The Government has published a guidance note designed to help owners and occupiers understand how new rules requiring display energy certificates (DECs) in large public buildings will work in practice. The guidance also explains the responsibilities...

As the shipping community is truly internationally based, issues can often arise when a formal claim is issued in the English High Court that then has to be served outside the UK jurisdiction.  For example, if a dispute arises between a ship ow...

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As the government pronounced illegal on the practice of companies relying on subcontract workers for a long time such as the cases in Paris Baguette and Mando-Hella, the whole industry in shock. This is not just restricted to manufacturers but is spread to services and the food franchise industry as well. The corporate sector expected on September 24 that companies like Tous Les Jours, Samsung Electronics service centers, and LG U+ will likely face the same problem any time soon after the Min...

More than 220,000 Somalis have been internally displaced due to armed conflict and natural disasters while facing deadly coronavirus since the start of 2020, the UN Refugee Agency said Friday. “UNHCR, the UN Refugee Agency, fears these multiple, compounding emergencies will lead to devastating consequences unless there is a strong and coordinated response from the […]

The post Conflict, flood left thousands displaced in Somalia: UN appeared first on Horseed Media • Somali News.

As governments around the world battle to contain Coronavirus, the scale of economic disruption and impact on businesses cannot be underestimated. It is easy to see why some have predicted a rise in disputes work arising out of the unfolding global ...

La r�ponse de l'�tat du S�n�gal �...

Alger -Le nombre de fonctionnaires...

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CARICOM-CUBA SUMMIT Toward the indispensable political, economic and social integration of Latin America and the Caribbean Key remarks by President Raúl Castro opening the Fifth CARICOM-Cuba Summit in Havana, December 8, 2014

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Governments in the region need to invest more in prevention and response to the long-term impacts of disaster displacement.

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ATMISP7

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Title: Breast Cancer Risks Not Same for Hispanic Women
Category: Health News
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Title: CRISPR Used Inside Person's Body For First Time
Category: Health News
Created: 3/4/2020 12:00:00 AM
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KoreaMed Synapse, a digital archive and reference linking platform of Korean medical journals, is now using NCBI’s new PubReader presentation style to display their full-text journal articles. KoreaMed’s database of 122 journals now includes a blue ‘PubReader’ icon for each full-text article. NCBI launched PubReader in December 2012 as a convenient new way to view full-text articles in PubMed Central on desktops as well as tablets and mobile devices. In tandem with the launch, NCBI made the code used to create PubReader freely available on GitHub.

As of August 2016, PMC is home to four million articles! To make this wealth of full-text content easier to navigate, PMC has rolled out a few updates:

1) Search Result Filters
On all search results pages, you will now see filters (similar to PubMed’s filters) on the left-hand side that allow you to filter your results by article attributes, publication date, research funder, and search fields. These filters replace the Limits page and allow you to more readily:

• find open access articles (PMC has more than 1.35 million open access articles that can be reused according to their license statements),
• explore PMC’s rich historical content from NLM's back issue digitization project,
• browse research supported by PMC-participating funding organizations (click "Customize" to view additional funder options),
• and much more.

You can now also quickly add articles that are under a 12-month or less embargo in PMC to your search results by selecting the “Include embargoed articles” filter option under Text Availability. See the PMC User Guide for more information on these filters.

2) Reference List Display
Using related article data available in PMC, articles that cite papers that have been either retracted or named in a Findings of Research Misconduct issued by the HHS Office of Research Integrity and not yet retracted will now include a red hyperlink to the relevant notice directly from the article’s reference list. This update will help users more easily identify post-publication updates to existing research.

In collaboration with Europe PMC, PMC has rolled out several updates to our article display in order to enhance the transparency and readability of the content.

Navigating from the PMC record to the PubMed record has been made easier by the addition of hyperlinked PubMed IDs (PMIDs) in the upper right-hand corner of article records. Clicking the PMID link will take you to the corresponding citation record in PubMed.

The PMC Disclaimer link has also been moved out of the Copyright and License information section for easier discovery and access. This page describes what content is included in PMC as well as other important NCBI and NLM disclaimer information.

Additionally, two changes have been implemented to improve the functionality of author names. Users can now click on an author name to view the author’s affiliation(s). Users also have the option of running a quick author name search in PMC by clicking the linked author name in “Find articles by [author name]”. In the example pictured above, the search would be for “Sawyer SL”[Author].

And finally, figures and tables have been moved inline in the article display. By moving away from the thumbnail display, PMC hopes to make it easier for users to view figure and table data as they read articles. Users may still click on the figure/table title or “Open in separate window” (as available) link for a closer look.

We hope these updates improve the overall user experience in PMC and look forward to hearing your feedback.

References

Screenshots from:

Qiao, Y., Yang, J., Liu, L., Zeng, Y., Ma, J., Jia, J., … Wang, Y. (2018). Successful treatment with pazopanib plus PD-1 inhibitor and RAK cells for advanced primary hepatic angiosarcoma: a case report. BMC Cancer, 18, 212. http://doi.org/10.1186/s12885-018-3996-3

Stabell, A. C., Meyerson, N. R., Gullberg, R. C., Gilchrist, A. R., Webb, K. J., Old, W. M., … Sawyer, S. L. (2018). Dengue viruses cleave STING in humans but not in nonhuman primates, their presumed natural reservoir. eLife, 7, e31919. http://doi.org/10.7554/eLife.31919

Both articles made available under a CC-BY license.

ABSTRACT

Clostridioides difficile is an important nosocomial pathogen that causes approximately 500,000 cases of C. difficile infection (CDI) and 29,000 deaths annually in the United States. Antibiotic use is a major risk factor for CDI because broad-spectrum antimicrobials disrupt the indigenous gut microbiota, decreasing colonization resistance against C. difficile. Vancomycin is the standard of care for the treatment of CDI, likely contributing to the high recurrence rates due to the continued disruption of the gut microbiota. Thus, there is an urgent need for the development of novel therapeutics that can prevent and treat CDI and precisely target the pathogen without disrupting the gut microbiota. Here, we show that the endogenous type I-B CRISPR-Cas system in C. difficile can be repurposed as an antimicrobial agent by the expression of a self-targeting CRISPR that redirects endogenous CRISPR-Cas3 activity against the bacterial chromosome. We demonstrate that a recombinant bacteriophage expressing bacterial genome-targeting CRISPR RNAs is significantly more effective than its wild-type parent bacteriophage at killing C. difficile both in vitro and in a mouse model of CDI. We also report that conversion of the phage from temperate to obligately lytic is feasible and contributes to the therapeutic suitability of intrinsic C. difficile phages, despite the specific challenges encountered in the disease phenotypes of phage-treated animals. Our findings suggest that phage-delivered programmable CRISPR therapeutics have the potential to leverage the specificity and apparent safety of phage therapies and improve their potency and reliability for eradicating specific bacterial species within complex communities, offering a novel mechanism to treat pathogenic and/or multidrug-resistant organisms.

IMPORTANCE Clostridioides difficile is a bacterial pathogen responsible for significant morbidity and mortality across the globe. Current therapies based on broad-spectrum antibiotics have some clinical success, but approximately 30% of patients have relapses, presumably due to the continued perturbation to the gut microbiota. Here, we show that phages can be engineered with type I CRISPR-Cas systems and modified to reduce lysogeny and to enable the specific and efficient targeting and killing of C. difficile in vitro and in vivo. Additional genetic engineering to disrupt phage modulation of toxin expression by lysogeny or other mechanisms would be required to advance a CRISPR-enhanced phage antimicrobial for C. difficile toward clinical application. These findings provide evidence into how phage can be combined with CRISPR-based targeting to develop novel therapies and modulate microbiomes associated with health and disease.

ABSTRACT

While there is no effective vaccine against Chlamydia trachomatis infection, previous work has demonstrated the importance of C. trachomatis-specific CD4⁺ T cells (NR1 T cells) in pathogen clearance. Specifically, NR1 T cells have been shown to be protective in mice, and this protection depends on the host’s ability to sense the cytokine gamma interferon (IFN-). However, it is unclear what role NR1 production or sensing of IFN- plays in T cell homing to the genital tract or T cell-mediated protection against C. trachomatis. Using two-photon microscopy and flow cytometry, we found that naive wild-type (WT), IFN-^–/–, and IFN-R^–/– NR1 T cells specifically home to sections in the genital tract that contain C. trachomatis. We also determined that protection against infection requires production of IFN- from either NR1 T cells or endogenous cells, further highlighting the importance of IFN- in clearing C. trachomatis infection.

IMPORTANCE Chlamydia trachomatis is an important mucosal pathogen that is the leading cause of sexually transmitted bacterial infections in the United States. Despite this, there is no vaccine currently available. In order to develop such a vaccine, it is necessary to understand the components of the immune response that can lead to protection against this pathogen. It is well known that antigen-specific CD4⁺ T cells are critical for Chlamydia clearance, but the contexts in which they are protective or not protective are unknown. Here, we aimed to characterize the importance of gamma interferon production and sensing by T cells and the effects on the immune response to C. trachomatis. Our work here helps to define the contexts in which antigen-specific T cells can be protective, which is critical to our ability to design an effective and protective vaccine against C. trachomatis.

ABSTRACT

Theory, simulation, and experimental evolution demonstrate that diversified CRISPR-Cas immunity to lytic viruses can lead to stochastic virus extinction due to a limited number of susceptible hosts available to each potential new protospacer escape mutation. Under such conditions, theory predicts that to evade extinction, viruses evolve toward decreased virulence and promote vertical transmission and persistence in infected hosts. To better understand the evolution of host-virus interactions in microbial populations with active CRISPR-Cas immunity, we studied the interaction between CRISPR-immune Sulfolobus islandicus cells and immune-deficient strains that are infected by the chronic virus SSV9. We demonstrate that Sulfolobus islandicus cells infected with SSV9, and with other related SSVs, kill uninfected, immune strains through an antagonistic mechanism that is a protein and is independent of infectious virus. Cells that are infected with SSV9 are protected from killing and persist in the population. We hypothesize that this infection acts as a form of mutualism between the host and the virus by removing competitors in the population and ensuring continued vertical transmission of the virus within populations with diversified CRISPR-Cas immunity.

IMPORTANCE Multiple studies, especially those focusing on the role of lytic viruses in key model systems, have shown the importance of viruses in shaping microbial populations. However, it has become increasingly clear that viruses with a long host-virus interaction, such as those with a chronic lifestyle, can be important drivers of evolution and have large impacts on host ecology. In this work, we describe one such interaction with the acidic crenarchaeon Sulfolobus islandicus and its chronic virus Sulfolobus spindle-shaped virus 9. Our work expands the view in which this symbiosis between host and virus evolved, describing a killing phenotype which we hypothesize has evolved in part due to the high prevalence and diversity of CRISPR-Cas immunity seen in natural populations. We explore the implications of this phenotype in population dynamics and host ecology, as well as the implications of mutualism between this virus-host pair.

Place—a confluence of the social, economic, political, physical, and built environments—is fundamental to our understanding of health and health inequities among marginalized racial groups in the United States. Moreover, racism, defined as a system of structuring opportunity and assigning value based on the social interpretation of how one looks (i.e., race), has shaped the places people live in North Carolina. This problem is deeply imbedded in all of our systems, from housing to health care, affecting the ability of every resident of the state to flourish and thrive.

Key Points

The CRISPR/Cas9 nucleases have been widely applied for genome editing in various organisms. Cas9 nucleases complexed with a guide RNA (Cas9–gRNA) find their targets by scanning and interrogating the genomic DNA for sequences complementary to the gRNA. Recognition of the DNA target sequence requires a short protospacer adjacent motif (PAM) located outside this sequence. Given that the efficiency of target location may depend on the strength of interactions that promote target recognition, here we sought to compare affinities of different Cas9 nucleases for their cognate PAM sequences. To this end, we measured affinities of Cas9 nucleases from Streptococcus pyogenes, Staphylococcus aureus, and Francisella novicida complexed with guide RNAs (gRNAs) (SpCas9–gRNA, SaCas9–gRNA, and FnCas9–gRNA, respectively) and of three engineered SpCas9–gRNA variants with altered PAM specificities for short, PAM-containing DNA probes. We used a “beacon” assay that measures the relative affinities of DNA probes by determining their ability to competitively affect the rate of Cas9–gRNA binding to fluorescently labeled target DNA derivatives called “Cas9 beacons.” We observed significant differences in the affinities for cognate PAM sequences among the studied Cas9 enzymes. The relative affinities of SpCas9–gRNA and its engineered variants for canonical and suboptimal PAMs correlated with previous findings on the efficiency of these PAM sequences in genome editing. These findings suggest that high affinity of a Cas9 nuclease for its cognate PAM promotes higher genome-editing efficiency.

Site-specific arrest of RNA polymerases (RNAPs) is fundamental to several technologies that assess RNA structure and function. Current in vitro transcription “roadblocking” approaches inhibit transcription elongation by blocking RNAP with a protein bound to the DNA template. One limitation of protein-mediated transcription roadblocking is that it requires inclusion of a protein factor extrinsic to the minimal in vitro transcription reaction. In this work, we developed a chemical approach for halting transcription by Escherichia coli RNAP. We first established a sequence-independent method for site-specific incorporation of chemical lesions into dsDNA templates by sequential PCR and translesion synthesis. We then show that interrupting the transcribed DNA strand with an internal desthiobiotin-triethylene glycol modification or 1,N6-etheno-2'-deoxyadenosine base efficiently and stably halts Escherichia coli RNAP transcription. By encoding an intrinsic stall site within the template DNA, our chemical transcription roadblocking approach enables display of nascent RNA molecules from RNAP in a minimal in vitro transcription reaction.

Interpretation of a 3D seismic survey located on the western margin of the Northern North Sea Basin demonstrates how the propagation, overlap and linkage of two north–south-striking, en echelon normal fault segments exerted a powerful influence over prospective subtle stratigraphic traps. The relay ramp that formed between the segments appears to have focused sediment dispersal, controlled reservoir distribution and aided post-depositional petroleum migration. Integration of electrical well log data, root-mean-square (RMS)-amplitude analysis and biostratigraphy with seismic interpretation demonstrates that a series of elongate, linear, sand-prone (reservoir) channel complexes characterize the depositional slopes generated by fault growth. The combination of synsedimentary rotation of bedding due to fault propagation and associated footwall uplift led to erosion and truncation of a laterally extensive, older channelized system (Lower Sequence), the downdip parts of which extend beyond the relay ramp. Its subsequent drape by transgressive shales created the subtle stratigraphic trap that now hosts the Cladhan Field, with charge occurring because the sandstones belonging to the Lower Sequence extend as far as the active kitchen in the neighbouring (hanging-wall) depocentre situated downdip and to the east. In contrast, the exploration of a younger, Upper Sequence of sandstones has proven to be disappointing due to their more restricted distribution, lack of access to charge, and occurrence of faults that offset and breach the thin end of the stratigraphic wedge. The implication is that partially breached relay ramps not only provide a preferential site for syn-rift clastic reservoirs to develop but also form important migration pathways through which oil passed from a petroleum kitchen into a trap.

Thematic collection: This article is part of the Under-explored plays and frontier basins of the UK continental shelf collection available at: http://www.lyellcollection.org/cc/under-explored-plays-and-frontier-basins-of-the-uk-continental-shelf