Transition from the Couette-Taylor system to the plane Couette system

We discuss the flow between concentric rotating cylinders in the limit of large radii where the system approaches plane Couette flow. We discuss how in this limit the linear instability that leads to the formation of Taylor vortices is lost and how the character of the transition approaches that of planar shear flows. In particular, a parameter regime is identified where fractal distributions of life times and spatiotemporal intermittency occur. Experiments in this regime should allow to study the characteristics of shear flow turbulence in a closed flow geometry.Comment: 5 pages, 5 figure

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity

First insights into the phylogenetic diversity of Mycobacterium tuberculosis in Nepal

BACKGROUND: Tuberculosis (TB) is a major public health problem in Nepal. Strain variation in Mycobacterium tuberculosis may influence the outcome of TB infection and disease. To date, the phylogenetic diversity of M. tuberculosis in Nepal is unknown. METHODS AND FINDINGS: We analyzed 261 M. tuberculosis isolates recovered from pulmonary TB patients recruited between August 2009 and August 2010 in Nepal. M. tuberculosis lineages were determined by single nucleotide polymorphisms (SNP) typing and spoligotyping. Drug resistance was determined by sequencing the hot spot regions of the relevant target genes. Overall, 164 (62.8%) TB patients were new, and 97 (37.2%) were previously treated. Any drug resistance was detected in 50 (19.2%) isolates, and 16 (6.1%) were multidrug-resistant. The most frequent M. tuberculosis lineage was Lineage 3 (CAS/Delhi) with 106 isolates (40.6%), followed by Lineage 2 (East-Asian lineage, includes Beijing genotype) with 84 isolates (32.2%), Lineage 4 (Euro-American lineage) with 41 (15.7%) isolates, and Lineage 1 (Indo-Oceanic lineage) with 30 isolates (11.5%). Based on spoligotyping, we found 45 different spoligotyping patterns that were previously described. The Beijing (83 isolates, 31.8%) and CAS spoligotype (52, 19.9%) were the dominant spoligotypes. A total of 36 (13.8%) isolates could not be assigned to any known spoligotyping pattern. Lineage 2 was associated with female sex (adjusted odds ratio [aOR] 2.58, 95% confidence interval [95% CI] 1.42-4.67, p = 0.002), and any drug resistance (aOR 2.79; 95% CI 1.43-5.45; p = 0.002). We found no evidence for an association of Lineage 2 with age or BCG vaccination status. CONCLUSIONS: We found a large genetic diversity of M. tuberculosis in Nepal with representation of all four major lineages. Lineages 3 and 2 were dominating. Lineage 2 was associated with clinical characteristics. This study fills an important gap on the map of the M. tuberculosis genetic diversity in the Asian reg

Two new rapid SNP-typing methods for classifying Mycobacterium tuberculosis complex into the main phylogenetic lineages

There is increasing evidence that strain variation in Mycobacterium tuberculosis complex (MTBC) might influence the outcome of tuberculosis infection and disease. To assess genotype-phenotype associations, phylogenetically robust molecular markers and appropriate genotyping tools are required. Most current genotyping methods for MTBC are based on mobile or repetitive DNA elements. Because these elements are prone to convergent evolution, the corresponding genotyping techniques are suboptimal for phylogenetic studies and strain classification. By contrast, single nucleotide polymorphisms (SNP) are ideal markers for classifying MTBC into phylogenetic lineages, as they exhibit very low degrees of homoplasy. In this study, we developed two complementary SNP-based genotyping methods to classify strains into the six main human-associated lineages of MTBC, the 'Beijing' sublineage, and the clade comprising Mycobacterium bovis and Mycobacterium caprae. Phylogenetically informative SNPs were obtained from 22 MTBC whole-genome sequences. The first assay, referred to as MOL-PCR, is a ligation-dependent PCR with signal detection by fluorescent microspheres and a Luminex flow cytometer, which simultaneously interrogates eight SNPs. The second assay is based on six individual TaqMan real-time PCR assays for singleplex SNP-typing. We compared MOL-PCR and TaqMan results in two panels of clinical MTBC isolates. Both methods agreed fully when assigning 36 well-characterized strains into the main phylogenetic lineages. The sensitivity in allele-calling was 98.6% and 98.8% for MOL-PCR and TaqMan, respectively. Typing of an additional panel of 78 unknown clinical isolates revealed 99.2% and 100% sensitivity in allele-calling, respectively, and 100% agreement in lineage assignment between both methods. While MOL-PCR and TaqMan are both highly sensitive and specific, MOL-PCR is ideal for classification of isolates with no previous information, whereas TaqMan is faster for confirmation. Furthermore, both methods are rapid, flexible and comparably inexpensive

New complex investigations of the Novhorod-Siverskyi Upper Palaeolithic site

In the article the materials of the Novhorod-Siverskyi site research both in the 1930's, and relatively recently, are analyzed. First of all, attention is paid to the faunal collection. The faunal associations from old excavations are coherent, typical of a cold steppe environment from the glacial period, near a riparian forest. However, it seems to result to a mix between natural taphonomic complexes and animal remains associated with human activity. Judging by the flint collection from the old excavations, the site was inhabited by representatives of the Pushkari type. New research yielded two archaeological layers that are very poor in flint artefacts. Concerning fauna, the faunal spectrum is restricted in both layers, with the woolly mammoth, the woolly rhinoceros, the horse and the reindeer in the lower and upper layers. In the upper layer there are also the bison, the fox and the hare. According to taphonomic observations, the bones had remained for a long time at an open air before being buried, in subsurface in a wet environment but few submitted to precipitations in link with permafrost activities. Particularly in the lower layer (2) some remains appear to be in place, while others seem to have been imported by hydraulic phenomena, either from the top of the promontory or from the Desna River. In the upper layer (1), some bones show possible anthropogenic impacts of breakage, linked to marrow recovery. In both layers we have some cranial and postcranial elements, mainly from adults sensu lato which could correspond to human predation. They could correspond to temporary camps of quite small human groups, potentially occupied at the end of the cold season/ beginning of the warm season.Новгород-Сіверську стоянку відкрив і досліджував М. Я. Рудинський у 1933 р. Основні роботи на ній були проведені у 1936—1938 рр. під керівництвом І. Г. Підоплічка. У зв’язку із виявленням нових артефактів у 2011 р. на стоянці було здійснено нові невеликі дослідження. Стаття присвячена аналізу в першу чергу фауністичного комплексу стоянки, а також містить дані типологічного аналізу крем’яної колекції. За колекцією кременю з досліджень 1930-х рр., стоянка була заселена носіями пушкарівського типу. На нашу думку, навряд чи варто говорити про епіграветську домішку. Якщо припускати іншокультурну складову колекції, то, скоріше за все, на її роль може претендувати фрагмент двобічнообробленого знаряддя (рис. 3: 1). Судячи з фауністичних решток розкопок попередніх років, фауністичні комплекси є цілісними, характерними для холодного степового середовища льодовикового періоду біля прибережного лісу. Тим не менше це, здається, є наслідком поєднання решток тварин, похованих природним чином та безпосередньо пов’язаних із людською діяльністю. Під час останніх досліджень стоянки було виявлено два культурні шари з бідним крем’яним інвентарем. В обох шарах з останніх розкопок мало знахідок фауни і фауністичний спектр досить обмежений. Згідно з тафономічними спостереженнями, кістки тривалий час залишалися на відкритому повітрі, перш ніж потрапили у вологий ґрунт, але лише деякі з них мають сліди, пов’язані з дією вічної мерзлоти. Нижній шар (2) дав кістки шерстистого мамонта, шерстистого носорога, коня та північного оленя. Деякі кістки, імовірно, лежали in situ, інші, мабуть, були переміщені під дією водних потоків або з вершини мису, або з річки Десни. У верхньому шарі (1) були залишки шерстистого мамонта, шерстистого носорога, коня, північного оленя, зубра, лисиці та зайця. Отже, видове різноманіття фауни верхнього шару є більшим, ніж нижнього. Кістки з можливими слідами розбивання можуть бути пов’язані з добуванням кісткового мозку давніми людьми. В обох шарах присутні кістки переважно дорослих особин sensu lato, наявність яких цілком може бути пов’язана з людською діяльністю, зокрема полюванням. Ці шари можуть відповідати тимчасовим таборам досить невеликих людських груп, що могли існувати в кінці холодної/на початку теплої пори року. За результатами останніх досліджень, Новгород-Сіверська стоянка потребує додаткових розкопок у ще придатних для цього частинах.Новгород-Северская стоянка была открыта и исследовалась М. Я. Рудинским в 1933 г. Основные работы на ней были проведены в 1936—1938 гг. под руководством И. Г. Пидопличко. В связи с выявлением новых артефактов в 2011 г. на стоянке были проведены новые небольшие исследования. Статья посвящена анализу в первую очередь фаунистического комплекса стоянки, а также приводятся данные типологического анализа кремневой коллекции. Судя по коллекции кремня из исследований 1930-х гг., стоянка была заселена представителями пушкарёвского типа памятников. По нашему мнению, вряд ли стоит говорить об эпиграветтской примеси. Если допускать инокультурную составляющую коллекции, то, скорее всего, на её роль может претендовать фрагмент двусторонне обработанного орудия (рис. 3: 1). Судя по фаунистическим остаткам из раскопок предыдущих лет, фаунистические комплексы являются целостными, характерными для холодной степной среды ледникового периода около прибрежного леса. Тем не менее это, кажется, является результатом сочетания остатков животных, захороненных естественным образом и непосредственно связанных с человеческой деятельностью. В ходе последних исследований стоянки было обнаружено два культурных слоя с бедным кремневым инвентарем. В обоих слоях мало находок фауны и фаунистический спектр весьма ограничен. Согласно тафономическим наблюдениям, кости долгое время оставались на открытом воздухе, прежде чем попали во влажный грунт, но лишь некоторые из них имеют следы, связанные с действием вечной мерзлоты. Нижний слой (2) дал кости шерстистого мамонта, шерстистого носорога, лошади и северного оленя. Некоторые кости, вероятно, находились in situ, другие вероятно были перемещены действием водных потоков или с вершины мыса, или из реки Десны. В верхнем слое (1) обнаружены кости шерстистого мамонта, шерстистого носорога, лошади, северного оленя, бизона, лисы и зайца. Таким образом, он более разнообразен, чем нижний слой. Кости с возможными следами разбивания могут быть связаны с добычей костного мозга древними людьми. В обоих слоях присутствуют кости преимущественно взрослых особей sensu lato, наличие которых вполне может быть связано с человеческой деятельностью, в частности охотой. Эти слои могут соответствовать временным лагерям достаточно небольших человеческих групп, которые могли существовать в конце холодного/вначале теплого времени года. Судя по результатам последних исследований, Новгород-Северская стоянка требует дополнительных раскопок в еще пригодных для этого участках

Molecular epidemiology, drug susceptibility and economic aspects of tuberculosis in mubende district, Uganda

<div><p>Background</p><p>Tuberculosis (TB) remains a global public health problem whose effects have major impact in developing countries like Uganda. This study aimed at investigating genotypic characteristics and drug resistance profiles of <i>Mycobacterium tuberculosis</i> isolated from suspected TB patients. Furthermore, risk factors and economic burdens that could affect the current control strategies were studied.</p><p>Methods</p><p>TB suspected patients were examined in a cross-sectional study at the Mubende regional referral hospital between February and July 2011. A questionnaire was administered to each patient to obtain information associated with TB prevalence. Isolates of <i>M. tuberculosis</i> recovered during sampling were examined for drug resistance to first line anti-TB drugs using the BACTEC-MGIT960^TMsystem. All isolates were further characterized using deletion analysis, spoligotyping and MIRU-VNTR analysis. Data were analyzed using different software; MIRU-VNTR <i>plus</i>, SITVITWEB, BioNumerics and multivariable regression models.</p><p>Results</p><p><i>M. tuberculosis</i> was isolated from 74 out of 344 patients, 48 of these were co-infected with HIV. Results from the questionnaire showed that previously treated TB, co-infection with HIV, cigarette smoking, and overcrowding were risk factors associated with TB, while high medical related transport bills were identified as an economic burden. Out of the 67 isolates that gave interpretable results, 23 different spoligopatterns were detected, nine of which were novel patterns. T2 with the sub types Uganda-I and Uganda-II was the most predominant lineage detected. Antibiotic resistance was detected in 19% and multidrug resistance was detected in 3% of the isolates.</p><p>Conclusion</p><p>The study detected <i>M. tuberculosis</i> from 21% of examined TB patients, 62% of whom were also HIV positive. There is a heterogeneous pool of genotypes that circulate in this area, with the T2 lineage being the most predominant. High medical related transport bills and drug resistance could undermine the usefulness of the current TB strategic interventions.</p></div

Thioflavine-T and Congo Red reveal the polymorphism of insulin amyloid fibrils when probed by polarization-resolved fluorescence microscopy.

International audienceAmyloid fibrils are protein misfolding structures that involve a β-sheet structure and are associated with the pathologies of various neurodegenerative diseases. Here we show that Thioflavine-T and Congo Red, two major dyes used to image fibrils by fluorescence assays, can provide deep structural information when probed by means of polarization-resolved fluorescence microscopy. Unlike fluorescence anisotropy or fluorescence detected linear dichroism imaging, this technique allows to retrieve simultaneously both mean orientation and orientation dispersion of the dye, used here as a reporter of the fibril structure. We have observed that insulin amyloid fibrils exhibit a homogeneous behavior over the fibrils' length, confirming their structural uniformity. In addition, these results reveal the existence of various structures among the observed fibrils' population, in spite of a similar aspect when imaged with conventional fluorescence microscopy. This optical nondestructive technique opens perspectives for in vivo structural analyses or high throughput screening

Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.We thank S. Lecher, S. Li and J. Zallet for technical support. Calculations were performed at the sciCORE scientific computing core facility at the University of Basel. This work was supported by the Swiss National Science Foundation (grants 310030_166687 (S.G.) and 320030_153442 (M.E.) and Swiss HIV Cohort Study grant 740 to L.F.), the European Research Council (309540-EVODRTB to S.G.), TB-PAN-NET (FP7-223681 to S.N.), PathoNgenTrace projects (FP7-278864-2 to S.N.), SystemsX.ch (S.G.), the German Center for Infection Research (DZIF; S.N.), the Novartis Foundation (S.G.), the Natural Science Foundation of China (91631301 to Q.G.), and the National Institute of Allergy and Infectious Diseases (5U01-AI069924-05) of the US National Institutes of Health (M.E.)

Mycobacterium tuberculosis causing tuberculous lymphadenitis in Maputo, Mozambique

BACKGROUND: The zoonosis bovine tuberculosis (TB) is known to be responsible for a considerable proportion of extrapulmonary TB. In Mozambique, bovine TB is a recognised problem in cattle, but little has been done to evaluate how Mycobacterium bovis has contributed to human TB. We here explore the public health risk for bovine TB in Maputo, by characterizing the isolates from tuberculous lymphadenitis (TBLN) cases, a common manifestation of bovine TB in humans, in the Pathology Service of Maputo Central Hospital, in Mozambique, during one year. RESULTS: Among 110 patients suspected of having TBLN, 49 had a positive culture result. Of those, 48 (98 %) were positive for Mycobacterium tuberculosis complex and one for nontuberculous mycobacteria. Of the 45 isolates analysed by spoligotyping and Mycobacterial Interspersed Repetitive Unit - Variable Number Tandem Repeat (MIRU-VNTR), all were M. tuberculosis. No M. bovis was found. Cervical TBLN, corresponding to 39 (86.7 %) cases, was the main cause of TBLN and 66.7 % of those where from HIV positive patients. We found that TBLN in Maputo was caused by a variety of M. tuberculosis strains. The most prevalent lineage was the EAI (n?=?19; 43.2 %). Particular common spoligotypes were SIT 48 (EAI1_SOM sublineage), SIT 42 (LAM 9), SIT 1 (Beijing) and SIT53 (T1), similar to findings among pulmonary cases. CONCLUSIONS: M. tuberculosis was the main etiological agent of TBLN in Maputo. M. tuberculosis genotypes were similar to the ones causing pulmonary TB, suggesting that in Maputo, cases of TBLN arise from the same source as pulmonary TB, rather than from an external zoonotic source. Further research is needed on other forms of extrapulmonary TB and in rural areas where there is high prevalence of bovine TB in cattle, to evaluate the risk of transmission of M. bovis from cattle to humans.Swedish International Development Cooperation Agency / Department for Research Cooperation (Sida/SAREC) through Eduardo Mondlane University and Karolinska Institutet Research and Training (KIRT) collaboratio