A MORC protein complex modulates epigenetic control of gene expression through interaction with heterochromatin.

Dynamic control of gene expression is critical for blood stage development of malaria parasites. Here, we used multi-omic analyses to investigate transcriptional regulation by the chromatin-associated microrchidia protein, MORC, during asexual blood stage development of the human malaria parasite . We show that MORC (PF3D7_1468100) interacts with a suite of nuclear proteins, including APETALA2 (ApiAP2) transcription factors (AP2-G5, AP2-O5, AP2-I, PF3D7_0420300, PF3D7_0613800, PF3D7_1107800, and PF3D7_1239200), a DNA helicase DS60 (PF3D7_1227100), and other chromatin remodelers (CHD1 and EELM2).

Analysis of the optical performance of intraocular lenses using profilometric measurements.

Purpose: The aim of this study was to develop a methodology, based on profilometer measurements to assess the optical behaviour of Intraocular Lenses (IOls). The "Modulation Transfer Function through-object" (MTF through-object) based on vergence object displacement was calculated for different pupil sizes and pseudophakic eyes. Tilt and decentration were also analysed in a realistic cornea eye model.

The genetically encoded calcium indicator GCaMP3 reveals spontaneous calcium oscillations at asexual stages of the human malaria parasite Plasmodium falciparum.

Most protocols used to study the dynamics of calcium (Ca) in the malaria parasite are based on dyes, which are invasive and do not allow discrimination between the signal from the host cell and the parasite. To avoid this pitfall, we have generated a parasite line expressing the genetically encoded calcium sensor GCaMP3. The PfGCaMP3 parasite line is an innovative tool for studying spontaneous intracellular Ca oscillations without external markers.

Melatonin as a Circadian Marker for Rhythms.

, a digenetic parasite, requires a host and a vector for its life cycle completion. Most species display circadian rhythmicity during their intraerythrocytic cycle within the host, aiding in immune evasion. This rhythmicity, however, diminishes in in vitro cultures, highlighting the importance of host-derived signals for synchronizing the parasite's asexual cycle.

Validation of a New Test for Measuring the Contrast Sensitivity Function (Optopad-CSF) at Near Vision.

Our purpose is to develop and validate a new iPad-based contrast sensitivity (CS) test for measuring the contrast sensitivity function at near vision (Optopad-CSF). A total of 200 eyes of 100 healthy subjects (ages 17-63) were evaluated in a comparative study between the Optopad-CSF test (near vision) and the CSV-1000E test (distance vision). The agreement between tests was assessed with the index of contrast sensitivity (ICS) and the area under the curve (AUC).

Integrated analysis of the transcriptome and its interaction with the metabolome in metabolic associated fatty liver disease: Gut microbiome signatures, correlation networks, and effect of PNPLA3 genotype.

Interactions between communities of the gut microbiome and with the host could affect the onset and progression of metabolic associated fatty liver disease (MAFLD), and can be useful as new diagnostic and prognostic biomarkers. In this study, we performed a multi-omics approach to unravel gut microbiome signatures from 32 biopsy-proven patients (10 simple steatosis -SS- and 22 steatohepatitis -SH-) and 19 healthy volunteers (HV). Human and microbial transcripts were differentially identified between groups (MAFLD vs.

Changes in K Concentration as a Signaling Mechanism in the Apicomplexa Parasites and .

During their life cycle, apicomplexan parasites pass through different microenvironments and encounter a range of ion concentrations. The discovery that the GPCR-like SR25 in is activated by a shift in potassium concentration indicates that the parasite can take advantage of its development by sensing different ionic concentrations in the external milieu. This pathway involves the activation of phospholipase C and an increase in cytosolic calcium.

Combining IP affinity chromatography and bioinformatics reveals a novel protein-IP binding site on MDR1 transporter.

Intracellular Ca mobilization induced by second messenger IP controls many cellular events in most of the eukaryotic groups. Despite the increasing evidence of IP-induced Ca in apicomplexan parasites like , responsible for malaria infection, no protein with potential function as an IP-receptor has been identified. The use of bioinformatic analyses based on previously known sequences of IP-receptor failed to identify potential IP-receptor candidates in any .

Decoding the Role of Melatonin Structure on Human Malaria Parasites Synchronization Using 2-Sulfenylindoles Derivatives.

Melatonin acts to synchronize the parasite's intraerythrocytic cycle by triggering the phospholipase -inositol 1,4,5-trisphosphate (PLC-IP) signaling cascade. Compounds with an indole scaffold impair in vitro proliferation of blood-stage malaria parasites, indicating that this class of compounds is potentially emerging antiplasmodial drugs. Therefore, we aimed to study the role of the alkyl and aryl thiol moieties of 14 synthetic indole compounds against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) strains of .

Analysis and comparison of monofocal, extended depth of focus and trifocal intraocular lens profiles.

To test the feasibility of using profilometers to extract information about IOL surfaces design. A standard monofocal IOL (Tecnis 1), a monofocal IOL that provided some depth of focus (Eyhance), an extended depth of focus IOL based on refractive optics (Mini Well) and a trifocal IOL based on diffractive optics were used in this study (Tecnis Synergy). The surface topography of the IOLs was measured by using a multimode optical profilometer.

Reducing non-attendance in outpatient appointments: predictive model development, validation, and clinical assessment.

Background: Non-attendance to scheduled hospital outpatient appointments may compromise healthcare resource planning, which ultimately reduces the quality of healthcare provision by delaying assessments and increasing waiting lists. We developed a model for predicting non-attendance and assessed the effectiveness of an intervention for reducing non-attendance based on the model.

Methods: The study was conducted in three stages: (1) model development, (2) prospective validation of the model with new data, and (3) a clinical assessment with a pilot study that included the model as a stratification tool to select the patients in the intervention.

Contribution of Transcriptome to Elucidate the Biology of Plasmodium spp.

The present review discusses some of the new technologies that have been applied to elucidate how Plasmodium spp escape from the immune system and subvert the host physiology to orchestrate the regulation of its biological pathways. Our manuscript describes how techniques such as microarray approaches, RNA-Seq, and single-cell RNA sequencing have contributed to the discovery of transcripts and changed the concept of gene expression regulation in closely related malaria parasite species. Moreover, the text highlights the contributions of high-throughput RNA sequencing for the current knowledge of malaria parasite biology, physiology, vaccine target, and the revelation of new players in parasite signaling.

Malaria parasites and circadian rhythm: New insights into an old puzzle.

•Discuss molecular components for the coordination of circadian rhythm of malaria parasites inside the vertebrate host.•Synthetic indole compounds show antimalarial activity against 3D7.• synchronizes in cell culture upon melatonin treatment.

Evidence of G-Protein-Coupled Receptors (GPCR) in the Parasitic Protozoa -Sensing the Host Environment and Coupling within Its Molecular Signaling Toolkit.

Throughout evolution, the need for single-celled organisms to associate and form a single cluster of cells has had several evolutionary advantages. In complex, multicellular organisms, each tissue or organ has a specialty and function that make life together possible, and the organism as a whole needs to act in balance and adapt to changes in the environment. Sensory organs are essential for connecting external stimuli into a biological response, through the senses: sight, smell, taste, hearing, and touch.

Identifying Plasmodium falciparum receptor activation using bioluminescence resonance energy transfer (BRET)-based biosensors in HEK293 cells.

Throughout evolution the need for unicellular organisms to associate and form a single cluster of cells had several evolutionary advantages. G protein coupled receptors (GPCRs) are responsible for a large part of the senses that allow this clustering to succeed, playing a fundamental role in the perception of cell's external environment, enabling the interaction and coordinated development between each cell of a multicellular organism. GPCRs are not exclusive to complex multicellular organisms.

Molecular basis of synchronous replication of malaria parasites in the blood stage.

The search for host factors that leads to malaria parasite synchronization has been the focus of several laboratories. The host hormone melatonin synchronizes Plasmodium falciparum in culture by increasing the number of mature parasite stages through a PLC-IP3 activation. Melatonin signaling is linked to crosstalk between Ca-cAMP that results in PKA activation.

The Knockout for G Protein-Coupled Receptor-Like PfSR25 Increases the Susceptibility of Malaria Parasites to the Antimalarials Lumefantrine and Piperaquine but Not to Medicine for Malaria Venture Compounds.

Previously we have reported that the G protein-coupled receptor (GPCR)-like PfSR25 in is a potassium (K) sensor linked to intracellular calcium signaling and that knockout parasites (PfSR25-) are more susceptible to oxidative stress and antimalarial compounds. Here, we explore the potential role of PfSR25 in susceptibility to the antimalarial compounds atovaquone, chloroquine, dihydroartemisinin, lumefantrine, mefloquine, piperaquine, primaquine, and pyrimethamine and the Medicine for Malaria Venture (MMV) compounds previously described to act on egress/invasion (MMV006429, MMV396715, MMV019127, MMV665874, MMV665878, MMV665785, and MMV66583) through comparative assays with PfSR25- and 3D7 parasite strains, using flow cytometry assays. The IC and IC results show that lumefantrine and piperaquine have greater activity on the PfSR25- parasite strain when compared to 3D7.

A nuclear protein, PfMORC confers melatonin dependent synchrony of the human malaria parasite P. falciparum in the asexual stage.

The host hormone melatonin is known to modulate the asexual cell-cycle of the human malaria parasite Plasmodium falciparum and the kinase PfPK7 is fundamental in the downstream signaling pathways. The nuclear protein PfMORC displays a histidine kinase domain and is involved in parasite cell cycle control. By using a real-time assay, we show a 24 h (h) rhythmic expression of PfMORC at the parasite asexual cycle and the expression is dramatically changed when parasites were treated with 100 nM melatonin for 17 h.

Intracellular Ca Signaling in Protozoan Parasites: An Overview with a Focus on Mitochondria.

Ca signaling has been involved in controling critical cellular functions such as activation of proteases, cell death, and cell cycle control. The endoplasmatic reticulum plays a significant role in Ca storage inside the cell, but mitochondria have long been recognized as a fundamental Ca pool. Protozoan parasites such as , , and display a Ca signaling toolkit with similarities to higher eukaryotes, including the participation of mitochondria in Ca-dependent signaling events.

New method to improve the quality of vision in cataractous keratoconus eyes.

To analyze using optical simulations if the proper use of a segmented intraocular lens (IOL) can improve the visual outcomes compared to the implantation of a spherical monofocal IOL. The wavefront profile of the Mplus (Oculentis) and a monofocal IOLs with the phase transformation introduced by each IOL were calculated using a Hartmann-Shack wavefront sensor. In addition, the wavefront profile of schematic eye models of various keratoconus conditions was obtained and was propagated to the IOLs.

Development of a Flow Cytometry-Based Functional Assay to Study Anti-TNF Mechanisms of Action and Capture Donor Heterogeneity.

TNF is a key cytokine in autoimmune diseases like rheumatoid arthritis, and TNF antagonists are commonly prescribed therapeutics. Although anti-TNF drugs have enabled a very significant progress in this field, disease heterogeneity remains and causes diversity in patient response. These challenges increase the need for anti-TNF characterization tools that may open perspectives toward the development of personalized medicine.

Melatonin action in Plasmodium infection: Searching for molecules that modulate the asexual cycle as a strategy to impair the parasite cycle.

Half of the world's population lives in countries at risk of malaria infection, which results in approximately 450,000 deaths annually. Malaria parasites infect erythrocytes in a coordinated manner, with cycle durations in multiples of 24 hours, which reflects a behavior consistent with the host's circadian cycle. Interference in cycle coordination can help the immune system to naturally fight infection.