bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrinsic oscillatory activity arising within the electrically coupled AII amacrine–ON cone bipolar cell network is driven by voltage‐gated Na+ channels
Authors: Trenholm Stuart , Borowska Joanna , Zhang Jiawei , Hoggarth Alex , Johnson Kyle , Barnes Steven , Lewis Timothy J. , Awatramani Gautam B. 
Published: March 2012

Key points
In mouse models for retinal degeneration, photoreceptor death leads to membrane oscillation in the remnant AII amacrine–ON cone bipolar cell network through an unknown mechanism.
We found such oscillations require voltage‐gated Na+ channels and gap junctions but not hyperpolarization‐activated currents (Ih).
Na+ channels are expressed predominantly in AII amacrine cells and Ih in ON cone bipolar cells, and appear to interact via gap junctions to shape oscillations.
Similar intrinsic oscillations arose in the wild‐type (wt) AII amacrine–ON cone bipolar cell network when photoreceptor inputs to bipolar cells were pharmacologically occluded.
Computational modelling captures experimental findings when a low level of cellular heterogeneity is introduced in the coupled network.
These unique insights into the cellular mechanisms underlying spontaneous activity in the degenerating retina might aid in designing the most effective strategies to restore vision using retinal prosthesis.
Abstract  In the rd1 mouse model for retinal degeneration, the loss of photoreceptors results in oscillatory activity (∼10–20 Hz) within the remnant electrically coupled network of retinal ON cone bipolar and AII amacrine cells. We tested the role of hyperpolarization‐activated currents (Ih), voltage‐gated Na+ channels and gap junctions in mediating such oscillatory activity. Blocking Ih (1 mm Cs+) hyperpolarized the network and augmented activity, while antagonizing voltage‐dependent Na+ channels (1 μm TTX) abolished oscillatory activity in the AII amacrine–ON cone bipolar cell network. Voltage‐gated Na+ channels were only observed in AII amacrine cells, implicating these cells as major drivers of activity. Pharmacologically uncoupling the network (200 μm meclofenamic acid (MFA)) blocked oscillations in all cells indicating that Na+ channels exert their influence over multiple cell types within the network. In wt retina, occluding photoreceptor inputs to bipolar cells (10 μm NBQX and 50 μm l‐AP4) resulted in a mild (∼10 mV) hyperpolarization and the induction of oscillatory activity within the AII amacrine–ON cone bipolar cell network. These oscillations had similar properties to those observed in rd1 retina, suggesting that no major degeneration‐induced network rewiring is required to trigger spontaneous oscillations. Finally, we constructed a simplified computational model that exhibited Na+ channel‐dependent network oscillations. In this model, mild heterogeneities in channel densities between individual neurons reproduced our experimental findings. These results indicate that TTX‐sensitive Na+ channels in AII amacrine cells trigger degeneration‐induced network oscillations, which provide a persistent synaptic drive to downstream remnant neurons, thus appearing to replace photoreceptors as the principal drivers of retinal activity.
In Vitro
Antimicrobial Susceptibility to Isepamicin of 6,296 Enterobacteriaceae Clinical Isolates Collected at a Tertiary Care University Hospital in Greece
Authors: Maraki Sofia , Samonis George , Karageorgopoulos Drosos E. , Mavros Michael N. , Kofteridis Diamantis , Falagas Matthew E. 
Published: March 2012

ABSTRACT

The reevaluation of “forgotten” antibiotics can identify new therapeutic options against extensively drug-resistant Gram-negative pathogens. We sought to investigate isepamicin in this regard. We retrospectively evaluated the antimicrobial susceptibility to isepamicin of
Enterobacteriaceae
sp. isolates from unique patients, collected at the microbiological laboratory of the University Hospital of Heraklion, Crete, Greece, from 2004 to 2009. Susceptibility testing was done with the automated Vitek 2 system. The breakpoints for susceptibility to isepamicin, tigecycline, and other antibiotics were those proposed by the Comité de l'Antibiogramme de la Société Française de Microbiologie (CA-SFM), the FDA, and the CLSI, respectively. A total of 6,296 isolates were studied, including primarily 3,401 (54.0%)
Escherichia coli
, 1,040 (16.5%)
Klebsiella pneumoniae
, 590 (9.4%)
Proteus mirabilis
, and 460 (7.3%)
Enterobacter
sp. isolates. Excluding the species with intrinsic resistance to each antibiotic, antimicrobial susceptibility was highest for colistin (5,275/5,441 isolates [96.9%]) and isepamicin (6,103/6,296 [96.9%]), followed by meropenem (5,890/6,296 [93.6%]), imipenem (5,874/6,296 [93.3%]), and amikacin (5,492/6,296 [87.2%]). The antimicrobial susceptibility of the 1,040
K. pneumoniae
isolates was highest for isepamicin (95.3%), followed by colistin (89.3%) and meropenem (63.0%). Regarding resistant
K. pneumoniae
isolates, susceptibility to isepamicin was observed for 91.1% of the 392, 87.7% of the 375, and 85.6% of the 111 isolates that were nonsusceptible to the carbapenems, all other aminoglycosides, and colistin, respectively. Isepamicin exhibited high
in vitro
activity against almost all of the
Enterobacteriaceae
species. It could particularly serve as a last-resort therapeutic option for carbapenem-resistant
K. pneumoniae
in our region, where it is endemic, as it does not show considerable cross-resistance with other aminoglycosides.
Development of a Robust Cytopathic Effect-Based High-Throughput Screening Assay To Identify Novel Inhibitors of Dengue Virus
Authors: McCormick Kevin D. , Liu Shufeng , Jacobs Jana L. , Marques Ernesto T. A. , Sluis-Cremer Nicolas , Wang Tianyi 
Published: March 2012

ABSTRACTWe have developed a robust cytopathic effect-based high-throughput screening assay to identify inhibitors of dengue virus (DENV) infection. Screening of a small natural product library yielded 11 hits. Four of these were found to be potent inhibitors of DENV, although serotype differences were noted. Taken together, these data suggest that screening of larger and more complex molecule libraries may result in the identification of more potent and specific DENV inhibitors.
Tetanus Toxin and Botulinum Toxin A Utilize Unique Mechanisms To Enter Neurons of the Central Nervous System
Authors: Blum Faith C. , Chen Chen , Kroken Abby R. , Barbieri Joseph T. 
Published: March 2012

ABSTRACT
Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the most toxic proteins for humans. While BoNTs cause flaccid paralysis, TeNT causes spastic paralysis. Characterized BoNT serotypes enter neurons upon binding dual receptors, a ganglioside and a neuron-specific protein, either synaptic vesicle protein 2 (SV2) or synaptotagmin, while TeNT enters upon binding gangliosides as dual receptors. Recently, TeNT was reported to enter central nervous system (CNS) neurons upon synaptic vesicle cycling that was mediated by the direct binding to SV2, implying that TeNT and BoNT utilize common mechanisms to enter CNS neurons. This prompted an assessment of TeNT entry into CNS neurons, using the prototypic BoNT serotype A as a reference for SV2-mediated entry into synaptic vesicles, analyzing the heavy-chain receptor binding domain (HCR) of each toxin. Synaptic vesicle cycling stimulated the entry of HCR/A into neurons, while HCR/T entered neurons with similar levels of efficiency in depolarized and nondepolarized neurons. ImageJ analysis identified two populations of cell-associated HCR/T in synaptic vesicle cycling neurons, a major population which segregated from HCR/A and a minor population which colocalized with HCR/A. HCR/T did not inhibit HCR/A entry into neurons in competition experiments and did not bind SV2, the protein receptor for BoNT/A. Intoxication experiments showed that TeNT efficiently cleaved VAMP2 in depolarized neurons and neurons blocked for synaptic vesicle cycling. These experiments demonstrate that TeNT enters neurons by two pathways, one independent of stimulated synaptic vesicle cycling and one by synaptic vesicles independent of SV2, showing that TeNT and BoNT/A enter neurons by unique mechanisms.
The Sum1/Ndt80 Transcriptional Switch and Commitment to Meiosis in Saccharomyces cerevisiae
Authors: Winter Edward 
Published: March 2012

SUMMARY

Cells encounter numerous signals during the development of an organism that induce division, differentiation, and apoptosis. These signals need to be present for defined intervals in order to induce stable changes in the cellular phenotype. The point after which an inducing signal is no longer needed for completion of a differentiation program can be termed the “commitment point.” Meiotic development in the yeast
Saccharomyces cerevisiae
(sporulation) provides a model system to study commitment. Similar to differentiation programs in multicellular organisms, the sporulation program in yeast is regulated by a transcriptional cascade that produces early, middle, and late sets of sporulation-specific transcripts. Although critical meiosis-specific events occur as early genes are expressed, commitment does not take place until middle genes are induced. Middle promoters are activated by the Ndt80 transcription factor, which is produced and activated shortly before most middle genes are expressed. In this article, I discuss the connection between Ndt80 and meiotic commitment. A transcriptional regulatory pathway makes
NDT80
transcription contingent on the prior expression of early genes. Once Ndt80 is produced, the recombination (pachytene) checkpoint prevents activation of the Ndt80 protein. Upon activation, Ndt80 triggers a positive autoregulatory loop that leads to the induction of genes that promote exit from prophase, the meiotic divisions, and spore formation. The pathway is controlled by multiple feed-forward loops that give switch-like properties to the commitment transition. The conservation of regulatory components of the meiotic commitment pathway and the recently reported ability of Ndt80 to increase replicative life span are discussed.
Diatom-inferred decline of macrophyte abundance in lakes of southern Quebec, Canada
Authors: Vermaire Jesse C. , Prairie Yves T. , Gregory-Eaves Irene 
Published: March 2012

Submerged macrophytes play a central role in lake ecosystem functioning; however, their long-term dynamics are poorly understood. We have used the paleolimnological top–bottom approach to reconstruct changes in whole-lake macrophyte biomass between predisturbance and present-day conditions in 37 southern Quebec lakes. Estimates of whole-lake macrophyte biomass were produced using a diatom-based multivariate regression tree model (MRT) and modern analogue approach. Both approaches indicated an overall pattern of declining macrophyte abundance in the region. Based on MRT analysis, 80% of study lakes were classified as historically being in the macrophyte-dominated state, but now only 43% of the lakes are currently in this state. The lakes that shifted MRT group were found to have significantly (p = 0.03) greater building densities in their catchments compared with lakes that did not shift state. These results suggest that human impacts, primarily nutrient inputs and water level fluctuations, have played a role in reducing macrophyte abundance in southern Quebec lakes. Because submerged macrophyte beds help stabilize lake ecosystems and act as a phosphorus sink, a reduction in whole-lake macrophyte biomass could make lake ecosystems more susceptible to eutrophication.
Heterologous expression of bacterial nitric oxide synthase gene: a potential biological method to control biofilm development in the environment
Authors: Liu Pulin , Huang Qiaoyun , Chen Wenli 
Published: March 2012

The nitric oxide synthase gene from Bacillus subtilis was heterologously expressed in Pseudomonas putida using a broad-host expression vector. Both the performance of the nitric oxide-specific fluorescent probe and the quantitative assessment of the nitric oxide end products demonstrated the generation of nitric oxide. The endogenous nitric oxide increased the motility of P. putida and decreased the capacity of P. putida and other multispecies bacteria to develop biofilms. On the practical side, endogenous nitric oxide offers an advantage in generating continuous, controllable levels of nitric oxide, which suggests a new method to use nitric oxide in the control of biofilms.
Investigating the influence of LiDAR ground surface errors on the utility of derived forest inventories
Authors: Tinkham Wade T. , Smith Alistair M.S. , Hoffman Chad , Hudak Andrew T. , Falkowski Michael J. , Swanson Mark E. , Gessler Paul E. 
Published: March 2012

Light detection and ranging, or LiDAR, effectively produces products spatially characterizing both terrain and vegetation structure; however, development and use of those products has outpaced our understanding of the errors within them. LiDAR’s ability to capture three-dimensional structure has led to interest in conducting or augmenting forest inventories with LiDAR data. Prior to applying LiDAR in operational management, it is necessary to understand the errors in LiDAR-derived estimates of forest inventory metrics (i.e., tree height). Most LiDAR-based forest inventory metrics require creation of digital elevation models (DEM), and because metrics are calculated relative to the DEM surface, errors within the DEMs propagate into delivered metrics. This study combines LiDAR DEMs and 54 ground survey plots to investigate how surface morphology and vegetation structure influence DEM errors. The study further compared two LiDAR classification algorithms and found no significant difference in their performance. Vegetation structure was found to have no influence, whereas increased variability in the vertical error was observed on slopes exceeding 30°, illustrating that these algorithms are not limited by high-biomass western coniferous forests, but that slope and sensor accuracy both play important roles. The observed vertical DEM error translated into ±1%–3% error range in derived timber volumes, highlighting the potential of LiDAR-derived inventories in forest management.
Dendrochronological analysis of baldcypress (Taxodium distichum) responses to climate and contrasting flood regimes
Authors: Keim Richard F. , Amos J. Blake 
Published: March 2012

Baldcypress (Taxodium distichum (L.) Rich.) has been used extensively for dendrochronological reconstruction of climate and is a key species in globally important wetlands with complex, poorly understood relationships between hydrological and ecological processes. To better understand ecosystem responses to changing climate and hydrology and to test whether hydrological or climatological variables are most reflected in chronologies, we developed tree-ring chronologies for six stagnant or riverine swamps in the Mississippi River deltaic plain and modeled growth responses to historical hydrology (51 years of data) and climate (111 years of data). Decoupled flooding and local climate in this deltaic setting allowed for relatively independent assessments of the roles of hydrology and climate in baldcypress growth. Depth of annual flooding was positively correlated with growth that year but negatively correlated with growth in the ensuing year for both riverine and stagnant swamps. Depth of 10-year mean flooding was positively correlated with growth in riverine swamps but negatively correlated with growth in stagnant swamps. Results corroborate previous findings that long-term, stagnant flooding reduces productivity, but growth at these deltaic sites was less correlated with climatic variables than elsewhere. At least in these frequently flooded sites, baldcypress tree rings appear to be a better long term record of hydrological history than of climatic history.
Effects of forest management legacies on spruce budworm (Choristoneura fumiferana) outbreaks
Authors: Robert Louis-Etienne , Kneeshaw Daniel , Sturtevant Brian R. 
Published: March 2012

The “silvicultural hypothesis” of spruce budworm ( Choristoneura fumiferana Clem.) dynamics postulates that increasing severity of spruce budworm outbreaks over the last century resulted from forest conditions created by past management activities. Yet, definitive tests of the hypothesis remain elusive. We examined spruce budworm outbreak dynamics (synchrony, periodicity, and intensity) in the 20th century using historical reconstruction from tree-ring chronologies sampled within 19 sites in a large ecoregion located on the border of Minnesota and Ontario. The study encompassed three areas affected by contrasting management legacies: a fine-grained area (Minnesota, six sites, average cut size = 17 ha), a coarse-grained area (Ontario, six sites, average cut size 10 times that of Minnesota), and a conservation zone (seven sites) with little recent harvest activity overlapping the border. Results suggest important differences in outbreak dynamics between the forest management zones that cannot be explained by differences in climate among sample sites. Budworm outbreaks within the conservation zone were more synchronous, with more trees per site affected and less frequent outbreaks than sites sampled within fine-scale managed areas. Outbreak dynamics within forests managed at coarser scales suggest a mixture of the conservation and fine-scale management zone outbreak patterns. Potential factors affecting differences in the observed outbreak patterns include forest pattern, composition, and age. Our study generally supports the silvicultural hypothesis and emphasizes that management legacy effects on spruce budworm dynamics should be observable at landscape scales, as well as at local scales.
Losses in understory diversity over three decades in an old-growth cool-temperate forest in Michigan, USA
Authors: Woods Kerry D. , Hicks David J. , Schultz Jan 
Published: March 2012

Diversity in temperate forests is concentrated in the understory, but understory dynamics are poorly understood for old-growth forests. We use repeated measurements of more than eight hundred 1 m2plots over three decades to assess patterns of understory diversity in old-growth mesic and wet forests in northern Michigan, USA. We ask whether diversity changes systematically over time and whether dynamics are related to spatial scale. We find, for all habitats, significant understory diversity loss at square-metre scales but not at coarser scales. Total herbaceous cover, however, remained constant or increased in total and for nearly all frequent species, and no species were lost overall. We explore hypotheses about diversity regulation by exploring correlations with habitat, canopy composition, and properties of understory species. Nonindigenous plants are rare at the study site, earthworm invasion is not apparent, and deer browse is not intense. Diversity changes may be related to ecological guild membership. We suggest that the general loss of fine-scale diversity is driven by either changing canopy composition or competitive dynamics within the understory community. Management for diversity maintenance in temperate forests must address understory communities; if herbaceous diversity is scale dependent and unstable over decadal time frames, management approaches need to account for factors driving changes.
Identification of representative sampling heights for specific gravity and moisture content in plantation-grown loblolly pine (Pinus taeda)
Authors: Antony Finto , Schimleck Laurence R. , Daniels Richard F. 
Published: March 2012

Conventionally, increment cores collected at breast height (1.4 m) have been used to measure wood properties of standing loblolly pine (Pinus taeda L.) trees. This height has been used because of the ease of sampling and cost involved in extracting the cores. In this study, the efficacy of a breast-height core to represent whole-tree specific gravity (SG) and moisture content (MC) was examined. The sampling height that best represents whole-tree SG and MC was identified using the correlation between volume-weighted whole-tree SG and MC with SG and MC measurements collected at different heights within a tree. We found a high correlation between observed whole-disk SG and MC with volume-weighted whole-tree SG and MC at most sampling heights. The strength of the correlation followed a skewed parabolic curve form for both wood properties. The strongest correlations were observed between 4.6 and 6.1 m, with marginally lower correlations at the base of the tree, and the weakest correlations were observed towards the tip of the tree. In addition, it was found that the number of stands and trees that need to be sampled to achieve a certain accuracy in overall mean whole-tree SG and MC was greater if breast height was used as a sampling height compared with the most representative sampling heights identified (4.6 m for SG and 6.1 m for MC).
Woody debris and tree regeneration dynamics following severe wildfires in Arizona ponderosa pine forests
Authors: Roccaforte John P. , Fulé Peter Z. , Chancellor W. Walker , Laughlin Daniel C. 
Published: March 2012

Severe forest fires worldwide leave behind large quantities of dead woody debris and regenerating trees that can affect future ecosystem trajectories. We studied a chronosequence of severe fires in Arizona, USA, spanning 1 to 18 years after burning to investigate postfire woody debris and regeneration dynamics. Snag densities varied over time, with predominantly recent snags in recent fires and broken or fallen snags in older fires. Coarse woody debris peaked at > 60 Mg/ha in the time period 6–12 years after fire, a value higher than previously reported in postfire fuel assessments in this region. However, debris loadings on fires older than 12 years were within the range of recommended management values (11.2–44.8 Mg/ha). Overstory and regeneration were most commonly dominated by sprouting deciduous species. Ponderosa pine ( Pinus ponderosa C. Lawson var. scopulorum Engelm.) overstory and regeneration were completely lacking in 50% and 57% of the sites, respectively, indicating that many sites were likely to experience extended periods as shrublands or grasslands rather than returning rapidly to pine forest. More time is needed to see whether these patterns will remain stable, but there are substantial obstacles to pine forest recovery: competition with sprouting species and (or) grasses, lack of seed sources, and the forecast of warmer, drier climatic conditions for coming decades.