Publications by authors named "Derron A Alves"

Resistance arteries, which include small arteries and arterioles, play essential roles in regulating blood pressure and tissue perfusion. Dysfunction in these arteries can lead to various cardiovascular conditions such as hypertension, atherosclerosis, and heart failure, as well as neurovascular conditions. The examination of human resistance arteries is crucial for understanding cardiovascular disease mechanisms and developing targeted therapeutic strategies.

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Background: Sepsis is a leading cause of death world-wide. Identifying novel host-directed therapeutic targets may improve sepsis outcomes.

Methods: Six nonhuman primates were infected with Klebsiella pneumoniae to induce septic shock and provided supportive care for up to 72 hours.

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sporozoites, the stage that initiates a malaria infection, must invade the mosquito salivary glands (SGs) before transmitting to a vertebrate host. However, the effects of sporozoite invasion on salivary gland physiology and saliva composition remain largely unexplored. We examined the impact of infection on salivary glands using high-resolution proteomics, gene expression, and morphological analysis.

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After the 2022-2023 Sudan virus (SUDV) disease outbreak in Uganda, we studied SUDV persistence in nonhuman primates that had survived acute infection without therapeutic intervention. We identified SUDV persistence in the vitreous chamber and immediately adjacent tissue in the eyes as well as in the seminiferous tubules in the testes but not in common target organs typically infected during the acute phase of disease. Specifically, SUDV persists primarily in macrophages in the eyes and Sertoli cells in the testes.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, remains endemic worldwide ~5 years since the first documented case. Severe COVID-19 is widely considered to be caused by a dysregulated immune response to SARS-CoV-2 within the respiratory tract. Circulating levels of the chemokine CXCL10 are strongly positively associated with poor outcome; however, its precise role in pathogenesis and its suitability as a therapeutic target have remained undefined.

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Background: Severe malaria is associated with impaired nitric oxide (NO) synthase (NOS)-dependent vasodilation, and reversal of this deficit improves survival in murine models. Malaria might have selected for genetic polymorphisms that increase endothelial NO signaling and now contribute to heterogeneity in vascular function among humans. One protein potentially selected for is alpha globin, which, in mouse models, interacts with endothelial NOS (eNOS) to negatively regulate NO signaling.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, remains endemic worldwide. Circulating levels of the chemokine CXCL10 are strongly positively associated with poor outcome; however, its precise role in SARS-CoV-2 pathogenesis and its suitability as a therapeutic target have remained undefined. Here, we challenged mice genetically deficient in Cxcl10 with a mouse-adapted strain of SARS-CoV-2.

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Article Synopsis
  • The development of intranasal vaccines for respiratory viruses is increasing, but currently only a live-attenuated influenza vaccine is approved for this method in the U.S.
  • This study focused on the influenza virus and explored a novel structure of hemagglutinin (HA) called spike nanobicelles (SNB), which are lipid disc complexes that may enhance immune response.
  • Using these SNBs, researchers found that intranasal immunization led to the production of broad-spectrum antibodies and protection against various strains of H1N1, potentially paving the way for more effective universal influenza vaccines.
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Article Synopsis
  • The evolution of blood-feeding insects, like mosquitoes, involves adaptations that help them consume blood while avoiding the host's immune responses.
  • Anopheles gambiae salivary apyrase (AgApyrase) plays a key role in blood meal hemostasis by inhibiting platelet aggregation and facilitating the conversion of plasminogen to plasmin, which helps in degrading fibrin and promotes Plasmodium transmission.
  • Immunizing against AgApyrase can inhibit Plasmodium infection and transmission, suggesting potential strategies for preventing malaria spread.
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Background: Chronic norovirus infection (CNI) causes significant morbidity in immunocompromised patients. No effective prevention or treatment currently exists.

Methods: Two patients with inborn errors of immunity, X-linked severe combined immunodeficiency (X-SCID) and DOCK8 deficiency, were followed longitudinally for clinical course, immune reconstitution, norovirus-specific T-cell (NST) response, B-cell reconstitution, and norovirus-specific antibody production.

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Background: Better understanding of the interaction between metabolism and immune response will be key to understanding physiology and disease. Tumor Necrosis Factor-alpha (TNFα) has been studied widely. However, despite the extensive knowledge about TNFα, the cytokine appears to induce not only variable, but often contradictory, effects on inflammation and cell proliferation.

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Norovirus infection can cause gastrointestinal disease in humans. Development of therapies and vaccines against norovirus have been limited by the lack of a suitable and reliable animal model. Here we established rhesus macaques as an animal model for human norovirus infection.

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SARS-CoV-2 continues to pose a global threat, and current vaccines, while effective against severe illness, fall short in preventing transmission. To address this challenge, there's a need for vaccines that induce mucosal immunity and can rapidly control the virus. In this study, we demonstrate that a single immunization with a novel gorilla adenovirus-based vaccine (GRAd) carrying the pre-fusion stabilized Spike protein (S-2P) in non-human primates provided protective immunity for over one year against the BA.

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Intranasal mucosal vaccines can more effectively induce mucosal immune responses against SARS-CoV-2. Here, we show in hamsters that an intranasal subunit mucosal vaccine boost with the beta variant S1 can prevent weight loss, in addition to reducing viral load, which cannot be studied in macaques that don't develop COVID-like disease. Protective efficacy against both viral load and weight loss correlated with serum antibody titers.

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Article Synopsis
  • Mosquito salivary proteins, especially salivary apyrase (AgApyrase), play a key role in managing blood clotting during a mosquito bite, which is important for the transmission of diseases like malaria.
  • The study shows that AgApyrase activates a human protein called tissue plasminogen activator, leading to increased plasmin production that helps mosquitoes digest blood more effectively and increases their infection rates.
  • Immunizing against AgApyrase was found to reduce mosquito infection and limit the spread of malaria, suggesting potential new methods for preventing transmission of the disease.
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C57BL/6J (B6) mice are commonly affected by ulcerative dermatitis (UD), a disease of unknown etiology with poor response to treatment. To study the possible role of diet in UD, we compared skin changes in B6 female mice fed a high-fat diet with those of mice fed a control diet. In addition, skin samples from mice with no, mild, moderate, and severe clinical signs of UD were examined by light and transmission electron microscopy (TEM).

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As new vaccine technologies and platforms, such as nanoparticles and novel adjuvants, are developed to aid in the establishment of a universal influenza vaccine, studying traditional influenza split/subunit vaccines should not be overlooked. Commercially available vaccines are typically studied in terms of influenza A H1 and H3 viruses but influenza B viruses need to be examined as well. Thus, there is a need to both understand the limitations of split/subunit vaccines and develop strategies to overcome those limitations, particularly their ability to elicit cross-reactive antibodies to the co-circulating Victoria (B-V) and Yamagata (B-Y) lineages of human influenza B viruses.

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Introduction: U.S. Army Veterinary Corps provides highly skilled and adaptive veterinary professionals to protect and improve the health of people and animals while enhancing readiness throughout the DOD.

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Tularemia is a severe, zoonotic infection caused by the Gram-negative bacterium . Inhalation results in a rapid, severe bacterial pneumonia and sepsis, which can be lethal. Because the cynomolgus macaque is the accepted nonhuman primate model for tularemia, we conducted a natural history study of pneumonic tularemia by exposing macaques to target inhaled doses of 50, 500, or 5000 colony forming units (CFU) of subsp.

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Neosporosis is a common cause of abortion in cattle worldwide but is rare in horses. Here, the first case of histologically, ultrastructurally, immunohistochemically, and molecularly confirmed equine abortion caused by neosporosis is reported. Samples of lung, heart, liver, skeletal muscle, tongue, brain, and the placenta from a female fetus aborted at 280 days of gestation were fixed in formalin and submitted for diagnosis.

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A 9-year-old golden retriever dog was diagnosed with a left retrobulbar mass. Fine-needle aspirations and incisional biopsies resulted in discordant diagnoses: myxosarcoma/myxoma or rhadomyosarcoma, respectively. Immunohistochemistry following exenteration allowed definitive diagnosis of malignant peripheral nerve sheath tumor with fibromyxomatous differentiation.

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