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Официальный форум ВолгГМУ _ Кафедры университета _ Анонсы статей

Автор: Immunology 25.2.2014, 10:15

Mechanism of Tc toxin action revealed in molecular detail
Ученые из института Макса Планка представили удивительно подробную визуализацию действия токсина, которым пользуются Yersinia pestis и Photorhabdus luminescens. Авторы использовали рентгеновскую кристаллографию и http://www.nkj.ru/news/23384/. Механизм "смертельной инъекции" описан в свеженькой статье в Nature. Обратите внимание, что среди авторов значится и автор российского происхождения Руслан Ефремов. Руслан окончил аспирантуру в Московском физико-техническом институте в 2005 году, после чего получил постдоки в Англии и Германии.


Tripartite Tc toxin complexes of bacterial pathogens perforate the host membrane and translocate toxic enzymes into the host cell, including in humans. The underlying mechanism is complex but poorly understood. Here we report the first, to our knowledge, high-resolution structures of a TcA subunit in its prepore and pore state and of a complete 1.7 megadalton Tc complex. The structures reveal that, in addition to a translocation channel, TcA forms four receptor-binding sites and a neuraminidase-like region, which are important for its host specificity. pH-induced opening of the shell releases an entropic spring that drives the injection of the TcA channel into the membrane. Binding of TcB/TcC to TcA opens a gate formed by a six-bladed β-propeller and results in a continuous protein translocation channel, whose architecture and properties suggest a novel mode of protein unfolding and translocation. Our results allow us to understand key steps of infections involving Tc toxins at the molecular level.

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13015.html

http://www.immunology-allergy.org/JournalPapers/Images/nature13015-sf8.jpg

Автор: Immunology 2.3.2014, 19:01

Diagnosis and classification of drug-induced autoimmunity (DIA)
Статья посвящена аутоиммунным реакциям, провоцируемым применением лекарств. Аутоиммунные заболевания, проявляемые чаще всего волчаночным синдромом, могут вызываться такими препаратами, как прокаинамид, гидралазин и др. В статье приведены диагностические критерии, позволяющие диагностировать такие состояния.


Since sulfadiazine associated lupus-like symptoms were first described in 1945, certain drugs have been reported to interfere with the immune system and induce a series of autoimmune diseases (named drug-induced autoimmunity, DIA), exemplified by systemic lupus erythematosus (SLE). Among the drugs, procainamide and hydralazine are considered to be associated with the highest risk for developing lupus, while quinidine has a moderate risk, and all other drugs have low or very low risk. More recently, drug-induced lupus has been associated with the use of newer biological modulators, such as tumor necrosis factor (TNF)-alpha inhibitors and cytokines. In addition to lupus, other major autoimmune diseases, including vasculitis and arthritis, have also been associated with drugs. Because resolution of symptoms generally occurs after cessation of the offending drugs, early diagnosis is crucial for treatment strategy and improvement of prognosis. Unfortunately, it is difficult to establish standardized criteria for DIA diagnosis. Diagnosis of DIA requires identification of a temporal relationship between drug administration and the onset of symptoms, but the relative risk with respect to dose and duration for each drug has rarely been determined. DIA is affected by multiple genetic and environmental factors, leading to difficulties in establishing a list of global clinical features that are characteristic of most or all DIA patients. Moreover, the distinction between authentic DIA and unmasking of a latent autoimmune disease also poses challenges. In this review, we summarize the highly variable clinical features and laboratory findings of DIA, with an emphasis on the diagnostic criteria.

http://www.sciencedirect.com/science/article/pii/S0896841114000079

http://www.immunology-allergy.org/JournalPapers/Images/DrugInducedAutoimmunity_JofAutoimmunity_2014.jpg

http://www.immunology-allergy.org/JournalPapers/DrugInducedAutoimmunity_JofAutoimmunity_2014.pdf

Счетчик на момент публикации: 70

Автор: Immunology 2.3.2014, 21:22

Occupational Asthma
Профессиональная бронхиальная астма, что тут еще скажешь.


Asthma is common in the general population, including those in the workforce. Work exposures can cause or exacerbate asthma and can also be associated with asthma variants (e.g., eosinophilic bronchitis3 and aluminum potroom asthma) as well as symptoms that mimic asthma (e.g., the irritable larynx syndrome). In addition, even non–work-related asthma can affect the ability to work. This review focuses on current data about occupational asthma, defined as asthma due to conditions attributable to work exposures and not to causes outside the workplace.
One important and common subtype of work-related asthma that is not addressed further in this review is work-exacerbated asthma. As recently reviewed, work-related exacerbation of asthma — ranging from single transient exacerbations after an unusual exposure to daily work-related worsening that can mimic occupational asthma — may occur in up to 25% of working persons with asthma.


http://www.nejm.org/doi/full/10.1056/NEJMra1301758

http://www.immunology-allergy.org/JournalPapers/Images/OccupationalAsthma_NeJM_2014.jpg

http://www.immunology-allergy.org/JournalPapers/OccupationalAsthma_NeJM_2014.pdf

Счетчик на момент публикации: 86

Автор: Immunology 11.3.2014, 9:32

Structure of a type IV secretion system
Британские ученые раскрыли секрет устойчивости некоторых бактерий к антибиотикам, сообщается в статье, опубликованной в научном журнале Nature.
В частности, ученые изучили имеющуюся у бактерий секреторную систему IV типа, отвечающую за всасывание веществ через бактериальную клеточную стенку. Им удалось установить, что система действует посредством двух механизмов — один расположен на внутренней стенке мембраны, а второй — на внешней. По мнению ученых, посредством этой системы происходит обмен генетическим материалом между бактериями, что и обуславливает появление определенной устойчивости против антибиотиков.
Исследователи надеются, что с помощью их разработки будет возможно эффективно бороться с антибиотикоустойчивыми формами коклюша и пневмонии.



Bacterial type IV secretion systems translocate virulence factors into eukaryotic cells, distribute genetic material between bacteria and have shown potential as a tool for the genetic modification of human cells. Given the complex choreography of the substrate through the secretion apparatus4, the molecular mechanism of the type IV secretion system has proved difficult to dissect in the absence of structural data for the entire machinery. Here we use electron microscopy to reconstruct the type IV secretion system encoded by the Escherichia coli R388 conjugative plasmid. We show that eight proteins assemble in an intricate stoichiometric relationship to form an approximately 3 megadalton nanomachine that spans the entire cell envelope. The structure comprises an outer membrane-associated core complex1 connected by a central stalk to a substantial inner membrane complex that is dominated by a battery of 12 VirB4 ATPase subunits organized as side-by-side hexameric barrels. Our results show a secretion system with markedly different architecture, and consequently mechanism, to other known bacterial secretion systems

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13081.html

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13081.html

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13081.html

Счетчик на момент публикации: 152

Автор: Immunology 18.3.2014, 11:27

Management of Skin Abscesses in the Era of Methicillin-Resistant Staphylococcus aureus
Ведение больных с абсцессами кожи в эпоху метициллин-резистентного S. aureus


Abscesses are one of the most common skin conditions managed by general practitioners and emergency physicians. The incidence of skin abscesses has increased, and this increase has coincided with the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA). In many parts of the world, MRSA infections are now the most common cause of skin abscesses. Community-associated MRSA has also been found to cause severe infections — including necrotizing pneumonia, necrotizing fasciitis, purpura fulminans, and severe sepsis — in nonimmunocompromised hosts; however, its apparently increased virulence as compared with that of health care–associated strains and methicillin-susceptible S. aureus is incompletely understood. Along with the increases in the incidence of skin abscesses and MRSA infections, other changes that potentially affect abscess care have occurred. Bedside ultrasonography has become increasingly available in emergency departments and hospitals. Traditional surgical practices have been systematically tested, and new techniques developed. Prevention strategies have also been investigated. Despite these changes, the management of skin abscesses is highly variable.
In this article, we describe our approach to the management of common skin abscesses that generally involve the extremities and trunk. Lesions that may require unique surgical approaches or that have a more complex microbiologic basis, such as abscesses in the perineal area, are not addressed. Whenever possible, our recommendations are based on randomized trials. However, many of the recommendations are based on small, observational studies or expert opinion; thus, we recognize that there may be disagreement with some of our recommendations. Nevertheless, the approach we advise has been shown to be workable and useful in our practice.


http://www.nejm.org/doi/full/10.1056/NEJMra1212788




http://www.nejm.org/doi/pdf/10.1056/NEJMra1212788

Счетчик на момент публикации: 181

Автор: Immunology 20.3.2014, 13:07

Hepatitis B
Апдейт по гепатиту В на сайте British Medical Journal - BMJ Best Practice


Summary



http://bestpractice.bmj.com/best-practice/monograph/127.html



Счетчик на момент публикации: 207

Автор: Immunology 12.4.2014, 21:58

Multistate Point-Prevalence Survey of Health Care–Associated Infections
Отчет исследования CDC по внутрибольничным инфекциям


Elimination of health care–associated infections is a priority of the Department of Health and Human Services. Considerable success in prevention has been reported for some infections, particularly central-catheter–associated bloodstream infections. Continued improvements in patient safety depend on maintaining a comprehensive understanding of the epidemiology of health care–associated infections. Currently, no single U.S. surveillance system can provide estimates of the burden of all types of such infections across acute care patient populations. The most recent estimate produced by the Centers for Disease Control and Prevention (CDC) and published in 2007 — 1.7 million health care–associated infections per year — relied on historical data combined with contemporary hospitalization data.6 The CDC surveillance system for health care–associated infections, the National Healthcare Safety Network (NHSN), provides information on incidence rates of common infections. Most hospitals limit reporting to device-associated infections, selected surgical-site infections, and infections due to Clostridium difficile and methicillin-resistant Staphylococcus aureus (MRSA). Therefore, the NHSN cannot provide national-scale data on the overall burden and distribution of health care–associated infections across acute care patient populations.
To address this knowledge gap, the CDC began a three-phase effort in 2009 to develop and conduct a multistate prevalence survey of health care–associated infections and use of antimicrobial agents. Prevalence surveys have been used in other countries to describe the scope and magnitude of the problem of such infections. The CDC effort culminated in 2011 in a large-scale survey that estimated the prevalence of health care–associated infections in acute care hospitals, determined the distribution of these infections according to infection site and pathogen, and generated updated estimates of the national burden of these infections.


http://www.nejm.org/doi/full/10.1056/NEJMoa1306801#t=article



Счетчик на момент публикации: 247

The production and regulation of IgE by the immune system
Обзор Nature Reviews Immunology по регуляции продукции IgE


IgE not only provides protective immunity against helminth parasites but can also mediate the type I hypersensitivity reactions that contribute to the pathogenesis of allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. Despite the importance of IgE in immune biology and allergic pathogenesis, the cells and the pathways that produce and regulate IgE are poorly understood. In this Review, we summarize recent advances in our understanding of the production and the regulation of IgE in vivo, as revealed by studies in mice, and we discuss how these findings compare to what is known about human IgE biology.

http://www.nature.com/nri/journal/v14/n4/abs/nri3632.html


http://www.immunology-allergy.org/JournalPapers/Images/IgEproductionAndRegulation_NRI_2014.jpg

http://www.immunology-allergy.org/JournalPapers/IgEproductionAndRegulation_NRI_2014.pdf

Счетчик на момент публикации: 247

Leukocyte migration in the interstitial space of non-lymphoid organs
Миграция лейкоцитов в интестициальном пространстве нелимфоидных органов. Щикаааарный обзор, посвящен новейшим данным, полученным с использованием современных методов визуализации, включая прижизненную конфокальную и мультифотонную микроскопию


Leukocyte migration through interstitial tissues is essential for mounting a successful immune response. Interstitial motility is governed by a vast array of cell-intrinsic and cell-extrinsic factors that together ensure the proper positioning of immune cells in the context of specific microenvironments. Recent advances in imaging modalities, in particular intravital confocal and multi-photon microscopy, have helped to expand our understanding of the cellular and molecular mechanisms that underlie leukocyte navigation in the extravascular space. In this Review, we discuss the key factors that regulate leukocyte motility within three-dimensional environments, with a focus on neutrophils and T cells in non-lymphoid organs.

http://www.nature.com/nri/journal/v14/n4/abs/nri3641.html


http://www.immunology-allergy.org/JournalPapers/Images/LeukocyteMigration_NRI_2014.jpg

http://www.immunology-allergy.org/JournalPapers/LeukocyteMigration_NRI_2014.pdf

Next-gen immunohistochemistry
Новейший метод исследования - комбинация иммуногистохимии с масс-спектрометрией - описывается в последнем выпуске Nature Methods.


The combination of mass spectroscopy with immunohistochemistry allows highly multiplexed, directly quantitative imaging of tissue samples for both basic and clinical research.

http://www.nature.com/nmeth/journal/v11/n4/full/nmeth.2896.html


http://www.immunology-allergy.org/JournalPapers/Images/MassSpecIHC_NatMethods_2014.jpg

http://www.immunology-allergy.org/JournalPapers/MassSpecIHC_NatMethods_2014.pdf

Автор: Immunology 18.4.2014, 13:06

Life at the beginning: perturbation of the microbiota by antibiotics in early life and its role in health and disease
Как антибиотики в раннем детстве влияют на здоровье в дальнейшей жизни? Обзор в мартовском Nature Immunology


This Commentary discusses how treatment with antibiotics in infancy shapes host immunity and influences susceptibility later in life to diseases mediated by the immune system.

http://www.nature.com/ni/journal/v15/n4/full/ni.2847.html


http://www.nature.com/ni/journal/v15/n4/images/ni.2847-F1.jpg

http://www.aaronbushell.com/wp-content/uploads/2013/02/disappointment.jpg
Полный текст статьи, увы, недоступен, потому что сервер, на который молятся все ученые России - sci-hub.org - временно перестал функционировать. Поддержка сервера требует средств - гораздо меньше, чем требуется на подписку на все необходимые журналы. На сайте sci-hub.org есть вся необходимая информация о том, как финансово поддержать проект. Я сегодня перечислил им 60 рублей - всё, что оставалось на банковской карте.

Автор: Immunology 26.4.2014, 11:44

Degenerate target sites mediate rapid primed CRISPR adaptation
Проливая новый свет на ключевую бактериальную иммунную систему


Исследователи из Университета Новой Зеландии в Отаго и Нидерландах по-новому взглянули на удивительно гибкую иммунную систему, присутствующую в бактериях для борьбы с вирусами и другими чужеродными захватчиками ДНК. Команда во главе с д-ром Питером Финерана из Департамента микробиологии и иммунологии изучает генетическую основу адаптивного иммунитета у бактерий, которые вызывают гниение картофеля и у бактерий E.coli. Недавно они обнаружили, что эти бактериальные иммунные системы гораздо более устойчивы и отзывчивы, чем считалось ранее. Их последние заключения имеют последствия для улучшения нашего понимания бактериальной эволюции, в том числе распространения генов, устойчивых к антибиотикам.

Ученые изучают адаптивную иммунную систему под названием CRISPR- CAS, которая характерна для половины всех видов бактерий и почти всем одноклеточным микробам в домене архей. Роль CRISPR-CAS в предоставлении иммунитета была обнаружена только в последнее десятилетие. Система создает генетическую память инфекций вирусами и плазмидами, это небольшие молекулы мобильных ДНК, которые могут перемещаться между организмами.

Доктор Финеран говорит, что система крадет образцы генетического материала захватчика и хранит их в банке памяти, чтобы он мог сразу признать будущие воздействия и нейтрализовать атаку. Он может хранить до 600 образцов, а также может передать эти воспоминания последующим поколениям бактерий.

«То, что мы уже обнаружили, что в то время как вирусы и плазмиды могут уклониться от прямого признания путем приобретения множественных мутаций, система начинаеи быстро создавать новый иммунитет, захватывая новый образец мутированного генетического материала. Это удивительно гибкая и надежная иммунная система для таких простых одноклеточных организмов». Доктор Финарен говорит, что система отражает древнюю и продолжающуюся гонку коэволюционных вооружений между бактериями, с одной стороны, и вирусов и плазмид, с другой.


http://www.pnas.org/content/early/2014/04/04/1400071111.abstract?sid=5488ae00-17bd-43f7-85ed-952183581777

Автор: Immunology 2.5.2014, 13:02

ANTIGEN PROCESSING AND PRESENTATION
Пока созревают серьезные публикации, не грех и посочинять образовательные статейки smile.gif Текст и рисунки - мои.


In order to be capable of engaging the key elements of adaptive immunity (specificity, memory, diversity, self/nonself discrimination), antigens have to be processed and presented to immune cells. Antigen presentation is mediated by MHC class I molecules, and the class II molecules found on the surface of antigen-presenting cells (APCs) and certain other cells.

http://bitesized.immunology.org/systems-processes/antigen-processing-and-presentation


http://bitesized.immunology.org/wp-content/uploads/2014/03/Antigen-processing-and-presentation-MHCI-Figure-1.jpg

http://bitesized.immunology.org/?wpdmact=process&did=MTgyLmhvdGxpbms=

Автор: Immunology 23.5.2014, 17:51

Acute Infectious Diarrhea in Immunocompetent Adults
Про поносик smile.gif


In the United States, approximately 179 million cases of acute diarrhea occur each year, amounting to 0.6 bouts per person per year. In one study, the estimated prevalence of diarrhea among adults the month before questioning was 3 to 7%, with the rate dependent on age, and 8% among children 5 years of age or younger.1 A similar rate of acute diarrhea among adults was reported recently in Germany.2 In the United States, 83% of deaths from acute diarrhea occur in adults 65 years of age or older. Hospital-associated Clostridium difficile–associated diarrhea is the most prevalent cause of fatal illness, followed by norovirus infection3; both are common in residents of nursing homes. 4
Diarrhea is generally defined as the passage of three or more unformed stools per day, often in addition to other enteric symptoms, or the passage of more than 250 g of unformed stool per day. On the basis of its duration, diarrhea can be classified as acute (<14 days), persistent (14 to 29 days), or chronic (≥30 days). Gastroenteritis, which is often due to viral infection involving the stomach and small intestine, is associated with vomiting and diarrhea.
This review addresses the clinical approach to the diagnosis and management of acute diarrhea in immunocompetent adults, summarizes contemporary clinical controversies, and discusses research needed in the field.


http://www.nejm.org/doi/full/10.1056/NEJMra1301069?query=TOC

Автор: Immunology 2.6.2014, 11:42

Metabolomic strategies for the identification of new enzyme functions and metabolic pathways
Знаете ли вы, что из более 70 ферментов E. coli, участвующих в гликолизе и цикле трикарбоновых кислот, лишь 4 являются необходимыми? "Лишние" ферменты создают альтернативные, компенсаторные пути метаблизма, а это - один из механизмов устойчивости к антибиотикам. О том, как изучают новые ферменты и открывают новые функции "старых" ферментов - в наисвежайшем обзоре EMBO Reports

Recent technological advances in accurate mass spectrometry and data analysis have revolutionized metabolomics experimentation. Activity‐based and global metabolomic profiling methods allow simultaneous and rapid screening of hundreds of metabolites from a variety of chemical classes, making them useful tools for the discovery of novel enzymatic activities and metabolic pathways. By using the metabolome of the relevant organism or close species, these methods capitalize on biological relevance, avoiding the assignment of artificial and non‐physiological functions. This review discusses state‐of‐the‐art metabolomic approaches and highlights recent examples of their use for enzyme annotation, discovery of new metabolic pathways, and gene assignment of orphan metabolic activities across diverse biological sources.

http://embor.embopress.org/content/15/6/657?etoc


http://embor.embopress.org/content/embor/15/6/657/F4.large.jpg

http://embor.embopress.org/content/15/6/657.full.pdf

Автор: Immunology 5.6.2014, 22:46

Вот, показывал же фильм про это на лекциях. Фаговая терапия и её большое будущее:

http://www.scientificamerican.com/article/antibiotic-resistance-revitalizes-century-old-virus-therapy/

For decades, patients behind the Iron Curtain were denied access to some of the best antibiotics developed in the West. To make do, the Soviet Union invested heavily in the use of bacteriophages — viruses that kill bacteria — to treat infections. Phage therapy is still widely used in Russia, Georgia and Poland, but never took off elsewhere. “This is a virus, and people are afraid of viruses,” says Mzia Kutateladze, who is the head of the scientific council at the Eliava Institute in Tbilisi, which has been studying phages and using them to treat patients for nearly a century.

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