Leucine-rich repeat kinase 2 allosteric modulators

The present invention relates to binding agents of human Leucine-rich Repeat Kinase 2 (LRRK2). More particular, allosteric modulators of LRRK2 activity have been identified, for targeting LRRK2 in human cells, while leaving LRRK2 subcellular localisation unaffected. Even more specifically, protein binding agents for allosteric modulation of LRRK2 kinase activity are disclosed, comprising immunoglobulin single variable domains (ISVDs) binding to human LRRK2 with nanomolar affinity. The invention thus reveals means and methods for a novel LRRK2 targeting approach through allosteric modulation of its activity for use in treatment of LRRK2-related pathologies, such as Parkinson's disease, as well as for use in detection of LRRK2 in vitro and in vivo, and for use as a diagnostic

Molecular Characterization of Nepali Potato Cultivars Using Randomly Amplified Polymorphic DNA (Rapd) Markers

Randomly amplified polymorphic DNA (RAPD) was used to study the genetic diversity of four local cultivars of potato. Amplification with ten arbitrary decamer primers produced 29 different marker bands of which 69.0% were polymorphic. The size range of the amplified DNAs ranged between 370 bp and 2500 bp. On average, 17.5 alleles per genotype were amplified using the RAPD primers. With the selected primers sufficient polymorphism could be detected to allow identification of individual genotypes. A dendrogram displaying the relative genetic similarities between the genotypes showed a range of 55.2-69.0% similarity

Molecular Characterization of Nepali Potato Cultivars using Randomly Amplified Polymorphic DNA (RAPD) Markers

Randomly amplified polymorphic DNA (RAPD) was used to study the genetic diversity of four local cultivars of potato. Amplification with ten arbitrary decamer primers produced 29 different marker bands of which 69.0% were polymorphic. The size range of the amplified DNAs ranged between 370 bp and 2500 bp. On average, 17.5 alleles per genotype were amplified using the RAPD primers. With the selected primers sufficient polymorphism could be detected to allow identification of individual genotypes. A dendrogram displaying the relative genetic similarities between the genotypes showed a range of 55.2-69.0% similarity

Prosthetics for low-and-middle-income countries (LMICs) : challenges and opportunities

The World Health Organisation estimates that 650 million people worldwide are disabled. Of those people, 80% currently live in Low- and Middle-Income countries (LMICs) that are often at various stages of economic development depending on active conflict or post conflict state. Fewer than 3% of persons with disabilities in LMIC’s have access to required rehabilitation services. Without access to the rehabilitation they require, those with disability may become entrenched in a cycle of poverty. There is a need for functional prosthetics which are affordable, robust, reliable and fit-for- purpose in resource constrained settings of LMICs. To address some of those LMICs developmental challenges, an integrated multidisciplinary partnership was convened between Indian and UK Engineers, Prosthetists, Healthcare professionals and experts from prosthesis manufactures, and public health NGOs. This consortium held exclusive networking meetings both in India and UK, supported by the UK Academy of Medical Sciences under Global Challenges Research Fund Networking Grants. The team also engaging with interdisciplinary research for developing Upcycled Plastic Prosthetic supported by the UK’s Royal Academy of Engineering Frontiers follow-on grant. This symposium will be delivering the findings from those research projects involved with LMICs as well as the UK stakeholders to inform the current thinking on the LMICs prosthetics requirements. These includes the unmet need of the LMICs amputees, capacity building to build skills across career stages with partners in LMICs during the preliminary trials of Upcycled Plastic Prosthetic, as well as integrating hands-off casting for prosthetic socket fabrication in LMICs protocol

Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren's syndrome condition

Primary Sjogren’s syndrome (pSS) is a systemic autoimmune disease that is characterized by the infiltration of immune cells. Although the loss of salivary gland function is a major manifestation observed in pSS, the factors that could promote these changes in salivary gland tissue in pSS is not yet determined. Herein, we provide evidence that loss of alpha-1 antiproteinase antitrypsin could contribute to the induction of pSS. Alpha-1 antiproteinase antitrypsin belongs to the family of serpin proteins that function as protease inhibitors and protect secretory cells against proteases, especially to elastases that is secreted from lymphocytes. Importantly, expression of alpha-1 antiproteinase antitrypsin was decreased (more than 3-fold), along with an increase in elastase expression, in pSS samples when compared with age-matched non-SS-SICCA patients. Consistent with the human data, loss of alpha-1 antiproteinase antitrypsin, as well as an increase in immune infiltration, was observed in IL14α transgenic mice that exhibit SS like symptoms. Moreover, an age-dependent increase in elastase expression was observed in IL14α transgenic mice along with a decrease in total saliva secretion. Importantly, a 4-fold increase in microRNA132 expression, but not in other microRNAs, and increased DNA methylation in the promoter/noncoding region of serpina gene was observed in pSS, which could be responsible for the inhibition of alpha-1 antiproteinase antitrypsin expression in salivary gland cells of pSS patients. Together, these findings demonstrate that epigenetic regulations that include DNA methylation and microRNAs that could modulate the expression of alpha-1 antiproteinase antitrypsin in salivary glands and could be involved in the onset of pSS