Using DNA extracted from a finger bone found in Denisova Cave in southern Siberia, we have sequenced the genome of an archaic hominin to about 1.9-fold coverage. This individual is from a group that shares a common origin with Neanderthals. This population was not involved in the putative gene flow from Neanderthals into Eurasians; however, the data suggest that it contributed 4–6% of its genetic material to the genomes of present-day Melanesians. We designate this hominin population ‘Denisovans’ and suggest that it may have been widespread in Asia during the Late Pleistocene epoch. A tooth found in Denisova Cave carries a mitochondrial genome highly similar to that of the finger bone. This tooth shares no derived morphological features with Neanderthals or modern humans, further indicating that Denisovans have an evolutionary history distinct from Neanderthals and modern humans.

/pdf/genetic-history-of-an-archaic-hominin-group-from-denisova-4fnoshsaj4.pdf

Genetic history of an archaic hominin group from Denisova Cave in Siberia

The microbiota is vital for the development of the immune system and homeostasis. Changes in microbial composition and function, termed dysbiosis, in the respiratory tract and the gut have recently been linked to alterations in immune responses and to disease development in the lungs. In this Opinion article, we review the microbial species that are usually found in healthy gastrointestinal and respiratory tracts, their dysbiosis in disease and interactions with the gut-lung axis. Although the gut-lung axis is only beginning to be understood, emerging evidence indicates that there is potential for manipulation of the gut microbiota in the treatment of lung diseases.

/pdf/emerging-pathogenic-links-between-microbiota-and-the-gut-kqqzn58nt1.pdf

Emerging pathogenic links between microbiota and the gut-lung axis

Electrophoretic deposition (EPD) is attracting increasing attention as an effective technique for the processing of biomaterials, specifically bioactive coatings and biomedical nanostructures. The well-known advantages of EPD for the production of a wide range of microstructures and nanostructures as well as unique and complex material combinations are being exploited, starting from well-dispersed suspensions of biomaterials in particulate form (microsized and nanoscale particles, nanotubes, nanoplatelets). EPD of biological entities such as enzymes, bacteria and cells is also being investigated. The review presents a comprehensive summary and discussion of relevant recent work on EPD describing the specific application of the technique in the processing of several biomaterials, focusing on (i) conventional bioactive (inorganic) coatings, e.g. hydroxyapatite or bioactive glass coatings on orthopaedic implants, and (ii) biomedical nanostructures, including biopolymer–ceramic nanocomposites, carbon nanotube coatings, tissue engineering scaffolds, deposition of proteins and other biological entities for sensors and advanced functional coatings. It is the intention to inform the reader on how EPD has become an important tool in advanced biomaterials processing, as a convenient alternative to conventional methods, and to present the potential of the technique to manipulate and control the deposition of a range of nanomaterials of interest in the biomedical and biotechnology fields.

https://royalsocietypublishing.org/doi/pdf/10.1098/rsif.2010.0156.focus

Electrophoretic deposition of biomaterials

https://hal.archives-ouvertes.fr/hal-02397593/document

Review of titanium surface modification techniques and coatings for antibacterial applications.

Inflammation is a hallmark of stroke pathology. The cytokines, tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6, modulate tissue injury in experimental stroke and are therefore potential targets in future stroke therapy. The effect of these cytokines on infarct evolution depends on their availability in the ischemic penumbra in the early phase after stroke onset, corresponding to the therapeutic window (<4.5 hours), which is similar in human and experimental stroke. This review summarizes a large body of literature on the spatiotemporal and cellular production of TNF, IL-1, and IL-6, focusing on the early phase in experimental and human stroke. We also review studies of cytokines in blood and cerebrospinal fluid in stroke. Tumor necrosis factor and IL-1 are upregulated early in peri-infarct microglia. Newer literature suggests that IL-6 is produced by microglia, in addition to neurons. Tumor necrosis factor- and IL-1-producing macrophages infiltrate the infarct and peri-infarct with a delay. This information is discussed in the context of suggestions that neuronal sensitivity to ischemia may be modulated by cytokines. The fact that TNF and IL-1, and suppossedly also IL-6, are produced by microglia within the therapeutic window place these cells centrally in potential future stroke therapy.

https://journals.sagepub.com/doi/pdf/10.1038/jcbfm.2012.88

Inflammatory cytokines in experimental and human stroke

The invention relates to a method for inhibiting an ADAM protease, comprising inhibiting binding to an integrin-binding loop of a disintegrin domain in the ADAM protease. Also provided are cyclic peptides which inhibit binding to an integrin-binding loop of an ADAM protease, as well as associated pharmaceutical compositions, uses and methods of treatment.

Cyclic peptides as ADAM protease inhibitors

Infection is often a complication following joint replacement surgery and the use of antibiotic-impregnated cements is emerging to be a potentially effective clinical procedure that may assist in reducing the incidence of deep infection. The main advantage of local antibiotic delivery is the ability to achieve high levels of antibiotic at the target site without increasing systemic toxicity whilst providing sustained release over prolonged periods of time. Although antibiotic-loaded bone cements have been in use in Europe for over 30 years, they were approved by the US Food and Drug Administration (FDA) in 2003 and are now being increasingly used as a local drug delivery system. The present chapter examines the literature and discusses the effect of antibiotics on the physico-mechanical properties of cements and their clinical efficacy.

Antibiotic-loaded bone cements

Background: Infections of the root canal space involve polymicrobial biofilms and lead to chronic, low grade inflammatory responses arising from the seeding of microbes and by-products. Acute exacerbation and/or disseminating infections occur when established microbial communities undergo sudden changes in phenotypic behaviour. Methods: Within clinical endodontic infections, we assessedcategorical determinants comprising, and changing microbial composition of, chronic polymicrobial infections and their association with amoebae. After standardised assessment, primary or secondary infections underwent sampling and DNA processing, targeting bacteria, fungi and amoebae, including 16S high-throughput sequencing. After taxonomic assignment, community composition was correlated with clinical signs and symptoms. Diversity and abundance analyses were carried out in relation to the presence of non-bacterial amplicons. Results: Clinical specimens revealed two distinct community clusters, where specific changes correlated with clinical signs. An association between the compositions of microbiomes was found between these groups and the presence of Entamoeba gingivalis in 44% of cases. When amoebae were present in endodontic infections, we demonstrate changes in microbial community structure that mirror those observed in treatment-resistant or recurrent infections. Conclusions: Amoeba are present in endodontic infections at a high prevalence, and may promote increased virulence by enrichment for phagocytosis-resistant bacteria.

https://www.mdpi.com/2077-0383/9/11/3700/pdf

Amoebae in Chronic, Polymicrobial Endodontic Infections Are Associated with Altered Microbial Communities of Increased Virulence

Electrohydrodynamic spraying has recently emerged as a powerful method of producing nano-structured hydroxyapatite (nHA) coatings for biomedical implants. To enhance the mechanical properties of these coatings, a subsequent heat treatment is normally needed. However, whether this process significantly influences the coated surface morphology and cellular responses still needs to be systematically studied and documented. In this investigation, the morphology, composition and resultant surface roughness of the nHA coating surfaces were examined, prior to in vitro cytocompatibility, proliferation and cell morphological assessments using primary alveolar human osteoblast-like (aHOB) cells. After heat treatment of nHA coatings prepared using electrohydrodynamic spraying, it was found that the coated surface roughness reduced from a pre heat treated average of 4.2 μm to a post heat treated roughness of 2.9 μm, 2.5 μm and 2.1 μm at 500°C, 700°C and 900°C, respectively. The in vitro study determined a favourable osteoblast response to all substrates examined, with no statistical difference between the samples examined, as determined by the AlamarBlue proliferation assay over 21 days in culture. Confocal microscopy and scanning electron microscopy further demonstrated cell proliferation and adhesive adaptation on the experimental substrates.

Garrit Koller

Papers

Cyclic peptides as ADAM protease inhibitors

Antibiotic-loaded bone cements

Amoebae in Chronic, Polymicrobial Endodontic Infections Are Associated with Altered Microbial Communities of Increased Virulence

Effect of heat treatment of nano-hydroxyapatite coatings prepared using electrohydrodynamic deposition

The impact of an enhanced infection control protocol on the microbial community profile in molar root canal treatment-an in vivo NGS molecular study.