Biology subjects

Martin, A. M.

Publications and source records attributed to Martin, A. M..

4 recordsLinked to original sources

bioRxiv2022

Exponential magnetophoretic gradient for the direct isolation of basophils from whole blood in a microfluidic system

Despite their rarity in peripheral blood, basophils play important roles in allergic disorders and other diseases including sepsis and COVID-19. Existing basophil isolation methods require many manual steps and suffer from significant variability in purity and recovery. We report an integrated basophil isolation device (i-BID) in microfluidics for negative immunomagnetic selection of basophils directly from 100 L of whole blood within 10 minutes. We use a simulation-driven pipeline to design a magnetic separation module to apply an exponentially increasing magnetic force to capture magnetically tagged non-basophils flowing through a microtubing sandwiched between magnetic flux concentrators sweeping across a Halbach array. The exponential profile captures non-basophils effectively while preventing their excessive initial buildup causing clogging. The i-BID isolates basophils with a mean purity of 93.9%{+/-}3.6% and recovery of 95.6%{+/-}3.4% without causing basophil degradation or unintentional activation. Our i-BID has the potential to enable basophil-based point-of-care diagnostics such as rapid allergy assessment.

immunology↗

bioRxiv2021

Sarcoptic mange outbreak decimates South American camelid populations in San Guillermo National Park, Argentina

Sarcoptic mange epidemics can devastate wildlife populations. In 2014, mange was first detected in vicuna (Vicugna vicugna) and guanaco (Lama guanicoe) in San Guillermo National Park (SGNP), Argentina. This study characterized the potential source and the impacts of the outbreak in 2017-2019. Transect surveys indicated a sharp decrease in the density of live vicuna and guanaco by 68% and 77%, respectively, from May 2017 to June 2018. By April 2019 no vicuna or guanaco were recorded on transect surveys, suggesting a near-extinction at the local level. Clinical signs consistent with mange (e.g. intense pruritus, hyperkeratosis, alopecia) were observed in 24% of live vicuna (n = 478) and 33% of live guanaco (n = 12) during surveys, as well as in 94% of vicuna carcasses (n = 124) and 85% of guanaco carcasses (n = 20) opportunistically examined during the study period. Histological examination (n = 15) confirmed sarcoptic mange as the cause of the cutaneous lesions. Genetic characterization revealed that Sarcoptes scabiei recovered from seven vicuna (n = 13) and three guanaco (n = 11) shared the same genotype, which is consistent with a single source and recent origin of the epidemic. A governmental livestock incentive program introduced llama (Lama glama) in areas adjacent to SGNP in 2009, some of which reportedly had alopecic scaling consistent with sarcoptic mange. We hypothesize that the introduction of mange-infected llama may have triggered the outbreak in wild camelids which has now put them at a high risk of local extinction. This unprecedented event highlights that the accidental introduction of disease may be underestimated at the onset yet can have devastating effects on native ungulate populations with potentially profound effects at the community and ecosystem levels.

zoology↗

bioRxiv2020

Endoderm Nitric Oxide Signals to Regulate Nascent Development of Cardiac Progenitors in Chicken Embryos

Heart development in the chicken embryo is regulated by a concert of cardiogenic morphogens and signaling molecules, but the physiological signal molecule nitric oxide(NO) has not been studied in the context of heart formation. A dynamic investigation of endoderm NO formation demonstrates for the first time a correlation with the established development events of the cardiac heart fields and heart tube. Manipulation of endoderm NO signaling demonstrate a role of NO signaling in the differentiation and proliferation of cardiac progenitors for heart tube formation and cardiac heart field development. To investigate NO in the proliferation of myocardial cells in the heart tube embryos, a computer vision based artificial intelligence approach is followed to automate the long and tedious job of counting cells in a large image dataset. We document NO as an important signaling molecule in the regulation of nascent embryonic cardiogenesis whose effects on other early cardiogenic morphogens is unknown.

developmental biology↗

bioRxiv2020

The low-density lipoprotein receptor-related protein-1 is essential for Dengue virus infection

Dengue virus (DENV) causes the most prevalent and rapidly spreading arboviral disease of humans. It enters human cells by receptor-mediated endocytosis. Numerous cell surface proteins have been proposed as DENV entry factors. Among these, the phosphatidylserine receptor TIM-1 is the only one known to mediate virus internalization. However, several cellular models lacking TIM-1 are permissive to DENV infection, suggesting that other receptors exist. Here we show that the Low-density lipoprotein receptor-related protein-1 (LRP1) binds DENV virions by interacting with the DIII of the viral envelope glycoprotein. DENV infection is effectively inhibited by the purified receptor at 5x10-8 mol/L and the interaction of the envelope protein with LRP1 is also blocked by a natural ligand of LRP1. Depletion of LRP1 causes 100-fold lower production of infectious virus than controls. Our results indicate that LRP1 is another DENV receptor thus, becoming an attractive target to evaluate for the development of effective antiviral drugs against DENV. Author summaryDengue virus (DENV) is a complex of four related viruses, recognized as serotypes, designated as DENV1-4. Any of the four DENV serotypes can cause a self-limited disease of mild flu-like symptoms known as dengue or its life threatening form, severe dengue, with hemorrhagic manifestations, organ impairment and shock. This disease is widely spread in tropical and sub-tropical areas worldwide, where the incidence of severe dengue has been increasing steadily. So far, efforts that target components of the viral replication machinery in order to develop a specific antiviral drug for dengue disease patients have failed. Thus, identifying the cell surface receptors used by DENV to enter host cells would provide a new molecular target to develop inhibitory drugs. Here, we evaluate the Low density lipoprotein receptor-related protein-1 (LRP1) as a putative DENV receptor. We present evidence demonstrating that LRP1 binds DENV through the viral envelope protein. We show that the production of infective virus is impaired on cells lacking LRP1, and that purified LRP1 is a potent blocker of DENV infection. These results are consistent with LRP1 playing an important role on DENV entry, making this receptor a molecule of interest on the investigation for medical treatments of dengue/severe dengue disease.

biochemistry↗