bluuebunny/crossref_metadata_2025 huggingface dataset:
Factor analysis and internal consistency evaluation of the FAMCARE Scale for use in the long-term care setting
Authors: Rodriguez Keri L. , Bayliss Nichole K. , Jaffe Emily , Zickmund Susan , Sevick Mary Ann
Published: March 2010

Objective:

The FAMCARE Scale was originally designed to measure family satisfaction with advanced cancer care. The current study evaluated the instrument's psychometric qualities when used in the long-term care (LTC) setting.

Method:

In a prospective cohort study in 2004, the 20-item instrument was administered via telephone to family members of 51 patients receiving LTC in Veterans Affairs facilities. Satisfaction scores on a 5-point Likert scale were used for factor analysis and internal consistency evaluation.

Results:

Although 16 patients were in geriatric palliative care and 35 were in nursing home care, scores of their family members did not vary based on care unit. The total satisfaction score was high, with a mean (SD) of 44.7 (11.9) and a Cronbach alpha of 0.94. Inter-item correlations were low for care availability items (range, 0.01–0.59). Two items—availability of a hospital bed and availability of nurses to the family—had low eigenvalues (0.26 and 0.18, respectively) and weak correlations with the total score (0.23 and 0.16, respectively).

Significance of results:

In the LTC setting, FAMCARE appears to have good internal consistency, but it may be preferable to exclude the two items with weak correlations and to use a 10-point visual analog scale.
What does ‘intent to destroy’ in genocide mean?
Authors: Ambos Kai
Published: March 2010

Genocide is a crime with a double mental element, i.e. a general intent as to the underlying acts, and an ulterior intent with regard to the ultimate aim of the destruction of the group. The prevailing view in the case-law interprets the respective ‘intent to destroy’ requirement as a special or specific intent (dolus specialis) stressing its volitional or purpose-based tendency. While this view has been followed for a long time in legal doctrine without further ado, it has recently been challenged by knowledge- and structure-based approaches, which have not received sufficient attention. A historical, literal, systematic and teleological interpretation of the ‘intent to destroy’ requirement, taking into account the particular structure of the genocide offence and the meaning of ‘intent’ in comparative law, reveals that the traditional view can no longer be maintained. It should be replaced by a combined structure- and knowledge-based approach that distinguishes according to the status and role of the (low-, mid- and top-level) perpetrators. Thus, the purpose-based intent should be upheld only with regard to the top- and mid-level perpetrators, whereas for the low-level perpetrators knowledge of the genocidal context should suffice. Lastly, this new approach requires a fresh look at the ‘intent to destroy’ requirement in cases of participation in genocide.
Neurodermitis
Authors: Schmid-Grendelmeier Peter , Ballmer-Weber Barbara K.
Published: March 2010

Die Neurodermitis ist eine der häufigsten entzündlichen Hauterkrankungen und betrifft bei Kindern bis zu 20 %, bei Erwachsenen etwa 5 % der Bevölkerung. Sie ist multifaktoriell bedingt: neben genetischen Faktoren spielen Veränderung der Hautstruktur und epidermalen Barriere, ein veränderte Reaktionsbereitschaft des Immunsystem sowie neurogene und exogene Faktoren wie Allergene und mikrobielle Ursachen eine Rolle. Aufgrund der Anamnese und der typischen Kardinalsymptome trockene Haut, Pruritus und oft symmetrischer, chronisch-rezidivierender Ekzeme kann die Diagnose meist klinisch gestellt werden. Ergänzende Abklärungen umfassen vor allem den Nachweis allfällig relevanter Sensibilisierungen auf Nahrungsmittel im Kleinkindesalter sowie auf Hausstaubmilben und den Hefepilz Malassezia im Erwachsenenalter sowie den Ausschluss anderer, allenfalls komplizierender Dermatosen. Die Behandlung richtet sich nach dem Ausmaß der Erkrankung und basiert auf einer Basistherapie mit rückfettenden, hautpflegenden Maßnahmen. Sowie der Meidung allfällig bekannter Provokationsfaktoren und Allergene. Ergänzend können bei floriden Ekzemherden vor allem topische Steroide von mäßiger bis mittlere Potenz gezielt und punktuell eingesetzt werden. Bei ausbleibender Steroidwirkung oder allfälligern Nebenwirkungen können auch die sogenannten topischen Calcineurininhibitoren Pimecrolimus und Tacrolimus, eingesetzt werden. Im weiteren stehen Phototherapie, antimikrobielle Maßnahmen und bei schweren Verläufen auch verschiedene systemisch wirksame Immunmodulatoren zur Verfügung.
Dermatochirurgie – der operative Pfeiler der Dermatologie
Authors: Hafner Jürg , Läuchli Severin , Bogdan Inja , French Lars E.
Published: March 2010

Die Dermatochirurgie ist der operative Pfeiler des medizinisch-chirurgischen Fachs Dermatologie. Insbesondere der starke Anstieg der Hautkrebserkrankungen hatte in den westlichen Ländern eine erhebliche Bedarfssteigerung an kompetent ausgeführter Dermatochirurgie zur Folge. Das Beispiel „Hautkrebs“ veranschaulicht plausibel, dass der Dermatologie in der Abklärung, der differenzierten Indikationsstellung und der Durchführung konservativer, semi-invasiver und chirurgischer Behandlungsoptionen und in der Zusammenarbeit mit den plastisch-rekonstruktiven Fächern eine zentrale Rolle zusteht. Die chirurgische Dermatologie hat in den letzten zwei Jahrzehnten wertvolle Impulse bei der mikrographischen Chirurgie von Hautkrebs, der Verfeinerungen der Lokalanästhesietechniken, der Nagelchirurgie, der Wund- und Narbenbehandlung, der Laserchirurgie der Haut und der Sentinellymphknotenbiopsie beim malignen Melanom geleistet.
Tropical mesopause: Is it always close to 100 km?
Authors: Venkat Ratnam M. , Patra A. K. , Krishna Murthy B. V.
Published: March 2010

Global distribution of mesopause using observations of Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) aboard the Thermosphere‐Ionosphere‐Mesosphere Energetics and Dynamics satellite is studied with special emphasis on tropical latitudes. Temperature structure of the mesosphere and lower thermosphere over Gadanki (13.5°N, 79.2°E), a tropical latitude location in India, has been studied in detail. The mesopause altitude at Gadanki is observed to be in the range of 87–105 km with a mean of ∼98 km, and the temperature is in the range of 160–205 K with a mean of ∼170 K. A secondary temperature minimum is observed in the height region of 75–80 km with temperature in the range of 175–195 K. Although the mesopause temperature and altitude show pronounced short‐term variability, on a seasonal mean basis, the variation in these two parameters is rather small. There is no significant long‐term variation in mesopause altitude. The height of the secondary minimum, however, is found to show semiannual variation with a maximum in solstices and a minimum in equinoxes. Thus, the variabilities in the height and temperature of the mesopause and the secondary minimum reported here are different from the two‐level mesopause reported previously for middle and high latitudes. Another significant result that comes from the time series analysis of mesopause temperature is a decreasing trend with a rate of ∼0.72 ± 0.05 K/yr. Furthermore, the long‐term mean profile of temperature does not show the secondary minimum, providing strong support that it could be due to shorter scale tides and gravity waves. The possible implications of the mesopause temperature structure on various physical processes occurring in the mesosphere and the lower thermosphere are discussed.
Mercury in the marine boundary layer and seawater of the South China Sea: Concentrations, sea/air flux, and implication for land outflow
Authors: Fu Xuewu , Feng Xinbin , Zhang Gan , Xu Weihai , Li Xiangdong , Yao Hen , Liang Peng , Li Jun , Sommar Jonas , Yin Runsheng , Liu Na
Published: March 2010

Using R/V Shiyan 3 as a sampling platform, measurements of gaseous elemental mercury (GEM), surface seawater total mercury (THg), methyl mercury (MeHg), and dissolved gaseous mercury (DGM) were carried out above and in the South China Sea (SCS). Measurements were collected for 2 weeks (10 to 28 August 2007) during an oceanographic expedition, which circumnavigated the northern SCS from Guangzhou (Canton), Hainan Inland, the Philippines, and back to Guangzhou. GEM concentrations over the northern SCS ranged from 1.04 to 6.75 ng m−3 (mean: 2.62 ng m−3, median: 2.24 ng m−3). The spatial distribution of GEM was characterized by elevated concentrations near the coastal sites adjacent to mainland China and lower concentrations at stations in the open sea. Trajectory analysis revealed that high concentrations of GEM were generally related to air masses from south China and the Indochina peninsula, while lower concentrations of GEM were related to air masses from the open sea area, reflecting great Hg emissions from south China and Indochina peninsula. The mean concentrations of THg, MeHg, and DGM in surface seawater were 1.2 ± 0.3 ng L−1, 0.12 ± 0.05 ng L−1, and 36.5 ± 14.9 pg L−1, respectively. In general, THg and MeHg levels in the northern SCS were higher compared to results reported from most other oceans/seas. Elevated THg levels in the study area were likely attributed to significant Hg delivery from surrounding areas of the SCS primarily via atmospheric deposition and riverine input, whereas other sources like in situ production by various biotic and abiotic processes may be important for MeHg. Average sea/air flux of Hg in the study area was estimated using a gas exchange method (4.5 ± 3.4 ng m−2 h−1). This value was comparable to those from other coastal areas and generally higher than those from open sea environments, which may be attributed to the reemission of Hg previously transported to this area.
Observations of the radiation divergence in the surface layer and its implication for its parameterization in numerical weather prediction models
Authors: Steeneveld G. J. , Wokke M. J. J. , Groot Zwaaftink C. D. , Pijlman S. , Heusinkveld B. G. , Jacobs A. F. G. , Holtslag A. A. M.
Published: March 2010

This paper presents the results of 5 months of in situ observations of the diurnal cycle of longwave radiative heating rate in the lower part of the atmospheric boundary layer over grassland, with a particular focus on nighttime conditions. The observed longwave radiative heating is minimal at the evening transition, with a median value of −1.8 K h−1 between 1.3 and 10 m and −0.5 K h−1 between 10 and 20 m, respectively. After the transition, its magnitude gradually decreases during the night. For individual clear calm nights, a minimal radiative heating rate of −3.5 and −2.0 K h−1 was found for the two indicated layers. The total radiative heating rate appears dominantly controlled by the upward longwave flux divergence. Surprisingly, at noon a radiative heating rate of ∼1 K h−1 was found between 1.3 and 10 m for clear calm days. The availability of these radiation divergence measurements enables evaluation of the model performance for the temperature tendency caused by radiation divergence. The mesoscale model MM5 performs poorly for the stable boundary layer, because it overestimates the surface temperature and wind speed, while it underestimates the magnitude of radiative cooling. Some computationally efficient methods based on physical modeling, statistical modeling, and dimensional analysis are proposed by examining the gathered data set. The physical modeling approach appears to perform best.
Experimental and Preliminary Clinical Evidence of an Ischemic Zone with Prolonged Negative DC Shifts Surrounded by a Normally Perfused Tissue Belt with Persistent Electrocorticographic Depression
Authors: Oliveira-Ferreira Ana I , Milakara Denny , Alam Mesbah , Jorks Devi , Major Sebastian , Hartings Jed A , Lückl Janos , Martus Peter , Graf Rudolf , Dohmen Christian , Bohner Georg , Woitzik Johannes , Dreier Jens P ,   for the COSBID study group
Published: March 2010

In human cortex it has been suggested that the tissue at risk is indicated by clusters of spreading depolarizations (SDs) with persistent depression of high-frequency electrocorticographic (ECoG) activity. We here characterized this zone in the ET-1 model in rats using direct current (DC)-ECoG recordings. Topical application of the vasoconstrictor endothelin-1 (ET-1) induces focal ischemia in a concentration-dependent manner restricted to a region exposed by a cranial window, while a healthy cortex can be studied at a second naïve window. SDs originate in the ET-1-exposed cortex and invade the surrounding tissue. Necrosis is restricted to the ET-1-exposed cortex. In this study, we discovered that persistent depression occurred in both ET-1-exposed and surrounding cortex during SD clusters. However, the ET-1-exposed cortex showed longer-lasting negative DC shifts and limited high-frequency ECoG recovery after the cluster. DC-ECoG recordings of SD clusters with persistent depression from patients with aneurysmal subarachnoid hemorrhage were then analyzed for comparison. Limited ECoG recovery was associated with significantly longer-lasting negative DC shifts in a similar manner to the experimental model. These preliminary results suggest that the ischemic zone in rat and human cortex is surrounded by a normally perfused belt with persistently reduced synaptic activity during the acute injury phase.
Role of cellular bioenergetics in smooth muscle cell proliferation induced by platelet-derived growth factor
Authors: Perez Jessica , Hill Bradford G. , Benavides Gloria A. , Dranka Brian P. , Darley-Usmar Victor M.
Published: March 2010

Abnormal smooth muscle cell proliferation is a hallmark of vascular disease. Although growth factors are known to contribute to cell hyperplasia, the changes in metabolism associated with this response, particularly mitochondrial respiration, remain unclear. Given the increased energy requirements for proliferation, we hypothesized that PDGF (platelet-derived growth factor) would stimulate glycolysis and mitochondrial respiration and that this elevated bioenergetic capacity is required for smooth muscle cell hyperplasia. To test this hypothesis, cell proliferation, glycolytic flux and mitochondrial oxygen consumption were measured after treatment of primary rat aortic VSMCs (vascular smooth muscle cells) with PDGF. PDGF increased basal and maximal rates of glycolytic flux and mitochondrial oxygen consumption; enhancement of these bioenergetic pathways led to a substantial increase in the mitochondrial reserve capacity. Interventions with the PI3K (phosphoinositide 3-kinase) inhibitor LY-294002 or the glycolysis inhibitor 2-deoxy-D-glucose abrogated PDGF-stimulated proliferation and prevented augmentation of glycolysis and mitochondrial reserve capacity. Similarly, when L-glucose was substituted for D-glucose, PDGF-dependent proliferation was abolished, as were changes in glycolysis and mitochondrial respiration. Interestingly, LDH (lactate dehydrogenase) protein levels and activity were significantly increased after PDGF treatment. Moreover, substitution of L-lactate for D-glucose was sufficient to increase mitochondrial reserve capacity and cell proliferation after treatment with PDGF; these effects were inhibited by the LDH inhibitor oxamate. These results suggest that glycolysis, by providing substrates that enhance the mitochondrial reserve capacity, plays an essential role in PDGF-induced cell proliferation, underscoring the integrated metabolic response required for proliferation of VSMCs in the diseased vasculature.
Myogenic regulatory factors regulate M-cadherin expression by targeting its proximal promoter elements
Authors: Hsiao Sheng Pin , Chen Shen Liang
Published: March 2010

M- and N-cadherin are members of the Ca2+-dependent cell–cell adhesion molecule family. M-cadherin is expressed predominantly in developing skeletal muscles and has been implicated in terminal myogenic differentiation, particularly in myoblast fusion. N-cadherin-mediated cell–cell adhesion also plays an important role in skeletal myogenesis. In the present study, we found that both genes were differentially expressed in C2C12 and Sol8 myoblasts during myogenic differentiation and that the expression of M-cadherin was preferentially enhanced in slow-twitch muscle. Interestingly, most MRFs (myogenic regulatory factors) significantly activated the promoter of M-cadherin, but not that of N-cadherin. In line with this, overexpression of MyoD in C3H10T1/2 fibroblasts strongly induced endogenous M-cadherin expression. Promoter analysis in silico and in vitro identified an E-box (from −2 to +4) abutting the transcription initiation site within the M-cadherin promoter that is bound and differentially activated by different MRFs. The activation of the M-cadherin promoter by MRFs was also modulated by Bhlhe40 (basic helix–loop–helix family member e40). Finally, chromatin immunoprecipitation proved that MyoD as well as myogenin binds to the M-cadherin promoter in vivo. Taken together, these observations identify a molecular mechanism by which MRFs regulate M-cadherin expression directly to ensure the terminal differentiation of myoblasts.
Modelling Barrett's oesophagus
Authors: Kong Jianping , Stairs Douglas B. , Lynch John P.
Published: March 2010

Barrett's oesophagus is the replacement of normal squamous oesophageal epithelium with an intestinalized columnar epithelium. Although some insight has been gained as to what Barrett's oesophagus is, how this columnar epithelium emerges from within a stratified squamous epithelium remains an unanswered question. We have sought to determine whether oesophageal keratinocytes can be trans-differentiated into Barrett's oesophagus cells. Using an Affymetrix microarray, we found unexpectedly that gene-expression patterns in the Barrett's oesophagus were only slightly more similar to the normal small intestine than they were to the normal oesophagus. Thus gene-expression patterns suggest significant molecular similarities remain between Barrett's oesophagus cells and normal squamous oesophageal epithelium, despite their histological resemblance with intestine. We next determined whether directed expression of intestine-specific transcription factors could induce intestinalization of keratinocytes. Retroviral-mediated Cdx2 (Caudal-type homeobox 2) expression in immortalized human oesophageal keratinocytes engineered with human telomerase reverse transcriptase (EPC2-hTERT cells) could be established transiently, but not maintained, and was associated with a reduction in cell proliferation. Co-expression of cyclin D1 rescued proliferation in the Cdx2-expressing cells, but co-expression of dominant-negative p53 did not. Cdx2 expression in the EPC2-hTERT.D1 cells did not induce intestinalization. However, when combined with treatments that induce chromatin remodelling, there was a significant induction of Barrett's oesophagus-associated genes. Studies are ongoing to determine whether other intestinal transcription factors, either alone or in combination, can provoke greater intestinalization of oesophageal keratinocytes. We conclude that, on the basis of gene-expression patterns, Barrett's oesophagus epithelial cells may represent an intermediate between oesophageal keratinocytes and intestinal epithelial cells. Moreover, our findings suggest that it may be possible to induce Barrett's oesophagus epithelial cells from oesophageal keratinocytes by altering the expression of certain critical genes.
Genetic diversity during the development of Barrett's oesophagus-associated adenocarcinoma: how, when and why?
Authors: Graham Trevor A. , McDonald Stuart A.C.
Published: March 2010

Recent investigations into Barrett's oesophagus at the level of individual crypts have found significant genetic heterogeneity within a single lesion. Furthermore, this genetic diversity has been shown to predict cancer development. In the present article, we review the genetic alterations implicated in disease progression in Barrett's oesophagus and discuss how genetic diversity could arise during tumorigenesis. Three arguments are discussed: a high mutation rate coupled with strong selection, clonal interaction driving progression, and a hitherto unidentified alteration that disrupts epithelial cell homoeostasis. Suggestions are made for future research to distinguish which of these theories is the predominant mechanism in Barrett's oesophagus-associated tumorigenesis.
Orchestrating serine resolvases
Authors: Rice Phoebe A. , Mouw Kent. W. , Montaño Sherwin P. , Boocock Martin R. , Rowland Sally-J. , Stark W. Marshall
Published: March 2010

A remarkable feature of the serine resolvases is their regulation: the wild-type enzymes will catalyse intra- but not inter-molecular recombination, can sense the relative orientation of their sites and can exchange strands directionally, despite the fact that there is no net release of chemical bond energy. The key to this regulation is that they are only active within a large intertwined complex called the ‘synaptosome’. Because substrate topology greatly facilitates (or, in other cases, inhibits) formation of the synaptosome, it acts as a ‘topological filter’. Within the defined topology of the synaptosome, strand exchange releases supercoiling tension, providing an energy source to bias the reaction direction. The regulatory portion of this complex contains additional copies of the recombinase and sometimes other DNA-bending proteins. We are using a combination of X-ray crystallography, biochemistry and genetics to model the full synaptic complex and to understand how the regulatory portion activates the crossover-site-bound recombinases.
Site-specific recombination by φC31 integrase and other large serine recombinases
Authors: Smith Margaret C.M. , Brown William R.A. , McEwan Andrew R. , Rowley Paul A.
Published: March 2010

Most temperate phages encode an integrase for integration and excision of the prophage. Integrases belong either to the λ Int family of tyrosine recombinases or to a subgroup of the serine recombinases, the large serine recombinases. Integration by purified serine integrases occurs efficiently in vitro in the presence of their cognate (~50 bp) phage and host attachment sites, attP and attB respectively. Serine integrases require an accessory protein, Xis, to promote excision, a reaction in which the products of the integration reaction, attL and attR, recombine to regenerate attP and attB. Unlike other directional recombinases, serine integrases are not controlled by proteins occupying accessory DNA-binding sites. Instead, it is thought that different integrase conformations, induced by binding to the DNA substrates, control protein–protein interactions, which in turn determine whether recombination proceeds. The present review brings together the evidence for this model derived from the studies on φC31 integrase, Bxb1 integrase and other related proteins.
Maintaining a sense of direction during long-range communication on DNA
Authors: Szczelkun Mark D. , Friedhoff Peter , Seidel Ralf
Published: March 2010

Many biological processes rely on the interaction of proteins with multiple DNA sites separated by thousands of base pairs. These long-range communication events can be driven by both the thermal motions of proteins and DNA, and directional protein motions that are rectified by ATP hydrolysis. The present review describes conflicting experiments that have sought to explain how the ATP-dependent Type III restriction–modification enzymes can cut DNA with two sites in an inverted repeat, but not DNA with two sites in direct repeat. We suggest that an ATPase activity may not automatically indicate a DNA translocase, but can alternatively indicate a molecular switch that triggers communication by thermally driven DNA sliding. The generality of this mechanism to other ATP-dependent communication processes such as mismatch repair is also discussed.
Confirmed rare copy number variants implicate novel genes in schizophrenia
Authors: Tam Gloria W.C. , van de Lagemaat Louie N. , Redon Richard , Strathdee Karen E. , Croning Mike D.R. , Malloy Mary P. , Muir Walter J. , Pickard Ben S. , Deary Ian J. , Blackwood Douglas H.R. , Carter Nigel P. , Grant Seth G.N.
Published: March 2010

Understanding how cognitive processes including learning, memory, decision making and ideation are encoded by the genome is a key question in biology. Identification of sets of genes underlying human mental disorders is a path towards this objective. Schizophrenia is a common disease with cognitive symptoms, high heritability and complex genetics. We have identified genes involved with schizophrenia by measuring differences in DNA copy number across the entire genome in 91 schizophrenia cases and 92 controls in the Scottish population. Our data reproduce rare and common variants observed in public domain data from >3000 schizophrenia cases, confirming known disease loci as well as identifying novel loci. We found copy number variants in PDE10A (phosphodiesterase 10A), CYFIP1 [cytoplasmic FMR1 (Fragile X mental retardation 1)-interacting protein 1], K+ channel genes KCNE1 and KCNE2, the Down's syndrome critical region 1 gene RCAN1 (regulator of calcineurin 1), cell-recognition protein CHL1 (cell adhesion molecule with homology with L1CAM), the transcription factor SP4 (specificity protein 4) and histone deacetylase HDAC9, among others (see http://www.genes2cognition.org/SCZ-CNV). Integrating the function of these many genes into a coherent model of schizophrenia and cognition is a major unanswered challenge.
TorsinA and DYT1 dystonia: a synaptopathy?
Authors: Warner Thomas T. , Granata Alassandra , Schiavo Giampietro
Published: March 2010

DYT1 dystonia is an autosomal dominant movement disorder, characterized by early onset of involuntary sustained muscle contractions. It is caused by a 3-bp deletion in the DYT1 gene, which results in the deletion of a single glutamate residue in the C-terminus of the protein TA (torsinA). TA is a member of the AAA+ (ATPase associated with various cellular activities) family of chaperones with multiple functions in the cell. There is no evidence of neurodegeneration in DYT1 dystonia, which suggests that mutant TA leads to functional neuronal abnormalities, leading to dystonic movements. In recent years, different functional roles have been attributed to TA, including being a component of the cytoskeleton and the NE (nuclear envelope), and involvement in the secretory pathway and SV (synaptic vesicle) machinery. The aim of the present review is to summarize these findings and the different models proposed, which have contributed to our current understanding of the function of TA, and also to discuss the evidence implicating TA in SV function.
Presynaptic dysfunction in Huntington's disease
Authors: Rozas José L. , Gómez-Sánchez Leonardo , Tomás-Zapico Cristina , Lucas José J. , Fernández-Chacón Rafael
Published: March 2010

HD (Huntington's disease) is produced by the expression of mutant forms of the protein htt (huntingtin) containing a pathologically expanded poly-glutamine repeat. For unknown reasons, in HD patients and HD mouse models, neurons from the striatum and cerebral cortex degenerate and lead to motor dysfunction and dementia. Synaptic transmission in those neurons becomes progressively altered during the course of the disease. However, the relationship between synaptic dysfunction and neurodegeneration in HD is not yet clear. Are there early specific functional synaptic changes preceding symptoms and neurodegeneration? What is the role of those changes in neuronal damage? Recent experiments in a Drosophila model of HD have showed that abnormally increased neurotransmitter release might be a leading cause of neurodegeneration. In the present review, we summarize recently described synaptic alterations in HD animal models and discuss potential underlying molecular mechanisms.
The developmental roles of FMRP
Authors: Till Sally M.
Published: March 2010

FXS (Fragile X syndrome) is the most common genetically inherited form of cognitive impairment. The predominant cause of the syndrome is the loss of a single protein, FMRP (Fragile X mental retardation protein). Many of the cognitive and behavioural features found in Fragile X individuals emerge during childhood and are associated with abnormal organization of cortical connections. However, although FMRP is expressed as early as embryogenesis, relatively little is known about its roles during development or how this may influence FXS phenotypes in adulthood. The present review focuses specifically on the evidence for the functions of FMRP during embryonic and early postnatal development. The current knowledge of the role of FMRP in FXS will be briefly summarized before addressing how alterations in the formation and refinement of neuronal connections and synaptic function that result from the loss of FMRP may in turn influence behaviours that are expressed during the first few postnatal weeks. I will then briefly highlight some outstanding questions about the developmental roles of FMRP and their possible relationship to symptoms found in adults with FXS.
Errant ensembles: dysfunctional neuronal network dynamics in schizophrenia
Authors: Jones Matt W.
Published: March 2010

Most complex psychiatric disorders cannot be explained by pathology of a single brain region, but arise as a consequence of dysfunctional interactions between brain regions. Schizophrenia, in particular, has been described as a ‘disconnection syndrome’, but similar principles are likely to apply to depression and ADHD (attention deficit hyperactivity disorder). All these diseases are associated with impaired co-ordination of neural population activity, which manifests as abnormal EEG (electroencephalogram) and LFP (local field potential) oscillations both within and across subcortical and cortical brain regions. Importantly, it is increasingly possible to link oscillations and interactions at distinct frequencies to the physiology and/or pathology of distinct classes of neurons and interneurons. Such analyses increasingly implicate abnormal levels, timing or modulation of GABA (γ-aminobutyric acid)-ergic inhibition in brain disease. The present review discusses the evidence suggesting that dysfunction of a particular class of interneurons, marked by their expression of the calcium-binding protein parvalbumin, could contribute to the broad range of neurophysiological and behavioural symptoms characteristic of schizophrenia.
S-acylation by the DHHC protein family
Authors: Greaves Jennifer , Chamberlain Luke H.
Published: March 2010

A family of 23 DHHC (Asp-His-His-Cys) proteins that function as mammalian S-acyltransferases has been identified, reinvigorating the study of protein S-acylation. Recent studies have continued to reveal how S-acylation affects target proteins, and have provided glimpses of how DHHC-substrate specificity might be achieved.
Caenorhabditis elegans: a useful tool to decipher neurodegenerative pathways
Authors: Johnson James R. , Jenn Robert C. , Barclay Jeff W. , Burgoyne Robert D. , Morgan Alan
Published: March 2010

Neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases affect millions of people. These disorders are age-dependent, progressive and, at present, incurable. A practical and relevant model is needed to investigate the molecular determinants of these debilitating diseases. Mammalian models are often prohibitively expensive, time-consuming and very complex. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for the investigation of the pathophysiology of these disorders. We describe recent findings in this area and show how C. elegans is being used to broaden our knowledge of human neurodegenerative diseases.
Life after meiosis: patterning the angiosperm male gametophyte
Authors: Borg Michael , Twell David
Published: March 2010

Pollen grains represent the highly reduced haploid male gametophyte generation in angiosperms. They play an essential role in plant fertility by generating and delivering twin sperm cells to the embryo sac to undergo double fertilization. The functional specialization of the male gametophyte and double fertilization are considered to be key innovations in the evolutionary success of angiosperms. The haploid nature of the male gametophyte and its highly tractable ontogeny makes it an attractive system to study many fundamental biological processes, such as cell fate determination, cell-cycle progression and gene regulation. The present mini-review encompasses key advances in our understanding of the molecular mechanisms controlling male gametophyte patterning in angiosperms. A brief overview of male gametophyte development is presented, followed by a discussion of the genes required at landmark events of male gametogenesis. The value of the male gametophyte as an experimental system to study the interplay between cell fate determination and cell-cycle progression is also discussed and exemplified with an emerging model outlining the regulatory networks that distinguish the fate of the male germline from its sister vegetative cell. We conclude with a perspective of the impact emerging data will have on future research strategies and how they will develop further our understanding of male gametogenesis and plant development.
Self-incompatibility in Papaver: identification of the pollen S-determinant PrpS
Authors: Poulter Natalie S. , Wheeler Michael J. , Bosch Maurice , Franklin-Tong Vernonica E.
Published: March 2010

Many flowering plants are hermaphrodite, posing the problem of self-fertilization and the subsequent loss of the genetic fitness of the offspring. To prevent this, many plants have developed a genetically controlled mechanism called self-incompatibility (SI). When the male and female S-determinants match, self (incompatible) pollen is recognized and rejected before fertilization can occur. In poppy (Papaver rhoeas), the pistil S-determinant (PrsS) is a small secreted protein that interacts with incompatible pollen, initiating a Ca2+-dependent signalling network. SI triggers several downstream events, including depolymerization of the cytoskeleton, phosphorylation of two soluble inorganic pyrophosphatases and an MAPK (mitogen-activated protein kinase). This culminates in PCD (programmed cell death) involving several caspase-like activities. The recent discovery of the Papaver pollen S-determinant PrpS marks a significant step forward in the understanding of the Papaver SI system. PrpS encodes a ~20 kDa predicted transmembrane protein which has no homology with known proteins. It is specifically expressed in pollen, linked to the pistil S-determinant, and displays the high polymorphism expected of an S-locus determinant. The present review focuses on the discovery and characterization of PrpS which strongly support the hypothesis that Papaver SI is triggered by the interaction of PrsS and PrpS.
Functional genomics of pollen tube–pistil interactions in Arabidopsis
Authors: Palanivelu Ravishankar , Johnson Mark A.
Published: March 2010

The pollen tube represents an attractive model system for functional genomic analysis of the cell–cell interactions that mediate guided cellular growth. The pollen tube extends through pistil tissues and responds to guidance cues that direct the tube towards an ovule, where it releases sperm for fertilization. Pollen is readily isolated from anthers, where it is produced, and can be induced to produce a tube in vitro. Interestingly, pollen tube growth is significantly enhanced in pistils, and pollen tubes are rendered competent to respond to guidance cues after growth in a pistil. This potentiation of the pollen tube by the pistil suggested that pollen tubes alter their gene-expression programme in response to their environment. Recently, the transcriptomes of pollen tubes grown in vitro or through pistil tissues were determined. Significant changes in the transcriptome were found to accompany growth in vitro and through the pistil tissues. Reverse genetic analysis of pollen-tube-induced genes identified a new set of factors critical for pollen tube extension and navigation of the pistil environment. Recent advances reviewed in the present paper suggest that functional genomic analysis of pollen tubes has the potential to uncover the regulatory networks that shape the genetic architecture of the pollen tube as it responds to migratory cues produced by the pistil.
Male gamete biology in flowering plants
Authors: Russell Scott D. , Gou Xiaoping , Wei Xiaoping , Yuan Tong
Published: March 2010

Flowering plant reproduction is characterized by double fertilization, in which two diminutive brother sperm cells initiate embryo and endosperm. The role of the male gamete, although studied structurally for over a century at various levels, is still being explored on a molecular and cellular level. The potential of the male to influence development has been historically underestimated and the reasons for this are obvious: limitations provided by maternal imprinting, the much greater cellular volume of female gametes and the general paucity of paternal effects. However, as more is known about molecular expression of chromatin-modifying proteins, ubiquitin pathway proteins and transcription factors in sperm cells, as well as their ability to achieve effect by intaglio expression, passing transcripts directly into translation, the role of the male is likely to expand. Much of the expression in the male germline that appears to be distinct from patterns of pollen vegetative cell expression may be the result of chromosomal level regulation of transcription.
Floral stem cells: from dynamic balance towards termination
Authors: Sun Bo , Ito Toshiro
Published: March 2010

During early flower development in Arabidopsis, floral stem cells proliferate and produce a sufficient amount of cells that are recruited for organogenesis. However, after the central organ primordia initiate, stem cell activity in the floral meristem is terminated to ensure the differentiation of a fixed number of floral organs. Underlying this process, the genetic programme regulating the fate of floral meristems undergoes a shift from a spatially balanced signalling scheme for stem cell maintenance to a temporally controlled transcriptional scheme for stem cell termination. Precise timing of stem cell termination is a key issue for flower development, which is secured by the orchestration of multiple regulators in transcriptional and epigenetic regulation.
Protein interactions and subcellular localization in S-RNase-based self-incompatibility
Authors: Sims Thomas L. , Patel Avani , Shrestha Pratima
Published: March 2010

The recent identification of several proteins playing key roles in S-RNase-based gametophytic self-incompatibility has led both to a greater understanding of the molecular biology of this response, as well as to questions regarding the precise mechanism by which compatible pollen tubes are recognized and accepted. A proposed variant SCFSLF (where SCF is SSK1/cullin/F-box and SLF is S-locus F-box) ubiquitin ligase complex is thought to play a central role in recognizing and inhibiting non-self S-RNases, but the exact role of ubiquitination remains unclear. How the possible sequestration of non-self S-RNases in a pollen vacuolar compartment can be reconciled with the need for protein interaction between S-RNase and the SCFSLF complex needs to be determined. Current work to answer these questions focuses on more precisely defining quantitative protein interactions and subcellular localization of proteins involved in S-RNase-based gametophytic self-incompatibility.
Female gametophyte-controlled pollen tube guidance
Authors: Márton Mihaela-Luiza , Dresselhaus Thomas
Published: March 2010

During the evolution of flowering plants, their sperm cells have lost mobility and are transported from the stigma to the female gametophyte via the pollen tube to achieve double fertilization. Pollen tube growth and guidance is largely governed by the maternal sporophytic tissues of the stigma, style and ovule. However, the last phase of the pollen tube path is under female gametophyte control and is expected to require extensive cell–cell communication events between both gametophytes. Until recently, little was known about the molecules produced by the female gametophyte that are involved in this process. In the present paper, we review the most recent development in this field and focus on the role of secreted candidate signalling ligands.
Let's get physical: gamete interaction in flowering plants
Authors: Sprunck Stefanie
Published: March 2010

Fertilization comprises a series of precisely orchestrated steps that culminate in the fusion of male and female gametes. The most intimate steps during fertilization encompass gamete recognition, adhesion and fusion. In animals, some binding-effector proteins and enzymes have been identified that act on the cell surfaces of the gametes to regulate gamete compatibility and fertilization success. In contrast, exploring plant gamete interaction during double fertilization, a characteristic trait of flowering plants, has been hampered for a long time because of the protected location of the female gametes and technical limitations. Over the last couple of years, however, the use of advanced methodologies, new imaging tools and new mutants has provided deeper insights into double fertilization, at both the cellular and the molecular level, especially for the model plant Arabidopsis thaliana. Most likely, one consequence of inventing double fertilization may be the co-evolution of special molecular mechanisms to govern each successful sperm delivery and efficient gamete recognition and fusion. In vivo imaging of double fertilization and the recent discovery of numerous female-gametophyte-specific expressed genes encoding small secreted proteins, some of whom were found to be essential for the fertilization process, support this hypothesis. Nevertheless, recent findings indicate that at least the membrane-merger step in plant gamete interaction may rely on an ancient and widely used gamete fusion system.
Regulation of plant gene expression by alternative splicing
Authors: Simpson Craig G. , Manthri Sujatha , Raczynska Katarzyna Dorota , Kalyna Maria , Lewandowska Dominika , Kusenda Branislav , Maronova Monika , Szweykowska-Kulinska Zofia , Jarmolowski Artur , Barta Andrea , Brown John W.S.
Published: March 2010

AS (alternative splicing) is a post-transcriptional process which regulates gene expression through increasing protein complexity and modulating mRNA transcript levels. Regulation of AS depends on interactions between trans-acting protein factors and cis-acting signals in the pre-mRNA (precursor mRNA) transcripts, termed ‘combinatorial’ control. Dynamic changes in AS patterns reflect changes in abundance, composition and activity of splicing factors in different cell types and in response to cellular or environmental cues. Whereas the SR protein family of splicing factors is well-studied in plants, relatively little is known about other factors influencing the regulation of AS or the consequences of AS on mRNA levels and protein function. To address fundamental questions on AS in plants, we are exploiting a high-resolution RT (reverse transcription)–PCR system to analyse multiple AS events simultaneously. In the present paper, we describe the current applications and development of the AS RT–PCR panel in investigating the roles of splicing factors, cap-binding proteins and nonsense-mediated decay proteins on AS, and examining the extent of AS in genes involved in the same developmental pathway or process.
Recent developments in photorespiration research
Authors: Bauwe Hermann
Published: March 2010

Photorespiration is the light-dependent release of CO2 initiated by Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase) during oxygenic photosynthesis. It occurs during the biochemical reactions of the photorespiratory C2 cycle, which is an ancillary metabolic process that allows photosynthesis to occur in oxygen-containing environments. Recent research has identified the genes for many plant photorespiratory enzymes, allowing precise functional analyses by reverse genetics. Similar studies with cyanobacteria disclosed the evolutionary origin of photorespiratory metabolism in these ancestors of plastids.
Exploiting induced variation to dissect quantitative traits in barley
Authors: Druka Arnis , Franckowiak Jerome , Lundqvist Udda , Bonar Nicola , Alexander Jill , Guzy-Wrobelska Justyna , Ramsay Luke , Druka Ilze , Grant Iain , Macaulay Malcolm , Vendramin Vera , Shahinnia Fahimeh , Radovic Slobodanka , Houston Kelly , Harrap David , Cardle Linda , Marshall David , Morgante Michele , Stein Nils , Waugh Robbie
Published: March 2010

The identification of genes underlying complex quantitative traits such as grain yield by means of conventional genetic analysis (positional cloning) requires the development of several large mapping populations. However, it is possible that phenotypically related, but more extreme, allelic variants generated by mutational studies could provide a means for more efficient cloning of QTLs (quantitative trait loci). In barley (Hordeum vulgare), with the development of high-throughput genome analysis tools, efficient genome-wide identification of genetic loci harbouring mutant alleles has recently become possible. Genotypic data from NILs (near-isogenic lines) that carry induced or natural variants of genes that control aspects of plant development can be compared with the location of QTLs to potentially identify candidate genes for development­-related traits such as grain yield. As yield itself can be divided into a number of allometric component traits such as tillers per plant, kernels per spike and kernel size, mutant alleles that both affect these traits and are located within the confidence intervals for major yield QTLs may represent extreme variants of the underlying genes. In addition, the development of detailed comparative genomic models based on the alignment of a high-density barley gene map with the rice and sorghum physical maps, has enabled an informed prioritization of ‘known function’ genes as candidates for both QTLs and induced mutant genes.
Genistein: a natural isoflavone with a potential for treatment of genetic diseases
Authors: Węgrzyn Grzegorz , Jakóbkiewicz-Banecka Joanna , Gabig-Cimińska Magdalena , Piotrowska Ewa , Narajczyk Magdalena , Kloska Anna , Malinowska Marcelina , Dziedzic Dariusz , Gołębiewska Izabela , Moskot Marta , Węgrzyn Alicja
Published: March 2010

Genistein [4′,5,7-trihydroxyisoflavone or 5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one] is a natural isoflavone occurring in many plants known to possess various biological activities, ranging from phyto-oestrogenic to antioxidative actions. Recent studies indicated that this isoflavone can also be considered as a drug for as yet untreatable genetic diseases. In the present review, we discuss a plausible use of genistein in treatment of two genetic disorders: CF (cystic fibrosis) and MPS (mucopolysaccharidosis). Although various biological actions of genistein are employed in these two cases, in vitro studies, tests on animal models and pilot clinical trials suggest that this plant-derived compound might be a real hope for patients suffering from severe inherited disorders with relatively complicated pathomechanisms, including those affecting the central nervous system.