bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Intravenous Ondansetron to Prevent Vomiting Episodes in Acute Gastroenteritis: A Randomized, Double Blind, and Controlled Trial
Authors: Rerksuppaphol Sanguansak , Rerksuppaphol Lakkana
Published: October 2010

Acute gastroenteritis is one of the most common infectious diseases of childhood. Its symptoms are vomiting, diarrhea, and dehydration. In the emergency ward, intravenous rather than oral rehydration is usually preferred because of the high likelihood of emesis. Treatments to reduce emesis are of value in improving the rehydration procedure. Our study is a double-blind randomized trial and proposes the use of ondansetron as an anti-emetic drug to treat children with acute gastroenteritis. Seventy-four in-patients, aged 3 months to 15 years, were enrolled and randomly assigned to an ondansetron or placebo group. Inclusion criteria were the diagnosis of acute gastroenteritis and the absence of other diseases or allergies to drugs. A single bolus (0.15 mg/kg) of ondansetron was injected intravenously; normal 0.9% saline solution was used as a placebo. This treatment induced vomiting cessation in the ondansetron group significantly in comparison to the placebo group. The length of the hospital stay and the oral rehydration fluid volume were similar in the two groups and no adverse effects were noticed. Thus, safety, low cost, and overall bene­fit of ondansetron treatment suggests that this drug can be administered successfully to children with acute gastroenteritis.
Cell-cell adhesion proteins in melanocytic pilomatrix carcinoma
Authors: Soler Alejandro Peralta , Kindel Susan E , McCloskey Gayle , Burchette James L
Published: October 2010

Tumors of the matrix of rigid structures include matrical tumors of the hairs, nails, and teeth. These tumors share similar phenotypical and signaling features. Although benign matrical hair tumors are among the most common of these tumors, hair matrix tumors containing pigmented melanocytes are very rare. The malignant variant called melanocytic pilomatrix carcinoma contains benign colonizing dendritic melanocytes admixed with the carcinomatous follicular matrical cells.

We studied the expression of cadherins and β-catenin in melanocytic pilomatrix carcinoma because cadherin/catenin-dependent cell-cell adhesion and signals play a critical role in the development of hair and hair tumors. We examined the expression of E- and P-cadherin and the multifunctional protein β-catenin in two cases of melanocytic pilomatrix carcinoma by immunohistochemistry. E- and P-cadherin are expressed at the cell membrane. In contrast, β-catenin is distributed uniformly in the nucleus and cytoplasm of all tumor cells. The diffuse nuclear and cytoplasmic β-catenin expression found in melanocytic pilomatrix carcinomas is indicative of transcriptional activation and β-catenin-induced cell transformation.

This is the first report of cadherin/catenin expression in melanocytic pilomatrix carcinoma. Although the study is limited by the number of these rare tumors, the data add information for the understanding of disease mechanisms in hair matrical tumors. Matrical tumors of the hairs share phenotypical features with other matrical tumors and show nuclear translocation of β-catenin, suggesting a transcriptional activating rather than a cellcell adhesion function.
Mucosa-associated lymphoid tissue lymphoma and concurrent adenocarcinoma of the prostate
Authors: Kang Jung Julie , Eaton Michael S , Ma Yanling , Streeter Oscar , Kumar Parvesh
Published: October 2010

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the prostate is a rare disease that characteristically follows an indolent course. It is believed that infection or chronic inflammation may be triggers for malignant transformation in the prostate, but it is of unknown etiology. Reports of MALT lymphomas of the prostate with other concurrent primary prostate cancers are even more limited. We present the unique case of a 67-year-old male with concurrent adenocarcinoma of the prostate and primary MALT lymphoma of the prostate. The patient was treated with standard therapy for prostate adenocarcinoma, which would also treat a primary MALT lymphoma. He has been disease-free for over one year for both his primary malignancies. This case confirms that MALT lymphoma can arise concurrently with adenocarcinoma of the prostate.
Processing EO-1 Hyperion data using ISDAS
Authors: Hitchcock R , White H P
Published: October 2010

With increased global interest and development of hyperspectral spaceborne and airborne sensors, high spectral and spatial Earth observation data will become more readily available. With this improvement in spectral and spatial resolution comes the need to have
more rigorous image preprocessing. Spectral and spatial registration and radiometric response need to be characterized and applied more frequently, possibly on a scene-by-scene basis, depending on the stability of the sensor. This requires a system that can evaluate a data set and determine
parameters efficiently and independently.

A preprocessing procedure to transform at-sensor signals to at-surface reflectance for Earth observation hyperspectral imagery has been developed at the Canada Centre for Remote Sensing, Natural Resources Canada (CCRS, NRCan). This process examines an image cube for bad pixels (stripes) and noise
levels, determines spectral (smile effect) and spatial (keystone) registration per pixel, as well as evaluating the image cube for optimal signal gain and offset, and applies relevant corrections. Where applicable, a scene-based (vicarious) calibration procedure can also be applied.

This procedure has been implemented in the Imaging Spectrometer Data Analysis System (ISDAS) developed at CCRS. The following document outlines how to apply the detection and correction algorithms to derived at-surface reflectance from at-sensor radiance, using an EO-1 Hyperion image acquisition as
an example data source.
Minimal generating sets of Reidemeister moves
Authors: Polyak Michael
Published: October 2010

It is well known that any two diagrams representing the same oriented link are related by a finite sequence of Reidemeister moves Ω, Ω2 and Ω3. Depending on orientations of fragments involved in the moves, one may distinguish 4 different versions of each of the Ω1 and Ω2 moves, and 8 versions of the Ω3 move. We introduce a minimal generating set of 4 oriented Reidemeister moves, which includes two Ω1 moves, one Ω2 move, and one Ω3 move. We then study which other sets of up to 5 oriented moves generate all moves, and show that only few of them do. Some commonly considered sets are shown not to be generating. An unexpected non-equivalence of different Ω3 moves is discussed.
Downscaling of METEOSAT SEVIRI 0.6 and 0.8 μm channel radiances utilizing the high-resolution visible channel
Authors: Deneke H. M. , Roebeling R. A.
Published: October 2010

Abstract. An algorithm is introduced to downscale the 0.6 and 0.8 μm spectral channels of the METEOSTAT SEVIRI satellite imager from 3×3 km2 (LRES) to 1×1 km2 (HRES) resolution utilizing SEVIRI's high-resolution visible channel (HRV). Intermediate steps include the coregistration of low- and high-resolution images, lowpass filtering of the HRV channel with the spatial response function of the narrowband channels, and the estimation of a least-squares linear regression model for linking high-frequency variations in the HRV and narrowband images. The importance of accounting for the sensor spatial response function for matching reflectances at different spatial resolutions is demonstrated, and an estimate of the accuracy of the downscaled reflectances is provided. Based on a 1-year dataset of Meteosat SEVIRI images, it is estimated that on average, the reflectance of a HRES pixel differs from that of an enclosing LRES pixel by standard deviations of 0.049 and 0.052 in the 0.6 and 0.8 μm channels, respectively. By applying our downscaling algorithm, explained variance of 98.2 and 95.3 percent are achieved for estimating these deviations, corresponding to residual standard deviations of only 0.007 and 0.011 for the respective channels. For this dataset, a minor misregistration of the HRV channel relative to the narrowband channels of 0.36±0.11 km in East and 0.06±0.10 km in South direction is observed and corrected for, which should be negligible for most applications.
Sub-10 nm particle growth by vapor condensation – effects of vapor molecule size and particle thermal speed
Authors: Nieminen T. , Lehtinen K. E. J. , Kulmala M.
Published: October 2010

Abstract. The growth of freshly formed nanoparticles has been investigated. A new analytical expression based on a recently developed exact solution for the condensational growth rate has been derived. Based on the new growth rate, a new approximate but accurate analytical expression for growth time has been derived. The expression includes transition regime effects on growth, molecule size effects on the collision cross section and particle thermal speed effects on the relative collisional speeds – the last two of which are typically neglected, but may have significant effects when dealing with the growth of freshly nucleated particles. To demonstrate the use of the derived expressions, the contribution of sulphuric acid and organic compounds on sub 3 nm and sub 10 nm particle growth rates has been studied. For sulphuric acid also the effect of hydration as function of relative humidity has been taken into account. According to the new expression the sulphuric acid concentration needed for 1 nm/h growth in sub 3 nm range is ca. 1.5×107 cm−3, which is a factor of 1.5 smaller than values typically used in aerosol physics based on standard model in kinetic regime.
Groundwater contamination due to lead (Pb) migrating from Richmond municipal landfill into Matsheumhlope aquifer: evaluation of a model using field observations
Authors: Kubare M. , Mutsvangwa C. , Masuku C.
Published: October 2010

Abstract. Disposal of solid waste in landfills is an economic option for many municipalities in developing countries where alternatives like incineration and composting are costly. However, groundwater pollution from the leachate generated within the landfill and migrating through the bottom liner material into the underlying groundwater aquifers remains a major public health concern. In our study, we evaluated the application of a mathematical model to determine the aerial extent of unacceptable groundwater contamination due to lead migrating from the Richmond landfill leachate into the underlying Matsheumhlope unconfined aquifer. A one-dimensional advection-dispersion model was applied to predict the down-gradient migration of lead into the aquifer. Linear sorption and first-order decay were considered as the dominant contaminant sink mechanisms for lead. Lead concentrations in the monitoring wells at the landfill site were used as the source term. The lead migration from the landfill was determined by water quality sampling from boreholes situated down-gradient of the landfill. The model simulations gave a good fit of the field results. The safe distance for potable water abstraction was determined to be 400 m, and the model simulations showed that the aerial extent of the pollution will increase with time. The model is most sensitive to the partition coefficient, hydraulic conductivity and longitudinal dispersivity, whilst it exhibits no sensitivity to the lead decay coefficient.
Status of satellite precipitation retrievals
Authors: Kidd C. , Levizzani V.
Published: October 2010

Abstract. Satellites offer an unrivalled vantage point to observe and measure Earth system processes and parameters. Precipitation (rain and snow) in particular, benefit from such observations since precipitation is spatially and temporally highly variable and overcomes some of the deficiencies of conventional gauge and radar measurements. This paper provides an overall review of quantitative precipitation estimation, covering the basis of the satellite systems used in the observation of precipitation and the dissemination of this data, the processing of these measurements to generate the rainfall estimates and the availability, verification and validation of these precipitation estimates.
River Flow Forecasting: a Hybrid Model of Self Organizing Maps and Least Square Support Vector Machine
Authors: Ismail S. , Samsudin R. , Shabri A.
Published: October 2010

Abstract. Successful river flow time series forecasting is a major goal and an essential procedure that is necessary in water resources planning and management. This study introduced a new hybrid model based on a combination of two familiar non-linear method of mathematical modeling: Self Organizing Map (SOM) and Least Square Support Vector Machine (LSSVM) model referred as SOM-LSSVM model. The hybrid model uses the SOM algorithm to cluster the training data into several disjointed clusters and the individual LSSVM is used to forecast the river flow. The feasibility of this proposed model is evaluated to actual river flow data from Bernam River located in Selangor, Malaysia. Their results have been compared to those obtained using LSSVM and artificial neural networks (ANN) models. The experiment results show that the SOM-LSSVM model outperforms other models for forecasting river flow. It also indicates that the proposed model can forecast more precisely and provides a promising alternative technique in river flow forecasting.
Assessment of high-resolution satellite rainfall for streamflow simulation in medium watersheds of the East African highlands
Authors: Bitew M. M. , Gebremichael M.
Published: October 2010

Abstract. The objective is to assess the suitability of commonly used high-resolution satellite rainfall products (CMORPH, TMPA 3B42RT, TMPA 3B42 and PERSIANN) as input to the semi-distributed hydrological model SWAT for daily streamflow simulation in two watersheds (Koga at 299 km2 and Gilgel Abay at 1656 km2) of the East African highlands. First, the model is calibrated for each watershed with respect to each rainfall product input for the period 2003–2004. Then daily streamflow simulations for the validation period 2006–2007 are made from SWAT using rainfall input from each source and corresponding model parameters; comparison of the simulations to the observed streamflow at the outlet of each watershed forms the basis for the conclusions of this study. Results reveal that the utility of satellite rainfall products as input to SWAT for daily streamflow simulation strongly depends on the product type. The 3B42RT and CMORPH simulations show consistent and modest skills in their simulations but underestimate the large flood peaks, while the 3B42 and PERSIANN simulations have inconsistent performance with poor or no skills. Not only are the microwave-based algorithms (3B42RT, CMORPH) better than the infrared-based algorithm (PERSIANN), but the infrared-based algorithm PERSIANN also has poor or no skills for streamflow simulations. The satellite-only product (3B42RT) performs much better than the satellite-gauge product (3B42), indicating that the algorithm used to incorporate rain gauge information with the goal of improving the accuracy of the satellite rainfall products is actually making the products worse, pointing to problems in the algorithm. The effect of watershed area on the suitability of satellite rainfall products for streamflow simulation also depends on the rainfall product. Increasing the watershed area from 299 km2 to 1656 km2 improves the simulations obtained from the 3B42RT and CMORPH (i.e. products that are more reliable and consistent) rainfall inputs while it deteriorates the simulations obtained from the 3B42 and PERSIANN (i.e. products that are unstable and inconsistent) rainfall inputs.
A comparison of basal reflectivity and ice velocity in East Antarctica
Authors: Jacobel R. W. , Lapo K. E. , Stamp J. R. , Youngblood B. W. , Welch B. C. , Bamber J. L.
Published: October 2010

Abstract. Ground-based radio echo sounding data acquired along the 1700 km US-ITASE traverse have been used to determine ice attenuation and relative basal reflectivity across the major catchments funneling ice from East Antarctica to the Ross Ice Shelf. We find that basal reflectivity varies locally by up to 40 dB which we interpret as due to changes in the phase state at the bed. Some, though not all, areas of high local reflectivity are observed to have flat-lying bed reflections indicative of sub-glacial lakes. We compare basal reflectivity to ice balance velocity and find a general association of higher flow speeds with high radar reflection strength. This set of observations from two independent remotely sensed geophysical data sets extends the range of field observations to the interior of East Antarctica and confirms the importance of basal lubrication on modulating the ice dynamics of the largest ice sheet on the planet.
Proprioceptive Sensory Feedback
Authors: Grey MJ
Published: October 2010

Proprioceptors are sensors that provide information about orientation of the body relative to the body's orientation with respect to gravity, movement of the body relative to the external medium and movements and forces in localised regions of the body. Muscle spindles are primarily responsible for position and movement sense, Golgi tendon organs provide the sense of force and the vestibular system provides the sense of balance. Feedback from proprioceptors feedback is essential for the accurate execution of movement execution. For voluntary limb movements in primates, proprioceptive feedback can regulate the generation of motor command by correcting errors using negative feedback loops; providing timing cues about an ongoing movement to initiate commands required at a later time within a movement sequence; and by providing signals used in the planning of movements by providing information about starting limb position to set parameters of feedforward commands. Proprioceptive feedback is also required to modify motor commands slowly in response to alterations in the biomechanical properties of the limbs.

Key Concepts:

Proprioception is a peripherally derived kinaesthetic sense.

Position and movement sense is provided by muscle spindles.

Muscle tension is sensed by Golgi tendon organs.

The centrally derived sense of effort gives information about force and heaviness of objects.

Proprioceptors project to the motor cortex via the dorsal columns and to the cerebellum via spinocerebellar tracts.

Proprioceptive information is used in the spinal regulation of rhythmic movements.
Complement: Measurement
Authors: North Jonathan
Published: October 2010

The complement system comprises a group of serum proteins and cell membrane receptors that function primarily to fight infection. Clinically, measurement of complement pathway activity and individual component levels is of value in (i) cases of suspected immunodeficiency with deficiencies of soluble components, including lectins, and of receptors leading to particular patterns of infection and (ii) conditions that involve complement activation such as systemic lupus erythematosis and renal translantion. This article describes functional and immunochemical methods that can be established in‐house or are available commercially. Until recently, measurement of complement in clinical situations has been aimed at identifying deficiency, of either level or function or activation. Mutations resulting in increased function have been identified for one component and this has opened a new area of research with clinical implications.

Key Concepts:

Correct sample collection and storage is essential for measurement of complement.

Immunochemical measurement of circulating complement components can be performed by commercial assays, usually ELISA.

Functional complement assays are required to detect deficiencies that do not affect immunochemical levels.

Functional complement assays require buffers that are of the correct ionic strength and provide the requisite ions as well as being of the correct pH.

Biosensor assays allow affinity and kinetic studies of complement component interaction.
Plant Embryogenesis (Zygotic and Somatic)
Authors: Harada John J , Belmonte Mark F , Kwong Raymond W
Published: October 2010

Zygotic embryogenesis in higher plants describes the developmental period in which the zygote undergoes a series of differentiation events, leading to the formation of a mature embryo. Establishment of the major embryonic organs and shoot and root apical meristems occur though partitioning events along the apical–basal axis, and many of these events are guided by the hormoneauxin. Formation of the three embryonic tissue systems occurs along a radial axis perpendicular to the apical–basal axis. The mature zygotic embryo is generally developmentally arrested, metabolically quiescent and enclosed within maternal tissues of the seed. Somatic cells can be induced to divert from their normal fate and develop into embryos in a process termed somatic embryogenesis.Auxinand other plant hormones appear to play critical roles in inducing embryogenic competence. Zygotic and somatic embryogenesis represent parallel developmental programs in which cells acquire embryogenic cell fate and develop into mature embryos.

Key Concepts:

Embryo development can be divided into two phases: the morphogenesis phase in which the basic body plan of the embryo is established, and the maturation phase in which the embryo becomes tolerant of desiccation and accumulates storage macromolecules such as lipids, proteins and starch.

During its development, the embryo is divided into distinct domains along its apical–basal and radial axes.

Plant embryo formation represents a series of partitioning events in which organs and tissues are formed from larger domains.

Cell fate within the embryo is largely dependent on the position of the cell within the embryo body.

Plant cells are totipotent and have the ability to regenerate a fully differentiated organism.

Somatic embryos follow similar developmental patterns to their zygotic counterparts, and they occur naturally or are induced in culture.

Establishment of embryogenic competence occurs before the formation of the somatic embryo.
Electroporation
Authors: Nickoloff Jac A
Published: October 2010

Electroporation is a simple, rapid and efficient technique for introducing DNA, RNA, proteins and other bioactive molecules into cells and tissues. Electroporation involves the creation of transient, electrically induced membrane pores through which molecules pass into cytoplasmic and nuclear compartments. Because electroporation involves a physical process acting on cell membranes, it is effective with a wide range of cell types including bacterial, fungal, plant and animal cells. Electroporation is used to transiently or stably increase gene expression through transfection of plasmid‐borne gene expression cassettes or decrease gene expression using antisense RNA, small interfering RNA or short hairpin RNA systems. Recent advances have led to new techniques for tissue and organ electroporation in living animals. These techniques are increasingly used in clinical applications including gene therapy, cancer drug delivery and vaccination.

Key Concepts:

Gene transfer is fundamental to molecular genetic analysis in bacteria, plant and animal cells.

Electroporation introduces a wide variety of bioactive molecules into cells, including DNA, RNA, siRNA, proteins, drugs and dyes.

Electroporation creates transient membrane pores through which molecules pass into cytoplasmic and nuclear compartments.

Electroporation is used to transiently or stably upregulate or downregulate gene expression.

Electroporation is used to make stable genetic changes to chromosomes including gene knockout and knockin.

Electroporation of molecules into tissues and organs of living organisms is driving novel clinical applications including gene therapy, drug delivery and vaccination.

The cytotoxic effects of electroporation are being used in tissue ablation including direct killing of tumours.
Kovalevsky, Alexander Onufrevitch
Authors: Ulett Mark A
Published: October 2010

Russian embryologist and invertebrate zoologist Alexander Onufrevitch Kovalvsky (1840–1901) was one of the founders of cellular and evolutionary embryology. His acclaimed scientific work focused on embryological and invertebrate anatomy of amphioxus, ascidians and other invertebrates. The innovation of this work was to trace the history of adult tissues cell‐by‐cell from the original egg‐cell. Based on these studies, Kovalevsky proposed an evolutionary theory of germ layers and argued that the process of gastrulation is homologous among all animals. Along with his friend and colleague Ilja Iljich Metschnikoff, Kovalevsky published detailed descriptions of most major invertebrate groups. His combination of detailed embryological observations and evolutionary considerations make Kovalevsky one of the founders of an approach now called evolutionary developmental biology.

Key Concepts:

Kovalevsky was one of the founders of cellular and evolutionary embryology.

Kovalevsky was an embryologist and invertebrate zoologist.
X‐ray Diffraction at Synchrotron Light Sources
Authors: Helliwell John R
Published: October 2010

The elucidation of biological structure and function for macromolecules and their complexes is undertaken extensively using X‐ray diffraction. Synchrotron X‐radiation is widely used, due to its exceptional X‐ray brightness and tunability properties, in protein crystallography, fibre diffraction and solution scattering. The synchrotron is also now increasingly used in chemical crystallography of smaller molecules which obviously are very important with respect to all the various ligands that bind to biomolecules; a special feature is the use of the X‐ray intensity to overcome small crystal volume, in ways entirely analogous to biomolecular microcrystals. Techniques that are complementary to crystallography are electron microscopy (EM) and NMR spectroscopy for structure determination and the study of dynamics. Spectral monitoring of samples is undertaken in time‐resolved crystallography to identify structural intermediates and to monitor for radiation damage of biomolecules including metal atom oxidation state changes.

Key Concepts:

Structure and function relationships are key to understanding of biomolecules and their roles in life processes, the details of which are revealed at the atomic level by X‐ray diffraction.

Conformational changes and information on the dynamics of biomolecules can be determined from several structures in comparison or directly via freeze trapped or time‐resolved structures that have been determined by diffraction studies.

Multi‐macromolecular complexes being large and often flexible are especially challenging for crystallisation of sufficiently ordered crystals.

Synchrotron radiation sources provide intense and tunable X‐rays that are widely used properties but also the properties of the polarisation and the pulsed nature of these sources can be harnessed in special experiments.

Free Electron Lasers (FELs) and X‐ray FELs considerably extend the peak brightnesses available by upto 10 orders of magnitude and shorten the pulse lengths to a few tens of femtoseconds (from sub‐nanoseconds in synchrotrons).

Solving a crystal structure has presented special obstacles since the discovery of X‐ray diffraction but synchrotron radiation has opened up new possibilities based on anomalous X‐ray scattering.

Pharmaceutical design is possible based on a knowledge of the three‐dimensional structure of a protein receptor site for a ligand, an approach known as structure‐based drug discovery and optimisation.

Proteins and their ligands are studied extensively by crystallography either together or separately with the techniques of macromolecular and chemical crystallography, respectively.
Development and Evolution of the Vertebrate Ear's Neurosensory System
Authors: Fritzsch Bernd , Crapon de Caprona Marie‐Dominique
Published: October 2010

Ear development transforms an area of head ectoderm into a complex three‐dimensional structure carrying three types of sensory systems for gravistatic and angular acceleration sensation as well as hearing. Transformation of the otic ectoderm starts with the specification of neurosensory cells that differentiate into the essential components for the sensory processes, the hair cells, supporting cells and neurons. The role of proneural bHLH genes in this process is presented and put into the context of ear evolution to appreciate how cellular diversity is embedded into the diversification of the ear as whole as well as the evolution of novel sensory capacities in the ear. Ear neurosensory development is characterised by extensive cross‐regulation of multiple factors for cell type specification and fate fixation. Data suggesting that sensory epithelia may directly regulate the formation of their associated structures to guide specific stimuli to the sensory epithelia are presented.

Key Concepts:

Numerous coexpressed factors regulate transformation of general epidermis to prosensory otic ectoderm.

Proneural basic‐Helix–Loop–Helix proteins define cell fate through cross‐regulative interaction.

Sensory epithelia regulate formation of accessory structures including aspects of ear morphogenesis.

Ear development can best be understood in the context of ear evolution.
Micro
RNAs
and Human Disease
Authors: Marin‐Muller Christian , Yao Qizhi , Chen Changyi
Published: October 2010

Micro
ribonucleic acids
(miRNAs) are a group of small, noncoding RNA molecules 20–22 nucleotides (nt) in length that are predicted to control the activity of approximately 30% of all protein‐coding genes in mammals. Their importance in fine‐tuning the regulation of gene expression is evident in the fact that miRNA dysregulation plays important roles in many diseases, including cancer, cardiovascular disease, diabetes, mental disorders and viral infection. As our understanding of the biogenesis and mechanisms of action of miRNAs has grown over the past decade, so has the promise that miRNAs can serve as valuable therapeutic targets for a large number of diseases. Thus, using miRNAs as therapeutics is the next frontier for the study of these molecules in human disease.

Key Concepts:

The first miRNA (
lin‐4
) was identified in nematodes in 1993.

miRNAs are now predicted to control the activity of approximately 30% of all protein‐coding genes in mammals.

miRNAs regulate gene expression at the posttranscriptional level.

miRNAs function by targeting a specific region of a target mRNA typically located in the 3′ untranslated region (UTR).

miRNAs can function indirectly as either tumour suppressors or oncogenes.

miR‐1 was observed to play a key role in cardiomyocyte differentiation.

miR‐375 regulates insulin secretion by targeting myotrophin.

Expression of miR‐107 decreases early in Alzheimer disease.

miR‐122 is essential for hepatitis C virus (HCV) replication in the liver.
Gap Junctions and Connexins: The Molecular Genetics of Deafness
Authors: Nickel Regina , Forge Andrew
Published: October 2010

Mutations in the gene

GJB2

encoding the gap‐junction protein
connexin 26
(
Cx26
), in particular, and in

GJB6

coding for
connexin 30
(
Cx30
) are the most common cause of autosomal recessive sensorineural hearing loss in many world populations. Variants of

GJB2

are also associated with dominant forms of both nonsyndromic and syndromic deafness. A complex picture of the roles of gap junctions in cochlear physiology has emerged. Rather than being mere conduits for the circulation of potassium ions in the inner ear, gap junctions have been implicated in the maintenance of metabolic homeostasis and in intercellular signalling among nonsensory cells. Studies of mutant channels and mouse models for
connexin
‐related deafness have provided valuable insights into the heterogeneous mechanisms by which
connexin
mutations may cause cochlear dysfunction. Despite recent advances it is still not fully understood what roles gap junctions play in the inner ear and how
connexin
mutations cause deafness.

Key Concepts:

GJB2
and
GJB6
have been mapped to the DFNB1 locus, which accounts for up to 50% of all cases of autosomal recessive nonsyndromic hearing loss.

Molecular genetic tests for DFNB1 should include DNA sequencing of the
GJB2
exons and mutation analysis for
GJB6
deletions.

The identification of factors underlying the phenotypic variability of connexin‐related hearing loss may improve clinical diagnosis and genetic counselling.

A better understanding of the role of gap‐junctional communication in the inner ear and the structure–function relationships of connexin proteins is required for the development of mechanism‐based treatments of connexin‐associated hearing loss.
Membrane Transport in Guard Cells
Authors: Chen Zhong‐Hua , Blatt Michael R
Published: October 2010

One of the most fascinating processes in land plants is the ability to regulate gas exchange and transpiration by the opening and closing of the stomatal pore. The guard cells of stomata serve dual, sometimes conflicting functions in regulating photosynthetic carbon dioxide uptake while minimising water loss by transpiration. Guard cells incorporate complex, flexible and robust membrane transport and control mechanisms. The dominant pathways for potassium, anion, calcium and proton transport have been characterised, both at the plasma membrane and tonoplast, much of this work drawing on electrophysiological techniques such as voltage and patch clamping. Recent genetic and genomic advances have led to the identification of the corresponding genes for several of these transporters. This article summarises the recent progress in guard cell membrane transport and outlooks for a systems biological approach using quantitative kinetic and homeostatic modelling to guide future research work.

Key Concepts:

Guard cells depend on concurrent regulation of parallel and antiparallel transport pathways.

Plasma membrane and tonoplast transport must be coordinated for stomatal function.

Quantitative approaches to kinetic and homeostatic modelling in guard cells will greatly benefit stomatal biology.
Autism: Animal Models
Authors: Bauman Melissa D , Crawley Jacqueline N , Berman Robert F
Published: October 2010

Autism is a life‐long pervasive neurodevelopmental disorder characterised by deficits in social interaction, language development and communication, abnormal repetitive behaviours and severely restricted interests. Autism has proven difficult to study because of the complexity of its behavioural symptoms, complicated genetics and lack of reliable biomarkers. Progress has been made, however, in the development of animal models that allow investigators to model some of the core symptoms of autism, including deficits in social interactions, aspects of social communication and stereotyped, repetitive behaviours. Specific hypotheses can now be formulated and tested using these animal models. This article describes some of the major behavioural approaches and animal models developed to study neurodevelopmental disorders, with a focus on autism spectrum disorders.

Key Concepts:

Autism is a complex disorder whose underlying biology is being studied using rodent and nonhuman primate animal models.

Rodents and nonhuman primates are social animals with rich and complex behavioural repertories that make them useful for modelling neurodevelopmental disorders.

Many of the behaviours that reflect core deficits in autism, including social communication, social interaction and stereotypies, can be modelled in rodents and nonhuman primates.

Inbred strains of mice can be used to discover genes important for the expression of complex behaviours and can provide insight into the neurobiology of social interactions and social communication.

Genetic manipulations possible in mice provide a powerful strategy for investigating the genetic substrates of the disorder, including deletions or overexpression of genes thought to be involved in the aetiology of autism.

Animal models of neurodevelopmental disorders, while important and useful, typically only model specific aspects of a disorder rather that recapitulating its full symptomatology.
Non‐BDNAStructure and Mutations Causing Human Genetic Disease
Authors: Bacolla Albino , Cooper David N , Vasquez Karen M
Published: October 2010

In addition to the canonical right‐handed double helix, several noncanonicaldeoxyribonucleic acid(DNA) secondary structures have been characterised, including quadruplexes, triplexes, slipped/hairpins, Z‐DNA and cruciforms. The formation of these structures is mediated by repetitive sequence motifs, such as G‐rich sequences, purine/pyrimidine tracts, direct (tandem) repeats, alternating purine–pyrimidines and inverted repeats, respectively. Such repeats are abundant in the human genome and are found in association with specific classes of genes, supporting a role for them in gene regulation or protein function. Repetitive sequence motifs are also commonly found at sites of chromosomal alteration, including gross rearrangements and copy number variations (CNVs) associated with both disease and phenotypic variation. Finally, variable number tandem repeats (VNTRs) or microsatellites are present in many gene regulatory regions. Characterised by an inherent capacity to expand spontaneously, such sequences are not only known to cause >30 neurological diseases but may also contribute to human disease susceptibility. The formation of alternative non‐B DNA structures is believed to promote genomic alterations by impeding efficient DNA replication and repair.

Key Concepts:

The structure of DNA is polymorphic as well as its sequence; in addition to the canonical right‐handed double helix (B‐DNA), repetitive sequences can also adopt alternative (non‐B DNA) conformations such as quadruplexes, triplexes, slipped/hairpins, Z‐DNA and cruciforms.

Repetitive DNA sequences are found at locations within many human genes that suggest they can either affect transcription or alternatively encode homopolymeric amino acid runs that could be important for either protein–protein or protein–DNA/RNA interactions.

The integrity of the Y‐chromosome depends on large inverted repeats, which have the capacity to form cruciform structures that may potentiate intrachromosomal recombination.

Copy number variation (CNV) is a form of genetic alteration that, by involving thousands of loci in the genome, contributes to human individuality.

Repetitive sequences capable of forming non‐B DNA are found at sites of chromosomal breaks, CNVs and other rearrangements such as translocations and gene conversion events, which can contribute to human genetic disease.

The recurrent translocation t(22;11) events associated with Emanuel syndrome are mediated by cruciform structures that occur at inverted repeats.

Tandem repeats (microsatellites) may expand within gene sequences, contributing to more than 30 neurological diseases. Present in variable number in genes in the population, they may contribute to human disease susceptibility.

Experiments in model systems and bioinformatic analyses support the conclusion that repetitive sequences trigger genomic instability by adopting non‐B DNA conformations.

Non‐B DNA structures stimulate mutations via mechanisms that alter DNA synthesis and repair.
Reproductive Strategies of the Malaria Parasite
Authors: Merino Santiago , Martínez‐de la Puente Josué
Published: October 2010

In spite of its tiny size and its apparent simply life cycle, several recent studies have shown that malaria parasites and their close relatives are able to modify in a relatively complex way their reproductive strategies. Malaria parasites are able to change population sex ratios to optimise reproductive success according to postulates of ‘local mate competition’ theory but also to assure fertilisation following predictions of ‘fertility insurance’ hypothesis. In addition, other potential reproductive strategies of these parasites, as multiple erythrocytic infections, are more probably a defensive mechanism of hosts than a parasitic adaptation. Malaria parasites adapt to environmental circumstances including hosts defences and number of competing parasite lineages present in the host to maximise reproductive and transmission success. The knowledge of these adaptive mechanisms will allow advances in the fight against malaria parasites.

Key Concepts:

Malaria parasites adapt to hosts responses and parasite competition by changing sex ratios in a way that maximise reproductive and transmission success.

Multiple erythrocytic invasions are not a parasite reproductive strategy but could be a defensive mechanism of hosts.
Rates of change and sensitivity to change in cartilage morphology in healthy knees and in knees with mild, moderate, and end‐stage radiographic osteoarthritis: Results from 831 participants from the osteoarthritis initiative
Authors: Eckstein Felix , Nevitt Michael , Gimona Alberto , Picha Kristen , Lee Jennifer H. , Davies Richard Y. , Dreher Donatus , Benichou Olivier , Le Graverand Marie‐Pierre Hellio , Hudelmaier Martin , Maschek Susanne , Wirth Wolfgang ,   Osteoarthritis Initiative Investigators Group
Published: October 2010

Objective

To study the longitudinal rate of (and sensitivity to) change of knee cartilage thickness across defined stages of radiographic osteoarthritis (OA), specifically healthy knees and knees with end‐stage radiographic OA.

Methods

One knee of 831 Osteoarthritis Initiative participants was examined: 112 healthy knees, without radiographic OA or risk factors for knee OA, and 719 radiographic OA knees (310 calculated Kellgren/Lawrence [K/L] grade 2, 300 calculated K/L grade 3, and 109 calculated K/L grade 4). Subregional change in thickness was assessed after segmentation of weight‐bearing femorotibial cartilage at baseline and 1 year from coronal magnetic resonance imaging (MRI). Regional and ordered values (OVs) of change were compared by baseline radiographic OA status.

Results

Healthy knees displayed small changes in plates and subregions (±0.7%; standardized response mean [SRM] ±0.15), with OVs being symmetrically distributed close to zero. In calculated K/L grade 2 knees, changes in cartilage thickness were small (<1%; minimal SRM −0.22) and not significantly different from healthy knees. Knees with calculated K/L grade 3 showed substantial loss of cartilage thickness (up to −2.5%; minimal SRM −0.35), with OV1 changes being significantly (P < 0.05) greater than those in healthy knees. Calculated K/L grade 4 knees displayed the largest rate of loss across radiographic OA grades (up to −3.9%; minimal SRM −0.51), with OV1 changes also significantly (P < 0.05) greater than in healthy knees.

Conclusion

MRI‐based cartilage thickness showed high rates of loss in knees with moderate and end‐stage radiographic OA, and small rates (indistinguishable from healthy knees) in mild radiographic OA. From the perspective of sensitivity to change, end‐stage radiographic OA knees need not be excluded from longitudinal studies using MRI cartilage morphology as an end point.
Systematic review and meta‐analysis: Anti–tumor necrosis factor α therapy and cardiovascular events in rheumatoid arthritis
Authors: Barnabe Cheryl , Martin Billie‐Jean , Ghali William A.
Published: October 2010

Objective

Control of rheumatoid arthritis (RA) may reduce the risk of cardiovascular events. We sought to systematically assess the association between anti–tumor necrosis factor α (anti‐TNFα) therapy in RA and cardiovascular event rates.

Methods

Observational cohorts and randomized controlled trials (RCTs) reporting on cardiovascular events (all events, myocardial infarction [MI], congestive heart failure, and cerebrovascular accident [CVA]) in RA patients treated with anti‐TNFα therapy compared to traditional disease‐modifying antirheumatic drugs were identified from a search of PubMed (1950 to November 2009), EMBase (1980 to November 2009), and conference abstracts. Relative risks (RRs) or hazard ratios and 95% confidence intervals (95% CIs) were extracted. If the incidence was reported, additional data were extracted to calculate an incidence density ratio and its variance.

Results

The systematic review and meta‐analysis include 16 and 11 publications, respectively. In cohort studies, anti‐TNFα therapy was associated with a reduced risk for all cardiovascular events (pooled adjusted RR 0.46; 95% CI 0.28, 0.77), MI (pooled adjusted RR 0.81; 95% CI 0.68, 0.96), and CVA (pooled adjusted RR 0.69; 95% CI 0.53, 0.89). Meta‐analysis of RCTs also produced a point estimate indicating lower risk of cardiovascular events, but this was not statistically significant (pooled RR 0.85; 95% CI 0.28, 2.59).

Conclusion

Anti‐TNFα therapy is associated with a reduced risk of all cardiovascular events, MI, and CVA in observational cohorts. There was heterogeneity among cohort studies and possible publication bias. The point estimate of the effect from RCTs is underpowered with wide 95% CIs, and cardiovascular events were secondary outcomes, but RCTs also demonstrated a trend toward decreased risk.
Pain sensitivity and pain reactivity in osteoarthritis
Authors: Lee Yvonne C. , Lu Bing , Bathon Joan M. , Haythornthwaite Jennifer A. , Smith Michael T. , Page Gayle G. , Edwards Robert R.
Published: October 2010

Objective

To assess experimental pain sensitivity and compare the inflammatory response to pain in 26 osteoarthritis (OA) patients and 33 age‐ and sex‐matched controls from the general population in order to examine the nature of the association between pain and inflammation in OA.

Methods

The participants underwent psychophysical pain testing to assess pain sensitivity in response to heat, cold, and mechanical stimuli. Blood samples were taken at baseline and at 4 time points after testing to determine the effect of acute pain on C‐reactive protein (CRP), interleukin‐6 (IL‐6), IL‐1β, and tumor necrosis factor α levels.

Results

OA patients had lower pressure pain thresholds (P ≤ 0.003) and higher heat pain ratings (P ≤ 0.04) than controls across multiple body sites. OA patients had higher CRP levels than controls (P = 0.007). CRP levels did not change in response to pain testing. Although not statistically significant, OA patients tended to have higher IL‐6 levels than controls (P = 0.12). IL‐6 levels increased after pain testing in OA patients and controls (P < 0.0001), but the amount of increase was not different between the 2 groups. Among OA patients, heightened pain sensitivity was associated with elevated CRP and IL‐6 levels (P ≤ 0.05).

Conclusion

Compared with controls, OA patients are more sensitive to experimental pain at multiple body sites. IL‐6 levels in OA patients and controls exhibited reactivity to acute painful stimuli, increasing at similar rates after psychophysical pain testing.