Transmission tree of the highly pathogenic avian influenza (H5N1) epidemic in Israel, 2015

The transmission tree of the Israeli 2015 epidemic of highly pathogenic avian influenza (H5N1) was modelled by combining the spatio-temporal distribution of the outbreaks and the genetic distance between virus isolates. The most likely successions of transmission events were determined and transmission parameters were estimated. It was found that the median infectious pressure exerted at 1 km was 1.59 times (95% CI 1.04, 6.01) and 3.54 times (95% CI 1.09, 131.75) higher than that exerted at 2 and 5 km, respectively, and that three farms were responsible for all seven transmission events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0393-2) contains supplementary material, which is available to authorized users

Microneedles: A New Frontier in Nanomedicine Delivery

This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an emerging and exciting area of pharmaceutical sciences research within the remit of transdermal drug delivery and as such will undoubtedly continue to grow with the emergence of new formulation and fabrication methodologies for particles and MN. Firstly, the fundamental aspects of skin architecture and structure are outlined, with particular reference to their influence on NP and MP penetration. Following on from this, a variety of different particles are described, as are the diverse range of MN modalities currently under development. The review concludes by highlighting some of the novel delivery systems which have been described in the literature exploiting these two approaches and directs the reader towards emerging uses for nanomedicines in combination with MN

Veterinary Molecular Diagnostics

In veterinary molecular diagnostics, samples originating from animals are tested. Developments in the farm animals sector and in our societal attitude towards pet animals have resulted in an increased demand for fast and reliable diagnostic techniques. Molecular diagnostics perfectly matches this increased demand. Veterinary molecular diagnostics primarily focuses on the detection, identification, and genotyping of pathogens. Techniques are comparable to those used in the human molecular diagnostic field. In veterinary diagnosis, these techniques are applied to either the diagnosis of diseases in individual animals and herds or to assess the disease status of a herd. Notable features of veterinary molecular diagnostics are the sampling of a diagnostic unit for herd diagnoses, which can compensate test characteristics and, to a lesser extent, the high RNA/DNA loads in cases of animal disease outbreaks. To further identify bacteria, numerous genotyping techniques are used, including whole genome sequencing (WGS). To characterise viruses, WGS is the method of choice. The applications of molecular techniques in molecular diagnostics and molecular epidemiology are presented in two case studies: Q fever and the highly pathogenic avian influenz

Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans

Animal experiments have shown that nonhuman primates, cats, ferrets, hamsters, rabbits, and bats can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, SARS-CoV-2 RNA has been detected in felids, mink, and dogs in the field. Here, we describe an in-depth investigation using whole-genome sequencing of outbreaks on 16 mink farms and the humans living or working on these farms. We conclude that the virus was initially introduced by humans and has since evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period, several weeks before detection. Despite enhanced biosecurity, early warning surveillance, and immediate culling of animals in affected farms, transmission occurred between mink farms in three large transmission clusters with unknown modes of transmission. Of the tested mink farm residents, employees, and/or individuals with whom they had been in contact, 68% had evidence of SARS-CoV-2 infection. Individuals for which whole genomes were available were shown to have been infected with strains with an animal sequence signature, providing evidence of animal-to-human transmission of SARS-CoV-2 within mink farms

Psoriasis-associated late cornified envelope) proteins have antibacterial activity

Late cornified envelope (LCE) genes, located in the epidermal differentiation complex on chromosome 1, encode a family of 18 proteins of unknown function, whose expression is largely restricted to the epidermis. Deletion of two members, LCE3B and LCE3C (LCE3B/C‐del), is a widely replicated psoriasis risk factor that interacts with the major psoriasis‐risk gene HLA‐C*06:02. Disease‐associated genetic risk factors often involve noncoding variants, which has precluded understanding of their functional consequences in complex diseases. We aimed to investigate the expression and function of the LCE proteins to explain the biology that underlies the association between LCE3B/C‐del and psoriasis. We used cis‐expression quantitative trait locus analysis and functional assays of LCE proteins in in vivo skin and three‐dimensional epidermal models. RNA‐seq data from normal and psoriatic human skin revealed that LCE3B/C‐del was associated with a significant induction of LCE3A, directly adjacent to LCE3B/C‐del. This phenomenon was most strongly present in normal skin, where the LCE3A gene is silent when LCE3B and LCE3C are present. We confirmed these findings in a three‐dimensional epidermal equivalent model using primary keratinocytes from LCE3B/C‐del genotyped donors. Functional analysis did not support a role for LCE proteins in epidermal barrier function, but revealed that psoriasis‐associated LCE3 proteins, and LCE3A in particular, have defensin‐like antimicrobial activity against a broad variety of bacterial taxa at low micromolar concentrations. Our findings identify a hitherto unknown biological function for LCE3 proteins and suggest a central role for LCE3A in epidermal host defence and LCE3B/C‐del‐mediated psoriasis risk