bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Multicellular Aggregates in Biofilm Formation
Authors: Kragh Kasper N. , Hutchison Jaime B. , Melaugh Gavin , Rodesney Chris , Roberts Aled E. L. , Irie Yasuhiko , Jensen Peter Ø. , Diggle Stephen P. , Allen Rosalind J. , Gordon Vernita , Bjarnsholt Thomas 
Published: March 2016

ABSTRACT

In traditional models of
in vitro
biofilm development, individual bacterial cells seed a surface, multiply, and mature into multicellular, three-dimensional structures. Much research has been devoted to elucidating the mechanisms governing the initial attachment of single cells to surfaces. However, in natural environments and during infection, bacterial cells tend to clump as multicellular aggregates, and biofilms can also slough off aggregates as a part of the dispersal process. This makes it likely that biofilms are often seeded by aggregates and single cells, yet how these aggregates impact biofilm initiation and development is not known. Here we use a combination of experimental and computational approaches to determine the relative fitness of single cells and preformed aggregates during early development of
Pseudomonas aeruginosa
biofilms. We find that the relative fitness of aggregates depends markedly on the density of surrounding single cells, i.e., the level of competition for growth resources. When competition between aggregates and single cells is low, an aggregate has a growth disadvantage because the aggregate interior has poor access to growth resources. However, if competition is high, aggregates exhibit higher fitness, because extending vertically above the surface gives cells at the top of aggregates better access to growth resources. Other advantages of seeding by aggregates, such as earlier switching to a biofilm-like phenotype and enhanced resilience toward antibiotics and immune response, may add to this ecological benefit. Our findings suggest that current models of biofilm formation should be reconsidered to incorporate the role of aggregates in biofilm initiation.

IMPORTANCE
During the past decades, there has been a consensus around the model of development of a biofilm, involving attachment of single planktonic bacterial cells to a surface and the subsequent development of a mature biofilm. This study presents results that call for a modification of this rigorous model. We show how free floating biofilm aggregates can have a profound local effect on biofilm development when attaching to a surface. Our findings show that an aggregate landing on a surface will eventually outcompete the biofilm population arising from single cells attached around the aggregate and dominate the local biofilm development. These results point to a regime where preformed biofilm aggregates may have a fitness advantage over planktonic cells when it comes to accessing nutrients. Our findings add to the increasingly prominent comprehension that biofilm lifestyle is the default for bacteria and that planktonic single cells may be only a transition state at the most.
Cryo-electron Microscopy Structures of Chimeric Hemagglutinin Displayed on a Universal Influenza Vaccine Candidate
Authors: Tran Erin E. H. , Podolsky Kira A. , Bartesaghi Alberto , Kuybeda Oleg , Grandinetti Giovanna , Wohlbold Teddy John , Tan Gene S. , Nachbagauer Raffael , Palese Peter , Krammer Florian , Subramaniam Sriram 
Published: March 2016

ABSTRACT
Influenza viruses expressing chimeric hemagglutinins (HAs) are important tools in the quest for a universal vaccine. Using cryo-electron tomography, we have determined the structures of a chimeric HA variant that comprises an H1 stalk and an H5 globular head domain (cH5/1 HA) in native and antibody-bound states. We show that cH5/1 HA is structurally different from native HA, displaying a 60° rotation between the stalk and head groups, leading to a novel and unexpected “open” arrangement of HA trimers. cH5/1N1 viruses also display higher glycoprotein density than pH1N1 or H5N1 viruses, but despite these differences, antibodies that target either the stalk or head domains of hemagglutinins still bind to cH5/1 HA with the same consequences as those observed with native H1 or H5 HA. Our results show that a large range of structural plasticity can be tolerated in the chimeric spike scaffold without disrupting structural and geometric aspects of antibody binding.

IMPORTANCE
Chimeric hemagglutinin proteins are set to undergo human clinical trials as a universal influenza vaccine candidate, yet no structural information for these proteins is available. Using cryo-electron tomography, we report the first three-dimensional (3D) visualization of chimeric hemagglutinin proteins displayed on the surface of the influenza virus. We show that, unexpectedly, the chimeric hemagglutinin structure differs from those of naturally occurring hemagglutinins by displaying a more open head domain and a dramatically twisted head/stalk arrangement. Despite this unusual spatial relationship between head and stalk regions, virus preparations expressing the chimeric hemagglutinin are fully infectious and display a high glycoprotein density, which likely helps induction of a broadly protective immune response.
Chasing Ebola through the Endosomal Labyrinth
Authors: Aman M. Javad 
Published: March 2016

ABSTRACT

During virus entry, the surface glycoprotein of Ebola virus (EBOV) undergoes a complex set of transformations within the endosomal network. Tools to study EBOV entry have been limited to static immunofluorescence or biochemical and functional analysis. In a recent article in
mBio
, Spence et al. reported a novel, live-cell-imaging method that tracks this transformational journey of EBOV in real time [J. S. Spence, T. B. Krause, E. Mittler, R. K. Jangra, and K. Chandran, mBio 7(1):e01857-15, 2016, http://dx.doi.org/10.1128/mBio.01857-15]. The assay validates known mechanisms of EBOV entry and sheds light on some novel intricacies. Direct evidence supports the hypothesis that fusion is a rare event that starts in maturing early endosomes, is completed in late endosomes, and occurs entirely in Niemann-Pick C1 (NPC1)-positive (NPC1
+
) compartments. The study demonstrated that lipid mixing and productive fusion are temporally decoupled, with different energetic barriers and a protease-dependent step between the two events. Analysis of the mechanism of action of an important class of EBOV neutralizing antibodies, such as KZ52 and ZMapp, provides direct evidence that these antibodies act by inhibiting the membrane fusion.
Investigation of the Genetics and Biochemistry of Roseobacticide Production in the
Roseobacter
Clade Bacterium Phaeobacter inhibens
Authors: Wang Rurun , Gallant Étienne , Seyedsayamdost Mohammad R. 
Published: March 2016

ABSTRACT

Roseobacter
clade bacteria are abundant in surface waters and are among the most metabolically diverse and ecologically significant species. This group includes opportunistic symbionts that associate with micro- and macroalgae. We have proposed that one representative member,
Phaeobacter inhibens
, engages in a dynamic symbiosis with the microalga
Emiliania huxleyi
. In one phase, mutualistically beneficial molecules are exchanged, including the
Roseobacter
-produced antibiotic tropodithietic acid (TDA), which is thought to protect the symbiotic interaction. In an alternative parasitic phase, triggered by algal senescence, the bacteria produce potent algaecides, the roseobacticides, which kill the algal host. Here, we employed genetic and biochemical screens to identify the roseobacticide biosynthetic gene cluster. By using a transposon mutagenesis approach, we found that genes required for TDA synthesis—the
tda
operon and
paa
catabolon—are also necessary for roseobacticide production. Thus, in contrast to the one-cluster–one-compound paradigm, the
tda
gene cluster can generate two sets of molecules with distinct structures and bioactivities. We further show that roseobacticide production is quorum sensing regulated via an
N
-acyl homoserine lactone signal (3-OH–C
10
-HSL). To ensure tight regulation of algaecide production, and thus of a lifestyle switch from mutualism to parasitism, roseobacticide biosynthesis necessitates the presence of both an algal senescence molecule and a quorum sensing signal.

IMPORTANCE
Marine
Roseobacter
species are abundant in the oceans and engage in symbiotic interactions with microscopic algae. One member,
P. inhibens
, produces the antibiotic TDA and a growth hormone thought to protect and promote algal growth. However, in the presence of molecules released by senescing algae, the bacteria produce potent algaecides, the roseobacticides, which kill the host. We examined the regulatory networks and biosynthetic genes required for roseobacticide production. We found that
P. inhibens
uses largely the same set of genes for production of both TDA and roseobacticides, thus providing a rare case in which one gene cluster synthesizes two structurally and functionally distinct molecules. Moreover, we found roseobacticide production to be regulated by quorum sensing. Thus, two small molecules, the algal metabolite and the quorum-sensing signal, ensure tight control in the production of roseobacticides. These results highlight the role of small molecules in regulating microbial symbioses.
Taxonomy, Physiology, and Natural Products of Actinobacteria
Authors: Barka Essaid Ait , Vatsa Parul , Sanchez Lisa , Gaveau-Vaillant Nathalie , Jacquard Cedric , Klenk Hans-Peter , Clément Christophe , Ouhdouch Yder , van Wezel Gilles P. 
Published: March 2016

SUMMARYActinobacteriaare Gram-positive bacteria with high G+C DNA content that constitute one of the largest bacterial phyla, and they are ubiquitously distributed in both aquatic and terrestrial ecosystems. ManyActinobacteriahave a mycelial lifestyle and undergo complex morphological differentiation. They also have an extensive secondary metabolism and produce about two-thirds of all naturally derived antibiotics in current clinical use, as well as many anticancer, anthelmintic, and antifungal compounds. Consequently, these bacteria are of major importance for biotechnology, medicine, and agriculture.Actinobacteriaplay diverse roles in their associations with various higher organisms, since their members have adopted different lifestyles, and the phylum includes pathogens (notably, species ofCorynebacterium,Mycobacterium,Nocardia,Propionibacterium, andTropheryma), soil inhabitants (e.g.,MicromonosporaandStreptomycesspecies), plant commensals (e.g.,Frankiaspp.), and gastrointestinal commensals (Bifidobacteriumspp.).Actinobacteriaalso play an important role as symbionts and as pathogens in plant-associated microbial communities. This review presents an update on the biology of this important bacterial phylum.
Complex regional pain syndrome in children: incidence and clinical characteristics
Authors: Abu-Arafeh Hashem , Abu-Arafeh Ishaq 
Published: March 2016

ObjectiveTo study the clinical and epidemiological characteristics of complex regional pain syndrome (CRPS) in children.Patients and methodsAll children and adolescents under 16 years of age with a new diagnosis of CRPS who were reported to the Scottish Paediatric Surveillance Unit were included. Patients’ recruitment ran between 1 November 2011 and 31 October 2015. Information was collected on patients’ demography, clinical features, investigations, management and impact of disease on child and family. The diagnosis of CRPS was made on fulfilling the clinical criteria of the International Association for the Study of Pain.Results26 cases of CRPS were reported over 4 years, giving a minimum estimated incidence of 1.16/100 000 (95% CI 0.87 to 1.44/100 000) children 5–15 years of age. Nineteen patients were female (73%) and mean age at diagnosis was 11.9 (range 5.5–15.4 years). The median interval between onset of symptoms and diagnosis was 2 months (range 1–12). The majority of children have single site involvement, with legs been more often affected than arms and the right side is more often affected than the left. There was a clear trauma at onset of the illness in 19 children and possible nerve injury in one. All investigations were normal and several treatment modalities were used with variable success. The disease had significant impacts on the patients’ education and family lives.ConclusionsThe estimated incidence of CRPS is 1.2/100 000 children 5–15 years old. The diagnosis of CRPS is often delayed. CRPS has a significant impact on children and their families.
Potential workload in applying clinical practice guidelines for patients with chronic conditions and multimorbidity: a systematic analysis
Authors: Buffel du Vaure Céline , Ravaud Philippe , Baron Gabriel , Barnes Caroline , Gilberg Serge , Boutron Isabelle 
Published: March 2016

ObjectivesTo describe the potential workload for patients with multimorbidity when applying existing clinical practice guidelines.DesignSystematic analysis of clinical practice guidelines for chronic conditions and simulation modelling approach.Data sourcesNational Guideline Clearinghouse index of US clinical practice guidelines.Study selectionWe identified the most recent guidelines for adults with 1 of 6 prevalent chronic conditions in primary care (ie hypertension, diabetes, coronary heart disease (CHD), chronic obstructive pulmonary disease (COPD), osteoarthritis and depression).Data extractionFrom the guidelines, we extracted all recommended health-related activities (HRAs) such as drug management, self-monitoring, visits to the doctor, laboratory tests and changes of lifestyle for a patient aged 45–64 years with moderate severity of conditions.Simulation modelling approachFor each HRA identified, we performed a literature review to determine the potential workload in terms of time spent on this HRA. Then, we used a simulation modelling approach to estimate the potential workload needed to comply with these recommended HRAs for patients with several of these chronic conditions.ResultsDepending on the concomitant chronic condition, patients with 3 chronic conditions complying with all the guidelines would have to take a minimum of 6 to a maximum of 13 medications per day, visit a health caregiver a minimum of 1.2 to a maximum of 5.9 times per month and spend a mean (SD) of 49.6 (27.3) to 71.0 (34.5) h/month in HRAs. The potential workload increased greatly with increasing number of concomitant conditions, rising to 18 medications per day, 6.6 visits per month and 80.7 (35.8) h/month in HRAs for patients with 6 chronic conditions.
Factors affecting Japanese retirees' healthcare service utilisation in Malaysia: a qualitative study
Authors: Kohno Ayako , Nik Farid Nik Daliana , Musa Ghazali , Abdul Aziz Norlaili , Nakayama Takeo , Dahlui Maznah 
Published: March 2016

ObjectiveWhile living overseas in another culture, retirees need to adapt to a new environment but often this causes difficulties, particularly among those elderly who require healthcare services. This study examines factors affecting healthcare service utilisation among Japanese retirees in Malaysia.DesignWe conducted 6 focus group discussions with Japanese retirees and interviewed 8 relevant medical services providers in-depth. Guided by the Andersen Healthcare Utilisation Model, we managed and analysed the data, using QSR NVivo 10 software and the directed content analysis method.SettingWe interviewed participants at Japan Clubs and their offices.Participants30 Japanese retirees who live in Kuala Lumpur and Ipoh, and 8 medical services providers.ResultsWe identified health beliefs, medical symptoms and health insurance as the 3 most important themes, respectively, representing the 3 dimensions within the Andersen Healthcare Utilisation Model. Additionally, language barriers, voluntary health repatriation to Japan and psychological support were unique themes that influence healthcare service utilisation among Japanese retirees.ConclusionsThe healthcare service utilisation among Japanese retirees in Malaysia could be partially explained by the Andersen Healthcare Utilisation Model, together with some factors that were unique findings to this study. Healthcare service utilisation among Japanese retirees in Malaysia could be improved by alleviating negative health beliefs through awareness programmes for Japanese retirees about the healthcare systems and cultural aspects of medical care in Malaysia.
Investigating kidney donation as a risk factor for hypertension and microalbuminuria: findings from the Swiss prospective follow-up of living kidney donors
Authors: Thiel Gilbert T , Nolte Christa , Tsinalis Dimitrios , Steiger Jürg , Bachmann Lucas M 
Published: March 2016

ObjectivesTo assess the role of nephrectomy as a risk factor for the development of hypertension and microalbuminuria.DesignProspective, long-term follow-up study.SettingSwiss Organ Living-Donor Health Registry.ParticipantsAll living kidney donors in Switzerland between 1993 and 2009.InterventionsData on health status and renal function before 1 year and biennially after donation were collected.Primary and secondary outcome measuresComparison of 1-year and 5-year occurrences of hypertension among normotensive donors with 1-year and 5-year estimates from the Framingham hypertension risk score. Multivariate random intercept models were used to investigate changes of albumin excretion after donation, correcting for repeated measurements and cofactors such as age, male gender and body mass index.ResultsA total of 1214 donors contributed 3918 data entries with a completed biennial follow-up rate of 74% during a 10-year period. Mean (SD) follow-up of donors was 31.6 months (34.4). Median age at donation was 50.5 years (IQR 42.2–58.8); 806 donors (66.4%) were women. Donation increased the risk of hypertension after 1 year by 3.64 (95% CI 3.52 to 3.76; p<0.001). Those participants remaining normotensive 1 year after donation return to a risk similar to that of the healthy Framingham population. Microalbuminuria before donation was dependent on donor age but not on the presence of hypertension. After nephrectomy, hypertension became the main driver for changes in albumin excretion (OR 1.19; 95% CI 0.13 to 2.25; p=0.03) and donor age had no effect.ConclusionsNephrectomy propagates hypertension and increases susceptibility for the development of hypertension-induced microalbuminuria.
Maternal ethnicity and its impact on the haemodynamic and blood pressure response to labetalol for the treatment of antenatal hypertension
Authors: Stott D , Bolten M , Paraschiv D , Papastefanou I , Chambers J B , Kametas N A 
Published: March 2016

ObjectiveBlood pressure (BP) control outside pregnancy is associated with a reduction in adverse cardiovascular events, and in pregnancy with improved outcomes. Outside pregnancy, there is evidence β-blockers are less effective in controlling BP in black populations. However, in pregnancy, labetalol is recommended as a universal first-line treatment, without evidence for the impact of ethnicity on its efficacy. We sought to compare haemodynamic responses to labetalol in black and white pregnant patients.MethodsThis was a prospective observational cohort study in a London teaching hospital. Maternal haemodynamics were assessed in 120 pregnant women treated with labetalol monotherapy. Measurements were taken at presentation, 1 and 24 h after treatment. Participants were monitored regularly until delivery. Statistical analysis was performed by multilevel modelling.ResultsBoth groups exhibited similar temporal trends in haemodynamic changes over the first 24 h following labetalol. Both showed a reduction in BP and peripheral vascular resistance within 1 h and in heart rate after 24 h. There was no change in cardiac output and stroke volume in either group. BP control (<140/90) was achieved at 1 h in 79.7% of the white and 77% of the black cohort. At 24 h, control was achieved among 83.1% and 63.9%, and up to the immediate intrapartum period control was achieved in 89.8% and 70.4% of white and black patients, respectively.ConclusionsThere is no difference in the acute haemodynamic changes and hypertension can be controlled throughout pregnancy with labetalol monotherapy in excess of 70% pregnant black and white patients.
Optimising health and safety of people who inject drugs during transition from acute to outpatient care: narrative review with clinical checklist
Authors: Thakarar Kinna , Weinstein Zoe M , Walley Alexander Y 
Published: March 2016

AbstractThe opioid epidemic in the USA continues to worsen. Medical providers are faced with the challenge of addressing complications from opioid use disorders and associated injection drug use. Unsafe injection practices among people who inject drugs (PWID) can lead to several complications requiring acute care encounters in the emergency department and inpatient hospital. Our objective is to provide a narrative review to help medical providers recognise and address key health issues in PWID, who are being released from the emergency department and inpatient hospital. In the midst of rises in overdose deaths and infections such as hepatitis C, we highlight several health issues for PWID, including overdose and infection prevention. We provide a clinical checklist of actions to help guide providers in the care of these complex patients. The clinical checklist includes strategies also applicable to low-resource settings, which may lack addiction treatment options. Our review and clinical checklist highlight key aspects of optimising the health and safety of PWID.
Active Peptic Ulcer Disease in Patients with Hepatitis C Virus-Related Cirrhosis: The Role ofHelicobacter pyloriInfection and Portal Hypertensive Gastropathy
Authors: Dore Maria , Mura Daniela , Deledda Stefania , Maragkoudakis Emmanouil , Pironti Antonella , Realdi Giuseppe 
Published: March 2016

BACKGROUND & AIM:The relationship betweenHelicobacter pyloriinfection and peptic ulcer disease in cirrhosis remains controversial. The purpose of the present study was to investigate the role ofH pyloriinfection and portal hypertension gastropathy in the prevalence of active peptic ulcer among dyspeptic patients with compensated hepatitis C virus (HCV)-related cirrhosis.METHODS:Patients undergoing upper endoscopy with compensated HCV-related cirrhosis were enrolled. Child-Pugh's score was determined at the entry. Variceal size was measured endoscopically and the severity of portal hypertensive gastropathy was graded.H pyloriinfection status was determined by urea breath testing and/or histology.RESULTS:A total of 178 patients positive for HCV (A and B Child-Pugh's score) were prospectively included. The prevalence ofH pyloriinfection was 43%. An active peptic ulcer was found in 14 patients (8%) and was significantly more common among those withH pyloriinfection (16% versus 2% inH pyloriuninfected patients, odds ratio: 8.0). No association was observed betweenH pyloriinfection and variceal size, or hypertensive gastropathy.CONCLUSIONS:Patients with compensated cirrhosis andH pyloriinfection showed higher risk of developing a peptic ulcer. Clinical relevance of this result would be that dyspeptic patients with HCV-related cirrhosis may benefit from preventive screening and eradication ofH pylori, especially those with features of insufficient hemostasis.
Practice affairs committee
Authors: Sadowski Dan 
Published: March 2016

The Practice Affairs Committee has had a productive year representing the interests of gastroenterologists involved in clinical care. The principle mandate of the committee is to address all issues relevant to the practice of gastroenterology, such as participation in the development of clinical practice guidelines and education programs, and the facilitation of clinical research. A major activity in 2003 was participation in the drafting of several new clinical practice guidelines:Infliximab and the management of Crohn's disease;Screening for colorectal cancer; andManagement of gastroesophageal reflux disease.