Host Cell & Pathogen Interactions
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A translocator-specific export signal establishes the translocator–effector secretion hierarchy that is important for type III secretion system function

A translocator-specific export signal establishes the translocator–effector secretion hierarchy that is important for type III secretion system function | Host Cell & Pathogen Interactions | Scoop.it

Type III secretion systems are used by many Gram-negative pathogens to directly deliver effector proteins into the cytoplasm of host cells. To accomplish this, bacteria secrete translocator proteins that form a pore in the host-cell membrane through which the effector proteins are then introduced into the host cell. Evidence from multiple systems indicates that the pore-forming translocator proteins are exported before effectors, but how this secretion hierarchy is established is unclear. Here we used the Pseudomonas aeruginosa translocator protein PopD as a model to identify its export signals. The N-terminal secretion signal and chaperone, PcrH, are required for export under all conditions. Two novel signals in PopD, one proximal to the chaperone binding site and one at the very C-terminus of the protein, are required for export of PopD before effector proteins. These novel export signals establish the translocator–effector secretion hierarchy, which in turn, is critical for the delivery of effectors into host cells.

 

Amanda G. Tomalka, Charles M. Stopford, Pei-Chung Lee, Arne Rietsch


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Host Cell & Pathogen Interactions
Strategies of Microbial Virulence and Host Defense
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Maternal HIV status may disrupt normal microbiome development in uninfected infants

Maternal HIV status may disrupt normal microbiome development in uninfected infants | Host Cell & Pathogen Interactions | Scoop.it
A study led by researchers at The Saban Research Institute of Children's Hospital Los Angeles (CHLA) suggests that maternal HIV infection influences the microbiome of their HIV-uninfected infants. Their findings, reporte
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Complement in disease: a defence system turning offensive : Nature Reviews Nephrology : Nature Publishing Group

Complement in disease: a defence system turning offensive : Nature Reviews Nephrology : Nature Publishing Group | Host Cell & Pathogen Interactions | Scoop.it
The complement system, crosstalk connections, the involvement of complement in clinical conditions and promising therapeutic approaches. Review by Ricklin, Reis and Lambris, free to access for a limited time.

Via Gilbert C FAURE
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Gilbert C FAURE's curator insight, July 9, 1:56 PM
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Structure of Ebola virus’s glycoprotein reveals an Achilles heel 

Structure of Ebola virus’s glycoprotein reveals an Achilles heel  | Host Cell & Pathogen Interactions | Scoop.it

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Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics: Cell Reports

Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics: Cell Reports | Host Cell & Pathogen Interactions | Scoop.it
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Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics

Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics | Host Cell & Pathogen Interactions | Scoop.it
The homeobox NKX2 family of transcriptional factors has been shown to regulate fundamental developmental processes.
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Virus Hacks Host Genome, Steals CRISPR to Protect Itself

Virus Hacks Host Genome, Steals CRISPR to Protect Itself | Host Cell & Pathogen Interactions | Scoop.it
Viruses have often been described as the ultimate parasite, shedding all of their nonessential parts and leaving behind an extremely efficient genetic transfer apparatus. Phage viruses have evolved to infect various bacteria proficiently and hijack their replication machinery to make more viruses. Yet, this often doesn’t preclude a different virus from concomitantly infecting the same bacterium and competing with or overtaking the original phage invader.


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Ed Rybicki's curator insight, June 17, 6:24 AM
HATE the word "hack" in the context of infection: so lazy!
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How Gaming Is Helping Organizations Accelerate Recruitment

How Gaming Is Helping Organizations Accelerate Recruitment | Host Cell & Pathogen Interactions | Scoop.it
Using games to recruit is not a new concept.
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3D Structure Of Gene Transcription Activation Identified

3D Structure Of Gene Transcription Activation Identified | Host Cell & Pathogen Interactions | Scoop.it
The three-dimensional structure of a gene-specific transcription activation complex has been discovered by scientists at Rutgers University. This is the first structural and mechanistic description of the process cells use to turn on, or activate, specific genes in response to changes in cell type, developmental state and environment. Transcription is the first in a series of steps cells take to read out genetic information in DNA. Richard H. Ebright and other Rutgers scientists have shown how a transcription activator protein interacts with the enzyme (RNA polymerase) that cells use to perform transcription. They also show how the transcription activator protein
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The Telomeric Repeats of Human Herpesvirus 6A (HHV-6A) Are Required for Efficient Virus Integration

The Telomeric Repeats of Human Herpesvirus 6A (HHV-6A) Are Required for Efficient Virus Integration | Host Cell & Pathogen Interactions | Scoop.it
Author Summary Herpesviruses are ubiquitous pathogens that persist in the host for life. Two human herpesviruses (HHV-6A and HHV-6B) can integrate their genetic material into the telomeres of host chromosomes.
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Tiny Wire Can Detect A Single Virus In Your Urine

Tiny Wire Can Detect A Single Virus In Your Urine | Host Cell & Pathogen Interactions | Scoop.it
Testing technique could make a versatile new diagnostic tool

Via Ed Rybicki
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New approach to severe bacterial infections and sepsis

New approach to severe bacterial infections and sepsis | Host Cell & Pathogen Interactions | Scoop.it
Protein fragment could provide a defense when antibiotics fail | Researchers at Harvard-affiliated Boston Children’s Hospital are looking at new potential avenues for controlling both sepsis and the runaway bacterial infections that provoke it.
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Gene Regulation, Illustrated

Gene Regulation, Illustrated | Host Cell & Pathogen Interactions | Scoop.it
What are epigenetic modifications, and how might they play out across generations?

Via Dr. Stefan Gruenwald
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Cheap blood test can discriminate between bacterial, viral infections, study finds

Cheap blood test can discriminate between bacterial, viral infections, study finds | Host Cell & Pathogen Interactions | Scoop.it
Researchers at the Stanford University School of Medicine have made an important breakthrough in their ongoing efforts to develop a diagnostic test that can tell health-care providers whether a patient has a bacterial infectio
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Reverse Transcriptase with Proofreading Capabilities Created | The Scientist Magazine®

Reverse Transcriptase with Proofreading Capabilities Created | The Scientist Magazine® | Host Cell & Pathogen Interactions | Scoop.it
Using directed evolution, researchers selected a DNA polymerase to copy RNA into DNA.
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Scientists want to replace lab workhorse E. coli with the world’s fastest-growing bacterium

Scientists want to replace lab workhorse E. coli with the world’s fastest-growing bacterium | Host Cell & Pathogen Interactions | Scoop.it
<i>Vibrio natriegens</i> could save researchers valuable time

Via Gerd Moe-Behrens
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Sandia researchers discover mechanism for Rift Valley fever virus infection - Scienmag

Sandia researchers discover mechanism for Rift Valley fever virus infection - Scienmag | Host Cell & Pathogen Interactions | Scoop.it
LIVERMORE, Calif. -- Viruses can't live without us -- literally. As obligate parasites, viruses need a host cell to survive and grow. Scientists are exploiting this characteristic by developing t..
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Scientists unpack how Toxoplasma infection is linked to neurodegenerative disease - Scienmag

Scientists unpack how Toxoplasma infection is linked to neurodegenerative disease - Scienmag | Host Cell & Pathogen Interactions | Scoop.it
RIVERSIDE, Calif. - Toxoplasma gondii, a protozoan parasite about five microns long, infects a third of the world's population. Ingested via undercooked meat or unwashed vegetables, the parasite ..
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Researchers have managed to unlock a new CRISPR system that targets RNA, rather than DNA.

Researchers have managed to unlock a new CRISPR system that targets RNA, rather than DNA. | Host Cell & Pathogen Interactions | Scoop.it
Researchers from the Broad Institute of MIT and Harvard, Massachusetts Institute of Technology, the National Institutes of Health, Rutgers University- New Brunswick and the Skolkovo Institute of Science and Technology have characterized a new CRISPR system that targets RNA, rather than DNA.

The new approach has the potential to open a powerful avenue in cellular manipulation. Whereas DNA editing makes permanent changes to the genome of a cell, the CRISPR-based RNA-targeting approach may allow researchers to make temporary changes that can be adjusted up or down, and with greater specificity and functionality than existing methods for RNA interference.

In a study published today in Science, Feng Zhang and colleagues at the Broad Institute and the McGovern Institute for Brain Research at MIT, along with co-authors Eugene Koonin and his colleagues at the NIH, and Konstantin Severinov of Rutgers University-New Brunswick and Skoltech, report the identification and functional characterization of C2c2, an RNA-guided enzyme capable of targeting and degrading RNA.

The findings reveal that C2c2—the first naturally-occurring CRISPR system that targets only RNA to have been identified, discovered by this collaborative group in October 2015—helps protect bacteria against viral infection. They demonstrate that C2c2 can be programmed to cleave particular RNA sequences in bacterial cells, which would make it an important addition to the molecular biology toolbox.

The RNA-focused action of C2c2 complements the CRISPR-Cas9 system, which targets DNA, the genomic blueprint for cellular identity and function. The ability to target only RNA, which helps carry out the genomic instructions, offers the ability to specifically manipulate RNA in a high-throughput manner—and manipulate gene function more broadly. This has the potential to accelerate progress to understand, treat and prevent disease.

"C2c2 opens the door to an entirely new frontier of powerful CRISPR tools," said Feng Zhang, senior author, and Core Institute Member of the Broad Institute. "There are an immense number of possibilities for C2c2 and we are excited to develop it into a platform for life science research and medicine."

"The study of C2c2 uncovers a fundamentally novel biological mechanism that bacteria seem to use in their defense against viruses," said Eugene Koonin, senior author, and leader of the Evolutionary Genomics Group at the NIH. "Applications of this strategy could be quite striking."

Currently, the most common technique for performing gene knockdown is small interfering RNA (siRNA). According to the researchers, C2c2 RNA-editing methods suggest greater specificity and hold the potential for a wider range of applications, such as:

* Adding modules to specific RNA sequences to alter their function—how they are translated into proteins—which would make them valuable tools for large-scale screens and constructing synthetic regulatory networks, and
* Harnessing C2c2 to fluorescently tag RNAs as a means to study their trafficking and subcellular localization.

In this work, the team was able to precisely target and remove specific RNA sequences using C2c2 - lowering the expression level of the corresponding protein. This suggests C2c2 could represent an alternate approach to siRNA, complementing the specificity and simplicity of CRISPR-based DNA editing and offering researchers adjustable gene "knockdown" capability using RNA.

C2c2 has advantages that make it suitable for tool development:

* C2c2 is a two-component system, requiring only a single guide RNA to function, and
* C2c2 is genetically encodable—meaning the necessary components can be synthesized as DNA for delivery into tissue and cells.

"C2c2's greatest impact may be made on our understanding the role of RNA in disease and cellular function," said co-first author Omar Abudayyeh, a graduate student in the Zhang Lab.

*Source: Broad Institute of MIT and Harvard*
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Bacterial Outer Membrane Vesicles Mediate Cytosolic Localization of LPS and Caspase-11 Activation: Cell

Bacterial Outer Membrane Vesicles Mediate Cytosolic Localization of LPS and Caspase-11 Activation: Cell | Host Cell & Pathogen Interactions | Scoop.it
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Stem cell gene Oct4 helps to prevent heart attack, stroke, and counteracts aging

Stem cell gene Oct4 helps to prevent heart attack, stroke, and counteracts aging | Host Cell & Pathogen Interactions | Scoop.it

University of Virginia School of Medicine have discovered that a gene called Oct4 — which scientific dogma insists is inactive in adults — actually plays a vital role in preventing ruptured atherosclerotic plaques inside blood vessels, the underlying cause of most heart attacks and strokes.

 

The researchers found that Oct4 controls the conversion of smooth muscle cells into protective fibrous “caps” inside plaques, making the plaques less likely to rupture. They also discovered that the gene promotes many changes in gene expression that are beneficial in stabilizing the plaques. In addition, the researchers believe it may be possible to develop drugs or other therapeutic agents that target the Oct4 pathway as a way to reduce the incidence of heart attacks or stroke.

 

The researchers are also currently testing Oct4′s possible role in repairing cellular damage and healing wounds, which would make it useful for regenerative medicine.

 

Oct4 is one of the “stem cell pluripotency factors” described by Shinya Yamanaka, PhD, of Kyoto University, for which he received the 2012 Nobel Prize. His lab and many others have shown that artificial over-expression of Oct4 within somatic cells grown in a lab dish is essential for reprogramming these cells into induced pluripotential stem cells, which can then develop into any cell type in the body or even an entire organism.

 

“Finding a way to reactivate this pathway may have profound implications for health and aging,” said researcher Gary K. Owens, director of UVA’s Robert M. Berne Cardiovascular Research Center. “This could impact many human diseases and the field of regenerative medicine. [It may also] end up being the ‘fountain-of-youth gene,’ a way to revitalize old and worn-out cells.”


Via Dr. Stefan Gruenwald
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