved Issues
Authors: Costa Valerio , Gallo Maria Assunta , Letizia Francesca , Aprile Marianna , Casamassimi Amelia , Ciccodicola Alfredo
Published: September 2010

Peroxisome proliferator-activated receptor gamma (PPARγ) is one of the most extensively studied ligand-inducible transcription factors (TFs), able to modulate its transcriptional activity through conformational changes. It is of particular interest because of its pleiotropic functions: it plays a crucial role in the expression of key genes involved in adipogenesis, lipid and glucid metabolism, atherosclerosis, inflammation, and cancer. Its protein isoforms, the wide number of PPARγtarget genes, ligands, and coregulators contribute to determine the complexity of its function. In addition, the presence of genetic variants is likely to affect expression levels of target genes although the impact ofPPARGgene variations on the expression of target genes is not fully understood. The introduction of massively parallel sequencing platforms—in the Next Generation Sequencing (NGS) era—has revolutionized the way of investigating the genetic causes of inherited diseases. In this context, DNA-Seq for identifying—within both coding and regulatory regions ofPPARGgene—novel nucleotide variations and haplotypes associated to human diseases, ChIP-Seq for defining a PPARγbinding map, and RNA-Seq for unraveling the wide and intricate gene pathways regulated by PPARG, represent incredible steps toward the understanding of PPARγin health and disease.
Aesthetic Value of the Relationship between the Shapes of the Face and Permanent Upper Central Incisor
Authors: Farias Felipe de Oliveira , Ennes Jussara P. , Zorzatto José Roberto
Published: September 2010

The relationship between the shapes of face and teeth has been analyzed for esthetic purposes and exploited commercially. The methodology to assess this correlation, described in the literature, does not enable reliable application of the concepts. Digital photos of face and incisors of 100 youths were measured with the software Image Tool 3.0 and classified as to shape. The same photographs were also analyzed and classified by a visual criterion. Statistical analysis of the metrical classification was performed by Pearson's correlation coefficient. The Kappa test was used to determine the coefficient of agreement between the observers and the obtained data, and to assess the agreement between both classifications (metrical and visual). The classificatory analysis made by the observers indicated a marked level of disagreement, also identified between their classification and that obtained by metrical analysis. The results indicated no relationship between the shapes of the face and the central incisor.
Quantification of Persistence ofEscherichia coliO157:H7 in Contrasting Soils
Authors: Ibekwe A. Mark , Papiernik Sharon K. , Grieve Catherine M. , Yang Ching-Hong
Published: September 2010

Persistence ofEscherichia coli (E. coli)O157:H7 in the environment is a major concern to vegetable and fruit growers where farms and livestock production are in close proximity. The objectives were to determine the effects of preplant fumigation treatment on the survival ofE. coliO157:H7 in two soils and the effects of indigenous bacterial populations on the survival of this pathogen. Real-time PCR and plate counts were used to quantify the survival ofE. coliO157:H7 in two contrasting soils after fumigation with methyl bromide (MeBr) and methyl iodide (MeI). Ten days after fumigation,E. coliO157:H7 counts were significantly lower () in fumigated soils than in the non-fumigated. Direct comparison between MeBr and MeI within each soil indicated that these two fumigants showed similar impacts onE. coliO157:H7 survival. Microbial species diversity as determined by DGGE was significantly higher in clay soil than sandy soil and this resulted in higher initial decline in population in clay soil than in sandy soil. This study shows that if soil is contaminated withE. coliO157:H7, fumigation alone may not eliminate the pathogen, but may cause decrease in microbial diversity which may enhance the survival of the pathogen.
Beneficial Effect of the Traditional Chinese Drug Shu‐Xue‐Tong on Recovery of Spinal Cord Injury in the Rat
Authors: Jia Li-Yun , Yao An-Hui , Kuang Fang , Zhang Yu-Kai , Shen Xue-Feng , Ju Gong
Published: September 2010

Shu‐Xue‐Tong (SXT) is a traditional Chinese drug widely used to ameliorate stagnation of blood flow, such as brain or myocardial infarction. Whether SXT may have therapeutic value for spinal cord injury (SCI), during which ischemia plays an important role in its pathology, remains to be elucidated. We hypothesized that SXT may promote SCI healing by improving spinal cord blood flow (SCBF), and a study was thus designed to explore this possibility. Twenty‐five male Sprague‐Dawley rats were used. SCI was induced by compression, and SXT was administrated 24 h postinjury for 14 successive days. The effects of SXT were assessed by means of laser‐Doppler flowmetry, motor functional analysis (open‐field walking and footprint analysis), and histological analysis (hematoxylin‐eosin and thionin staining and NeuN immunohistochemistry). SXT significantly promoted SCBF of the contused spinal cord and enhanced the recovery of motor function. Histological analysis indicated that the lesion size was reduced, the pathological changes were ameliorated, and more neurons were preserved. Based on these results we conclude that SXT can effectively improve SCI.
Evaluation of the Potential of Brazilian Propolis against UV‐Induced Oxidative Stress
Authors: Fonseca Yris Maria , Marquele-Oliveira Franciane , Vicentini Fabiana T. M. C. , Furtado Niege Araçari J. C. , Sousa João Paulo B. , Lucisano-Valim Yara M. , Fonseca Maria José Vieira
Published: September 2010

This study investigated the potential use of topically and orally administered propolis extracts to prevent UV irradiation‐induced oxidative stress in skin. The results illustrated that green propolis extract (GPE) contained greater amounts of polyphenols, coumaric acid, drupanin, baccharin and artepillin C than did brown propolis extract (BPE). GPE showed higher antioxidant activity than BPE when the IC50 (concentration that caused 50% inhibition) values were compared. Interesting, the oral treatment of hairless mice demonstrated a recovery of 30.0% for GPE and 22.8% for BPE with respect to UV irradiation‐induced GSH depletion. The topical pretreatment of animals with both propolis extract solutions recovered around 14.0% of the depleted GSH. However, the employed treatments did not inhibit the increase of cutaneous proteinase secretion/activity caused by irradiation. These findings indicate that despite differences in composition and antioxidant properties, GPE and BPE both successfully prevent UV‐induced GSH depletion in vivo and are both promising antioxidant systems against oxidative stress in skin. Based on these findings, complementary studies should be performed to enhance our understanding of the protective effects of propolis extracts in skin.
Isolated and Combined Effects of Electroacupuncture and Meditation in Reducing Experimentally Induced Ischemic Pain: A Pilot Study
Authors: Choi Kyung-Eun , Musial Frauke , Amthor Nadine , Rampp Thomas , Saha Felix J. , Michalsen Andreas , Dobos Gustav J.
Published: September 2010

Acupuncture and meditation are promising treatment options for clinical pain. However, studies investigating the effects of these methods on experimental pain conditions are equivocal. Here, the effects of electroacupuncture (EA) and meditation on the submaximum effort tourniquet technique (SETT), a well‐established, opiate‐sensitive pain paradigm in experimental placebo research were studied. Ten experienced meditators (6 male subjects) and 13 nonmeditators (6 male subjects) were subjected to SETT (250 mmHG) on one baseline (SETT only) and two treatment days (additional EA contralaterally to the SETT, either at the leg on ST36 and LV3 or at the arm on LI4 and LI10 in randomized order). Numeric Rating Scale (NRS) ratings (scale 0–10) were recorded every 3 min. During baseline, meditation induced significantly greater pain tolerance in meditators when compared with the control group. Both the EA conditions significantly increased pain tolerance and reduced pain ratings in controls. Furthermore, EA diminished the group difference in pain sensitivity, indicating that meditators had no additional benefit from acupuncture. The data suggest that EA as a presumable bottom‐up process may be as effective as meditation in controlling experimental SETT pain. However, no combined effect of both the techniques could be observed.