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Biology subjects

Mengel, M.

Publications and source records attributed to Mengel, M..

2 recordsLinked to original sources

Escalating human exposure to tropical mosquito-borne viruses in Europe

Human-induced climate change has multiple public health impacts, including the expansion of the geographical range of vector-borne diseases. Pathogens such as dengue, chikungunya and Zika viruses, transmitted by Aedes mosquitos, can cause severe health outcomes ranging from acute febrile illness, chronic joint pain, to birth defects and even death. Evaluating the future risk of human population exposure is therefore crucial as large outbreaks could overwhelm healthcare systems. Europe, one of the fastest warming regions globally, harbours the competent mosquito vector Aedes albopictus in over 20 countries, making tropical Aedes-borne viruses an increasing threat to the continent, which has already experienced local outbreaks over the past two decades. Here we use an ecological niche modelling approach to assess past, present, and future risk of human population exposure to dengue, chikungunya, and Zika viruses in Europe. Our results show that recent climate change has already increased the potential exposure to these viruses, particularly across the Mediterranean basin, which is a current hotspot for local outbreaks. Major metropolitan areas in Spain, France, Italy, and Croatia are by now located in at-risk areas, and this risk is projected to intensify and expand northward by mid-century. Under a high greenhouse gas emissions scenario, European areas ecologically suitable for Aedes-borne virus circulation could increase by up to [~]70%, leading to an additional [~]50 million people living in areas at risk by the end of the century. These findings underscore the urgent need for strengthened vector and epidemiological surveillance, as well as preparedness strategies across newly suitable regions to anticipate future public health threats associated with these arboviral diseases.

ecology↗

Pathological meprin α expression associated with degradation of dermokine drives a psoriasis-like skin phenotype in a genetic mouse model

Keratinocyte proliferation and differentiation is regulated via proteolytic networks. Dysregulation of proteases within these networks can cause hyperproliferative and inflammatory skin disorders. In healthy skin the metalloprotease meprin is localized in the stratum basale. In contrast, in wound healing tissue and psoriatic lesions increased meprin levels are found in the upper epidermal layers. We developed a transgenic mouse model for inducible expression of pathological meprin levels (K5M) to investigate its epidermal degradome and identify molecular links to keratinocyte proliferation and skin inflammation. K5M mice developed a severe skin phenotype characterized by hyperkeratosis, acanthosis and parakeratosis accompanied by increased transepidermal water loss and a strong inflammatory response within six days after induction of meprin overexpression. Histological and molecular analyses showed that increasing meprin expression correlates with meprin activity and keratinocyte hyperproliferation. Proteomics analyses revealed massive changes in proteins associated with keratinocyte differentiation and epidermal barrier integrity already three days after induction. N-terminomics data indicated a dominant chymotryptic activity with elevated proteolytic turnover of proteins associated with the cytoskeleton, cellular stress responses and cell adhesion. By filtering for cleavage sites that match with the specificity of meprin , we identified highly elevated dermokine-derived peptides. Subsequent mass spectrometric analyses validated dermokine as a novel substrate of meprin and identified the cleavage site, which is highly conserved in mammals. Based on the striking similarities with the phenotype reported for dermokine {beta}{gamma}-/- mice, we propose meprin as a central regulator of keratinocyte proliferation and leukocyte recruitment by proteolytic inactivation of dermokine. Hence, pathological meprin activity could be a driver of hyperproliferative, inflammatory skin disorders like psoriasis vulgaris.

molecular biology↗