bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Basis for Metallic-Like Conductivity in Microbial Nanowires
Authors: Malvankar Nikhil S. , Vargas Madeline , Nevin Kelly , Tremblay Pier-Luc , Evans-Lutterodt Kenneth , Nykypanchuk Dmytro , Martz Eric , Tuominen Mark T. , Lovley Derek R. 
Published: March 2015

ABSTRACT

Direct measurement of multiple physical properties of
Geobacter sulfurreducens
pili have demonstrated that they possess metallic-like conductivity, but several studies have suggested that metallic-like conductivity is unlikely based on the structures of the G. sulfurreducens pilus predicted from homology models. In order to further evaluate this discrepancy, pili were examined with synchrotron X-ray microdiffraction and rocking-curve X-ray diffraction. Both techniques revealed a periodic 3.2-Å spacing in conductive, wild-type G. sulfurreducens pili that was missing in the nonconductive pili of strain Aro5, which lack key aromatic acids required for conductivity. The intensity of the 3.2-Å peak increased 100-fold when the pH was shifted from 10.5 to 2, corresponding with a previously reported 100-fold increase in pilus conductivity with this pH change. These results suggest a clear structure-function correlation for metallic-like conductivity that can be attributed to overlapping π-orbitals of aromatic amino acids. A homology model of the G. sulfurreducens pilus was constructed with a
Pseudomonas aeruginosa
pilus model as a template as an alternative to previous models, which were based on a
Neisseria gonorrhoeae
pilus structure. This alternative model predicted that aromatic amino acids in G. sulfurreducens pili are packed within 3 to 4 Å, consistent with the experimental results. Thus, the predictions of homology modeling are highly sensitive to assumptions inherent in the model construction. The experimental results reported here further support the concept that the pili of G. sulfurreducens represent a novel class of electronically functional proteins in which aromatic amino acids promote long-distance electron transport.

IMPORTANCE
The mechanism for long-range electron transport along the conductive pili of
Geobacter sulfurreducens
is of interest because these “microbial nanowires” are important in biogeochemical cycling as well as applications in bioenergy and bioelectronics. Although proteins are typically insulators, G. sulfurreducens pilus proteins possess metallic-like conductivity. The studies reported here provide important structural insights into the mechanism of the metallic-like conductivity of G. sulfurreducens pili. This information is expected to be useful in the design of novel bioelectronic materials.
Switching from a Unicellular to Multicellular Organization in an Aspergillus niger Hypha
Authors: Bleichrodt Robert-Jan , Hulsman Marc , Wösten Han A. B. , Reinders Marcel J. T. 
Published: March 2015

ABSTRACT

Pores in fungal septa enable cytoplasmic streaming between hyphae and their compartments. Consequently, the mycelium can be considered unicellular. However, we show here that Woronin bodies close ~50% of the three most apical septa of growing hyphae of
Aspergillus niger
. The incidence of closure of the 9th and 10th septa was even ≥94%. Intercompartmental streaming of photoactivatable green fluorescent protein (PA-GFP) was not observed when the septa were closed, but open septa acted as a barrier, reducing the mobility rate of PA-GFP ~500 times. This mobility rate decreased with increasing septal age and under stress conditions, likely reflecting a regulatory mechanism affecting septal pore diameter. Modeling revealed that such regulation offers effective control of compound concentration between compartments. Modeling also showed that the incidence of septal closure in A. niger had an even stronger impact on cytoplasmic continuity. Cytoplasm of hyphal compartments was shown not to be in physical contact when separated by more than 4 septa. Together, data show that apical compartments of growing hyphae behave unicellularly, while older compartments have a multicellular organization.

IMPORTANCE
The hyphae of higher fungi are compartmentalized by porous septa that enable cytosolic streaming. Therefore, it is believed that the mycelium shares cytoplasm. However, it is shown here that the septa of
Aspergillus niger
are always closed in the oldest part of the hyphae, and therefore, these compartments are physically isolated from each other. In contrast, only part of the septa is closed in the youngest part of the hyphae. Still, compartments in this hyphal part are physically isolated when separated by more than 4 septa. Even open septa act as a barrier for cytoplasmic mixing. The mobility rate through such septa reduces with increasing septal age and under stress conditions. Modeling shows that the septal pore width is set such that its regulation offers maximal control of compound concentration levels within the compartments. Together, we show for the first time that Aspergillus hyphae switch from a unicellular to multicellular organization.
RIG-I ATPase Activity and Discrimination of Self-RNA versus Non-Self-RNA
Authors: Anchisi Stéphanie , Guerra Jessica , Garcin Dominique 
Published: March 2015

ABSTRACT
Many RNA viruses are detected by retinoic acid-inducible gene i (RIG-I), a cytoplasmic sensor that triggers an antiviral response upon binding non-self-RNA that contains a stretch of double-stranded RNA (dsRNA) bearing a base-paired 5′ ppp nucleotide. To gain insight into how RIG-I discriminates between self-RNA and non-self-RNA, we used duplexes whose complementary bottom strand contained both ribo- and deoxynucleotides. These duplexes were examined for their binding to RIG-I and their relative abilities to stimulate ATPase activity, to induce RIG-I dimerization on the duplex, and to induce beta interferon (IFN-β) expression. We show that the chemical nature of the bottom strand is not critical for RIG-I binding. However, two key ribonucleotides, at positions 2 and 5 on the bottom strand, are minimally required for the RIG-I ATPase activity, which is necessary but not sufficient for IFN-β stimulation. We find that duplexes with shorter stretches of dsRNA, as model self-RNAs, bind less stably to RIG-I but nevertheless have an enhanced ability to stimulate the ATPase. Moreover, ATPase activity promotes RIG-I recycling on RIG-I/dsRNA complexes. Since pseudo-self-RNAs bind to RIG-I less stably, they are preferentially recycled by ATP hydrolysis that weakens the helicase domain binding of dsRNA. Our results suggest that one function of the ATPase is to restrict RIG-I signaling to its interaction with non-self-RNA. A model of how this discrimination occurs as a function of dsRNA length is presented.

IMPORTANCE
The innate immune response to pathogens is based on the discrimination between self-RNA and non-self-RNA. The main determinants of this detection for RNA viruses are specific pathogen-associated molecular patterns (PAMPs) of RNA, which are detected by dedicated cytoplasmic pattern recognition receptors (PRRs). RIG-I is a PRR that specifically detects short viral dsRNAs amid a sea of cellular RNAs. Here we study the determinants of this discrimination and how RIG-I ATPase activity, the only enzymatic activity of this sensor, contributes to its activation in a manner restricted to its interaction with non-self-RNAs. We also show how the innate immune response evolves during infection via IFN expression, from a state in which discrimination of self-RNA from non-self-RNA is most important to one in which this discrimination is sacrificed for the effectiveness of the antiviral response.
Glycan-Foraging Systems Reveal the Adaptation of Capnocytophaga canimorsus to the Dog Mouth
Authors: Renzi Francesco , Manfredi Pablo , Dol Mélanie , Fu Jian , Vincent Stéphane , Cornelis Guy Richard 
Published: March 2015

ABSTRACT

Capnocytophaga canimorsus
is known to form two kinds of cells on blood agar plates (coccoid and bacillary), evoking phase variation. When grown in coculture with animal cells these bacteria appeared only as bacilli, but in the presence of vancomycin they were round, indicating that coccoid shapes likely result from weakening of the peptidoglycan layer. Polysaccharide utilization locus 5 (
PUL5
) and sialidase mutant bacteria, unable to retrieve glycans from glycoproteins, grew less than wild-type bacteria and also appeared polymorphic unless GlcNAc was added, suggesting that C. canimorsus is unable to synthesize GlcNAc, an essential component of peptidoglycan. Accordingly, a genome analysis was conducted and revealed that C. canimorsus strain 5 lacks the GlmM and GlmU enzymes, which convert glucosamine into GlcNAc. Expression of the Escherichia coli GlmM together with the acetyltransferase domain of GlmU allowed
PUL5
mutant bacteria to grow normally, indicating that C. canimorsus is a natural auxotroph that relies on GlcNAc harvested from the host N-glycoproteins for peptidoglycan synthesis. Mucin, a heavily O-glycosylated protein abundant in saliva, also rescued growth and the shape of
PUL5
mutant bacteria. Utilization of mucin was found to depend on Muc, a Sus-like system encoded by
PUL9
. Contrary to all known
PUL-
encoded systems, Muc cleaves peptide bonds of mucin rather than glycosidic linkages. Thus, C. canimorsus has adapted to build its peptidoglycan from the glycan-rich dog's mouth glycoproteins.

IMPORTANCE
Capnocytophaga canimorsus
is a bacterium that lives as a commensal in the dog mouth and causes severe infections in humans.
In vitro
, it forms two kinds of cells (coccoid and bacillary), evoking phase variation. Here, we show that cell rounding likely results from weakening of the peptidoglycan layer due to a shortage of
N
-acetylglucosamine (GlcNAc). C. canimorsus cannot synthesize GlcNAc because of the lack of key enzymes. In its niche, the dog mouth, C. canimorsus retrieves GlcNAc by foraging glycans from salivary mucin and N-linked glycoproteins through two different apparatuses, Muc and Gpd, both of which are related to the Bacteroides starch utilization system. The Muc system is peculiar in the sense that the enzyme of the complex is a protease and not a glycosylhydrolase, as it cleaves peptide bonds in order to capture glycan chains. This study provides a molecular genetic demonstration for the complex adaptation of C. canimorsus to its ecological niche, the oral cavity of dogs.
Characterization of environmental conditions during microbial Mg-carbonate precipitation and early diagenetic dolomite crust formation: Brejo do Espinho, Rio de Janeiro, Brazil
Authors: Bahniuk Anelize , McKenzie Judith A. , Perri Edoardo , Bontognali Tomaso R. R. , Vögeli Natalie , Rezende Carlos Eduardo , Rangel Thiago Pessanha , Vasconcelos Crisogono 
Published: March 2015

Abstract

For many years, sedimentary dolomite rocks have been considered to be primarily a replacement product of the calcium carbonate components comprising the original limestone, a process known as secondary replacement dolomitization. Although numerous dolomite formations in the geological record are composed of fine-grained crystals of micritic dolomite, an alternative process, that is, direct precipitation, is often excluded because of the absence of visible or geochemical indicators supporting primary precipitation. In this research, we present a study of a modern coastal hypersaline lagoon, Brejo do Espinho, Rio de Janeiro State, Brazil, which is located in a special climatic regime where a well-defined seasonal cycle of wet and dry conditions occur. The direct precipitation of modern high-Mg calcite and Ca-dolomite mud from the lagoonal waters under low-temperature hypersaline conditions is associated with the activity of microbial organisms living in this restricted environment. The mud undergoes an early diagenetic transformation into a 100% dolomite crust on the margins of the lagoon. The biomineralization process, characterized by the variations of the physico-chemical conditions in this environment during the annual hydrological cycle, is integrated with isotopic analysis to define the early diagenetic processes responsible for the formation of both dolomitic mud and crust. The carbon isotope values indicate a contribution of respired organic carbon, which is greater for the crust (δ
13
C=−9.5‰ Vienna Pee Dee Belemnite (VPDB)) than mud (δ
13
C=−1.2‰ VPDB). The oxygen isotope values reflect a moderate degree of evaporation during mud formation (δ
18
O=1.1‰ VPDB), whereas it is greatly enhanced during early diagenetic crust formation (δ
18
O=4.2‰ VPDB). The clumped isotope formation temperature derived for the Brejo do Espinho mud is 34 °C, whereas it is 32 °C for the crust. These temperatures are consistent with the upper range of measured values during the dry season when the lagoon experiences the most hypersaline conditions.
Carbonate build-ups in lacustrine, hydrothermal and fluvial settings: comparing depositional geometry, fabric types and geochemical signature
Authors: Della Porta Giovanna 
Published: March 2015

Abstract
Carbonate build-ups in lakes, hydrothermal and fluvial settings are characterized by distinctive geometry, spatial distribution, fabrics and geochemical signature but also by some comparable features. Lake margin bioherms form continuous belts for hundreds of metres to kilometres, subparallel to shorelines. Sublacustrine spring mounds are spaced at hundreds of metres to kilometres and aligned along faults. Hydrothermal travertine mounds and aprons with planar clinoforms or terraced slopes are controlled by faults, thermal water discharge and substrate topography. Fluvial tufa barrages, cascades and terraced slopes are controlled by climate, vegetation and substrate gradient. The wide spectrum of carbonate microfabrics ranges from clotted peloidal micrite and laminated boundstone to crystalline dendrite cementstone. Non-marine carbonate microfabrics cannot be linked to specific depositional environments, and are not deterministic proxies for the interpretation of build-up architecture. Microfabric associations can be indicative, but not exclusive, of specific depositional environments and geometry. Stable isotope geochemistry is a useful tool to distinguish between hydrothermal, karstic freshwater and evaporative lake carbonates. Carbonate precipitation results from a continuum of abiotic and biologically influenced/induced processes in settings where carbonate supersaturation is largely driven by physico-chemical mechanisms and microbial biofilms, even if acting as passive low-energy surface sites for nucleation, are widely present.
Prognostic Factors of Early Morphological Response to Treatment with Ranibizumab in Patients with Wet Age-Related Macular Degeneration
Authors: Chrapek Oldřich , Jarkovský Jiří , Šín Martin , Studnička Jan , Kolář Petr , Jirková Barbora , Dušek Ladislav , Pitrová Šárka , Řehák Jiří 
Published: March 2015

Aim. To assess the significance of age, gender, baseline best corrected visual acuity, baseline macula thickness, and type and size of choroidal neovascularization in early morphological therapeutic response to ranibizumab treatment in patients with the wet form of age-related macular degeneration.Methods. From 09/2008 to 06/2013 we evaluated 1153 newly diagnosed, treatment-naïve patients treated with ranibizumab. Based on the morphological findings in the macula following the initial 3 injections of ranibizumab, the patients were divided into two groups based on active and inactive choroidal neovascularization.Results. After the initial 3 injections of ranibizumab, we examined the sample of 841 eyes with active CNV and 312 eyes with inactive CNV. In the inactive group, we found a statistically higher proportion of occult CNV (P<0.001) and lower incidence of CNV greater than 5DA (P < 0.001) compared with the active group. We found no statistically significant difference in age, gender, baseline best corrected visual acuity, or baseline macula thickness between the inactive and active groups.Conclusion. Occult CNV and CNV smaller than 5DA are optimistic factors for a better morphological therapeutic response at the beginning of ranibizumab treatment.
CSF1 Receptor Targeting in Prostate Cancer Reverses Macrophage-Mediated Resistance to Androgen Blockade Therapy
Authors: Escamilla Jemima , Schokrpur Shiruyeh , Liu Connie , Priceman Saul J. , Moughon Diana , Jiang Ziyue , Pouliot Frederic , Magyar Clara , Sung James L. , Xu Jingying , Deng Gang , West Brian L. , Bollag Gideon , Fradet Yves , Lacombe Louis , Jung Michael E. , Huang Jiaoti , Wu Lily 
Published: March 2015

AbstractGrowing evidence suggests that tumor-associated macrophages (TAM) promote cancer progression and therapeutic resistance by enhancing angiogenesis, matrix-remodeling, and immunosuppression. In this study, prostate cancer under androgen blockade therapy (ABT) was investigated, demonstrating that TAMs contribute to prostate cancer disease recurrence through paracrine signaling processes. ABT induced the tumor cells to express macrophage colony-stimulating factor 1 (M-CSF1 or CSF1) and other cytokines that recruit and modulate macrophages, causing a significant increase in TAM infiltration. Inhibitors of CSF1 signaling through its receptor, CSF1R, were tested in combination with ABT, demonstrating that blockade of TAM influx in this setting disrupts tumor promotion and sustains a more durable therapeutic response compared with ABT alone. Cancer Res; 75(6); 950–62. ©2015 AACR.
Immunohistochemical Loss of LKB1 Is a Biomarker for More Aggressive Biology in KRAS-Mutant Lung Adenocarcinoma
Authors: Calles Antonio , Sholl Lynette M. , Rodig Scott J. , Pelton Ashley K. , Hornick Jason L. , Butaney Mohit , Lydon Christine , Dahlberg Suzanne E. , Oxnard Geoffrey R. , Jackman David M. , Jänne Pasi A. 
Published: March 2015

Abstract
Purpose: LKB1 loss is common in lung cancer, but no assay exists to efficiently evaluate the presence or absence of LKB1. We validated an IHC assay for LKB1 loss and determined the impact of LKB1 loss in KRAS-mutant non–small cell lung cancer (NSCLC).
Experimental Design: We optimized and validated an IHC assay for LKB1 (clone Ley37D/G6) using a panel of lung cancer cell lines and tumors with known LKB1 mutations, including 2 patients with Peutz–Jeghers syndrome (PJS) who developed lung adenocarcinoma. We retrospectively analyzed tumors for LKB1 using IHC from 154 KRAS-mutant NSCLC patients, including 123 smokers and 31 never-smokers, and correlated the findings with patient and tumor characteristics and clinical outcome.
Results: LKB1 expression was lost by IHC in 30% of KRAS-mutant NSCLC (smokers 35% vs. never-smokers 13%, P = 0.017). LKB1 loss did not correlate with a specific KRAS mutation but was more frequent in tumors with KRAS transversion mutations (P = 0.029). KRAS-mutant NSCLC patients with concurrent LKB1 loss had a higher number of metastatic sites at the time of diagnosis (median 2.5 vs. 2, P = 0.01), higher incidence of extrathoracic metastases (P = 0.01), and developed brain metastasis more frequently (48% vs. 25%, P = 0.02). There was a nonsignificant trend to worse survival in stage IV KRAS-mutant NSCLC patients with LKB1 loss.
Conclusions: LKB1 IHC is a reliable and efficient assay to evaluate for loss of LKB1 in clinical samples of NSCLC. LKB1 loss is more common in smokers, and is associated with a more aggressive clinical phenotype in KRAS-mutant NSCLC patients, accordingly to preclinical models. Clin Cancer Res; 21(12); 2851–60. ©2015 AACR.
Self-Blood Pressure Monitoring in an Urban, Ethnically Diverse Population
Authors: Yi Stella S. , Tabaei Bahman P. , Angell Sonia Y. , Rapin Anne , Buck Michael D. , Pagano William G. , Maselli Frank J. , Simmons Alvaro , Chamany Shadi 
Published: March 2015

Background—
Hypertension is a leading risk factor for cardiovascular disease. Although control rates have improved over time, racial/ethnic disparities in hypertension control persist. Self-blood pressure monitoring, by itself, has been shown to be an effective tool in predominantly white populations, but less studied in minority, urban communities. These types of minimally intensive approaches are important to test in all populations, especially those experiencing related health disparities, for broad implementation with limited resources.

Methods and Results—

The New York City Health Department in partnership with community clinic networks implemented a randomized clinical trial (n=900, 450 per arm) to investigate the effectiveness of self-blood pressure monitoring in medically underserved and largely black and Hispanic participants. Intervention participants received a home blood pressure monitor and training on use, whereas control participants received usual care. After 9 months, systolic blood pressure decreased (intervention, 14.7 mm Hg; control, 14.1 mm Hg;
P
=0.70). Similar results were observed when incorporating longitudinal data and calculating a mean slope over time. Control was achieved in 38.9% of intervention and 39.1% of control participants at the end of follow-up; the time-to-event experience of achieving blood pressure control in the intervention versus control groups were not different from each other (logrank
P
value =0.91).

Conclusions—
Self-blood pressure monitoring was not shown to improve control over usual care in this largely minority, urban population. The patient population in this study, which included a high proportion of Hispanics and uninsured persons, is understudied. Results indicate these groups may have additional meaningful barriers to achieving blood pressure control beyond access to the monitor itself.

Clinical Trial Registration:

http://clinicaltrials.gov
. Unique Identifier: NCT01123577
The HEART Pathway Randomized Trial
Authors: Mahler Simon A. , Riley Robert F. , Hiestand Brian C. , Russell Gregory B. , Hoekstra James W. , Lefebvre Cedric W. , Nicks Bret A. , Cline David M. , Askew Kim L. , Elliott Stephanie B. , Herrington David M. , Burke Gregory L. , Miller Chadwick D. 
Published: March 2015

Background—
The HEART Pathway is a decision aid designed to identify emergency department patients with acute chest pain for early discharge. No randomized trials have compared the HEART Pathway with usual care.

Methods and Results—

Adult emergency department patients with symptoms related to acute coronary syndrome without ST-elevation on ECG (n=282) were randomized to the HEART Pathway or usual care. In the HEART Pathway arm, emergency department providers used the HEART score, a validated decision aid, and troponin measures at 0 and 3 hours to identify patients for early discharge. Usual care was based on American College of Cardiology/American Heart Association guidelines. The primary outcome, objective cardiac testing (stress testing or angiography), and secondary outcomes, index length of stay, early discharge, and major adverse cardiac events (death, myocardial infarction, or coronary revascularization), were assessed at 30 days by phone interview and record review. Participants had a mean age of 53 years, 16% had previous myocardial infarction, and 6% (95% confidence interval, 3.6%–9.5%) had major adverse cardiac events within 30 days of randomization. Compared with usual care, use of the HEART Pathway decreased objective cardiac testing at 30 days by 12.1% (68.8% versus 56.7%;
P
=0.048) and length of stay by 12 hours (9.9 versus 21.9 hours;
P
=0.013) and increased early discharges by 21.3% (39.7% versus 18.4%;
P
<0.001). No patients identified for early discharge had major adverse cardiac events within 30 days.

Conclusions—
The HEART Pathway reduces objective cardiac testing during 30 days, shortens length of stay, and increases early discharges. These important efficiency gains occurred without any patients identified for early discharge suffering MACE at 30 days.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique Identifier: NCT01665521.