bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying Tropical Dry Forest Type and Succession: Substantial Improvement with LiDAR
Authors: Martinuzzi Sebastián , Gould William A. , Vierling Lee A. , Hudak Andrew T. , Nelson Ross F. , Evans Jeffrey S. 
Published: July 2012

AbstractImproved technologies are needed to advance our knowledge of the biophysical and human factors influencing tropical dry forests, one of the world's most threatened ecosystems. We evaluated the use of light detection and ranging (LiDAR) data to address two major needs in remote sensing of tropical dry forests, i.e., classification of forest types and delineation of forest successional status. We evaluated LiDAR‐derived measures of three‐dimensional canopy structure and subcanopy topography using classification‐tree techniques to separate different dry forest types and successional stages in the Guánica Biosphere Reserve in Puerto Rico. We compared the LiDAR‐based results with classifications made from commonly used remote sensing data, including Landsat satellite imagery and radar‐based topographic data. The accuracy of the LiDAR‐based forest type classification (including native‐ and exotic‐dominated forest classes) was substantially higher than those from previously available data (kappa = 0.90 and 0.63, respectively). The best result was obtained when combining LiDAR‐derived metrics of canopy structure and topography, and adding Landsat spectral data did not improve the classification. For the second objective, we observed that LiDAR‐derived variables of vegetation structure were better predictors of forest successional status (i.e., mid‐secondary, late‐secondary, and primary forests) than was spectral information from Landsat. Importantly, the key LiDAR predictors identified within each classification‐tree model agreed with previous ecological knowledge of these forests. Our study highlights the value of LiDAR remote sensing for assessing tropical dry forests, reinforcing the potential for this novel technology to advance research and management of tropical forests in general.
Accounting for Algae
Authors: Pena Naomi , Frieden Dorian , Bird David Neil 
Published: July 2012

AbstractInterest and research in the use of algae for energy is growing but an analysis of the different methods for the accounting for the carbon dioxide (CO
2) emissions that result, is lacking. In this article, four accounting systems are evaluated for their completeness, simplicity, sectoral accuracy, and scale‐independence. Two options under the Kyoto Protocol (KP), a value‐chain (end‐user responsibility) approach, and Point of Uptake and Release (POUR) are evaluated.Algal material is used in biofuels, animal feeds, human foods, and food supplements, and a range of products such as paints, cosmetics, and plastics. There are also proposals for using algae as a soil amendment. This variety of uses for algal material together with the fact that it will probably contain carbon of fossil origin presents accounting challenges and reveals inconsistencies that have lain in the KPs treatment of biomass emissions. Furthermore, a key conclusion of the article is that neither proposed KP accounting approach for algae leads to correct accounting of emissions for all uses. Both value chain and POUR approaches more correctly and consistently account for algal emissions across uses. POUR offers the potential to provide comprehensive, consistent emission accounting across all uses of biomass, which represents a major step forward in accounting for CO
2 emissions due to use of biomass.
Reverse the Trend for Proximal Humeral Fractures: A Review of the Evidence for the Use of Reverse Shoulder Replacement in Acute Trauma
Authors: Taylor Clare , Cosker Thomas , Smith Christopher 
Published: July 2012

Background Proximal humeral fractures in the elderly population represent a particularly demanding subset of fractures. These have been traditionally treated with Hemi-arthroplasty (HA). Recently there has been a trend towards using a Reverse shoulder replacement (RSR) in some of these patients. The primary aim of the study was to systematically review the literature on the functional outcome scores for RSR in proximal humeral fractures and compare it with the best quality literature available for HA. Secondarily to compare range of movement, complication rates, re-operation rates and x-ray changes. Methods A systematic review of the literature was performed using the keywords: Delta, inverse, shoulder, trauma, and fracture. Only studies with 10 patients or more, presenting new data on the functional outcome scores of RSR for acute trauma were included. Studies reporting the use of RSR for fracture sequalae were excluded. These results were compared to the most comprehensive and up to date literature available for HA for proximal humeral fractures. Results Eight papers met the full inclusion and exclusion criteria. Data was available for 178 patients with a minimum follow-up of only 3 months. The mean absolute constant score for RSR patients was 54% and 57% for HA patients. RSR had an infection rate of 3%, a dislocation rate of 4% and an overall re-operation rate of 5.6%. Conclusion Functional outcomes and range of movements achieved by RSR seem to be similar to those achieved by HA and may eventually be proven to have better outcomes in a certain sub-group of patients. However, there is currently less than 200 patients reported in the literature with a very short term follow-up. RSR is more expensive than HA, and there is a definite learning curve associated with this prosthesis. Although RSR may be valuable in patients where a traditional HA is deemed not suitable, caution must be used until better quality research is available. Level of evidence: Level III systematic review of Level III studies
Diaphragmatic repair of hepatic hydrothorax with VATS after abdominal insufflation with CO2
Authors: Nakamura Y , Iwazaki M , Yasui N , Seki H , Matsumoto H , Masuda R , Nishiumi N , Shimada A 
Published: July 2012

AbstractHepatic hydrothorax is defined as the presence of a significant pleural effusion that develops in a patient with cirrhosis of the liver who does not have an underlying cardiac or pulmonary disease. There have been few published case reports dealing with hepatic hydrothorax treated surgically. Recently, we treated a patient with refractory hepatic hydrothorax by directly suturing the diaphragmatic defect during VATS. During surgery, the diaphragmatic defect was identified by using abdominal insufflation with CO
2. The defect was sutured and the diaphragm was covered by polyglycolic acid felt and fibrin glue. After surgery, the patient's pleural effusion improved, his postoperative course was uneventful and he did not require a drainage tube at discharge.
Control of neuronal excitability by NMDA‐type glutamate receptors in early developing binaural auditory neurons
Authors: Sanchez Jason Tait , Seidl Armin H. , Rubel Edwin W. , Barria Andres 
Published: July 2012

Key points
Mature nucleus laminaris (NL) neurons in the avian auditory brainstem respond with one or two action potentials to repetitive synaptic stimulation due to strong expression of low‐voltage‐activated K+ channels (KLVA) and other intrinsic factors.
We observe early in development, before the onset of hearing, NL neurons respond in similar fashion despite low expression of KLVA channels. At this age, synaptic NMDA‐type glutamate receptors (NMDA‐Rs) contain primarily the GluN2B subunit, which allow the summation of synaptic responses and keep voltage‐dependent Na+ channels inactivated.
Weaker Mg2+ blockade of NMDA‐Rs and an immature reuptake system cause a tonic NMDA‐R‐mediated current that sets the membrane potential at more depolarized values. Small KLVA conductances localized in dendrites prevent ramping depolarization and excessive excitability.
Our data show that before intrinsic properties are fully developed, NMDA‐Rs limit the output of NL neurons.
Abstract  Precise control of neuronal excitability in the auditory brainstem is fundamental for processing timing cues used for sound localization and signal discrimination in complex acoustic environments. In mature nucleus laminaris (NL), the first nucleus responsible for binaural processing in chickens, neuronal excitability is governed primarily by voltage‐activated potassium conductances (KVA). High levels of KVA expression in NL neurons result in one or two initial action potentials (APs) in response to high‐frequency synaptic activity or sustained depolarization. Here we show that during a period of synaptogenesis and circuit refinement, before hearing onset, KVA conductances are relatively small, in particular low‐voltage‐activated K+ conductances (KLVA). In spite of this, neuronal output is filtered and repetitive synaptic activity generates only one or two initial APs during a train of stimuli. During this early developmental time period, synaptic NMDA‐type glutamate receptors (NMDA‐Rs) contain primarily the GluN2B subunit. We show that the slow decay kinetics of GluN2B‐containing NMDA‐Rs allows synaptic responses to summate, filtering the output of NL neurons before intrinsic properties are fully developed. Weaker Mg2+ blockade of NMDA‐Rs and ambient glutamate early in development generate a tonic NMDA‐R‐mediated current that sets the membrane potential at more depolarized values. Small KLVA conductances, localized in dendrites, prevent excessive depolarization caused by tonic activation of NMDA‐Rs. Thus, before intrinsic properties are fully developed, NMDA‐Rs control the output of NL neurons during evoked synaptic transmission.
Megalin mediates transepithelial albumin clearance from the alveolar space of intact rabbit lungs
Authors: Buchäckert Yasmin , Rummel Sebastian , Vohwinkel Christine U. , Gabrielli Nieves M. , Grzesik Benno A. , Mayer Konstantin , Herold Susanne , Morty Rory E. , Seeger Werner , Vadász István 
Published: July 2012

Key points
Under physiological conditions the lung alveoli are impermeable to protein.
In patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) protein‐rich oedema fluid accumulates in the distal airspaces and leads to a life‐threatening impairment of alveolar gas exchange.
Albumin is a ligand of megalin, a member of the low‐density lipoprotein (LDL)‐receptor family.
We show that clearance of albumin from the distal air spaces is facilitated by active megalin‐mediated transport across the alveolar epithelium.
Understanding of protein clearance mechanisms in the lung may ultimately lead to novel therapeutic approaches for the treatment of ALI/ARDS.
Abstract  The alveolo‐capillary barrier is effectively impermeable to large solutes such as proteins. A hallmark of acute lung injury/acute respiratory distress syndrome is the accumulation of protein‐rich oedema fluid in the distal airspaces. Excess protein must be cleared from the alveolar space for recovery; however, the mechanisms of protein clearance remain incompletely understood. In intact rabbit lungs 29.8 ± 2.2% of the radio‐labelled alveolar albumin was transported to the vascular compartment at 37°C within 120 min, as assessed by real‐time measurement of 125I‐albumin clearance from the alveolar space. At 4°C or 22°C significantly lower albumin clearance (3.7 ± 0.4 or 16.2 ± 1.1%, respectively) was observed. Deposition of a 1000‐fold molar excess of unlabelled albumin into the alveolar space or inhibition of cytoskeletal rearrangement or clathrin‐dependent endocytosis largely inhibited the transport of 125I‐albumin to the vasculature, while administration of unlabelled albumin to the vascular space had no effect on albumin clearance. Furthermore, albumin uptake capacity was measured as about 0.37 mg ml−1 in cultured rat lung epithelial monolayers, further highlighting the (patho)physiological relevance of active alveolar epithelial protein transport. Moreover, gene silencing and pharmacological inhibition of the multi‐ligand receptor megalin resulted in significantly decreased albumin binding and uptake in monolayers of primary alveolar type II and type I‐like and cultured lung epithelial cells. Our data indicate that clearance of albumin from the distal air spaces is facilitated by an active, high‐capacity, megalin‐mediated transport process across the alveolar epithelium. Further understanding of this mechanism is of clinical importance, since an inability to clear excess protein from the alveolar space is associated with poor outcome in patients with acute lung injury/acute respiratory distress syndrome.
Systematic Analysis of Pyrazinamide-Resistant Spontaneous Mutants and Clinical Isolates of Mycobacterium tuberculosis
Authors: Stoffels Karolien , Mathys Vanessa , Fauville-Dufaux Maryse , Wintjens René , Bifani Pablo 
Published: July 2012

ABSTRACT

Pyrazinamide (PZA) is a first-line antitubercular drug known for its activity against persistent
Mycobacterium tuberculosis
bacilli. We set out to systematically determine the PZA susceptibility profiles and mutations in the pyrazinamidase (
pncA
) gene of a collection of multidrug-resistant tuberculosis (MDR-TB) clinical isolates and PZA-resistant (PZA
r
) spontaneous mutants. The frequency of acquired resistance to PZA was determined to be 10
−5
bacilli
in vitro
. Selection at a lower concentration of PZA yielded a significantly larger number of spontaneous mutants. The methodical approach employed allowed for determination of the frequency of the PZA
r
phenotype correlated with mutations in the
pncA
gene, which was 87.5% for the laboratory-selected spontaneous mutants examined in this study. As elucidated by structural analysis, most of the identified mutations were foreseen to affect protein activity through either alteration of an active site residue or destabilization of protein structure, indicating some preferential mutation site rather than random scattering. Twelve percent of the PZA
r
mutants did not have a
pncA
mutation, strongly indicating the presence of at least one other mechanism(s) of PZA
r
.
A Potential Substrate Binding Conformation of β-Lactams and Insight into the Broad Spectrum of NDM-1 Activity
Authors: Yuan Qinghui , He Lin , Ke Hengming 
Published: July 2012

ABSTRACT

New Delhi metallo-β-lactamase 1 (NDM-1) is a key enzyme that the pathogen
Klebsiella pneumonia
uses to hydrolyze almost all β-lactam antibiotics. It is currently unclear why NDM-1 has a broad spectrum of activity. Docking of the representatives of the β-lactam families into the active site of NDM-1 is reported here. All the β-lactams naturally fit the NDM-1 pocket, implying that NDM-1 can accommodate the substrates without dramatic conformation changes. The docking reveals two major binding modes of the β-lactams, which we tentatively name the S (substrate) and I (inhibitor) conformers. In the S conformers of all the β-lactams, the amide oxygen and the carboxylic group conservatively interact with two zinc ions, while the substitutions on the fused rings show dramatic differences in their conformations and positions. Since the bridging hydroxide ion/water in the S conformer is at the position for the nucleophilic attack, the S conformation may simulate the true binding of a substrate to NDM-1. The I conformer either blocks or displaces the bridging hydroxide ion/water, such as in the case of aztreonam, and is thus inhibitory. The docking also suggests that substitutions on the β-lactam ring are required for β-lactams to bind in the S conformation, and therefore, small β-lactams such as clavulanic acid would be inhibitors of NDM-1. Finally, our docking shows that moxalactam uses its tyrosyl-carboxylic group to compete with the S conformer and would thus be a poor substrate of NDM-1.
Prc Contributes to Escherichia coli Evasion of Classical Complement-Mediated Serum Killing
Authors: Wang Chin-Ya , Wang Shainn-Wei , Huang Wen-Chun , Kim Kwang Sik , Chang Nan-Shan , Wang Ying-Hsiang , Wu Meng-Hsing , Teng Ching-Hao 
Published: July 2012

ABSTRACTEscherichia coliis a common Gram-negative organism that causes bacteremia. Prc, a bacterial periplasmic protease, and its homologues are known to be involved in the pathogenesis of Gram-negative bacterial infections. The present study examined the role of Prc inE. colibacteremia and characterized the ability of theprcmutant of the pathogenicE. colistrain RS218 to cause bacteremia and survive in human serum. Theprcmutant of RS218 exhibited a decreased ability to cause a high level of bacteremia and was more sensitive to serum killing than strain RS218. This sensitivity was due to the mutant's decreased ability to avoid the activation of the antibody-dependent and -independent classical complement cascades as well as its decreased resistance to killing mediated by the membrane attack complex, the end product of complement system activation. The demonstration of Prc in the evasion of classical complement-mediated serum killing of pathogenicE. colimakes this factor a potential target for the development of therapeutic and preventive measures againstE. colibacteremia.
OxyR Activation in Porphyromonas gingivalis in Response to a Hemin-Limited Environment
Authors: Xie Hua , Zheng Cunge 
Published: July 2012

ABSTRACT

Porphyromonas gingivalis
is a Gram-negative obligately anaerobic bacterium associated with several forms of periodontal disease, most closely with chronic periodontitis. Previous studies demonstrated that OxyR plays an important role in the aerotolerance of
P. gingivalis
by upregulating the expression of oxidative-stress genes. Increases in oxygen tension and in H
2
O
2
both induce activation of OxyR. It is also known that
P. gingivalis
requires hemin as an iron source for its growth. In this study, we found that a hemin-limited growth environment significantly enhanced OxyR activity in
P. gingivalis
. As a result, expression of
sod
,
dps
, and
ahpC
was also upregulated. Using a chromatin immunoprecipitation quantitative PCR (qPCR) analysis, DNA binding of activated OxyR to the promoter of the
sod
gene was enhanced in
P. gingivalis
grown under hemin-limited conditions compared to excess-hemin conditions. Cellular tolerance of H
2
O
2
was also enhanced when hemin was limited in the growth medium of
P. gingivalis
. Our work supports a model in which hemin serves as a signal for the regulation of OxyR activity and indicates that
P. gingivalis
coordinately regulates expression of oxidative-stress-related genes by this hemin concentration-dependent pathway.
New Strategies in Pleural Mesothelioma: BAP1 and NF2 as Novel Targets for Therapeutic Development and Risk Assessment
Authors: Ladanyi Marc , Zauderer Marjorie G. , Krug Lee M. , Ito Tatsuo , McMillan Robert , Bott Matthew , Giancotti Filippo 
Published: July 2012

AbstractMalignant pleural mesothelioma (MPM) is a highly lethal cancer with limited therapeutic options. Recent work has focused on the frequent somatic inactivation of two tumor suppressor genes in MPM—NF2 (Neurofibromatosis type 2) and the recently identified BAP1 (BRCA associated protein 1). In addition, germline mutations in BAP1 have been identified that define a new familial cancer syndrome, which includes MPM, ocular melanoma, and other cancers. These recent advances may allow screening of high-risk individuals and the development of new therapies that target key pathways in MPM. Clin Cancer Res; 18(17); 4485–90. ©2012 AACR.
Targeting Stat3 Abrogates EGFR Inhibitor Resistance in Cancer
Authors: Sen Malabika , Joyce Sonali , Panahandeh Mary , Li Changyou , Thomas Sufi M. , Maxwell Jessica , Wang Lin , Gooding William E. , Johnson Daniel E. , Grandis Jennifer R. 
Published: July 2012

AbstractPurpose: EGF receptor (EGFR) is upregulated in most epithelial cancers where signaling through EGFR contributes to cancer cell proliferation and survival. The limited clinical efficacy of EGFR inhibitors suggests that identification of resistance mechanisms may identify new pathways for therapeutic targeting. STAT3 is upregulated in many cancers and activated via both EGFR-dependent and -independent pathways. In the present study, we tested the consequences of STAT3 inhibition in EGFR inhibitor–resistant head and neck squamous cell carcinoma (HNSCC) and bladder cancer models to determine whether STAT3 blockade can enhance responses to EGFR targeting.Experimental Design: pSTAT3 expression was assessed in human HNSCC tumors that recurred following cetuximab treatment. Cetuximab-sensitive and -resistant cell lines were treated with a STAT3 decoy to determine EC50 concentrations and the effects on STAT3 target gene expression by Western blotting. In vivo assays included evaluation of antitumor efficacy of STAT3 decoy in cetuximab-sensitive and -resistant models followed by immunoblotting for STAT3 target protein expression.Results: Targeting STAT3 with a STAT3 decoy reduced cellular viability and the expression of STAT3 target genes in EGFR inhibitor resistance models. The addition of a STAT3 inhibitor to EGFR blocking strategies significantly enhanced antitumor effects in vivo. Biopsies from HNSCC tumors that recurred following cetuximab treatment showed increased STAT3 activation compared with pretreatment biopsies.Conclusions: These results suggest that STAT3 activation contributes to EGFR inhibitor resistance both in HNSCC and bladder cancer where concomitant targeting of STAT3 may represent an effective treatment strategy. Clin Cancer Res; 18(18); 4986–96. ©2012 AACR.
Reexpression of Tumor Suppressor, sFRP1, Leads to Antitumor Synergy of Combined HDAC and Methyltransferase Inhibitors in Chemoresistant Cancers
Authors: Cooper Simon J. , von Roemeling Christina A. , Kang Kylie H. , Marlow Laura A. , Grebe Stefan K. , Menefee Michael E. , Tun Han W. , Colon-Otero Gerardo , Perez Edith A. , Copland John A. 
Published: July 2012

Abstract
Metastatic solid tumors are aggressive and mostly drug resistant, leading to few treatment options and poor prognosis as seen with clear cell renal cell carcinoma (ccRCC) and triple-negative breast cancer (TNBC). Therefore, the identification of new therapeutic regimes for the treatment of metastatic disease is desirable. ccRCC and TNBC cell lines were treated with the HDAC inhibitor romidepsin and the methyltransferase inhibitor decitabine, two epigenetic modifying drugs approved by the U.S. Food and Drug Administration for the treatment of various hematologic malignancies. Cell proliferation analysis, flow cytometry, quantitative PCR, and immunoblotting techniques were used to evaluate the antitumor synergy of this drug combination and identify the reexpression of epigenetically silenced tumor suppressor genes. Combinatorial treatment of metastatic TNBC and stage IV ccRCC cell lines with romidepsin/decitabine leads to synergistic inhibition of cell growth and induction of apoptosis above levels of individual drug treatments alone. Synergistic reexpression of the tumor suppressor gene secreted frizzled-related protein one (sFRP1) was observed in combinatorial drug-treated groups. Silencing sFRP1 (short hairpin RNA) before combinatorial drug treatment showed that sFRP1 mediates the growth inhibitory and apoptotic activity of combined romidepsin/decitabine. Furthermore, addition of recombinant sFRP1 to ccRCC or TNBC cells inhibits cell growth in a dose-dependent manner through the induction of apoptosis, identifying that epigenetic silencing of sFRP1 contributes to renal and breast cancer cell survival. Combinatorial treatment with romidepsin and decitabine in drug resistant tumors is a promising treatment strategy. Moreover, recombinant sFRP1 may be a novel therapeutic strategy for cancers with suppressed sFRP1 expression. Mol Cancer Ther; 11(10); 2105–15. ©2012 AACR.