bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and Characterization of the Novel Subunit CcoM in the
cbb
3
-Cytochrome
c
Oxidase from Pseudomonas stutzeri ZoBell
Authors: Kohlstaedt Martin , Buschmann Sabine , Xie Hao , Resemann Anja , Warkentin Eberhard , Langer Julian D. , Michel Hartmut 
Published: January 2016

ABSTRACT

Cytochrome
c
oxidases (C
c
Os), members of the heme-copper containing oxidase (HCO) superfamily, are the terminal enzymes of aerobic respiratory chains. The
cbb
3
-type cytochrome
c
oxidases (
cbb
3
-C
c
O) form the C-family and have only the central catalytic subunit in common with the A- and B-family HCOs. In
Pseudomonas stutzeri
, two
cbb
3
operons are organized in a tandem repeat. The atomic structure of the first
cbb
3
isoform (Cbb
3
-1) was determined at 3.2 Å resolution in 2010 (S. Buschmann, E. Warkentin, H. Xie, J. D. Langer, U. Ermler, and H. Michel, Science 329:327–330, 2010,
http://dx.doi.org/10.1126/science.1187303
). Unexpectedly, the electron density map of Cbb
3
-1 revealed the presence of an additional transmembrane helix (TMH) which could not be assigned to any known protein. We now identified this TMH as the previously uncharacterized protein PstZoBell_05036, using a customized matrix-assisted laser desorption ionization (MALDI)–tandem mass spectrometry setup. The amino acid sequence matches the electron density of the unassigned TMH. Consequently, the protein was renamed CcoM. In order to identify the function of this new subunit in the
cbb
3
complex, we generated and analyzed a CcoM knockout strain. The results of the biochemical and biophysical characterization indicate that CcoM may be involved in C
c
O complex assembly or stabilization. In addition, we found that CcoM plays a role in anaerobic respiration, as the ΔCcoM strain displayed altered growth rates under anaerobic denitrifying conditions.

IMPORTANCE
The respiratory chain has recently moved into the focus for drug development against prokaryotic human pathogens, in particular, for multiresistant strains (P. Murima, J. D. McKinney, and K. Pethe, Chem Biol 21:1423–1432, 2014,
http://dx.doi.org/10.1016/j.chembiol.2014.08.020
).
cbb
3
-C
c
O is an essential enzyme for many different pathogenic bacterial species, e.g.,
Helicobacter pylori
,
Vibrio cholerae
, and
Pseudomonas aeruginosa
, and represents a promising drug target. In order to develop compounds targeting these proteins, a detailed understanding of the molecular architecture and function is required. Here we identified and characterized a novel subunit, CcoM, in the
cbb
3
-C
c
O complex and thereby completed the crystal structure of the Cbb
3
oxidase from
Pseudomonas stutzeri
, a bacterium closely related to the human pathogen
Pseudomonas aeruginosa
.
The Combination of DNA Ploidy Status and PTEN/6q15 Deletions Provides Strong and Independent Prognostic Information in Prostate Cancer
Authors: Lennartz Maximilian , Minner Sarah , Brasch Sophie , Wittmann Hilko , Paterna Leonard , Angermeier Katja , Öztürk Eray , Shihada Rami , Ruge Mingu , Kluth Martina , Koop Christina , Wilczak Waldemar , Krech Till , Lebok Patrick , Wittmer Corinna , Heinzer Hans , Steuber Thomas , Adam Meike , Huland Hartwig , Graefen Markus , Haese Alexander , Simon Ronald , Sauter Guido , Schlomm Thorsten 
Published: January 2016

Abstract
Purpose: Aberrant DNA content has been discussed as a potential prognostic feature in prostate cancer.
Experimental Design: We analyzed the clinical significance of DNA ploidy in combination with prognostic relevant deletions of PTEN and 6q15 in 3,845 prostate cancers.
Result: The DNA status was diploid in 67.8%, tetraploid in 25.6%, and aneuploid in 6.8% of tumors, and deletions of PTEN and 6q15 occurred in 17.8% and 20.3% of tumors. Abnormal DNA content and deletions were linked to high Gleason score, advanced tumor stage, and positive nodal stage (P &lt; 0.0001 each). The risk of PSA recurrence increased from diploid to tetraploid and from tetraploid to aneuploid DNA status (P &lt; 0.0001 each). However, 40% of patients with Gleason score ≥4+4 and 55% of patients with PSA recurrence had diploid cancers. This fraction decreased to 21% (Gleason ≥4+4) and 29% (PSA recurrence) if PTEN and/or 6q deletion data were added to ploidy data to identify cancers with an aberrant DNA status. The significance of combining both deletions and ploidy was further demonstrated in a combined recurrence analysis. Presence of deletions increased the risk of PSA recurrence in diploid (P &lt; 0.0001), tetraploid (P &lt; 0.0001), and aneuploid cancers (P = 0.0049), and the combination of ploidy data and deletions provided clinically relevant information beyond the CAPRA-S nomogram. Multivariate modeling including preoperatively and postoperatively available parameters identified the “combined DNA status” as a strong independent predictor of poor patient outcome.
Conclusions: The combinatorial DNA content analysis involving general (ploidy) and specific events (deletions) has the potential for clinical utility in prostate cancer. Clin Cancer Res; 22(11); 2802–11. ©2016 AACR.
Serum Glycans as Risk Markers for Non–Small Cell Lung Cancer
Authors: Ruhaak L. Renee , Stroble Carol , Dai Jianliang , Barnett Matt , Taguchi Ayumu , Goodman Gary E. , Miyamoto Suzanne , Gandara David , Feng Ziding , Lebrilla Carlito B. , Hanash Samir 
Published: January 2016

Abstract
Previous studies have suggested occurrence of altered serum glycan profiles in patients with lung cancer. Here, we aimed to determine the predictive value of serum glycans to distinguish non–small cell lung cancer (NSCLC) cases from controls in prediagnostic samples using a previously validated predictive protein marker pro-SFTPB, as anchor. Blinded prediagnostic serum samples were obtained from the Carotene and Retinol Efficacy Trial (CARET), and included a discovery set of 100 NSCLC cases and 199 healthy controls. A second test set consisted of 108 cases and 216 controls. Cases and controls were matched for age at baseline (5-year groups), sex, smoking status (current vs. former), study enrollment cohort, and date of blood draw. Serum glycan profiles were determined by mass spectrometry. Twelve glycan variables were identified to have significant discriminatory power between cases and controls in the discovery set (AUC &gt; 0.6). Of these, four were confirmed in the independent validation set. A combination marker yielded AUCs of 0.74 and 0.64 in the discovery and test set, respectively. Four glycan variables exhibited significant incremental value when combined with pro-SFTPB compared with pro-SFTPB alone with AUCs of 0.73, 0.72, 0.72, and 0.72 in the test set, indicating that serum glycan signatures have relevance to risk assessment for NSCLC. Cancer Prev Res; 9(4); 317–23. ©2016 AACR.
Premalignancy in Prostate Cancer: Rethinking What We Know
Authors: De Marzo Angelo M. , Haffner Michael C. , Lotan Tamara L. , Yegnasubramanian Srinivasan , Nelson William G. 
Published: January 2016

Abstract
High-grade prostatic intraepithelial neoplasia (PIN) has been accepted as the main precursor lesion to invasive adenocarcinoma of the prostate, and this is likely to be the case. However, in an unknown number of cases, lesions fulfilling the diagnostic criteria for high-grade PIN may actually represent intra-acinar or intraductal spread of invasive carcinoma. Intriguingly, this possibility would not contradict many of the findings of previous epidemiologic studies linking high-grade PIN to carcinoma or molecular pathologic studies showing similar genomic (e.g., TMPRSS2-ERG gene fusion) as well as epigenomic and molecular phenotypic alterations between high-grade PIN and carcinoma. Also, this possibility would be consistent with previous anatomic studies in prostate specimens linking high-grade PIN and carcinoma in autopsy and other whole prostate specimens. In addition, if some cases meeting morphologic criteria for PIN actually represent intra-acinar spread of invasive carcinoma, this could be an important potential confounder of the interpretation of past clinical trials enrolling patients presumed to be without carcinoma, who are at high risk of invasive carcinoma. Thus, in order to reduce possible bias in future study/trial designs, novel molecular pathology approaches are needed to decipher when an apparent PIN lesion may be intra-acinar/intra-ductal spread of an invasive cancer and when it truly represents a precursor state. Similar approaches are needed for lesions known as intraductal carcinoma to facilitate better classification of them as true intra-ductal/acinar spread on one hand or as precursor high-grade PIN (cribriform type) on the other hand; a number of such molecular approaches (e.g., coevaluating TMPRSS-ERG fusion and PTEN loss) are already showing excellent promise. Cancer Prev Res; 9(8); 648–56. ©2016 AACR.
Paramedic Exposure to Out-of-Hospital Cardiac Arrest Resuscitation Is Associated With Patient Survival
Authors: Dyson Kylie , Bray Janet E. , Smith Karen , Bernard Stephen , Straney Lahn , Finn Judith 
Published: January 2016

Background—
Although out-of-hospital cardiac arrest (OHCA) is a major public health problem, individual paramedics are rarely exposed to these cases. In this study, we examined whether previous paramedic exposure to OHCA resuscitation is associated with patient survival.

Methods and Results—

For the period 2003 to 2012, we linked data from the Victorian Ambulance Cardiac Arrest Registry to Ambulance Victoria’s employment data set. We defined exposure as the number of times a paramedic attended an OHCA where resuscitation was attempted in the 3 years preceding each case. Using a multivariable model adjusting for known predictors of survival, we measured the association between paramedic OHCA exposure and patient survival to hospital discharge. During the study period, there were 4151 paramedics employed and 48 291 OHCAs (44% with resuscitation attempted). The median exposure of all paramedics was 2 (interquartile range 1–3) OHCAs/year. Eleven percent of paramedics were not exposed to any OHCA cases. Increased paramedic exposure was associated with reduced odds of attempted resuscitation (
P
<0.001). In the 3 years preceding each OHCA where resuscitation was attempted, the median exposure of the treating paramedics was 11 (interquartile range 6–17) OHCAs. Compared with patients treated by paramedics with a median of ≤6 exposures during the previous 3 years (7% survival), the odds of survival were higher for patients treated by paramedics with >6 to 11 (12%, adjusted odds ratio 1.26, 95% confidence interval 1.04–1.54), >11 to 17 (14%, adjusted odds ratio 1.29, 95% confidence interval 1.04–1.59), and >17 exposures (17%, adjusted odds ratio 1.50, 95% confidence interval 1.22–1.86). Paramedic years of experience were not associated with survival.

Conclusions—
Patient survival after OHCA significantly increases with the number of OHCAs that paramedics have previously treated.
Recharacterisation and photo-documentation of five North American Bursaphelenchus species from C.L. Massey’s type material
Authors: Kanzaki Natsumi , Giblin-Davis Robin M. , Center Barbara J. 
Published: January 2016

The type specimens of fiveBursaphelenchusspecies described by Massey,i.e.,B. bestiolus,B. corneolus,B. elytrus,B. newmexicanusandB. wilfordi, were re-examined and photo-documented to update their descriptions in light of a contemporary understanding of the genus. The presence of a lateral field, basal swelling of stylet, P1 ventral single papilla of males and a pair of three-celled structures in females, which were not described or mentioned in the original descriptions, were observed, although the number of lateral incisures were not clarified because of sample condition. Within these five species, the intrageneric groupings ofB. bestiolusandB. wilfordihad been unclear. In the present study, because of newly observed morphological characters,B. bestiolusis considered to belong to thehofmanni-group, and is close toB. talonusandB. rufipennis. These three species form a species complex and are distinguished from each other only by female tail morphology. The species status ofB. wilfordiis still unclear, although, based on spicule morphology and structure and arrangement of genital papillae, we consider it to belong to thehofmanni-group, close toB. parvispicularis,B. paraparvispicularisandB. osumiana. However, female characters ofB. wilfordiare also similar to members of thecocophilus-group andParasitaphelenchus. Re-isolation and molecular identification are necessary to confirm the status of these species. By contrast, the affiliations ofB. corneoluswith thehofmanni-group andB. elytrusandB. newmexicanuswith theeggersi-group were confirmed. Based upon its morphological traits,B. corneolusis close toB. gerberaeandB. paracorneolus, and is distinguished from these species by its spicule morphology, female tail morphology and female post-uterine sac length. However, male specimens ofB. corneoluswere not available for the present study and confirmation is necessary.Bursaphelenchus elytrusis similar toB. tusciaeand is distinguished from it by its spicule (condylus) morphology and excretory pore position.Bursaphelenchus newmexicanusis close toB. glochisand is distinguished from it mostly by morphometrics and spicule (condylus) morphology. However, morphometrics usually vary among individuals and populations of a species, necessitating morphometric and molecular comparisons of more isolates (strains) in order to clarify specific status.
A Linkage Observed between Austral Autumn Antarctic Oscillation and Preceding Southern Ocean SST Anomalies
Authors: Hu Chundi , Wu Qigang , Yang Song , Yao Yonghong , Chan Duo , Li Zhenning , Deng Kaiqiang 
Published: January 2016

Abstract
In this study, the authors apply a lagged maximum covariance analysis (MCA) to capture the cross-seasonal coupled patterns between the Southern Ocean sea surface temperature (SOSST) and extratropical 500-hPa geopotential height anomalies in the Southern Hemisphere, from which Niño-3.4 signals and their linear trends are removed to a certain extent. Statistically significant results show that the dominant feature of ocean–atmosphere interaction is likely the effect of atmosphere on SOSST anomalies, with a peak occurring when the atmosphere leads the SOSST by 1 month.
However, the most eye-capturing phenomenon is that the austral autumn atmospheric signal, characterized by a negatively polarized Antarctic Oscillation (AAO), is significantly related to the gradual evolution of preceding SOSST anomalies, suggesting that the SOSST anomalies tend to exert an effect on the Southern Hemisphere atmospheric circulation. A regression analysis based on SOSST anomaly centers confirms these features. It is also demonstrated that the gradual evolution of changes in SOSST is mainly driven by internal atmospheric variability via surface turbulent heat flux associated with cold or warm advection and that the atmospheric circulation experiences a change from a typical positive AAO to a negative phase in this process. These findings indicate that such a long lead cross-seasonal covariance could contribute to a successful prediction of AAO-related atmospheric circulation in austral autumn from the perspective of SOSST anomalies, with lead times up to 6–7 months.
Interbasin Transport of the Meridional Overturning Circulation
Authors: Jones C. S. , Cessi Paola 
Published: January 2016

AbstractThe meridional overturning circulation (MOC) is studied in an idealized domain with two basins connected by a circumpolar channel in the southernmost region. Flow is forced at the surface by longitude-independent wind stress, freshwater flux, and fast temperature relaxation to prescribed profiles. The only longitudinal asymmetry is that one basin is twice as wide as the other. Two states, a preferred one with sinking in the narrow basin and an asymmetrically forced one with sinking in the wide basin, are compared. In both cases, sinking is compensated by upwelling everywhere else, including the passive basin. Despite the greater area of the wide basin, the residual overturning transport is the same regardless of the location of sinking. The two basins exchange flow at their southern edge by a geostrophic transport balanced by the difference in the depth of isopycnals at the eastern boundaries of each basin. Gnanadesikan’s model for the upper branch of the MOC is extended to include two basins connected by a reentrant channel and is used to illustrate the basic properties of the flow: the layer containing the surface and intermediate water is shallower in the active basin than in the passive basin, and this difference geostrophically balances an exchange flow from the passive to the active basin. The exchange flow is larger when sinking occurs in the narrow basin. A visualization of the horizontal structure of the upper branch of the MOC shows that both the gyres and the meridional flow are important in determining the flow field.
Evaluation of Heating and Shearing on the Viscoelastic Properties of Calcium Hydroxyapatite Used in Injection Laryngoplasty
Authors: Mahboubi Hossein , Mohraz Ali , Verma Sunil P. 
Published: January 2016

ObjectiveTo compare the viscoelastic properties of calcium hydroxyapatite (CaHA) to carboxymethylcellulose (CMC) injectables used for injection laryngoplasty and determine if they are affected by heating and shearing.Study DesignExperimental.SettingUniversity laboratory.Subjects and MethodsVocal fold injection laryngoplasty with CaHA is oftentimes challenging due to the amount of pressure necessary to push the injectate through a needle. Anecdotal techniques, such as heating the product, have been suggested to facilitate injection. The viscoelastic properties of CaHA and CMC were measured with a rheometer. The effects of heating and shearing on sample viscoelasticity were recorded.ResultsCaHA was 9.5 times more viscous than CMC (43,100 vs 4540 Pa·s). Heating temporarily decreased the viscosity of CaHA by 32%. However, it also caused the viscosity to subsequently increase after time. Shearing of CaHA reduced its viscosity by 26%. Heating and shearing together temporarily reduced the viscosity of CaHA by 52%.ConclusionA combination of heating and shearing had a more profound effect than heating or shearing alone on the viscosity of CaHA, potentially making it easier to inject temporarily. Long‐term and in vivo studies are required to further analyze the effect of heating and shearing on CaHA injectables.
Transoral Surgical Anatomy and Clinical Considerations of Lateral Oropharyngeal Wall, Parapharyngeal Space, and Tongue Base
Authors: Gun Ramazan , Durmus Kasim , Kucur Cuneyt , Carrau Ricardo L. , Ozer Enver 
Published: January 2016

ObjectiveWith the emergence of transoral robotic approaches, head and neck surgeons are faced with an unfamiliar inside‐out head and neck anatomy. This study was performed to describe key anatomic landmarks and surgical considerations of transoral robotic resection of the lateral oropharyngeal wall, the parapharyngeal space, and the base of the tongue.Study DesignDescriptive transoral anatomic study.SettingAcademic anatomy laboratory and tertiary academic hospital.Subjects and MethodsTransoral dissections of the lateral pharyngeal wall, base of tongue, and parapharyngeal space were performed in 5 vascular silicone‐injected cadavers to illustrate anatomic landmarks from the inside‐out perspective. Lateral neck dissections were also performed to better appreciate the anatomic structures and to be more familiar with intraoperative anatomy.ResultsThe neurovascular and muscular structures located in parapharyngeal space, lateral oropharyngeal wall, and base of tongue were described. Surgical significance of key anatomic landmarks was emphasized with high‐quality illustrations.ConclusionA thorough understanding of transoral anatomy is crucial to perform transoral robotic surgery safely and efficiently. To understand inside‐out anatomy of base of tongue, lateral oropharyngeal wall, and parapharyngeal space, cadaveric dissection is highly beneficial and may help to shorten the learning curve for transoral robotic dissections.
Hospice assist at home: does the integration of hospice care in primary healthcare support patients to die in their preferred location – A retrospective cross-sectional evaluation study
Authors: de Graaf Everlien , Zweers Daniëlle , Valkenburg Anna CH , Uyttewaal Allegonda , Teunissen Saskia CCM 
Published: January 2016

Background: A majority of patients prefer to die at home. Specialist palliative care aims to improve quality of life. Hospice assist at home is a Dutch model of general/specialised palliative care within primary care, collaboratively built by general practitioners and a hospice. Aim: The aims of this study are to explore whether hospice assist at home service enables patients at hometo express end-of-life preferences and die in their preferred location. In addition, this study provides insight into symptomburden, stability and early referral. Design: A retrospective cross-sectional evaluation study was performed (December 2014–March 2015), using hospice assist at home patient records and documentation. Primary outcome includes congruence between preferred and actual place of death. Secondary outcomes include symptom burden, (in)stability and early identification. Setting/participants: Between June 2012 and December 2014, 130 hospice assist at home patients, living at home with a life expectancy <1 year, were enrolled. Hospice assist at home, a collaboration between general practitioners, district nurses, trained volunteers and a hospice team, facilitates (1) general practitioner–initiated consultation by Nurse Consultant Hospice, (2) fortnightly interdisciplinary consultations and (3) 24/7 hospice backup for patients, caregivers and professionals. Results: A total of 130 patients (62 (48%) men; mean age, 72 years) were enrolled, of whom 107/130 (82%) died and 5 dropped out. Preferred place of death was known for 101/107 (94%) patients of whom 91% patients died at their preferred place of death. Conclusion: Hospice assist at home service supports patients to die in their preferred place of death. Shared responsibility of proactive care in primary care collaboration enabled patients to express preferences. Hospice care should focus on local teamwork, to contribute to shared responsibilities in providing optimal palliative care.