A5090987797- Malaria Research and Control
- Mosquito-borne diseases and control
- Complement system in diseases
- Toxoplasma gondii Research Studies
- Peptidase Inhibition and Analysis
- Synthesis and Biological Evaluation
- Venomous Animal Envenomation and Studies
- Genomics, phytochemicals, and oxidative stress
- Calpain Protease Function and Regulation
- Caveolin-1 and cellular processes
- Viral Infections and Vectors
- Computational Drug Discovery Methods
- Immune cells in cancer
- Bioactive Compounds and Antitumor Agents
- Heparin-Induced Thrombocytopenia and Thrombosis
- Vector-borne infectious diseases
- Phagocytosis and Immune Regulation
- Biochemical and Structural Characterization
- Signaling Pathways in Disease
- Coccidia and coccidiosis research
- Blood Coagulation and Thrombosis Mechanisms
- RNA and protein synthesis mechanisms
- X-ray Diffraction in Crystallography
- Invertebrate Immune Response Mechanisms
- Cancer Genomics and Diagnostics
Keele University
2023-2024
Washington University in St. Louis
2009-2023
Johns Hopkins University
2023
Indiana University
2023
Indiana University School of Medicine
2023
University of Georgia
2023
Columbia University
2020
University of Manchester
2015-2018
University of Birmingham
2018
University of Perugia
2015
Plasmodium parasite entrance and exit Sweats fever are the hallmarks of malaria. Red blood cells replication factories for malaria parasites. Fever occurs when parasites' merozoite stages burst en masse from red into circulation. Nasamu et al. Pino discovered that two proteases, plasmepsin IX X, essential mass cell (see Perspective by Boddey). Plasmepsin X is also used merozoites to enter a fresh continue replicative cycle. These plasmepsins act regulating maturation enzymes required disrupt...
Significance Macrophages can be functionally reprogrammed by the tumor microenvironment to further growth and malignancy. In this study, we have discovered that pathological process is dependent on ERK5 MAPK. Accordingly, demonstrated inactivation of in macrophages blocked phosphorylation STAT3, a transcription factor crucial for determining macrophage polarity, impaired melanoma carcinoma grafts. These results raise possibility targeting protumor via anti-ERK5 therapy constitutes very...
Abstract The objectives of this study were to compare dengue virus (DENV) cases, deaths, case-fatality ratio [CFR], and meteorological parameters between the first recent decades century (2000–2010 vs. 2011–2022) describe trends, seasonality, impact change temperature rainfall patterns on transmission dynamics in Bangladesh. For period 2000–2022, cases death data from Bangladesh’s Ministry Health Family Welfare’s website, Bangladesh Meteorological Department analyzed. A Poisson regression...
Plasmodium falciparum encodes a single calpain that has distinct domain composition restricted to alveolates. To evaluate the potential of this protein as drug target, we assessed its essentiality. Both gene disruption by double cross-over and truncation recombination failed. We were also unable achieve allelic replacement using missense mutation at catalytic cysteine codon, although could obtain synonymous parasites. These results suggested proteolytic activity are important for optimal...
Abstract Background Post-transcriptional control of gene expression is suspected to play an important role in malaria parasites. In yeast and metazoans, part the stress response mediated through phosphorylation eukaryotic translation initiation factor 2α (eIF2α), which results selective mRNAs encoding stress-response proteins. Methods The impact starvation on state PfeIF2α was examined. Bioinformatic methods were used identify plasmodial eIF2α kinases. activity one these, PfeIK1,...
promotor mutations are present in >75% of bladder tumours; these also detectable urine. Previous studies have used urinary pellet DNA, and semi-quantitative methods unsuitable for detecting very low mutant allele frequencies.
Malaria is an infectious disease caused by Plasmodium parasites. It results in annual death-toll of ~ 600,000. Resistance to all medications currently use exists, and novel antimalarial drugs are urgently needed. Plasmepsin V (PmV) essential protease a highly promising target, which still lacks molecular characterization drug-like inhibitors. PmV, cleaving the PExEl motif, key enzyme for PExEl-secretion, indispensable parasitic process virulence infection. Here, we describe accessibility PmV...
Parasite egress from infected erythrocytes and invasion of new red blood cells are essential processes for the exponential asexual replication malaria parasite. These two tightly coordinated events take place in less than a minute part regulated mediated by proteases. Dipeptidyl aminopeptidases (DPAPs) papain-fold cysteine proteases that cleave dipeptides N-terminus protein substrates. DPAP3 was previously suggested to play an role parasite egress. However, little is known about its...
Histidine-rich protein II (HRPII) is secreted by Plasmodium falciparum during the blood stage of malaria infection. High plasma levels HRPII are associated with cerebral malaria, a severe and highly fatal complication malaria. has been shown to induce vascular leakage, hallmark in blood–brain barrier (BBB) animal models. We have discovered an important mechanism for BBB disruption that driven unique features HRPII. By characterizing serum from infected patients produced P. parasites culture,...
Summary The Plasmodium falciparum genome encodes a single calpain. By generating P. clones expressing C‐terminally tagged calpain, we localized this protein to the nucleolus. Pf_calpain possesses an unusual and long N‐terminal domain in which identified three subregions that are highly conserved among species. Two have putative targeting signals: myristoylation motif nuclear localization sequence. We assessed their functionality. Our data show sequence is active import contains embedded...
The presence of immunosuppressive macrophages that become activated in the tumor microenvironment constitutes a major factor responsible for growth and malignancy. In line with this knowledge, we report here macrophage proliferation is significant feature advanced stages cancer. Moreover, have found high proportion proliferating human tumors express ERK5. ERK5 was required supporting grafts mice. Furthermore, myeloid deficiency negatively impacted both resident infiltrated metastatic lung...
Thrombin is a primary target for the development of novel anticoagulants, since it plays two important and opposite roles in hemostasis: procoagulant anticoagulant. All thrombin functions are influenced by Na+ binding, which triggers transition this enzyme from an anticoagulant (slow) form to (fast) form. In previous studies, we have conveniently produced chemical synthesis analogues N-terminal fragment 1−47 hirudin HM2 containing noncoded amino acids displaying up ∼2700-fold more potent...
Abstract Hirudin is an anticoagulant polypeptide isolated from a medicinal leech that inhibits thrombin with extraordinary potency ( K d = 0.2‐1.0 pM) and selectivity. composed of compact N‐terminal region (residues 1‐47, cross‐linked by three disulfide bridges) binds to the active site thrombin, flexible C‐terminal tail 48‐64) interacts exosite I enzyme. To minimize sequence hirudin able bind also improve its therapeutic profile, several fragments have been prepared as potential...
Abstract Background The objectives of this study were to compare the dengue virus (DENV) infection, deaths, case-fatality ratio, as well meteorological parameters between first and recent decade (2000-2010 vs. 2011-2022) understand trends, seasonality, impact change temperature rainfall pattern on transmission dynamics Dengue in Bangladesh Methods For period 2000-2022, cases death data from Bangladesh’s Ministry Health Family Welfare’s website, Meteorological Department analyzed....
ABSTRACT Parasite egress from infected erythrocytes and invasion of new are essential for the exponential asexual replication malaria parasite, both processes regulated mediated by proteases. The putative cysteine protease dipeptidyl aminopeptidase 3 (DPAP3) was previously suggested to be parasite egress, but little is known about its biological function. Here, we demonstrate that DPAP3 has proteolytic activity, contrary studied DPAPs, removal prodomain not required activation....
Introduction The nitric oxide (NO) receptor soluble guanylyl cyclase (GC‐1) was first identified as a cytosolic enzyme but is now known to localize various cell membrane microdomains. We reported that in normal hearts, GC‐1 localizes caveolae, where it exhibits enhanced NO‐responsiveness. In failing caveolae‐localization of disrupted and outside caveolae oxidized. How dynamically away from unknown. hypothesized S‐palmitoylation, reversible, enzyme‐catalyzed, post‐translational modification...