bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization of Host Polyamines in Alternatively Activated Macrophages Promotes Chronic Infection by Brucella abortus
Authors: Kerrinnes Tobias , Winter Maria G. , Young Briana M. , Diaz-Ochoa Vladimir E. , Winter Sebastian E. , Tsolis Renée M. 
Published: December 2017

ABSTRACT

Treatment of intracellular bacterial pathogens with antibiotic therapy often requires a long course of multiple drugs. A barrier to developing strategies that enhance antibiotic efficacy against these pathogens is our poor understanding of the intracellular nutritional environment that maintains bacterial persistence. The intracellular pathogen
Brucella abortus
survives and replicates preferentially in alternatively activated macrophages (AAMs); however, knowledge of the metabolic adaptations promoting exploitation of this niche is limited. Here we show that one mechanism promoting enhanced survival in AAMs is a shift in macrophage arginine utilization from production of nitric oxide (NO) to biosynthesis of polyamines, induced by interleukin 4 (IL-4)/IL-13 treatment. Production of polyamines by infected AAMs promoted both intracellular survival of
B. abortus
and chronic infection in mice, as inhibition of macrophage polyamine synthesis or inactivation of the putative putrescine transporter encoded by
potIHGF
reduced both intracellular survival in AAMs and persistence in mice. These results demonstrate that increased intracellular availability of polyamines induced by arginase-1 expression in IL-4/IL-13-induced AAMs promotes chronic persistence of
B. abortus
within this niche and suggest that targeting of this pathway may aid in eradicating chronic infection.
NanI Sialidase Can Support the Growth and Survival of Clostridium perfringens Strain F4969 in the Presence of Sialyated Host Macromolecules (Mucin) or Caco-2 Cells
Authors: Li Jihong , McClane Bruce A. 
Published: December 2017

ABSTRACTEnterotoxin-producingClostridium perfringenstype A strains cause human gastrointestinal (GI) infections, including a very common food poisoning and 5 to 10% of all cases of antibiotic-associated diarrhea. This bacterium can utilize free sialic acid for growth, but most sialic acids in the GI tract are sequestered on macromolecules, such as the mucin proteins of mucus or glycoconjugates in host cells. However, manyC. perfringensstrains produce sialidases that might promote growth and survival by generating free sialic acid from those sialyated host macromolecules or by exposing underlying carbohydrates or proteins for digestion by other enzymes. The current study tested that possibility and found that theC. perfringensnonfoodborne human GI disease strain F4969 can use either a mucin preparation or Caco-2 cells, which are human enterocyte-like cells, to support its growth and survival. An isogenicnanInull mutant and complemented strain were used to show that this enhanced growth and survival using mucin or Caco-2 cells involved NanI, which is the major exosialidase of F4969 and many otherC. perfringensstrains. Experiments also suggested that, at least in part, this growth promotion involves utilization of NanI-generated sialic acid. In addition, a sialidase inhibitor named siastatin B reduced the growth and survival of F4969 growing with either the mucin preparation or Caco-2 cells. These findings suggest that, when produced, NanI may be a significant contributor toC. perfringenshuman GI infections by promoting the intestinal growth and survival of this bacterium. They also suggest the possibility that sialidase inhibitors might inhibitC. perfringensinfections.
Use of Proteins Identified through a Functional Genomic Screen To Develop a Protein Subunit Vaccine That Provides Significant Protection against Virulent Streptococcus suis in Pigs
Authors: Brockmeier Susan L. , Loving Crystal L. , Nicholson Tracy L. , Wang Jinhong , Peters Sarah E. , Weinert Lucy , Chaudhuri Roy , Seilly David J. , Langford Paul R. , Rycroft Andrew , Wren Brendan W. , Maskell Duncan J. , Tucker Alexander W. 
Published: December 2017

ABSTRACT

Streptococcus suis
is a bacterium that is commonly carried in the respiratory tract and that is also one of the most important invasive pathogens of swine, commonly causing meningitis, arthritis, and septicemia. Due to the existence of many serotypes and a wide range of immune evasion capabilities, efficacious vaccines are not readily available. The selection of
S. suis
protein candidates for inclusion in a vaccine was accomplished by identifying fitness genes through a functional genomics screen and selecting conserved predicted surface-associated proteins. Five candidate proteins were selected for evaluation in a vaccine trial and administered both intranasally and intramuscularly with one of two different adjuvant formulations. Clinical protection was evaluated by subsequent intranasal challenge with virulent
S. suis
. While subunit vaccination with the
S. suis
proteins induced IgG antibodies to each individual protein and a cellular immune response to the pool of proteins and provided substantial protection from challenge with virulent
S. suis
, the immune response elicited and the degree of protection were dependent on the parenteral adjuvant given. Subunit vaccination induced IgG reactive against different
S. suis
serotypes, indicating a potential for cross protection.
Regulated Release of Cryptococcal Polysaccharide Drives Virulence and Suppresses Immune Cell Infiltration into the Central Nervous System
Authors: Denham Steven T. , Verma Surbhi , Reynolds Raymond C. , Worne Colleen L. , Daugherty Joshua M. , Lane Thomas E. , Brown Jessica C. S. 
Published: December 2017

ABSTRACT

Cryptococcus neoformans
is a common environmental yeast and opportunistic pathogen responsible for 15% of AIDS-related deaths worldwide. Mortality primarily results from meningoencephalitis, which occurs when fungal cells disseminate to the brain from the initial pulmonary infection site. A key
C. neoformans
virulence trait is the polysaccharide capsule. Capsule shields
C. neoformans
from immune-mediated recognition and destruction. The main capsule component, glucuronoxylomannan (GXM), is found both attached to the cell surface and free in the extracellular space (as exo-GXM). Exo-GXM accumulates in patient serum and cerebrospinal fluid at microgram/milliliter concentrations, has well-documented immunosuppressive properties, and correlates with poor patient outcomes. However, it is poorly understood whether exo-GXM release is regulated or the result of shedding during normal capsule turnover. We demonstrate that exo-GXM release is regulated by environmental cues and inversely correlates with surface capsule levels. We identified genes specifically involved in exo-GXM release that do not alter surface capsule thickness. The first mutant, the
liv7
Δ strain, released less GXM than wild-type cells when capsule was not induced. The second mutant, the
cnag_00658
Δ strain, released more exo-GXM under capsule-inducing conditions. Exo-GXM release observed
in vitro
correlated with polystyrene adherence, virulence, and fungal burden during murine infection. Additionally, we found that exo-GXM reduced cell size and capsule thickness under capsule-inducing conditions, potentially influencing dissemination. Finally, we demonstrated that exo-GXM prevents immune cell infiltration into the brain during disseminated infection and highly inflammatory intracranial infection. Our data suggest that exo-GXM performs a distinct role from capsule GXM during infection, altering cell size and suppressing inflammation.
Toward Tuberculosis Vaccine Development: Recommendations for Nonhuman Primate Study Design
Authors: Laddy Dominick J. , Bonavia Aurelio , Hanekom Willem A. , Kaushal Deepak , Williams Ann , Roederer Mario , Seder Robert A. , Sharpe Sally , Verreck Frank A. W. , Darrah Patricia A. 
Published: December 2017

ABSTRACT
Clinical trials of novel tuberculosis (TB) vaccines are expensive, while global resources for TB vaccine development are limited. Therefore, there is a need for robust and predictive preclinical data to support advancement of candidate vaccines into clinical trials. Here, we provide a rationale for using the nonhuman primate as an essential component of these efforts, as well as guidance to the TB community for standardizing experimental design and aligning endpoints to facilitate development of new TB vaccines.
Cellular Concentrations of the Transporters DctA and DcuB and the Sensor DcuS of Escherichia coli and the Contributions of Free and Complexed DcuS to Transcriptional Regulation by DcuR
Authors: Wörner Sebastian , Surmann Kristin , Ebert-Jung Andrea , Völker Uwe , Hammer Elke , Unden Gottfried 
Published: December 2017

ABSTRACT

In
Escherichia coli
, the catabolism of C
4
-dicarboxylates is regulated by the DcuS-DcuR two-component system. The functional state of the sensor kinase DcuS is controlled by C
4
-dicarboxylates (like fumarate) and complexation with the C
4
-dicarboxylate transporters DctA and DcuB, respectively. Free DcuS (DcuS
F
) is known to be constantly active even in the absence of fumarate, whereas the DcuB-DcuS and DctA-DcuS complexes require fumarate for activation. To elucidate the impact of the transporters on the functional state of DcuS and the concentrations of DcuS
F
and DcuB-DcuS (or DctA-DcuS), the absolute levels of DcuS, DcuB, and DctA were determined in aerobically or anaerobically grown cells by mass spectrometry. DcuS was present at a constant very low level (10 to 20 molecules DcuS/cell), whereas the levels of DcuB and DctA were higher (minimum, 200 molecules/cell) and further increased with fumarate (12.7- and 2.7-fold, respectively). Relating DcuS and DcuB contents with the functional state of DcuS allowed an estimation of the proportions of DcuS in the free (DcuS
F
) and the complexed (DcuB-DcuS) states. Unexpectedly, DcuS
F
levels were always low (<2% of total DcuS), ruling out earlier models that show DcuS
F
as the major species under noninducing conditions. In the absence of fumarate, when DcuS
F
is responsible for basal
dcuB
expression, up to 8% of the maximal DcuB levels are formed. These suffice for DcuB-DcuS complex formation and basal transport activity. In the presence of fumarate (>100 μM), the DcuB-DcuS complex drives the majority of
dcuB
expression and is thus responsible for induction.

IMPORTANCE
Two-component systems (TCS) are major devices for sensing by bacteria and adaptation to environmental cues. Membrane-bound sensor kinases of TCS often use accessory proteins of unknown function. The DcuS-DcuR TCS responds to C
4
-dicarboxylates and requires formation of the complex of DcuS with C
4
-dicarboxylate transporters DctA or DcuB. Free DcuS (DcuS
F
) is constitutively active in autophosphorylation and was supposed to have a major role under specific conditions. Here, absolute concentrations of DcuS, DcuB, and DctA were determined under activating and nonactivating conditions by mass spectrometry. The relationship of their absolute contents to the functional state of DcuS revealed their contribution to the control of DcuS-DcuR
in vivo
, which was not accessible by other approaches, leading to a revision of previous models.
Effect of a newly designed observation, response and discharge chart in the Post Anaesthesia Care Unit on patient outcomes: a quasi-expermental study in Australia
Authors: Street Maryann , Phillips Nicole M , Mohebbi Mohammadreza , Kent Bridie 
Published: December 2017

ObjectivesThis study aimed to evaluate whether use of a discharge criteria tool for nursing assessment of patients in Post Anaesthesia Care Unit (PACU) would enhance nurses’ recognition and response to patients at-risk of deterioration and improve patient outcomes.MethodsA prospective non-randomised pre–post intervention study was conducted in three hospitals in Australia. Participants were adults undergoing elective surgery before (n=723) and after (n=694) implementation of the Post-Anaesthetic Care Tool (PACT).ResultsNursing response to patients at-risk of deterioration was higher using PACT, with more medical consultations initiated by PACU nurses (19% vs 30%, P<0.001) and more patients with Medical Emergency Team activation criteria modified by an anaesthetist while in PACU (6.5% vs 13.8%, P<0.001). There were higher rates of analgesia administration (37.3% vs 54.2%, P=0.001), nursing assessment of pain and documentation of ongoing analgesia prior to discharge (55% vs 85%, P<0.001). More adverse events were recorded in PACU after introduction of the PACT (8.3% vs 16.7%, P<0.001). The rate of adverse events after discharge from PACU remained constant (16.5%), but the rate of cardiac events (5.1% vs 2.6%, P=0.021) and clinical deterioration (8.7% vs 4.3%, P=0.001) following PACU discharge significantly decreased, using the PACT. Despite the increased number of patients with adverse events in phase 2, healthcare costs did not increase significantly. Length of stay in PACU and length of hospital admission for those patients who had an adverse event in PACU were significantly reduced after implementation of the PACT.ConclusionThis study found that using a structured discharge criteria tool, the PACT, enhanced nurses’ recognition and response to patients who experienced clinical deterioration, reduced length of stay for patients who experienced an adverse event in PACU and was cost-effective.
Early warning scores for detecting deterioration in adult hospital patients: a systematic review protocol
Authors: Gerry Stephen , Birks Jacqueline , Bonnici Timothy , Watkinson Peter J , Kirtley Shona , Collins Gary S 
Published: December 2017

IntroductionEarly warning scores (EWSs) are used extensively to identify patients at risk of deterioration in hospital. Previous systematic reviews suggest that studies which develop EWSs suffer methodological shortcomings and consequently may fail to perform well. The reviews have also identified that few validation studies exist to test whether the scores work in other settings. We will aim to systematically review papers describing the development or validation of EWSs, focusing on methodology, generalisability and reporting.MethodsWe will identify studies that describe the development or validation of EWSs for adult hospital inpatients. Each study will be assessed for risk of bias using the Prediction model Risk of Bias ASsessment Tool (PROBAST). Two reviewers will independently extract information. A narrative synthesis and descriptive statistics will be used to answer the main aims of the study which are to assess and critically appraise the methodological quality of the EWS, to describe the predictors included in the EWSs and to describe the reported performance of EWSs in external validation.Ethics and disseminationThis systematic review will only investigate published studies and therefore will not directly involve patient data. The review will help to establish whether EWSs are fit for purpose and make recommendations to improve the quality of future research in this area.PROSPERO registration numberCRD42017053324.
Microwave radiation effect with and without chemical seed treatments on halo blight infected seed, seed germination, plant vigour, and yield of dry beans
Authors: Friesen A.P. , Conner R.L. , Robinson D.E. , Barton W.R. , Chatterton S. , Gillard C.L. 
Published: December 2017

Halo blight, caused by Pseudomonas syringae pv. phaseolicola, is a seed-borne disease of dry bean (Phaseolus vulgaris L.) that lowers seed quality and yield. Over 2 yr, laboratory and field studies were conducted to evaluate the effect of microwave radiation on two market classes: navy (‘Envoy’) and white kidney (‘GTS 402’) bean. In the laboratory, seed germination and vigour decreased up to 15% after 40 s of microwave exposure, where <7% decrease was observed during 0–30 s. Disease plating showed no correlation between pathogen colonization of the seed and microwave radiation, as incidence of pathogen colonization was low across all exposure times. In field trials in Morden and Winkler, MB, microwave radiation was tested alone and in combination with copper hydroxide 53.8% and pyraclostrobin + fluxapyroxad + metalaxyl. Seed treatment with copper hydroxide slightly decreased the incidence of halo blight but had little impact on seed pick, hundred-seed weight, yield, or return on investment. Pyraclostrobin + fluxapyroxad + metalaxyl seed treatment had no effect on any of these parameters. Microwave radiation lowered seed emergence by up to 9% but did not reduce disease incidence and severity or increase yield or return of investment when applied alone or in combination with a chemical treatment.
Household food insecurity is independently associated with poor utilization of maternal healthcare services in Bangladesh
Authors: Bishwajit Ghose , Yaya Sanni 
Published: December 2017

Introduction: Food insecurity at the individual level has been shown to be associated with the adoption of risky behavior and poor healthcare-seeking behavior. However, the impact of household food insecurity (HFI) on the utilization of maternal healthcare services (MHS) remains unexplored. In this study, we aimed to investigate whether or not household food insecurity was associated with non/inadequate utilization of MHS. Methods: Participants consisted of 3562 mothers aged between 15 and 49 years and with at least one child. The outcome variable was the utilization of MHS, e.g., institutional delivery, attendance ante-, and pre-natal visits. The explanatory variables included various sociodemographic factors (e.g., age, residence, education, wealth) apart from HFI. HFI was measured using the Household Food Insecurity Access Scale (HFIAS). Result: The prevalence of non- and under-utilization of MHS was 5.3 and 36.5, respectively. In the multivariate analysis, HFI, wealth index, and educational level were independently associated with MHS status. The odds of non- and under-utilization of MHS were 3.467 (CI = 1.058–11.354) and 4.104 (CI = 1.794–9.388) times higher, respectively, among women from households reporting severe food insecurity. Conclusion: Severe HFI was significantly associated with both under- and non-utilization of MHS. Interventions programs that address HFI and the empowerment of women can potentially contribute to an increased utilization of MHS.
Classifying Galois groups of small iterates via rational points
Authors: Hindes Wade 
Published: December 2017

We establish several surjectivity theorems regarding the Galois groups of small iterates of [Formula: see text] for [Formula: see text]. To do this, we use explicit techniques from the theory of rational points on curves, including the method of Chabauty–Coleman and the Mordell–Weil sieve. For example, we succeed in finding all rational points on a hyperelliptic curve of genus 7, with rank 5 Jacobian, whose points parametrize quadratic polynomials with a “newly small” Galois group at the fifth stage of iteration.
Approximation Algorithms for Computing Maximin Share Allocations
Authors: Amanatidis Georgios , Markakis Evangelos , Nikzad Afshin , Saberi Amin 
Published: December 2017

We study the problem of computing maximin share allocations, a recently introduced fairness notion. Given a set of
n
agents and a set of goods, the maximin share of an agent is the best she can guarantee to herself, if she is allowed to partition the goods in any way she prefers, into
n
bundles, and then receive her least desirable bundle. The objective then is to find a partition, where each agent is guaranteed her maximin share. Such allocations do not always exist, hence we resort to approximation algorithms. Our main result is a 2/3-approximation that runs in polynomial time for any number of agents and goods. This improves upon the algorithm of Procaccia and Wang (2014), which is also a 2/3-approximation but runs in polynomial time only for a constant number of agents. To achieve this, we redesign certain parts of the algorithm in Procaccia and Wang (2014), exploiting the construction of carefully selected matchings in a bipartite graph representation of the problem. Furthermore, motivated by the apparent difficulty in establishing lower bounds, we undertake a probabilistic analysis. We prove that in randomly generated instances, maximin share allocations exist with high probability. This can be seen as a justification of previously reported experimental evidence. Finally, we provide further positive results for two special cases arising from previous works. The first is the intriguing case of three agents, where we provide an improved 7/8-approximation. The second case is when all item values belong to {0, 1, 2}, where we obtain an exact algorithm.
A First-in-Human Phase I Study of Subcutaneous Outpatient Recombinant Human IL15 (rhIL15) in Adults with Advanced Solid Tumors
Authors: Miller Jeffrey S. , Morishima Chihiro , McNeel Douglas G. , Patel Manish R. , Kohrt Holbrook E.K. , Thompson John A. , Sondel Paul M. , Wakelee Heather A. , Disis Mary L. , Kaiser Judith C. , Cheever Martin A. , Streicher Howard , Creekmore Steven P. , Waldmann Thomas A. , Conlon Kevin C. 
Published: December 2017

AbstractPurpose: Preclinical data established IL15 as a homeostatic factor and powerful stimulator of NK and CD8+ T-cell function, the basis for clinical testing.Experimental Design: A first-in-human outpatient phase I dose escalation trial of subcutaneous (SC) rhIL15 was conducted in refractory solid tumor cancer patients. Therapy consisted of daily (Monday–Friday) subcutaneous injections of rhIL15 for two consecutive weeks (10 total doses/cycle). Clinical response was assessed by RECIST. Pharmacokinetics of rhIL15 and immune biomarkers were evaluated.Results: Nineteen patients were treated with rhIL15 at dose levels of 0.25, 0.5, 1, 2, and 3 mcg/kg/day. Fourteen patients completed ≥ 2 cycles of therapy that was well tolerated. One serious adverse event (SAE), grade 2 pancreatitis, required overnight hospitalization. Enrollment was halted after a patient receiving 3 mcg/kg/day developed a dose-limiting SAE of grade 3 cardiac chest pain associated with hypotension and increased troponin. No objective responses were observed; however, several patients had disease stabilization including a renal cell carcinoma patient who continued protocol treatment for 2 years. The treatment induced profound expansion of circulating NK cells, especially among the CD56bright subset. A proportional but less dramatic increase was found among circulating CD8+ T cells with maximal 3-fold expansion for the 2 and 3 mcg/kg patients.Conclusions: SC rhIL15 treatment was well tolerated, producing substantial increases in circulating NK and CD8+ T cells. This protocol establishes a safe outpatient SC rhIL15 regimen of 2 mcg/kg/day dosing amenable to self-injection and with potential as a combination immunotherapeutic agent. Clin Cancer Res; 24(7); 1525–35. ©2017 AACR.