PAAR-repeat proteins sharpen and diversify the Type VI secretion system spike

The bacterial type VI secretion system (T6SS) is a large multi-component, dynamic macromolecular machine that plays an important role in the ecology of many Gram negative bacteria. T6SS is responsible for translocation of a wide range of toxic effector molecules allowing predatory cells to kill both prokaryotic as well as eukaryotic prey cells1-5. The T6SS organelle is functionally analogous to contractile tails of bacteriophages and is thought to attack cells by initially penetrating them with a trimeric protein complex called the VgrG spike6,7. Neither the exact protein composition of the T6SS organelle nor the mechanisms of effector selection and delivery are known. Here we report that proteins from the PAAR (Proline-Alanine-Alanine-aRginine) repeat superfamily form a sharp conical extension on the VgrG spike, which is further involved in attaching effector domains to the spike. The crystal structures of two PAAR-repeat proteins bound to VgrG-like partners show that these proteins function to sharpen the tip of the VgrG spike. We demonstrate that PAAR proteins are essential for T6SS- mediated secretion and target cell killing by Vibrio cholerae and Acinetobacter baylyi. Our results suggest a new model of the T6SS organelle in which the VgrG-PAAR spike complex is decorated with multiple effectors that are delivered simultaneously into target cells in a single contraction-driven translocation event

Spherical magnetic nanoparticles fabricated by laser target evaporation

Magnetic nanoparticles of iron oxide (MNPs) were prepared by the laser target evaporation technique (LTE). The main focus was on the fabrication of de-aggregated spherical maghemite MNPs with a narrow size distribution and enhanced effective magnetization. X-ray diffraction, transmission electron microscopy, magnetization and microwave absorption measurements were comparatively analyzed. The shape of the MNPs (mean diameter of 9 nm) was very close to being spherical. The lattice constant of the crystalline phase was substantially smaller than that of stoichiometric magnetite but larger than the lattice constant of maghemite. High value of Ms up to 300 K was established. The 300 K ferromagnetic resonance signal is a single line located at a field expected from spherical magnetic particles with negligible magnetic anisotropy. The maximum obtained concentration of water based ferrofluid was as high as 10g/l of magnetic material. In order to understand the temperature and field dependence of MNPs magnetization, we invoke the core-shell model. The nanoparticles is said to have a ferrimagnetic core (roughly 70 percent of the caliper size) while the shell consists of surface layers in which the spins are frozen having no long range magnetic order. The core-shell interactions were estimated in frame of random anisotropy model. The obtained assembly of de-aggregated nanoparticles is an example of magnetic nanofluid stable under ambient conditions even without an electrostatic stabilizer

Dialogical self strategies of self-organization: psychotherapy and restructuring of internal management

A identidade tem sido um conceito central na literatura em psicologia e na forma como as diferentes abordagens terapêuticas têm concebido os processos de mudança. Entre as inúmeras perspectivas desenvolvidas sobre essa dimensão do ser humano, destacamos o paradigma dialógico que tem vindo a influenciar de forma crescente a teoria e prática em psicoterapia. Segundo esta perspectiva, a funcionalidade psicológica está relacionada com o modo como os indivíduos conseguem articular e colocar em diálogo produtivo as suas várias vozes ou posições de identidade. Neste artigo apresentamos uma revisão da literatura sobre as estratégias que subjazem a essa capacidade auto-organizadora do sistema identitário e sobre as diretrizes que poderão orientar uma intervenção terapêutica dialógica quando essa capacidade se torna disfuncional.Self-concept has been playing a crucial role in psychological literature and in the way the different therapeutic approaches conceive the processes of change. From the diverse perspectives developed about this human dimension, we emphasise the dialogical paradigm that has been increasingly influential in the psychotherapeutic theory and practice. According to the dialogical perspective the psychological well-being is dependent on the way individuals articulate and maintain productive dialogues between the different voices of the self or “I-Positions”. In this paper we present a review of the literature on the strategies that underlie this self-regulatory ability of the self-system and the guidelines of the dialogical therapeutic intervention that could be used when these self-regulatory strategies become dysfunctional.(undefined

Inverting family GH156 sialidases define an unusual catalytic motif for glycosidase action

Sialic acids are a family of related sugars that play essential roles in many biological events intimately linked to cellular recognition in both health and disease. Sialidases are therefore orchestrators of cellular biology and important therapeutic targets for viral infection. Here, we sought to define if uncharacterized sialidases would provide distinct paradigms in sialic acid biochemistry. We show that a recently discovered sialidase family, whose first member EnvSia156 was isolated from hot spring metagenomes, defines an unusual structural fold and active centre constellation, not previously described in sialidases. Consistent with an inverting mechanism, EnvSia156 reveals a His/Asp active center in which the His acts as a Bronsted acid and Asp as a Bronsted base in a single-displacement mechanism. A pre-dominantly hydrophobic aglycone site facilitates accommodation of a variety of 2-linked sialosides; a versatility that offers the potential for glycan hydrolysis across a range of biological and technological platforms

A Promiscuous DNA Packaging Machine from Bacteriophage T4

Packaged viral genome can be removed from bacteriophage T4 capsid and the capsid refilled with any double-stranded DNA, single or multiple molecules, using a powerful ATP-fueled DNA packaging machine

Нейровизуализационные методики оценки головного мозга при сахарном диабете (литературный обзор)

Diabetes mellitus (DM) is associated with changes in the structure of the brain and deterioration of cognitive functions from mild to moderate according to neuropsychological testing. With the growing DM epidemic and the increasing number of people living to old age, cognitive dysfunctions associated with DM can have serious consequences for the future of public and practical health. Chronic hyperglycemia, severe episodes of hypoglycemia, and microvascular complications are important risk factors common for type 1 and type 2 diabetes. DM is also associated with structural and functional changes in the brain, which can be diagnosed by various types of magnetic resonance imaging (MRI) of the brain. In this review, we investigate studies conducted over the past two decades to improve the understanding of how DM effects the brain function and structure. We also describe the changes characteristic of type 1 and type 2 diabetes during standard MRI, functional MRI and proton magnetic-resonance spectroscopy (proton MRS) as well as their features.Сахарный диабет (СД) связан с изменениями в структуре головного мозга и ухудшением когнитивных функций от легкой до умеренной степени по данным нейропсихологического тестирования. В условиях растущей эпидемии СД и увеличения числа людей, доживающих до старости, когнитивная дисфункция, ассоциированная с СД, может иметь серьезные последствия для будущего общественного и практического здравоохранения. Хроническая гипергликемия, тяжелые эпизоды гипогликемии и микрососудистые осложнения являются важными факторами риска, общими для СД 1-го и 2-го типа. Также СД связан со структурными и функциональными изменениями в головном мозге, которые возможно диагностировать посредством различных вариантов магнитно-резонансной томографии (МРТ) головного мозга. В представленном обзоре рассмотрены исследования, проведенные за последние два десятилетия, чтобы улучшить понимание того, как СД влияет на функцию и структуру головного мозга. Также описаны изменения, характерные для СД 1-го и 2-го типа при проведении стандартной,  функциональной МРТ и протонной магнитно-резонансной спектроскопии, и их особенности

Viral capsids: Mechanical characteristics, genome packaging and delivery mechanisms

The main functions of viral capsids are to protect, transport and deliver their genome. The mechanical properties of capsids are supposed to be adapted to these tasks. Bacteriophage capsids also need to withstand the high pressures the DNA is exerting onto it as a result of the DNA packaging and its consequent confinement within the capsid. It is proposed that this pressure helps driving the genome into the host, but other mechanisms also seem to play an important role in ejection. DNA packaging and ejection strategies are obviously dependent on the mechanical properties of the capsid. This review focuses on the mechanical properties of viral capsids in general and the elucidation of the biophysical aspects of genome packaging mechanisms and genome delivery processes of double-stranded DNA bacteriophages in particular

Genetic Analysis of Anti-Amoebae and Anti-Bacterial Activities of the Type VI Secretion System in Vibrio cholerae

A type VI secretion system (T6SS) was recently shown to be required for full virulence of Vibrio cholerae O37 serogroup strain V52. In this study, we systematically mutagenized each individual gene in T6SS locus and characterized their functions based on expression and secretion of the hemolysin co-regulated protein (Hcp), virulence towards amoebae of Dictyostelium discoideum and killing of Escherichia coli bacterial cells. We group the 17 proteins characterized in the T6SS locus into four categories: twelve (VipA, VipB, VCA0109–VCA0115, ClpV, VCA0119, and VasK) are essential for Hcp secretion and bacterial virulence, and thus likely function as structural components of the apparatus; two (VasH and VCA0122) are regulators that are required for T6SS gene expression and virulence; another two, VCA0121 and valine-glycine repeat protein G 3 (VgrG-3), are not essential for Hcp expression, secretion or bacterial virulence, and their functions are unknown; the last group is represented by VCA0118, which is not required for Hcp expression or secretion but still plays a role in both amoebae and bacterial killing and may therefore be an effector protein. We also showed that the clpV gene product is required for Dictyostelium virulence but is less important for killing E. coli. In addition, one vgrG gene (vgrG-2) outside of the T6SS gene cluster was required for bacterial killing but another (vgrG-1) was not. However, a bacterial killing defect was observed when vgrG-1 and vgrG-3 were both deleted. Several genes encoded in the same putative operon as vgrG-1 and vgrG-2 also contribute to virulence toward Dictyostelium but have a smaller effect on bacterial killing. Our results provide new insights into the functional requirements of V. cholerae's T6SS in the context of secretion as well as killing of bacterial and eukaryotic phagocytic cells

Collaborating to Compete: Blood Profiling Atlas in Cancer (BloodPAC) Consortium

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136731/1/cpt666.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136731/2/cpt666_am.pd