bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosome Organization and Replisome Dynamics in Mycobacterium smegmatis
Authors: Santi Isabella , McKinney John D. 
Published: February 2015

ABSTRACT

Subcellular organization of the bacterial nucleoid and spatiotemporal dynamics of DNA replication and segregation have been studied intensively, but the functional link between these processes remains poorly understood. Here we use quantitative time-lapse fluorescence microscopy for single-cell analysis of chromosome organization and DNA replisome dynamics in
Mycobacterium smegmatis
. We report that DNA replication takes place near midcell, where, following assembly of the replisome on the replication origin, the left and right replication forks colocalize throughout the replication cycle. From its initial position near the cell pole, a fluorescently tagged chromosomal locus (
attB
, 245° from the origin) moves rapidly to the replisome complex just before it is replicated. The newly duplicated
attB
loci then segregate to mirror-symmetric positions relative to midcell. Genetic ablation of ParB, a component of the ParABS chromosome segregation system, causes marked defects in chromosome organization, condensation, and segregation. ParB deficiency also results in mislocalization of the DNA replication machinery and SMC (structural maintenance of chromosome) protein. These observations suggest that ParB and SMC play important and overlapping roles in chromosome organization and replisome dynamics in mycobacteria.

IMPORTANCE
We studied the spatiotemporal organization of the chromosome and DNA replication machinery in
Mycobacterium smegmatis
, a fast-growing relative of the human pathogen
Mycobacterium tuberculosis
. We show that genetic ablation of the DNA-binding proteins ParB and SMC disturbs the organization of the chromosome and causes a severe defect in subcellular localization and movement of the DNA replication complexes. These observations suggest that ParB and SMC provide a functional link between chromosome organization and DNA replication dynamics. This work also reveals important differences in the biological roles of the ParABS and SMC systems in mycobacteria versus better-characterized model organisms, such as
Escherichia coli
and
Bacillus subtilis
.
Choreography of the Mycobacterium Replication Machinery during the Cell Cycle
Authors: Trojanowski Damian , Ginda Katarzyna , Pióro Monika , Hołówka Joanna , Skut Partycja , Jakimowicz Dagmara , Zakrzewska-Czerwińska Jolanta 
Published: February 2015

ABSTRACT

It has recently been demonstrated that bacterial chromosomes are highly organized, with specific positioning of the replication initiation region. Moreover, the positioning of the replication machinery (replisome) has been shown to be variable and dependent on species-specific cell cycle features. Here, we analyzed replisome positions in
Mycobacterium smegmatis
, a slow-growing bacterium that exhibits characteristic asymmetric polar cell extension. Time-lapse fluorescence microscopy analyses revealed that the replisome is slightly off-center in mycobacterial cells, a feature that is likely correlated with the asymmetric growth of Mycobacterium cell poles. Estimates of the timing of chromosome replication in relation to the cell cycle, as well as cell division and chromosome segregation events, revealed that chromosomal origin-of-replication (
oriC
) regions segregate soon after the start of replication. Moreover, our data demonstrate that organization of the chromosome by ParB determines the replisome choreography.

IMPORTANCE
Despite significant progress in elucidating the basic processes of bacterial chromosome replication and segregation, understanding of chromosome dynamics during the mycobacterial cell cycle remains incomplete. Here, we provide
in vivo
experimental evidence that replisomes in
Mycobacterium smegmatis
are highly dynamic, frequently splitting into two distinct replication forks. However, unlike in
Escherichia coli
, the forks do not segregate toward opposite cell poles but remain in relatively close proximity. In addition, we show that replication cycles do not overlap. Finally, our data suggest that ParB participates in the positioning of newly born replisomes in M. smegmatis cells. The present results broaden our understanding of chromosome segregation in slow-growing bacteria. In view of the complexity of the mycobacterial cell cycle, especially for pathogenic representatives of the genus, understanding the mechanisms and factors that affect chromosome dynamics will facilitate the identification of novel antimicrobial factors.
Characterization of Host and Microbial Determinants in Individuals with Latent Tuberculosis Infection Using a Human Granuloma Model
Authors: Guirado Evelyn , Mbawuike Uchenna , Keiser Tracy L. , Arcos Jesus , Azad Abul K. , Wang Shu-Hua , Schlesinger Larry S. 
Published: February 2015

ABSTRACTGranulomas sit at the center of tuberculosis (TB) immunopathogenesis. Progress in biomarkers and treatment specific to the human granuloma environment is hindered by the lack of a relevant and tractable infection model that better accounts for the complexity of the host immune response as well as pathogen counterresponses that subvert host immunity in granulomas. Here we developed and characterized anin vitrogranuloma model derived from human peripheral blood mononuclear cells (PBMCs) and autologous serum. Importantly, we interrogated this model for its ability to discriminate between host and bacterial determinants in individuals with and without latent TB infection (LTBI). By the use of this model, we provide the first evidence that granuloma formation, bacterial survival, lymphocyte proliferation, pro- and anti-inflammatory cytokines, and lipid body accumulation are significantly altered in LTBI individuals. Moreover, we show a specific transcriptional signature ofMycobacterium tuberculosisassociated with survival within human granuloma structures depending on the host immune status. Our report provides fundamentally new information on how the human host immune status and bacterial transcriptional signature may dictate early granuloma formation and outcome and provides evidence for the validity of the granuloma model and its potential applications.IMPORTANCEIn 2012, approximately 1.3 million people died from tuberculosis (TB), the highest rate for any single bacterial pathogen. The long-term control of TB requires a better understanding ofMycobacterium tuberculosispathogenesis in appropriate research models. Granulomas represent the characteristic host tissue response to TB, controlling the bacilli while concentrating the immune response to a limited area. However, complete eradication of bacteria does not occur, sinceM. tuberculosishas its own strategies to adapt and persist. Thus, theM. tuberculosis-containing granuloma represents a unique environment for dictating both the host immune response and the bacterial response. Here we developed and characterized anin vitrogranuloma model derived from blood cells of individuals with latent TB infection that more accurately defines the human immune response and metabolic profiles ofM. tuberculosiswithin this uniquely regulated immune environment. This model may also prove beneficial for understanding other granulomatous diseases.
The association of environmental heat stress with performance: analysis of the 2014 FIFA World Cup Brazil
Authors: Nassis George P , Brito Joao , Dvorak Jiri , Chalabi Hakim , Racinais Sebastien 
Published: February 2015

ObjectiveThe 2014 FIFA World Cup Brazil included 64 matches in temperate to tropical environmental conditions. We analysed performance data in relation to the environmental conditions to identify potential association.MethodsWet-bulb globe temperature (WBGT) parameters were obtained at the centre of the field 1 h before the start of play. Environmental stress was estimated (low, moderate and high) for each match using WBGT and relative humidity. Various physical and technical performance indices were recorded during each match (average of both teams).ResultsOver the 64 matches, 28 were played under low, 20 under moderate and 16 under high environmental stress. There was no difference in actual playing time (p=0.517), total distance covered (p=0.491), number of goals scored (p=0.485) and number of cards (p=0.618) between the matches played under different environmental stress categories. The number of sprints was lower in high than in moderate or low environmental stress (−10%, p<0.05) but peak speed was unaffected. The distance covered at high intensity was also lower under high (24.8±2.8 m/min/player) than low environmental stress (26.9±2.3 m/min/player, p=0.02). Number of passes was not different but the rate of successful passes was higher under high (76.8±4.4%) than low (73.6±10.8%) environmental stress (p=0.031).ConclusionsTop-level players seem to modulate their activity pattern during matches in a hot and humid environment (ie, less high-intensity but more low-intensity running and successful passes) to preserve the global match characteristics (ie, similar actual playing time, total distance covered, peak running speed and goals scored).
Alterations in enzymatic antioxidant defence in diabetes mellitus − a rational approach
Authors: Szaleczky Erika , Prechl József , Fehér János , Somogyi Anikó 
Published: February 2015

Summary
Defence against the reactive oxidants produced during aerobic metabolism is a complex process and is provided by a system of enzymes and antioxidant compounds capable of preventing excess radical production, neutralising free radicals and repairing the damage caused by them. Regulation of the antioxidant system must provide sufficient, properly located, antioxidant compounds and enzymes. Damage to this system has been proved to play a role in various disorders. Long-term complications of diabetes mellitus are supposed to be partially mediated by oxidative stress. The authors summarise experimental and clinical investigations in this field and analyse the possible importance of the changes in the antioxidant system in the development of diabetic vascular complications.
Management of non-Hodgkin's lymphomas
Authors: Mounter P J , Lennard A L 
Published: February 2015

Summary
The non-Hodgkin's lymphomas (NHL) are a heterogenous group of disorders characterised by malignant proliferation of lymphoid cells. The cellular origin is relatively well established with subtypes corresponding to the various stages of lymphocyte differentiation. The term encompasses a hotchpotch of conditions with very different morphological appearance, behaviour and clinical outcome. NHL comprise 2.4% of all cancers, with incidence increasing with age. The commonest presentation is with progressive lymphadenopathy, though extranodal manifestations are present in a significant proportion. The clinical behaviour ranges from a benign, indolent course to rapidly progressive disease; prognosis varies from weeks to many years. Treatment is correspondingly diverse, from ‘watchful waiting’ to high-dose chemotherapy with bone marrow stem cell transplantation. Cure is possible in an increasing number of patients and much interest currently lies in identifying patients with high-risk disease necessitating the use of intensive treatment regimens.
Intra-operative localisation of skull base tumours. A case report using the ISG viewing wand in the management of trigeminal neuroma
Authors: McEvoy A W , Porter D G , Bradford R , Wright A 
Published: February 2015

Summary
Deep-seated skull base tumours provide as much a challenge to the surgeons' skills of localisation as to his technical abilities during the resection. These lesions are frequently inaccessible and lie adjacent to vital structures requiring extensive cerebral retraction for adequate exposure and direct visualisation. The ISG viewing wand is a newly developed image guidance system to aid direction of the operative approach and localisation of intracerebral pathology. We discuss its use in the management of a trigeminal neuroma.
Tuberculosis of the central nervous system
Authors: Garg Ravindra Kumar 
Published: February 2015

Summary
Tuberculous involvement of the brain and spinal cord are common neurological disorders in developing countries and have recently shown a resurgence in developed ones. Tuberculous meningitis is an important manifestation and is associated with high morbidity and mortality. Diagnosis is based on clinical features, cerebrospinal fluid changes, and imaging characteristics. Bacteriological confirmation is not possible in all cases as serological tests do not have sufficient sensitivity and specificity. The polymerase chain reaction shows promise for the future. Appropriate chemotherapeutic agents should be administered as early as possible, although there is no unanimity concerning chemotherapeutic regimens or optimal duration of treatment. The patient's clinical stage at presentation is the most important prognostic factor. The role of corticosteroids is controversial but they should be administered to all patients presenting in stage III. Surgical procedures are directed at management of the hydrocephalus. Focal lesions, intracranial tuberculomas, and tuberculous abscesses, are usually located in cerebral or cerebellar hemispheres, uncommonly in brainstem and very rarely in spinal cord. They do not usually require surgical intervention and respond well to antituberculous treatment, along with corticosteroids.
Production and evaluation of guidelines for the management of inflammatory bowel disease: the Leicester experience
Authors: Read A M , Stone M A , Rathbone B J , de Caestecker J , Wicks A C B , Longworth S , O'Shea C R , Baker R , Spence D , Hall A W , Kelly M J , Cannon J , Robinson R J , Hart A R , Miles P , Mayberry J F 
Published: February 2015

Summary
Consensus guidelines for the management of patients with inflammatory bowel disease were produced by gastroenterologists, gastrointestinal surgeons and a cross-section of general practitioners (GPs) from Leicestershire in order to develop a seamless pattern of care with a common approach to diagnosis and treatment. It was hoped that the guidelines would encourage a movement towards care in the community for many patients with stable disease and so speed up new consultation rates. The study then assessed the impact of these guidelines on the referral letters of GPs to hospital consultants, the prediction of disease and adherence to them on re-referring patients after discharge. The guidelines were distributed to all 487 GPs in the Leicester Health Authority area and the gastroenterology teams within the hospitals. The value of the guidelines was assessed by an audit of referral letters, the length of time from referral letter to out-patient appointment, both before and after the launch of the guidelines, adherence to the guidelines on re-referral, and monitoring the outcome of the discharged patients. Whilst the guidelines may have helped GPs to manage stable patients in the community, the content of referral letters and the diagnostic abilities of GPs were not seen to improve since the launch of the guidelines. However, only 5% of stable patients who were discharged from one clinic were re-referred for inflammatory bowel disease.
Brain parenchymal, subarachnoid racemose, and intraventricular cysticercosis in an Indian man
Authors: Ghosh D , Dubey T N , Prabhakar S 
Published: February 2015

Summary
The coexistence of brain parenchymal cysts at various stages of evolution, both intraventricular and subarachnoid racemose, is reported in a patient with neurocysticercosis. The condition has a variety of presentations, depending on the location of the cyst. This case is of particular interest because of the rarity of this condition in India.
Transmission of Helicobacter pylori
Authors: Stone Margaret A 
Published: February 2015

Summary
Helicobacter pylori is found predominantly in human gastric mucosa. Transfer of the bacterium remains an open topic, but it is likely that infection is usually acquired at a young age, particularly where lower socio-economic conditions prevail. Transmission via an external source such as water supply is a possibility but, in general, infection is probably passed from person to person. Arguments for and against faecal–oral, oral–oral and gastric–oral transmission have been presented, but the dominance of one of these routes is still to be determined.
Targeting pneumococcal vaccination to high-risk groups: a feasibility study in one general practice
Authors: Siriwardena A N 
Published: February 2015

Summary
The Department of Health recommends pneumococcal vaccination opportunistically or when immunising against influenza. This was a study in one general practice to assess the feasibility of targeting patients for pneumococcal vaccination in primary care. We also examined the rate of uptake of pneumococcal vaccine in identified risk groups after one year of a pneumococcal vaccination programme. A self-administered questionnaire was given to patients attending for influenza vaccine between September and December 1996. A total of 551/747 (73.8%) patients returned completed questionnaires. Few patients receiving influenza vaccination (133/509, 26%) were aware of pneumococcal vaccine. Only 55/108 (51%) of those given influenza vaccination were in a clinical risk group for pneumococcal vaccine. Attitudes towards vaccination were more positive and intention to take up pneumococcal vaccination significantly greater in high-risk patients compared to those who were not in a risk group. A targeted vaccination campaign directed at high-risk patients, both opportunistically and those attending for influenza vaccination over one year, resulted in the following proportions of patients in at-risk groups being vaccinated: coronary disease 144/312 (46%), diabetes 79/132 (60%), splenectomy 2/2 (100%), chronic obstructive airways disease and asthma 135/700 (19%), and chronic renal failure 5/9 (56%). Most doses of pneumococcal vaccine (336/463; 73%) were delivered to patients in high-risk groups. We conclude that a well-organised pneumococcal vaccination campaign can improve coverage of at-risk patients in general practice. Programmes to increase patient awareness of the vaccine, improved availability of vaccine, and practice guidelines, would help to target the vaccine to at-risk patients. Patients with chronic lung disease and asthma were particularly difficult to define and target in this study. A review of the UK guidelines, aligning those for pneumococcal and influenza vaccination and including patients over 65 years, would improve the logistics of vaccine delivery.
The use of hypnosis in gastroscopy: a comparison with intravenous sedation
Authors: Conlong Philip , Rees Wynne 
Published: February 2015

Summary
A total of 124 subjects who were undergoing routine endoscopy were randomly assigned to one of three groups. All three groups received lignocaine throat spray. The first group additionally received midazolam, the second received hypnosis, whilst the third only received lignocaine throat spray. Although hypnotised patients were deemed by an independent observer to be less agitated than the other two groups (p&lt;0.03), they reported the gastroscopy to be significantly more uncomfortable (p&lt;0.042) and scored higher in their memory for the procedure (p&lt;0.001). They also took slightly longer to induce than the midazolam group. The midazolam group on the other hand rated the procedure as significantly more comfortable although paradoxically were seen by an independent observer as being more agitated. They were also significantly more amnesic. The endoscopist encountered more procedural difficulties with this group but this did not reach levels of significance. Hypnosis was not shown to be an effective alternative to intravenous sedation in gastroscopy.
High-altitude illness induced by tooth root infection
Authors: Finsterer J 
Published: February 2015

Summary
High-altitude illness may occur after recent pulmonary infection, but high-altitude illness after root canal therapy has not been described previously. A 44-year-old man is presented who skied to a 3333 m high peak in the Eastern Alps one day after he had undergone root canal therapy because of a tooth root infection. After 4 hours above 3000 m severe symptoms of high-altitude illness, including pulmonary oedema, developed. His condition improved after immediate descent. The next day he presented with local and general signs of infection which were successfully treated with gingival incisions and antibiotics. In conclusion, acute tooth root infection and root canal therapy may induce high-altitude illness at an altitude just above 3000 m.
Early use of ‘open-air’ treatment for ‘pulmonary phthisis’ at the Dreadnought Hospital, Greenwich, 1900–1905
Authors: Cook G C 
Published: February 2015

Summary
The use of open-air treatment for tuberculosis (‘pulmonary phthisis’) at the Dreadnought Hospital, Greenwich from 1900 to 1905 is reviewed. A marked reduction in mean mortality rate compared to ‘orthodox’ management was observed.
Risk factors for acquisition of gentamicin-resistant enterococcal infection: a case-controlled study
Authors: Viagappan M , Holliman R E 
Published: February 2015

Summary
High-level gentamicin-resistant enterococci present problems in the treatment of infected patients, especially as synergy between penicillin and gentamicin is lost. Previous studies have suggested various risk factors for the acquisition of these enterococci. A case-controlled study was performed on 17 patients infected with resistant enterococci and 26 infected with sensitive strains who attended a London hospital. The key risk factors for acquisition of infection with high-level gentamicin-resistant enterococci were found to be prior prolonged antibiotic treatment, use of five or more antibiotics, and the presence of a urinary catheter. It is proposed that infection control measures should be targeted at patients at higher risk. In addition, control of antibiotic usage in a hospital may help to prevent acquisition and spread of these organisms.
Efficacy of statin therapy: possible effect of phenytoin
Authors: Murphy M J , Dominiczak M H 
Published: February 2015

Summary
Statins are currently the most widely prescribed lipid-lowering drugs. Individual statins are known to be metabolised by the CYP3A4 isoform of the cytochrome P450 system. The effect of CYP3A4 inducers such as phenytoin on the metabolism and efficacy of these agents is unknown. We report a patient with familial hypercholesterolaemia and epilepsy in whom the introduction and subsequent discontinuation of phenytoin were associated with marked changes in the lipid response to treatment with simvastatin and atorvastatin. The serum activity of γ-glutamyl transpeptidase may have acted as a marker of microsomal induction by phenytoin, since it rose markedly when phenytoin was introduced and returned to normal after it was discontinued.
Medication-induced oesophageal injury leading to broncho-oesophageal fistula
Authors: McAndrew N A , Greenway M W 
Published: February 2015

Summary
Medication-induced oesophageal injury is one of the least recognised side-effects of oral medication and, in contrast to other oesophageal pathologies, is rarely considered in the differential diagnosis of chest pain. We describe a case of medication-induced oesophageal injury with a rare complication in which the diagnosis was not considered until the characteristic features were demonstrated at endoscopy.