Functional biology of the Steel syndrome founder allele and evidence for clan genomics derivation of COL27A1 pathogenic alleles worldwide

© 2020, The Author(s). Previously we reported the identification of a homozygous COL27A1 (c.2089G\u3eC; p.Gly697Arg) missense variant and proposed it as a founder allele in Puerto Rico segregating with Steel syndrome (STLS, MIM #615155); a rare osteochondrodysplasia characterized by short stature, congenital bilateral hip dysplasia, carpal coalitions, and scoliosis. We now report segregation of this variant in five probands from the initial clinical report defining the syndrome and an additional family of Puerto Rican descent with multiple affected adult individuals. We modeled the orthologous variant in murine Col27a1 and found it recapitulates some of the major Steel syndrome associated skeletal features including reduced body length, scoliosis, and a more rounded skull shape. Characterization of the in vivo murine model shows abnormal collagen deposition in the extracellular matrix and disorganization of the proliferative zone of the growth plate. We report additional COL27A1 pathogenic variant alleles identified in unrelated consanguineous Turkish kindreds suggesting Clan Genomics and identity-by-descent homozygosity contributing to disease in this population. The hypothesis that carrier states for this autosomal recessive osteochondrodysplasia may contribute to common complex traits is further explored in a large clinical population cohort. Our findings auNorthwell Healthnt our understanding of COL27A1 biology and its role in skeletal development; and expand the functional allelic architecture in this gene underlying both rare and common disease phenotypes

Taming the pandemic? The importance of homemade plant-based foods and beverages as community responses to COVID-19

Household responses to COVID-19 in different corners of the world represent the primary health care that communities have relied on for preventing and mitigating symptoms. During a very complex and confusing time, in which public health services in multiple countries have been completely overwhelmed, and in some cases even collapsed, these first-line household responses have been quintessential for building physical, mental, and social resilience, and for improving individual and community health. This editorial discusses the outcomes of a rapid-response preliminary survey during the first phase of the pandemic among social and community contacts in five metropolises heavily affected by the COVID-19 health crisis (Wuhan, Milan, Madrid, New York, and Rio de Janeiro), and in twelve rural areas or countries initially less affected by the pandemic (Appalachia, Jamaica, Bolivia, Romania, Belarus, Lithuania, Poland, Georgia, Turkey, Pakistan, Cambodia, and South Africa). We summarized our perspectives as 17 case studies, observing that people have relied primarily on teas and spices (“food-medicines”) and that there exist clear international plant favorites, popularized by various new media. Urban diasporas and rural households seem to have repurposed homemade plant-based remedies that they use in normal times for treating the flu and other respiratory symptoms or that they simply consider healthy foods. The most remarkable shift in many areas has been the increased consumption of ginger and garlic, followed by onion, turmeric, and lemon. Our preliminary inventory of food medicines serves as a baseline for future systematic ethnobotanical studies and aims to inspire in-depth research on how use patterns of plant-based foods and beverages, both “traditional” and “new”, are changing during and after the COVID-19 pandemic. Our reflections in this editorial call attention to the importance of ethnobiology, ethnomedicine, and ethnogastronomy research into domestic health care strategies for improving community health

Surface Roughness of Commercial Composites after Different Polishing Protocols: An Analysis with Atomic Force Microscopy

Polishing may increase the surface roughness of composites, with a possible effect on bacterial growth and material properties. This preliminary in vitro study evaluates the effect of three different polishing systems (PoGo polishers, Enhance, Venus Supra) on six direct resin composites (Gradia Direct, Venus, Venus Diamond, Enamel Plus HFO, Tetric Evoceram, Filtek Supreme XT)

Anti-proliferative effect of Rosmarinus officinalis L. extract on human melanoma A375 cells

Rosemary (Rosmarinus officinalis L.) has been used since ancient times in traditional medicine, while nowadays various rosemary formulations are increasingly exploited by alternative medicine to cure or prevent a wide range of health disorders. Rosemary's bioproperties have prompted scientific investigation, which allowed us to ascertain antioxidant, anti-inflammatory, cytostatic, and cytotoxic activities of crude extracts or of pure components. Although there is a growing body of experimental work, information about rosemary's anticancer properties, such as chemoprotective or anti-proliferative effects on cancer cells, is very poor, especially concerning the mechanism of action. Melanoma is a skin tumor whose diffusion is rapidly increasing in the world and whose malignancy is reinforced by its high resistance to cytotoxic agents; hence the availability of new cytotoxic drugs would be very helpful to improve melanoma prognosis. Here we report on the effect of a rosemary hydroalcoholic extract on the viability of the human melanoma A375 cell line. Main components of rosemary extract were identified by liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS) and the effect of the crude extract or of pure components on the proliferation of cancer cells was tested by MTT and Trypan blue assays. The effect on cell cycle was investigated by using flow cytometry, and the alteration of the cellular redox state was evaluated by intracellular ROS levels and protein carbonylation analysis. Furthermore, in order to get information about the molecular mechanisms of cytotoxicity, a comparative proteomic investigation was performed