In malaria parasites, the regulation of mRNA translation, storage and degradation during development and life-stage transitions remains largely unknown. Here, we functionally characterized the DEAD-box RNA helicase PfDOZI in P. falciparum.
View Article and Find Full Text PDFDevelopment of Plasmodium-specific humoral immunity is critically dependent on CD4 Th cell responses and germinal center (GC) reactions during blood-stage Plasmodium infection. IL-21, a cytokine primarily produced by CD4 T cells, is an essential regulator of affinity maturation, isotype class-switching, B cell differentiation, and maintenance of GC reactions in response to many infection and immunization models. In models of experimental malaria, mice deficient in IL-21 or its receptor IL-21R fail to develop memory B cell populations and are not protected against secondary infection.
View Article and Find Full Text PDFMultiple vaccines have been developed and licensed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). While these vaccines reduce disease severity, they do not prevent infection. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract.
View Article and Find Full Text PDFCOVID-19 has cost millions of lives worldwide. The constant mutation of SARS-CoV-2 calls for thorough research to facilitate the development of variant surveillance. In this work, we studied the fundamental properties related to the optical identification of the receptor-binding domain (RBD) of SARS-CoV-2 spike protein, a key component of viral infection.
View Article and Find Full Text PDFTransmission of malaria parasites to the mosquito is mediated by sexual precursor cells, the gametocytes. Upon entering the mosquito midgut, the gametocytes egress from the enveloping erythrocyte while passing through gametogenesis. Egress follows an inside-out mode during which the membrane of the parasitophorous vacuole (PV) ruptures prior to the erythrocyte membrane.
View Article and Find Full Text PDFThe overall sensitivity of frontside-illuminated, silicon single-photon avalanche diode (SPAD) arrays has often suffered from fill factor limitations. The fill factor loss can however be recovered by employing microlenses, whereby the challenges specific to SPAD arrays are represented by large pixel pitch (> 10 µm), low native fill factor (as low as ∼10%), and large size (up to 10 mm). In this work we report on the implementation of refractive microlenses by means of photoresist masters, used to fabricate molds for imprints of UV curable hybrid polymers deposited on SPAD arrays.
View Article and Find Full Text PDFMalaria causes >600 thousand fatalities each year, with most cases attributed to the human-infectious Plasmodium falciparum species. Many rodent-infectious Plasmodium species, like Plasmodium berghei and Plasmodium yoelii, have been used as model species that can expedite studies of this pathogen. P.
View Article and Find Full Text PDFMalaria causes over 200 million infections and over 600 thousand fatalities each year, with most cases attributed to a human-infectious species, . Many rodent-infectious species, like , and , have been used as genetically tractable model species that can expedite studies of this pathogen. In particular, is an especially good model for investigating the mosquito and liver stages of parasite development because key attributes closely resemble those of .
View Article and Find Full Text PDFDespite ongoing efforts to control malaria infection, progress in lowering the number of deaths and infections appears to have stalled. The continued high incidence of malaria infection and mortality is in part due to emergence of parasites resistant to frontline antimalarials. This highlights the need for continued identification of novel protein drug targets.
View Article and Find Full Text PDFMalaria remains a global driver of morbidity and mortality. To generate new antimalarials, one must elucidate the fundamental cell biology of , the parasite responsible for the deadliest cases of malaria. A membranous and proteinaceous scaffold called the inner membrane complex (IMC) supports the parasite during morphological changes, including segmentation of daughter cells during asexual replication and formation of transmission-stage gametocytes.
View Article and Find Full Text PDFMultiple domestic and wild animal species are susceptible to SARS-CoV-2 infection. Cattle and swine are susceptible to experimental SARS-CoV-2 infection. The unchecked transmission of SARS-CoV-2 in animal hosts could lead to virus adaptation and the emergence of novel variants.
View Article and Find Full Text PDFMalaria is a devastating disease impacting over half of the world's population. Plasmodium parasites that cause malaria undergo obligatory development and replication in hepatocytes before infecting red blood cells and initiating clinical disease. While type I interferons (IFNs) are known to facilitate innate immune control to Plasmodium in the liver, how they do so has remained unresolved, precluding the manipulation of such responses to combat malaria.
View Article and Find Full Text PDFSome antimalarial drugs that have lost clinical usefulness have been repurposed for experimental applications. One example is sulfadiazine, an analog of -aminobenzoic acid (pABA), which inhibits the parasite's folate synthesis pathway to block DNA synthesis. Sulfadiazine treatment of mice infected with Plasmodium yoelii and P.
View Article and Find Full Text PDFTime-domain near-infrared optical tomography (TD NIROT) techniques based on diffuse light were gaining performance over the last years. They are capable of imaging tissue at several centimeters depth and reveal clinically relevant information, such as tissue oxygen saturation. In this work, we present the very first results of our SPAD camera-based TD NIROT reflectance system with a temporal resolution of ∼116 ps.
View Article and Find Full Text PDFAntibodies targeting the spike (S) and nucleocapsid (N) proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential tools. In addition to important roles in the treatment and diagnosis of infection, the availability of high-quality specific antibodies for the S and N proteins is essential to facilitate basic research of virus replication and in the characterization of mutations responsible for variants of concern. We have developed panels of mouse and rabbit monoclonal antibodies (mAbs) to the SARS-CoV-2 spike receptor-binding domain (S-RBD) and N protein for functional and antigenic analyses.
View Article and Find Full Text PDFProductive transmission of malaria parasites hinges upon the execution of key transcriptional and posttranscriptional regulatory events. While much is now known about how specific transcription factors activate or repress sexual commitment programs, far less is known about the production of a preferred mRNA homeostasis following commitment and through the host-to-vector transmission event. Here, we show that in Plasmodium parasites, the NOT1 scaffold protein of the CAF1/CCR4/Not complex is duplicated, and one paralogue is dedicated for essential transmission functions.
View Article and Find Full Text PDFPurpose: Guidelines from the National Institutes of Health support the use of balanced crystalloid solutions such as Normosol-R (Hospira, Lake Forest, IL) for patients with coronavirus disease 2019 (COVID-19). However, their clinical utility is hindered by a lack of Y-site compatibility data that is essential for use in patients with limited intravenous access. The objective of this study was to determine the physical compatibility of selected intensive care unit medications with Normosol-R.
View Article and Find Full Text PDFBackground And Aim: Preterm infants have a high incidence of brain lesions that may lead to long-term disabilities. Early diagnosis of cerebral ischemia and hemorrhage may enable protection of the brain by prevention or neuroprotective treatment. Our recently developed time-domain near-infrared optical tomography (TD NIROT) system provides images to diagnose neonatal brain injury.
View Article and Find Full Text PDFMillions of individuals who have recovered from SARS-CoV-2 infection may be eligible to participate in convalescent plasma donor programs, yet the optimal window for donating high neutralizing titer convalescent plasma for COVID-19 immunotherapy remains unknown. Here we studied the response trajectories of antibodies directed to the SARS-CoV-2 surface spike glycoprotein and in vitro SARS-CoV-2 live virus neutralizing titers (VN) in 175 convalescent donors longitudinally sampled for up to 142 days post onset of symptoms (DPO). We observed robust IgM, IgG, and viral neutralization responses to SARS-CoV-2 that persist, in the aggregate, for at least 100 DPO.
View Article and Find Full Text PDFBackground: Well-defined promoters are essential elements for genetic studies in all organisms, and enable controlled expression of endogenous genes, transgene expression, and gene editing. Despite this, there is a paucity of defined promoters for the rodent-infectious malaria parasites. This is especially true for Plasmodium yoelii, which is often used to study the mosquito and liver stages of malarial infection, as well as host immune responses to infection.
View Article and Find Full Text PDFIn many clinical applications it is relevant to observe dynamic changes in oxygenation. Therefore the ability of dynamic imaging with time domain (TD) near-infrared optical tomography (NIROT) will be important. But fast imaging is a challenge.
View Article and Find Full Text PDFNear infrared optical tomography (NIROT) is an emerging modality that enables imaging the oxygenation of tissue, which is a biomarker of tremendous clinical relevance. Measuring in reflectance is usually required when NIROT is applied in clinical scenarios. Single photon avalanche diode (SPAD) array technology provides a compact solution for time domain (TD) NIROT to gain huge temporal and spatial information.
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