bluuebunny/crossref_metadata_2025 huggingface dataset:
Synaptopathy: dysfunction of synaptic function?
Authors: Brose Nils , O'Connor Vincent , Skehel Paul
Published: March 2010

Synaptopathy is an increasingly popular term used to define key features of neurodegenerative and psychiatric disease. It implies that disruptions in synaptic structure and function are potentially the major determinant of such brain diseases. The Synaptopathies: Dysfunction of Synaptic Function Biochemical Society Focused Meeting brought together several invited speakers, supplemented with short communications from young scientists, who addressed this possibility. The talks spanned the full gamut of approaches that brought molecular, cellular, systems and whole-animal experimentation together to address how fundamental synaptic biology was increasingly informing on dysfunction in disease. The disease and models thereof discussed included Alzheimer's disease, prions, Huntington's disease, Parkinson's disease, schizophrenia and autism. The audience were asked to reflect on whether synaptopathy, although attractive and conceptually useful, provided a significant explanation as the cause of these major diseases. The breadth of the meeting reinforced the complexity of these brain diseases, supported the significance of synaptic dysfunction in disease, but left open the issue as to whether the prime cause of these disorders could be resolved as simple synaptic dysfunction. Thus, despite revealing a value of synaptopathy, further investigation will be required to reveal its balance in the cause and effect in each of the major brain diseases.
Endosomal sorting of AMPA receptors in hippocampal neurons
Authors: Hanley Jonathan G.
Published: March 2010

An important mechanism for the regulation of excitatory synaptic transmission in the hippocampus involves tight control of AMPAR [AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor] trafficking to alter the number or subtype of synaptic receptors. This is achieved via the multiple stages of the endosomal system. AMPARs constitutively cycle through early endosomes and recycling endosomes to maintain synaptic receptor numbers. However, on induction of synaptic plasticity, subtle alterations are made to this cycle by the action of specific AMPAR-interacting proteins and also via a number of additional proteins that regulate endosomal sorting more generally. During long-term depression, receptors are diverted to late endosomes and lysosomes rather than recycling back to the plasma membrane, hence reducing the number of receptors at the synapse. The increased number of synaptic AMPARs after induction of LTP (long-term potentiation) originates from the recycling compartment. In addition, transient changes in subunit composition may arise as a result of retention of AMPAR subtypes within the endosome during LTP. Aberrant trafficking after pathological insults such as oxygen/glucose deprivation or mechanical trauma also involves alterations in synaptic AMPAR subunit composition, leading to calcium influx that ultimately results in cell death.
Drug targets for amyloidosis
Authors: Kolstoe Simon E. , Wood Steve P.
Published: March 2010

The amyloid hypothesis indicates that protein misfolding is at the root of many neurodegenerative disorders. Small molecules targeting the formation, clearance, aggregation to toxic oligomers or SOD (superoxide dismutase)-like activities of Aβ (amyloid β-peptide) 1–42 have provided encouraging candidates for AD (Alzheimer's disease) medicines in animal models, although none have yet proved to be effective in human trials. We have been investigating approaches to treat systemic amyloidoses, conditions that show common features with some CNS (central nervous system) disorders. For TTR (transthyretin) amyloidosis, we are seeking small molecule compounds that stabilize the amyloidogenic protein and either prevent its structural transition to the crossed β fibres deposited in diseased tissues, or promote its clearance from circulation. Effective stabilizer compounds that simultaneously bind to both thyroxine-binding sites have been developed. A more generic approach involves targeting the plasma glycoprotein SAP (serum amyloid P component). This protein recognizes the misfolded polypeptide structures of amyloid deposits wherever they occur, and acts as a powerful anti-opsonin. We have developed a bivalent drug called CPHPC {(R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]-pyrrolidine-2-carboxylic acid} that cross-links pairs of pentameric SAP molecules and causes their rapid elimination from the circulation. This strategy raises the prospect of encouraging natural mechanisms to clear amyloid and recent work suggests that this approach extends to the CNS.
‘Holistic’ synaptogenesis
Authors: Poulopoulos Alexandros
Published: March 2010

Synapses between nerve cells in the mammalian brain are not only extremely numerous but also very diverse with respect to their structural and functional characteristics. This heterogeneity arises despite the fact that a set of common basic protein ‘building blocks’ is shared by many synapses. Among these, postsynaptic scaffolding proteins play a key role. They have the ability to assemble into membrane-tethered lattices and to adopt unique conformational states in different postsynaptic microenvironments, which may represent a key prerequisite of synapse heterogeneity. Analyses of such synaptic superstructures, rather than individual proteins and their interactions, are required to develop a mechanistic understanding of postsynaptic differentiation, synapse diversity, and dynamics.
Presynaptic roles of intracellular Ca2+ stores in signalling and exocytosis
Authors: Nizami Sohaib , Lee Vivian W.Y. , Davies Jennifer , Long Philip , Jovanovic Jasmina N. , Sihra Talvinder S.
Published: March 2010

The signalling roles of Ca2+ic (intracellular Ca2+) stores are well established in non-neuronal and neuronal cells. In neurons, although Ca2+ic stores have been assigned a pivotal role in postsynaptic responses to Gq-coupled receptors, or secondarily to extracellular Ca2+ influx, the functions of dynamic Ca2+ic stores in presynaptic terminals remain to be fully elucidated. In the present paper, we review some of the recent evidence supporting an involvement of Ca2+ic in presynaptic function, and discuss loci at which this source of Ca2+ may impinge. Nerve terminal preparations provide good models for functionally examining putative Ca2+ic stores under physiological and pathophysiological stimulation paradigms, using Ca2+-dependent activation of resident protein kinases as sensors for fine changes in intracellular Ca2+ levels. We conclude that intraterminal Ca2+ic stores may, directly or indirectly, enhance neurotransmitter release following nerve terminal depolarization and/or G-protein-coupled receptor activation. During conditions that prevail following neuronal ischaemia, increased glutamate release instigated by Ca2+ic store activation may thereby contribute to excitotoxicity and eventual synaptopathy.
Are synapses targets of nanoparticles?
Authors: Fedorovich Sergei V. , Alekseenko Alexandra V. , Waseem Tatyana V.
Published: March 2010

The last few years have been marked by real breakthroughs in the field of nanotechnology. Application of nanoparticles was proposed for diagnosis and treatment of different central nervous system diseases. Exposure to nanoparticles in vivo increases the risk of onset of neurodegenerative diseases and nanoparticles are apparently able to kill neurons in vitro. We suggested that presynaptic terminals of neurons are another target for nanoparticles, beyond the already established microglial cells. Ferritin was chosen as a prototypic nanoparticle model. We found that even a high concentration of ferritin, 800 μg/ml, was not able to induce spontaneous release of [14C]glutamate. In contrast, [14C]glutamate uptake was inhibited by ferritin in a dose-dependent fashion. As a next step, the influence of ferritin on the formation of reactive oxygen species was monitored using the fluorescent dye DCFH-DA (2′,7′-dichlorofluorescein diacetate). It was shown that ferritin leads to a dose-dependent formation of free radicals. We found that the ferritin-mediated changes in glutamatergic neurotransmission at presynaptic endings can result in neuronal damage and finally neurodegeneration.
Alzheimer's disease and amyloid β-peptide deposition in the brain: a matter of ‘aging’?
Authors: Moro Maria Luisa , Collins Matthew J. , Cappellini Enrico
Published: March 2010

Biomolecules can experience aging processes that limit their long-term functionality in organisms. Typical markers of protein aging are spontaneous chemical modifications, such as AAR (amino acid racemization) and AAI (amino acid isomerization), mainly involving aspartate and asparagine residues. Since these modifications may affect folding and turnover, they reduce protein functionality over time and may be linked to pathological conditions. The present mini-review describes evidence of AAR and AAI involvement in the misfolding and brain accumulation of Aβ (amyloid β-peptide), a central event in AD (Alzheimer's disease) synaptic dysfunctions. Structural alterations introduced by site-specific modifications linked to protein aging may affect Aβ production, polymerization and clearance, and therefore play a pivotal role in the pathogenesis of sporadic and genetic forms of AD. Early changes associated with molecular aging also have significant long-term consequences for Aβ folding and turnover. New fast, reproducible and accurate methods for the screening of protein aging markers in biological samples may contribute to improve diagnostic and therapeutic approaches in AD.
Disruption of neuronal function by soluble hyperphosphorylated tau in a Drosophila model of tauopathy
Authors: Cowan Catherine M. , Chee Francis , Shepherd David , Mudher Amritpal
Published: March 2010

Axonal microtubules are essential for transport of materials to the synapse. Compromised microtubules and synaptic loss have been demonstrated in AD (Alzheimer's disease), which is believed to contribute to cognitive dysfunction before neuronal death in the early stages of the disease. The mechanism by which hyperphosphorylated tau, the building block of neurofibrillary tangles, one of the pathological hallmarks of AD, disrupts neuronal and synaptic function is unclear. There is a theory that hyperphosphorylated tau does not bind effectively to microtubules and is no longer able to function in stabilizing them, thus axonal transport can no longer proceed efficiently. This leads to synaptic dysfunction. We have tested this theory in a Drosophila model of tauopathies in which we expressed human tau (h-tau). Using this model, we have tested all aspects of this hypothesis and have demonstrated that axonal transport does become compromised in the presence of hyperphosphorylated h-tau and this leads to synaptic and behavioural defects. We are currently investigating the mechanism by which hyperphosphorylated h-tau mediates this effect and are preliminary data indicate that this entails phospho-tau-mediated effects that are predicted by the tau–microtubule hypothesis, as well as novel effects. These deleterious effects of h-tau occur in the absence of tau filaments and before neuronal death. This sequence of pathogenic events may constitute the mechanism by which abnormal tau disrupts neuronal and synaptic function and contributes to cognitive impairment before neuronal death in the early stages of tauopathies such as AD.
Cell–cell interactions during patterning of theArabidopsisanther
Authors: Feng Xiaoqi , Dickinson Hugh G.
Published: March 2010

Key steps in the evolution of the angiosperm anther include the patterning of the concentrically organized microsporangium and the incorporation of four such microsporangia into a leaf-like structure. Mutant studies in the model plant Arabidopsis thaliana are leading to an increasingly accurate picture of (i) the cell lineages culminating in the different cell types present in the microsporangium (the microsporocytes, the tapetum, and the middle and endothecial layers), and (ii) some of the genes responsible for specifying their fates. However, the processes that confer polarity on the developing anther and position the microsporangia within it remain unclear. Certainly, data from a range of experimental strategies suggest that hormones play a central role in establishing polarity and the patterning of the anther initial, and may be responsible for locating the microsporangia. But the fact that microsporangia were originally positioned externally suggests that their development is likely to be autonomous, perhaps with the reproductive cells generating signals controlling the growth and division of the investing anther epidermis. These possibilities are discussed in the context of the expression of genes which initiate and maintain male and female reproductive development, and in the perspective of our current views of anther evolution.
Inter-cell-layer signalling during Arabidopsis ovule development mediated by the receptor-like kinase STRUBBELIG
Authors: Fulton Lynette , Vaddepalli Prasad , Yadav Ram Kishor , Batoux Martine , Schneitz Kay
Published: March 2010

Plant organs, such as ovules and flowers, arise through cellular events that are precisely co-ordinated between cells within and across clonally distinct cell layers. Receptor-like kinases are cell-surface receptors that perceive and relay intercellular information. In Arabidopsis the leucine-rich repeat receptor-like kinase STRUBBELIG (SUB) is required for integument initiation and outgrowth during ovule development, floral organ shape and the control of the cell division plane in the first subepidermal cell layer of floral meristems, among other functions. A major goal is to understand SUB-mediated signal transduction at the molecular level. Present evidence suggests that SUB affects neighbouring cells in a non-cell-autonomous fashion. In addition, our results indicate that SUB is an atypical, or kinase-dead, kinase. Forward genetics identified three genes, QUIRKY (QKY), ZERZAUST and DETORQUEO, that are thought to contribute to SUB-dependent signal transduction. QKY encodes a predicted membrane-bound protein with four cytoplasmic C2 domains. By analogy to animal proteins with related domain topology, we speculate that QKY may be involved in Ca2+-dependent signalling and membrane trafficking. Studying SUB-dependent signalling will contribute to our understanding of how atypical kinases mediate signal transduction and how cells co-ordinate their behaviour to allow organs, such as ovules, to develop their three-dimensional architecture.
Reproductive cross-talk: seed development in flowering plants
Authors: Nowack Moritz K. , Ungru Alexander , Bjerkan Katrine N. , Grini Paul E. , Schnittger Arp
Published: March 2010

Flowering plants have evolved to be a predominant life form on earth. A common principle of flowering plants and probably one of the main reasons for their evolutionary success is the rapid development of an embryo next to a supporting tissue called the endosperm. The embryo and the endosperm are protected by surrounding maternal tissues, the integuments, and the trinity of integuments, embryo and endosperm comprise the plant seed. For proper seed development, these three structures have to develop in a highly controlled and co-ordinated manner, representing a paradigm for cell–cell communication during development. Communication pathways between the endosperm and the seed coat are now beginning to be unravelled. Moreover, recently isolated mutants affecting plant reproduction have allowed a genetic dissection of seed development, and revealed that the embryo plays a previously unrecognized yet important role in co-ordinating seed development.
Through a generation darkly: small RNAs in the gametophyte
Authors: Grant-Downton Robert T.
Published: March 2010

The various classes of small non-coding RNAs are a fundamentally important component of the transcriptome. These molecules have roles in many essential processes such as regulation of gene expression at the transcriptional and post-transcriptional levels, guidance of DNA methylation and defence against selfish replicators such as transposons. Their diversity and functions in the sporophytic generation of angiosperms is well explored compared with the gametophytic generation, where little is known about them. Recent progress in understanding their abundance, diversity and function in the gametophyte is reviewed.
Recent achievements and trends in experimental plant biology
Authors: Strzałka Kazimierz
Published: March 2010

Between 21 and 25 September 2009, Krakow hosted the 4th Conference of the Polish Society of Experimental Plant Biology, co-organized with the Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, and supported by the Biochemical Society. The aim of the conference was to present and discuss the most important topics in different disciplines of plant experimental science as well as to facilitate the interaction and co-operation between scientists. To achieve this goal, about 30 top specialists in various areas of plant biology were invited to give plenary lectures in the following sessions: Plant structure and development; Plant–microbial interactions; Mitochondria and chloroplasts in cell metabolism; Stress tolerance in plants; Structural and functional organization of plant genomes; Mutants in developmental and metabolic studies; Secondary metabolites as pharmaceutics and nutraceutics; Plant membranes; and Integrating plant functions via signalling molecules: molecular mechanisms. Some of the main problems highlighted in the plenary lectures are briefly summarized in the present paper. Two poster sessions enabled a discussion of over 200 posters presented. The conference had an international character, its official language was English, and among the more than 350 participants, about 60 were from abroad. Several plenary lectures were prepared as short review papers and they are published in this issue of Biochemical Society Transactions.
Involvement of mitochondria in the control of plant cell NAD(P)H reduction levels
Authors: Rasmusson Allan G. , Wallström Sabá V.
Published: March 2010

NADPH and NADH mediate reductant flow between cellular processes, linking central carbon and energy metabolism with intermediary metabolism, stress defence and development. Recent investigations have revealed paths of functional interactions, and have suggested that mitochondrial NADPH oxidation, especially together with the oxidative pentose phosphate pathway, is an important regulator of the cytosolic NADPH reduction level. Furthermore, stress-dependent metabolic pathways substantially affect the NADPH reduction level in particular physiological situations. The mitochondrial impact on the NADPH reduction level provides a model example of the physiological significance of the mitochondrial NAD(P)H dehydrogenase set-up, which is more complex in plants than in other organisms.
Mutations in genes controlling the biosynthesis and accumulation of inositol phosphates in seeds
Authors: Rasmussen Søren K. , Ingvardsen Christina Rønn , Torp Anna Maria
Published: March 2010

Most of the phosphorus in the resting seed is stored inside protein storage vacuoles as PA (phytic acid; InsP6). The biosynthesis and accumulation of PA can be detected beginning from a few days after anthesis and seem to continue during seed development until maturation. The first step in PA biosynthesis is the formation of Ins3P by conversion of glucose 6-phosphate. This is then followed by a sequential and ordered phosphorylation of the remaining five positions of the inositol ring by a number of kinases, resulting in PA. Identification of low-PA mutants in cereals, legumes and Arabidopsis is instrumental for resolving the biosynthetic pathway and identification of genes controlling the accumulation of PA. Mutations in seven genes involved in the metabolism of PA have been identified and characterized among five plant species using induced mutagenesis and insertion elements. Understanding the biosynthetic pathway and genes controlling the accumulation of PA in plant seeds and how PA may balance the free phosphate is of importance for molecular breeding of crop plants, particularly cereals and legumes.
Light-driven regulatory mechanisms in the photosynthetic antenna complex LHCII
Authors: Gruszecki Wieslaw I.
Published: March 2010

Protection against strong-light-induced photodamage of the photosynthetic apparatus and entire organisms is a vital activity in plants and is also realized at the molecular level of the antenna complexes. Reported recently, the regulatory mechanisms which operate in the largest plant antenna complex, LHCII (light-harvesting complex II), based on light-driven processes, are briefly reviewed and discussed. Among those processes are the light-induced twisting of the configuration of the LHCII-bound neoxanthin, the light-induced configurational transition of the LHCII-bound violaxanthin, the light-induced trimer–monomer transition in LHCII and the blue-light-induced excitation quenching in LHCII. The physiological importance of the processes reviewed is also discussed with emphasis on the photoprotective excitation quenching and on possible involvement in the regulation of the xanthophyll cycle.
Phosphatidylinositol 4,5-bisphosphate regulates plant K+ channels
Authors: Wigoda Noa , Ma Xiaohong , Moran Nava
Published: March 2010

Phosphoinositides play an important role in both abiotic and biotic signalling in plants. The signalling cascade may include the production of second messengers by hydrolysis of PtdIns(4,5)P2. However, increasingly, PtdIns(4,5)P2 itself is shown to mediate signalling by regulating target proteins. The present mini-review summarizes the experimentally demonstrated effects of PtdIns(4,5)P2 on plant K+ channels and examines their structure for candidate sites of direct PtdIns(4,5)P2–protein interaction.
Phytochrome three-dimensional structures and functions
Authors: Hughes Jon
Published: March 2010

The complete three-dimensional sensory module structures of the Pr ground state of Synechocystis 6803 Cph1 and the unusual Pfr ground state of the bacteriophytochrome PaBphP (PDB codes 2VEA and 3C2W respectively) have now been solved, revealing an asymmetrical dumbbell form made up of a PAS (Period/ARNT/Singleminded)–GAF (cGMP phosphodiesterase/adenylate cyclase/FhlA) bidomain carrying the chromophore and the smaller PHY (phytochrome-specific) domain. The PHY domain is structurally related to the GAF family, but carries an unusual tongue-like structure which contacts the larger lobe to seal the chromophore pocket. In 2VEA, the tongue makes intimate contact with the helical N-terminus; both the N-terminus and the tongue structures are quite different in 3C2W. As expected, the structures reveal ZZZssa and ZZEssa chromophore conformations in 2VEA and 3C2W respectively, associated with tautomeric differences in several nearby tyrosine residues. Two salt bridges on opposite sides of the chromophore, as well as the associations of the C-ring propionates also differ. It is still unclear, however, which of these structural differences are associated with bacteriophytochromes compared with Cph1 and plant-type phytochromes, the unusual 3C2W Pfr ground state functionality compared with the Pr ground state or the Pr compared with Pfr photoisomerism. To access the latter unambiguously, both Pr and Pfr structures of the same molecule are required. New solid-phase NMR data for Cph1 in the Pr, Pfr and freeze-trapped intermediate states reveal unexpected changes in the chromophore during Pfr→Pr photoconversion. These, together with our efforts to solve the three-dimensional structure of a complete phytochrome molecule are also described.
Crossing the ‘Uncanny Valley’: Adaptation to Cartoon Faces Can Influence Perception of Human Faces
Authors: Chen Haiwen , Russell Richard , Nakayama Ken , Livingstone Margaret
Published: March 2010

In this study we assessed whether there is a single face space common to both human and cartoon faces by testing whether adaptation to cartoon faces can affect perception of human faces. Participants were shown Japanese animation cartoon videos containing faces with abnormally large eyes. The use of animated videos eliminated the possibility of position-dependent retinotopic adaptation (because the faces appear at many different locations) and more closely simulated naturalistic exposure. Adaptation to cartoon faces with large eyes significantly shifted preferences for human faces toward larger eyes, consistent with a common, non-retinotopic representation for both cartoon and human faces. This supports the possibility that there are representations that are specific to faces yet common to all kinds of faces.
Binocular Disparities, Motion Parallax, and Geometric Perspective in Patrick Hughes's ‘Reverspectives’: Theoretical Analysis and Empirical Findings
Authors: Rogers Brian , Gyani Alex
Published: March 2010

Patrick Hughes's ‘reverspective’ artworks provide a novel way of investigating the effectiveness of different sources of 3-D information for the human visual system. Our empirical findings show that the converging lines of simple linear perspective can be as effective as the rich array of 3-D cues present in natural scenes in determining what we see, even when these cues are in conflict with binocular disparities. Theoretical considerations reveal that, once the information provided by motion parallax transformations is correctly understood, there is no need to invoke higher-level processes or an interpretation based on familiarity or past experience in order to explain either the ‘reversed’ depth or the apparent, concomitant rotation of a reverspective artwork as the observer moves from side to side. What we see in reverspectives is the most likely real-world scenario (distal stimulus) that could have created the perspective and parallax transformations (proximal stimulus) that stimulate our visual systems.
The trainee assistant in nursing: a pilot exercise in building and retaining a workforce
Authors: Deshong Diane , Henderson Amanda
Published: March 2010

With increasing pressures on the skilled nursing workforce, strategies need to be developed to maximise the value of the existing workforce without impacting on the quality of care delivery. This paper reports on the introduction of a Commonwealth and State subsidised program for assistants-in-nursing (AINs) to assist in addressing the global nursing shortage. The program – which has included education sessions with registered nurses about the role of the AIN, delegation and supervision, and has also sustained support to the participants throughout the duration of their employment – has delivered benefits locally to the Princess Alexandra Hospital (PAH) and, broadly, to the nursing profession. Most of the participants completing the program have chosen to continue their employment at PAH or pursue further studies in nursing.
What is known about the topic?The shortage of skilled nurses means there is a need for innovative solutions to support the existing workforce.
What does this paper add?The development of an assistant-in-nursing role was seen as a successful development for a Queensland hospital.
What are the implications for practitioners?The trained assistants have largely remained employed in the area and 68% have gone on to further nursing education.
Benchmarking clinical indicators of quality for Australian residential aged care facilities
Authors: Courtney Mary , O'Reilly Maria T. , Edwards Helen , Hassall Stacey
Published: March 2010

To undertake exploratory benchmarking of a set of clinical indicators of quality care in residential care in Australia, data were collected from 107 residents within four medium-sized facilities (40–80 beds) in Brisbane, Australia. The proportion of residents in each sample facility with a particular clinical problem was compared with US Minimum Data Set quality indicator thresholds. Results demonstrated variability within and between clinical indicators, suggesting breadth of assessment using various clinical indicators of quality is an important factor when monitoring quality of care. More comprehensive and objective measures of quality of care would be of great assistance in determining and monitoring the effectiveness of residential aged care provision in Australia, particularly as demands for accountability by consumers and their families increase.
What is known about the topic?The key to quality improvement is effective quality assessment, and one means of evaluating quality of care is through clinical outcomes. The Minimum Data Set quality indicators have been credited with improving quality in United States nursing homes.
What does this paper add?The Clinical Care Indicators Tool was used to collect data on clinical outcomes, enabling comparison of data from a small Australian sample with American quality benchmarks to illustrate the utility of providing guidelines for interpretation.
What are the implications for practitioners?Collecting and comparing clinical outcome data would enable practitioners to better understand the quality of care being provided and whether practices required review. The Clinical Care Indicator Tool could provide a comprehensive and systematic means of doing this, thus filling a gap in quality monitoring within Australian residential aged care.
Using camera-trap data to model habitat use by bare-nosed wombats (Vombatus ursinus) and cattle (Bos taurus) in a south-eastern Australian agricultural riparian ecosystem
Authors: Borchard Philip , Wright Ian A.
Published: March 2010

Bare-nosed wombats (Vombatus ursinus) are an often important south-east Australian agricultural riparian species that may improve riparian landscape heterogeneity via their burrowing activity. At the same time they are often accused of causing soil erosion. As populations of wombats in other landscapes are under threat due to habitat disturbance, road mortality and disease, knowledge of the factors determining their use of riparian systems are important for their conservation and management. Since the European colonisation of Australia, riparian areas have been utilised by domestic cattle (Bos taurus), usually resulting in a decline in biodiversity. Camera-trap data was used to investigate the habitat use by wombats and cattle in remnant Eastern Riverine Forests. A total of 664 detections of animals from 13 species were made over the entire riparian-zone survey. Wombats were the most detected species, followed by cattle, then foxes and cats. Wombat and cattle activity varied significantly through the diurnal cycle, with wombats active from 1900 to 0700 hours and cattle active from 0700 to 1900 hours. There were no seasonal effects relating to the detection of either species. Feral species such as foxes, cats and rabbits were more frequently detected at sites highly disturbed by cattle. Results of this study illustrate the potential of camera-trapping for modelling habitat use by wombats and cattle and providing guidelines for the management of feral animals in remnant agricultural riparian habitats.
Search for cryptic Pseudomys shortridgei in suitable habitat in the south-east of South Australia
Authors: Haby Nerissa , Herpich Darren
Published: March 2010

Pseudomys shortridgei has been recorded from a restricted and fragmented distribution across southern Australia. Fossil deposits represented the species in mainland South Australia. However, the discovery of an extant population of P. shortridgei in the lower south-east of South Australia, and its morphological similarity to the more common Rattus fuscipes and R. lutreolus highlighted the need to verify the current distribution of the species. Existing vegetation community and systematic baseline biological survey data were used in a fast, cost-effective and systematic desktop assessment to identify the distribution of potentially suitable habitat. Attributes within 12 spatial layers were assigned a value of ecological relevance, reclassified and combined using weighted overlay analysis in ESRI ArcGIS 9.1. At ground-truthed sites, randomly assigned to the most suitable habitat within the ‘equal weightings’ output, understorey had been poorly represented by available data and some vegetation community classifications were no longer current. Despite this limitation, potentially suitable habitat was located within three remnants and targeted in a small mammal survey. From 1459 trap-nights, only Antechinus flavipes, R. fuscipes, Isoodon obesulus obesulus, Austrelaps superbus and Mus musculus were captured. It is unlikely that P. shortridgei inhabits the remnants targeted; however, further field surveys targeting smaller remnants or vegetation communities poorly represented by existing data used in the desktop assessment are recommended.
Movements and habitat selection by wild dogs in eastern Victoria
Authors: Robley Alan , Gormley Andrew , Forsyth David M. , Wilton Alan N. , Stephens Danielle
Published: March 2010

To investigate movements and habitat selection by wild dogs we attached satellite-linked global positioning system (GPS) units to nine wild dogs (Canis lupus dingo and Canis lupus familiaris) captured in eastern Victoria in summer 2007. Units estimated locations at 30-min intervals for the first six months and then at 480-min intervals for six more months. DNA testing revealed all these wild dogs to be related. Home ranges of males were almost three times larger than those of females (males: 124.3 km2 ± 56.3, n = 4; females: 45.2 km2 ± 17.3, n = 5) and both sexes preferred subalpine grassland, shrub or woodland at the landscape and home-range scales. Wild dogs were recorded more often than expected within 25 m of roads and less often than expected within 25 m of watercourses. Wild dogs displayed higher-velocity movements with shallow turning angles (generally forwards) that connected spatial and temporal clusters comprising slower-velocity, shorter, and sharper turning movements. One wild dog travelled 230 km in 9 days before returning to its home range and another travelled 105 km in 87 days. The home-range sizes reported in this study are much larger than previously reported in south-eastern Australia. This finding, together with previous studies, suggests that the spatial scale at which wild dog management occurs needs to be reconsidered.
Hepatocyte growth factor inhibits CNS autoimmunity by inducing tolerogenic dendritic cells and CD25
+
Foxp3
+
regulatory T cells
Authors: Benkhoucha Mahdia , Santiago-Raber Marie-Laure , Schneiter Gregory , Chofflon Michel , Funakoshi Hiroshi , Nakamura Toshikazu , Lalive Patrice H.
Published: March 2010

Immune-mediated diseases of the CNS, such as multiple sclerosis and its animal model, experimental autoimmune encephalitis (EAE), are characterized by the activation of antigen-presenting cells and the infiltration of autoreactive lymphocytes within the CNS, leading to demyelination, axonal damage, and neurological deficits. Hepatocyte growth factor (HGF) is a pleiotropic factor known for both neuronal and oligodendrocytic protective properties. Here, we assess the effect of a selective overexpression of HGF by neurons in the CNS of C57BL/6 mice carrying an HGF transgene (HGF-Tg mice). EAE induced either by immunization with myelin oligodendrocyte glycoprotein peptide or by adoptive transfer of T cells was inhibited in HGF-Tg mice. Notably, the level of inflammatory cells infiltrating the CNS decreased, except for CD25
+
Foxp3
+
regulatory T (T
reg
) cells, which increased. A strong T-helper cell type 2 cytokine bias was observed: IFN-γ and IL-12p70 decreased in the spinal cord of HGF-Tg mice, whereas IL-4 and IL-10 increased. Antigen-specific response assays showed that HGF is a potent immunomodulatory factor that inhibits dendritic cell (DC) function along with differentiation of IL-10–producing T
reg
cells, a decrease in IL-17–producing T cells, and down-regulation of surface markers of T-cell activation. These effects were reversed fully when DC were pretreated with anti-cMet (HGF receptor) antibodies. Our results suggest that, by combining both potentially neuroprotective and immunomodulatory effects, HGF is a promising candidate for the development of new treatments for immune-mediated demyelinating diseases associated with neurodegeneration such as multiple sclerosis.
Expanding metabolism for total biosynthesis of the nonnatural amino acid L-homoalanine
Authors: Zhang Kechun , Li Han , Cho Kwang Myung , Liao James C.
Published: March 2010

The dramatic increase in healthcare cost has become a significant burden to the world. Many patients are denied the accessibility of medication because of the high price of drugs. Total biosynthesis of chiral drug intermediates is an environmentally friendly approach that helps provide more affordable pharmaceuticals. Here we have expanded the natural metabolic capability to biosynthesize a nonnatural amino acid L-homoalanine, which is a chiral precursor of levetiracetam, brivaracetam, and ethambutol. We developed a selection strategy and altered the substrate specificity of ammonium-assimilating enzyme glutamate dehydrogenase. The specificity constant
k
cat
/
K

m

of the best mutant towards 2-ketobutyrate is 50-fold higher than that towards the natural substrate 2-ketoglutarate. Compared to transaminase IlvE and NADH-dependent valine dehydrogenases, the evolved glutamate dehydrogenase increased the conversion yield of 2-ketobutyrate to L-homoalanine by over 300% in aerobic condition. As a result of overexpressing the mutant glutamate dehydrogenase and
Bacillus subtilis
threonine dehydratase in a modified threonine-hyperproducing
Escherichia coli
strain (ATCC98082,
ΔrhtA
), 5.4 g/L L-homoalanine was produced from 30 g/L glucose (0.18 g/g glucose yield, 26% of the theoretical maximum). This work opens the possibility of total biosynthesis of other nonnatural chiral compounds that could be useful pharmaceutical intermediates.
Bluetongue virus coat protein VP2 contains sialic acid-binding domains, and VP5 resembles enveloped virus fusion proteins
Authors: Zhang Xing , Boyce Mark , Bhattacharya Bishnupriya , Zhang Xiaokang , Schein Stan , Roy Polly , Zhou Z. Hong
Published: March 2010

Bluetongue virus (BTV) is transmitted by blood-feeding insects (
Culicoides
sp.) and causes hemorrhagic diseases in livestock. BTV is a nonenveloped, double-stranded RNA (dsRNA) virus with two capsids: a well-studied, stable core enclosing the dsRNA genome and a highly unstable, poorly studied coat responsible for host cell attachment and entry. Here, based on cryo-electron microscopy (cryoEM), we report a 7-Å resolution structure of the infectious BTV virion, including the coat proteins. We show that unlike other dsRNA viruses, the VP2 attachment trimer has a triskelion shape composed of three tip domains branching from a central hub domain. We identify three putative sialic acid-binding pockets in the hub and present supporting biochemical data indicating sugar moiety binding is important for BTV infection. Despite being a nonenveloped virus, the putative VP5 membrane penetration trimer, located slightly inward of the VP2 attachment trimer, has a central coiled-coil α-helical bundle, similar to the fusion proteins of many enveloped viruses (e.g., HIV, herpesviruses, vesicular stomatitis virus, and influenza virus). Moreover, mapping of the amino acid sequence of VP5 to the secondary structural elements identified by cryoEM locates 15 amphipathic α-helical regions on the external surface of each VP5 trimer. The cryoEM density map also reveals few, weak interactions between the VP5 trimer and both the outer-coat VP2 trimer and the underlying core VP7 trimer, suggesting that the surface of VP5 could unfurl like an umbrella during penetration and shedding of the coat to release the transcriptionally active core particle.
Piccolo and bassoon maintain synaptic vesicle clustering without directly participating in vesicle exocytosis
Authors: Mukherjee Konark , Yang Xiaofei , Gerber Stefan H. , Kwon Hyung-Bae , Ho Angela , Castillo Pablo E. , Liu Xinran , Südhof Thomas C.
Published: March 2010

Piccolo and bassoon are highly homologous multidomain proteins of the presynaptic cytomatrix whose function is unclear. Here, we generated piccolo knockin/knockout mice that either contain wild-type levels of mutant piccolo unable to bind Ca
2+
(knockin), ∼60% decreased levels of piccolo that is C-terminally truncated (partial knockout), or <5% levels of piccolo (knockout). All piccolo mutant mice were viable and fertile, but piccolo knockout mice exhibited increased postnatal mortality. Unexpectedly, electrophysiology and electron microscopy of piccolo-deficient synapses failed to uncover a major phenotype either in acute hippocampal slices or in cultured cortical neurons. To unmask potentially redundant functions of piccolo and bassoon, we thus acutely knocked down expression of bassoon in wild-type and piccolo knockout neurons. Despite a nearly complete loss of piccolo and bassoon, however, we still did not detect an electrophysiological phenotype in cultured piccolo- and bassoon-deficient neurons in either GABAergic or glutamatergic synaptic transmission. In contrast, electron microscopy revealed a significant reduction in synaptic vesicle clustering in double bassoon/piccolo-deficient synapses. Thus, we propose that piccolo and bassoon play a redundant role in synaptic vesicle clustering in nerve terminals without directly participating in neurotransmitter release.
Outbreak of Carbapenem-Resistant Klebsiella pneumoniae in Puerto Rico Associated with a Novel Carbapenemase Variant
Authors: Gregory Christopher J. , Llata Eloisa , Stine Nicholas , Gould Carolyn , Santiago Luis Manuel , Vazquez Guillermo J. , Robledo Iraida E. , Srinivasan Arjun , Goering Richard V. , Tomashek Kay M.
Published: March 2010

Background.

Carbapenem-resistantKlebsiella pneumoniae(CRKP) is resistant to almost all antimicrobial agents, and CRKP infections are associated with substantial morbidity and mortality.

Objective.

To describe an outbreak of CRKP in Puerto Rico, determine risk factors for CRKP acquisition, and detail the successful measures taken to control the outbreak.

Design.

Two case-control studies.

Setting.

A 328-bed tertiary care teaching hospital.

Patients.

Twenty-six CRKP case patients identified during the outbreak period of February through September 2008, 26 randomly selected uninfected control patients, and 26 randomly selected control patients with carbapenem-susceptibleK. pneumoniae(CSKP) hospitalized during the same period.

Methods.

We performed active case finding, including retrospective review of the hospital's microbiology database and prospective perirectal surveillance culture sampling in high-risk units. Case patients were compared with each control group while controlling for time at risk. We sequenced theblaKPCgene with polymerase chain reaction for 7 outbreak isolates and subtyped these isolates with pulsed-field gel electrophoresis.

Results.

In matched, multivariable analysis, the presence of wounds (hazard ratio, 19.0 [95% confidence interval {CI}, 2.5-142.0]) was associated with CRKP compared with noK. pneumoniae.Transfer between units (adjusted odds ratio [OR], 7.5 [95% CI, 1.8-31.1]), surgery (adjusted OR, 4.0 [95% CI, 1.0-15.7]), and wounds (adjusted OR, 4.9 [95% CI, 1.1-21.8]) were independent risk factors for CRKP compared to CSKP. A novelK. pneumoniaecarbapenemase variant (KPC-8) was present in 5 isolates. Implementation of active surveillance for CRKP colonization and cohorting of CRKP patients rapidly controlled the outbreak.

Conclusions.

Enhanced surveillance for CRKP colonization and intensified infection control measures that include limiting the physical distribution of patients can reduce CRKP transmission during an outbreak.
Wide Variability in the Use of Antimicrobial Lock Therapy and Prophylaxis
among Infectious Diseases Consultants
Authors: Polgreen Philip M. , Beekmann Susan E. , Diekema Daniel J. , Sherertz Robert J.
Published: March 2010

We surveyed infectious diseases physicians to determine their practice
patterns with regard to both antimicrobial lock prophylaxis and antimicrobial lock
therapy. Antimicrobial lock prophylaxis is relatively uncommon; only 19% of
infectious diseases physicians reported using it at least once. Although
antimicrobial lock therapy is more commonly used, we found a significant variation
in practice patterns.
Absence of Association between Use of Ertapenem and Change in Antipseudomonal
Carbapenem Susceptibility Rates in 25 Hospitals
Authors: Eagye Kathryn J. , Nicolau David P.
Published: March 2010

Objective.

Ertapenem exposure has been reported to select for cross-resistance to
other carbapenems in Pseudomonas aeruginosa in
vitro. Single-center investigations report conflicting results. We evaluated
ertapenem use and antipseudomonal carbapenem susceptibility for 6 years
spanning the time of ertapenem adoption at each of 25 US hospitals.

Design.

Retrospective primary and secondary data analysis.

Methods.

Use density ratios for imipenem and meropenem (collectively, “other
carbapenems”) and ertapenem were derived from data in a commercial database on
the total number of grams used in the 3 years before and the 3 years after
adoption of ertapenem at each hospital. A general linear model using repeated
measures analysis of variance was used to explore associations between the
6-year change in antipseudomonal carbapenem susceptibility rates (determined
from hospital antibiograms) and ertapenem use in each year, while controlling
for other carbapenem use.

Results.

Ertapenem use increased once adopted. With regard to the postadoption
period, the median use density ratio for year 4 was 4.1 (interquartile range
[IQR], 1.7-5.2), for year 5 was 6.0 (IQR, 2.7-8.5), and for year 6 was 6.5
(IQR, 4.0-11.6). The median use density ratio for other carbapenem use for year
1 was 8.7 (IQR, 5.7-13.5), and by year 6 it had increased to 19.3 (IQR,
9.6-26.2). Change in mean antipseudomonal carbapenem susceptibility across time
(85% in year 1 to 82% in year 6) was not significant
(P = .22). Change in 6-year antipseudomonal
carbapenem susceptibility was not associated with ertapenem use in any year
while controlling for other carbapenem use (P
> .20 for all years of ertapenem use).

Conclusion.

Although significant change in P. aeruginosa
susceptibility to antipseudomonal carbapenems was not detected during this
multicenter study, which to our knowledge is the most extensive assessment to
date of this important drug use-susceptibility relationship, continued
evaluation of the relationship is prudent.
Analysis of Central Line–Associated Bloodstream Infections in the Intensive
Care Unit after Implementation of Central Line Bundles
Authors: Shuman Emily K. , Washer Laraine L. , Arndt Jennifer L. , Zalewski Christy A. , Hyzy Robert C. , Napolitano Lena M. , Chenoweth Carol E.
Published: March 2010

Central line-associated bloodstream infections (CLABSIs) have been reduced in
number but not eliminated in our intensive care units with use of central line
bundles. We performed an analysis of remaining CLABSIs. Many bloodstream
infections that met the definition of CLABSI had sources other than central lines
or represented contaminated blood samples.
Does the Specific Time of Day Used to Capture Data on Ventilator-Days Have an
Impact on the Documented Rates of Ventilator-Associated Pneumonia?
Authors: Talbot Thomas R. , Starmer John M.
Published: March 2010

Definitions of ventilator-associated pneumonia do not note a preferred daily
time for obtaining denominator data. We examined collecting data on the number of
ventilator-days at different times of day in 7 intensive care units. Rates of
ventilator-associated pneumonia did not significantly differ when denominator data
were collected at midnight, 8 AM, or 4 PM, supporting standard
definitions.