bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution, biogeography and systematics of the western Palaearctic Zamenis ratsnakes
Authors: Salvi Daniele , Mendes Joana , Carranza Salvador , Harris David James 
Published: June 2018

AbstractThe phylogenetic relationships between western Palaearctic Zamenis and Rhinechis ratsnakes have been troubled, with recent estimates based on the supermatrix approach questioning their monophyly and providing contradictory results. In this study, we generated a comprehensive molecular data set for Zamenis and closely related ratsnakes to assess their phylogenetic and systematic relationships and infer their spatial and temporal modes of diversification. We obtained a fully resolved and well‐supported phylogeny, which is consistent across markers, taxon‐sets and phylogenetic methods. The close phylogenetic relationship between Rhinechis and Zamenis is well‐established. However, the early branching pattern within this clade, and the position of R. scalaris and Z. hohenackeri, remains poorly supported. The Persian ratsnake Z. persicus is sister to the Mediterranean species Z. situla, Z. longissimus and Z. lineatus, of which Z. situla is sister to a clade containing the latter two species. These results are consistent with a recent phylogenomic study on ratsnakes based on hundreds of loci. Whereas, topological tests based on our data and evidence from such phylogenomic study strongly rejected previous phylogenetic estimates based on the supermatrix approach and demonstrate that these “mega‐phylogenies”, with hundreds of taxa and high levels of missing data, have recovered inconsistent relationships with spurious nodal support. Biogeographical and molecular dating analyses suggest an origin of the ancestor of Rhinechis and Zamenis in the Aegean region with early cladogenesis during the Late Miocene associated with the Aegean arch formation and support a scenario of east‐to‐west diversification. Finally, while we have little morphological and phylogenetic evidence for the distinctiveness between Rhinechis and Zamenis, a classification of them in a single genus, and the designation of Zamenis scalaris (Schinz, 1822), reflects better their evolutionary relationships.
Cytokinin Signaling in Mycobacterium tuberculosis
Authors: Samanovic Marie I. , Hsu Hao-Chi , Jones Marcus B. , Jones Victoria , McNeil Michael R. , Becker Samuel H. , Jordan Ashley T. , Strnad Miroslav , Xu Changcheng , Jackson Mary , Li Huilin , Darwin K. Heran 
Published: June 2018

ABSTRACT

It was recently reported that the human-exclusive pathogen
Mycobacterium tuberculosis
secretes cytokinins, which had only been known as plant hormones. While cytokinins are well-established, adenine-based signaling molecules in plants, they have never been shown to participate in signal transduction in other kingdoms of life.
M. tuberculosis
is not known to interact with plants. Therefore, we tested the hypothesis that cytokinins trigger transcriptional changes within this bacterial species. Here, we show cytokinins induced the strong expression of the
M. tuberculosis
gene Rv0077c. We found that Rv0077c expression is repressed by a TetR-like transcriptional repressor, Rv0078. Strikingly, cytokinin-induced expression of Rv0077c resulted in a loss of acid-fast staining of
M. tuberculosis
. While acid-fast staining is thought to be associated with changes in the bacterial cell envelope and virulence, Rv0077c-induced loss of acid-fastness did not affect antibiotic susceptibility or attenuate bacterial growth in mice, consistent with an unaltered mycolic acid profile of Rv0077c-expressing cells. Collectively, these findings show cytokinins signal transcriptional changes that can affect
M. tuberculosis
acid-fastness and that cytokinin signaling is no longer limited to the kingdom Plantae.

IMPORTANCE
Cytokinins have only previously been known as plant hormones. The discovery that they can be used as signaling molecules outside of plants broadens the repertoire of small molecules that can potentially affect gene expression in all domains of life.
Escherichia coli ZipA Organizes FtsZ Polymers into Dynamic Ring-Like Protofilament Structures
Authors: Krupka Marcin , Sobrinos-Sanguino Marta , Jiménez Mercedes , Rivas Germán , Margolin William 
Published: June 2018

ABSTRACT

ZipA is an essential cell division protein in
Escherichia coli
. Together with FtsA, ZipA tethers dynamic polymers of FtsZ to the cytoplasmic membrane, and these polymers are required to guide synthesis of the cell division septum. This dynamic behavior of FtsZ has been reconstituted on planar lipid surfaces
in vitro
, visible as GTP-dependent chiral vortices several hundred nanometers in diameter, when anchored by FtsA or when fused to an artificial membrane binding domain. However, these dynamics largely vanish when ZipA is used to tether FtsZ polymers to lipids at high surface densities. This, along with some
in vitro
studies in solution, has led to the prevailing notion that ZipA reduces FtsZ dynamics by enhancing bundling of FtsZ filaments. Here, we show that this is not the case. When lower, more physiological levels of the soluble, cytoplasmic domain of ZipA (sZipA) were attached to lipids, FtsZ assembled into highly dynamic vortices similar to those assembled with FtsA or other membrane anchors. Notably, at either high or low surface densities, ZipA did not stimulate lateral interactions between FtsZ protofilaments. We also used
E. coli
mutants that are either deficient or proficient in FtsZ bundling to provide evidence that ZipA does not directly promote bundling of FtsZ filaments
in vivo
. Together, our results suggest that ZipA does not dampen FtsZ dynamics as previously thought, and instead may act as a passive membrane attachment for FtsZ filaments as they treadmill.

IMPORTANCE
Bacterial cells use a membrane-attached ring of proteins to mark and guide formation of a division septum at midcell that forms a wall separating the two daughter cells and allows cells to divide. The key protein in this ring is FtsZ, a homolog of tubulin that forms dynamic polymers. Here, we use electron microscopy and confocal fluorescence imaging to show that one of the proteins required to attach FtsZ polymers to the membrane during
E. coli
cell division, ZipA, can promote dynamic swirls of FtsZ on a lipid surface
in vitro
. Importantly, these swirls are observed only when ZipA is present at low, physiologically relevant surface densities. Although ZipA has been thought to enhance bundling of FtsZ polymers, we find little evidence for bundling
in vitro
. In addition, we present several lines of
in vivo
evidence indicating that ZipA does not act to directly bundle FtsZ polymers.
The PGRS Domain of Mycobacterium tuberculosis PE_PGRS Protein Rv0297 Is Involved in Endoplasmic Reticulum Stress-Mediated Apoptosis through Toll-Like Receptor 4
Authors: Grover Sonam , Sharma Tarina , Singh Yadvir , Kohli Sakshi , P. Manjunath , Singh Aditi , Semmler Torsten , Wieler Lothar H. , Tedin Karsten , Ehtesham Nasreen Z. , Hasnain Seyed E. 
Published: June 2018

ABSTRACT

The genome of
Mycobacterium tuberculosis
, the causal organism of tuberculosis (TB), encodes a unique protein family known as the PE/PPE/PGRS family, present exclusively in the genus
Mycobacterium
and nowhere else in the living kingdom, with largely unexplored functions. We describe the functional significance of the PGRS domain of Rv0297, a member of this family.
In silico
analyses revealed the presence of intrinsically disordered stretches and putative endoplasmic reticulum (ER) localization signals in the PGRS domain of Rv0297 (Rv0297PGRS). The PGRS domain aids in ER localization, which was shown by infecting macrophage cells with
M. tuberculosis
and by overexpressing the protein by transfection in macrophage cells followed by activation of the unfolded protein response, as evident from increased expression of GRP78/GRP94 and CHOP/ATF4, leading to disruption of intracellular Ca
2+
homeostasis and increased nitric oxide (NO) and reactive oxygen species (ROS) production. The consequent activation of the effector caspase-8 resulted in apoptosis of macrophages, which was Toll-like receptor 4 (TLR4) dependent. Administration of recombinant Rv0297PGRS (rRv0297PGRS) also exhibited similar effects. These results implicate a hitherto-unknown role of the PGRS domain of the PE_PGRS protein family in ER stress-mediated cell death through TLR4. Since this protein is already known to be present at later stages of infection in human granulomas it points to the possibility of it being employed by
M. tuberculosis
for its dissemination via an apoptotic mechanism.

IMPORTANCE
Apoptosis is generally thought to be a defense mechanism in protecting the host against
Mycobacterium tuberculosis
in early stages of infection. However, apoptosis during later stages in lung granulomas may favor the bacterium in disseminating the disease. ER stress has been found to induce apoptosis in TB granulomas, in zones where apoptotic macrophages accumulate in mice and humans. In this study, we report ER stress-mediated apoptosis of host cells by the Rv0297-encoded PE_PGRS5 protein of
M. tuberculosis
exceptionally present in the pathogenic
Mycobacterium
genus. The PGRS domain of Rv0297 aids the protein in localizing to the ER and induces the unfolded protein response followed by apoptosis of macrophages. The effect of the Rv0297PGRS domain was found to be TLR4 dependent. This study presents novel insights on the strategies employed by
M. tuberculosis
to disseminate the disease.
Tracheobronchial stents in palliative care: a case series and literature review
Authors: Tjahjono Richard , Chin Ronald Yoon-Kong , Flynn Peter 
Published: June 2018

ObjectiveTo evaluate the outcomes of tracheobronchial stenting in patients with malignant central airway obstruction and assist practitioners in palliative settings in understanding the indications, contraindications and management of tracheobronchial stents.MethodsThis retrospective study involved a consecutive case series of palliative patients with central airway obstruction secondary to inoperable cancers who underwent tracheobronchial stenting at a single institution. The European Cooperative Oncology Group (ECOG) scale was used to evaluate patient functional status before and after tracheobronchial stenting.ResultsTwenty-three patients underwent tracheobronchial stenting for malignant central airway obstruction. The majority of patients presented with symptoms of worsening dyspnoea (21 of 23; 91%). Postoperatively, there was a significant improvement in mean ECOG performance status from 2.88±0.34 to 1.58±0.50 (p<0.01). There was no intraoperative mortality resulting from tracheobronchial stenting. Five patients (21.74%) re-presented to hospital due to worsening symptoms and required emergency bronchoscopy. Two patients had stent migration, requiring stent replacement. One patient restenosed from tumour granulation, requiring microdebrider to debulk the mass. Two patients had stent failure secondary to external tumour compression, leading to death.ConclusionTracheobronchial stenting is a safe and effective procedure that offers rapid palliation of symptoms and improvement in patient functional status.
Extending the Sydney Triage to Admission Risk Tool (START+) to predict discharges and short stay admissions
Authors: Ebker-White Anja , Bein Kendall J , Dinh Michael M 
Published: June 2018

ObjectiveThis study aims to validate previously reported triage tool titled Sydney Triage to Admission Risk Tool (START+) and investigate whether an extended version of the tool could be used to identify and stream appropriate short stay admissions to ED observation units or specialised short stay inpatient wards.MethodsThis was a prospective study at two metropolitan EDs in Sydney, Australia. Consecutive triage encounters were observed by a trained researcher and START scores calculated. The primary outcome was length of stay <48 hours. Multivariable logistic regression was used to estimate area under curve of receiver operator characteristic (AUROC) for START scores. The original START tool was then extended to include frailty and multiple or major comorbidities as additional variables to assess for further predictive accuracy.ResultsThere were 894 patients analysed during the study period. Of the 894 patients, there were 732 patients who were either discharged from ED or admitted for <2 days. The AUROC for the original START+ tool was 0.80 (95% CI 0.77 to 0.83). The presence of frailty was found to add a further five points and multiple comorbidities added another four points on top of the START score, and the AUROC for the extended START score 0.84 (95% CI 0.81 to 0.88).ConclusionThe overall performance of the extended ED disposition prediction tool that included frailty and multiple medical comorbidities significantly improved the ability of the START tool to identify patients likely to be discharged from ED or require short stay admission <2 days.Trial registration numberACTRN12618000426280
A Faster Subquadratic Algorithm for Finding Outlier Correlations
Authors: Karppa Matti , Kaski Petteri , Kohonen Jukka 
Published: June 2018

We study the problem of detecting
outlier pairs
of strongly correlated variables among a collection of
n
variables with otherwise weak pairwise correlations. After normalization, this task amounts to the geometric task where we are given as input a set of
n
vectors with unit Euclidean norm and dimension
d
, and for some constants 0<τ < ρ < 1, we are asked to find all the outlier pairs of vectors whose inner product is at least ρ in absolute value, subject to the promise that all but at most
q
pairs of vectors have inner product at most τ in absolute value.

Improving on an algorithm of Valiant [FOCS 2012; J. ACM 2015], we present a randomized algorithm that for Boolean inputs ({ −1,1}-valued data normalized to unit Euclidean length) runs in time Õ((
n

max,{ 1−γ +
M
(Δ γ ,γ),
M
(1−γ ,2 Δ γ)}

+
qdn
2γ
), where 0<γ < 1 is a constant tradeoff parameter and
M
(μ, ν) is the exponent to multiply an ⌊
n
μ
⌋ × ⌊
n
ν
⌋ matrix with an ⌊
n
ν
⌋ × ⌊
n
μ
⌋ matrix and Δ =1/(1−log
τ
ρ). As corollaries we obtain randomized algorithms that run in time Õ( (
n

2/ω 3−log
τ
ρ

+
qdn

2/(1−log
τ
ρ)3=log
ττ
ρ

) and in time õ( (
n

4 / 2+α (1−log
τ
ρ)

+
qdn

2/α (1−log
τ
ρ)2+α (1−log
τ
ρ)

>), where 2≤ ω <2.38 is the exponent for square matrix multiplication and 0.3<α ≤ 1 is the exponent for rectangular matrix multiplication. The notation Õ(ṡ) hides polylogarithmic factors in
n
and
d
whose degree may depend on ρ and τ. We present further corollaries for the light bulb problem and for learning sparse Boolean functions.
Cardiac Implantable Electronic Device Interrogation at Forensic Autopsy
Authors: Lacour Philipp , Buschmann Claas , Storm Christian , Nee Jens , Parwani Abdul Shokor , Huemer Martin , Attanasio Philipp , Boldt Leif-Hendrik , Rauch Geraldine , Kucher Andreas , Pieske Burkert , Haverkamp Wilhelm , Blaschke Florian 
Published: June 2018

Background:
Postmortem interrogations of cardiac implantable electronic devices (CIEDs), recommended at autopsy in suspected cases of sudden cardiac death, are rarely performed, and data on systematic postmortem CIED analysis in the forensic pathology are missing. The aim of the study was to determine whether nonselective postmortem CIED interrogations and data analysis are useful to the forensic pathologist to determine the cause, mechanism, and time of death and to detect potential CIED-related safety issues.

Methods:
From February 2012 to April 2017, all autopsy subjects in the department of forensic medicine at the University Hospital Charité who had a CIED underwent device removal and interrogation. Over the study period, 5368 autopsies were performed. One hundred fifty subjects had in total 151 CIEDs, including 109 pacemakers, 35 defibrillators, and 7 implantable loop recorders.

Results:
In 40 cases (26.7%) time of death and in 51 cases (34.0%) cause of death could not be determined by forensic autopsy. Of these, CIED interrogation facilitated the determination of time of death in 70.0% of the cases and clarified the cause of death in 60.8%. Device concerns were identified in 9 cases (6.0%), including 3 hardware, 4 programming, and 2 algorithm issues. One CIED was submitted to the manufacturer for a detailed technical analysis.

Conclusions:
Our data demonstrate the necessity of systematic postmortem CIED interrogation in forensic medicine to determine the cause and timing of death more accurately. In addition, CIED analysis is an important tool to detect potential CIED-related safety issues.
The Impact of Stratospheric Circulation Extremes on Minimum Arctic Sea Ice Extent
Authors: Smith Karen L. , Polvani Lorenzo M. , Tremblay L. Bruno 
Published: June 2018

AbstractGiven the rapidly changing Arctic climate, there is an urgent need for improved seasonal predictions of Arctic sea ice. Yet, Arctic sea ice prediction is inherently complex. Among other factors, wintertime atmospheric circulation has been shown to be predictive of summertime Arctic sea ice extent. Specifically, many studies have shown that the interannual variability of summertime Arctic sea ice extent (SIE) is anticorrelated with the leading mode of extratropical atmospheric variability, the Arctic Oscillation (AO), in the preceding winter. Given this relationship, the potential predictive role of stratospheric circulation extremes and stratosphere–troposphere coupling in linking the AO and Arctic SIE variability is examined. It is shown that extremes in the stratospheric circulation during the winter season, namely, stratospheric sudden warming (SSW) and strong polar vortex (SPV) events, are associated with significant anomalies in sea ice concentration in the Barents Sea in spring and along the Eurasian coastline in summer in both observations and a fully coupled, stratosphere-resolving general circulation model. Consistent with previous work on the AO, it is shown that SSWs, which are followed by the negative phase of the AO at the surface, result in sea ice growth, whereas SPVs, which are followed by the positive phase of the AO at the surface, result in sea ice loss, although the mechanisms in the Barents Sea and along the Eurasian coastline are different. The analysis suggests that the presence or absence of stratospheric circulation extremes in winter may play a nontrivial role in determining total September Arctic SIE when combined with other factors.
Submesoscale Baroclinic Instability in the Bottom Boundary Layer
Authors: Wenegrat Jacob O. , Callies Jörn , Thomas Leif N. 
Published: June 2018

AbstractWeakly stratified layers over sloping topography can support a submesoscale baroclinic instability mode, a bottom boundary layer counterpart to surface mixed layer instabilities. The instability results from the release of available potential energy, which can be generated because of the observed bottom intensification of turbulent mixing in the deep ocean, or the Ekman adjustment of a current on a slope. Linear stability analysis suggests that the growth rates of bottom boundary layer baroclinic instabilities can be comparable to those of the surface mixed layer mode and are relatively insensitive to topographic slope angle, implying the instability is robust and potentially active in many areas of the global oceans. The solutions of two separate one-dimensional theories of the bottom boundary layer are both demonstrated to be linearly unstable to baroclinic instability, and results from an example nonlinear simulation are shown. Implications of these findings for understanding bottom boundary layer dynamics and processes are discussed.
Training Pilots for Unexpected Events: A Simulator Study on the Advantage of Unpredictable and Variable Scenarios
Authors: Landman Annemarie , van Oorschot Peter , van Paassen M. M. (René) , Groen Eric L. , Bronkhorst Adelbert W. , Mulder Max 
Published: June 2018

Objective: This study tested whether simulator-based training of pilot responses to unexpected or novel events can be improved by including unpredictability and variability in training scenarios. Background: Current regulations allow for highly predictable and invariable training, which may not be sufficient to prepare pilots for unexpected or novel situations in-flight. Training for surprise will become mandatory in the near future. Method: Using an aircraft model largely unfamiliar to the participants, one group of 10 pilots (the unpredictable and variable [U/V] group) practiced responses to controllability issues in a relatively U/V manner. A control group of another 10 pilots practiced the same failures in a highly predictable and invariable manner. After the practice, performance of all pilots was tested in a surprise scenario, in which the pilots had to apply the learned knowledge. To control for surprise habituation and familiarization with the controls, two control tests were included. Results: Whereas the U/V group required more time than the control group to identify failures during the practice, the results indicated superior understanding and performance in the U/V group as compared to the control group in the surprise test. There were no significant differences between the groups in surprise or performance in the control tests. Conclusion: Given the results, we conclude that organizing pilot training in a more U/V way improves transfer of training to unexpected situations in-flight. Application: The outcomes suggest that the inclusion of U/V simulator training scenarios is important when training pilots for unexpected situations.
Hospitalization Trends and Comorbidities Among People With HIV/AIDS Compared With the Overall Hospitalized Population, Illinois, 2008-2014
Authors: Navon Livia 
Published: June 2018

Objectives: To understand trends in health care use among people living with HIV/AIDS (PLWHA), this study compared trends in hospitalization rates, comorbidities, and hospital death rates of hospitalized PLWHA with the overall hospitalized population in Illinois during 2008-2014. Methods: This study identified principal hospitalizations (the principal discharge diagnosis coded with an HIV-related billing code) and secondary HIV hospitalizations (a non-principal discharge diagnosis coded with an HIV-related billing code) from 2008-2014 Illinois hospital discharge data. Hospitalization rates among PLWHA were calculated using prevalence data from the Illinois Electronic HIV/AIDS Registry; US Census population estimates were used to calculate overall Illinois hospitalization rates. Joinpoint regression analysis was used to assess trends overall and among demographic subgroups. Comorbidities and discharge status for all hospitalizations were identified. Results: In 2014, the hospitalization rate was 2.2 times higher among PLWHA than among the overall Illinois hospitalized population. From 2008 to 2014, principal HIV hospitalization rates per 1000 PLWHA decreased by 48% (from 71 to 37) and secondary HIV hospitalization rates declined by 26% (from 296 to 218). The decline in the principal HIV hospitalization rate was steepest from 2008 to 2011 (annual percentage change = –16.0%; P = .003). Mood disorders, substance-related diagnoses, and schizophrenia accounted for 18% to 22% of principal hospitalizations among PLWHA compared with 7% to 8% of overall Illinois hospitalizations. Hepatitis as a comorbidity was more common among hospitalized PLWHA (18%-22%) than among the overall Illinois hospitalized population (1.4%-1.5%). Hospitalized PLWHA were 3 times more likely than the overall Illinois hospitalized population to die while hospitalized. Conclusions: HIV hospitalizations are largely preventable with appropriate treatment and adherence. Additional efforts to improve retention in HIV care that address comorbidities of PLWHA are needed.