AxonFinder: Automated segmentation of tumor innervating neuronal fibers.

Neurosignaling is increasingly recognized as a critical factor in cancer progression, where neuronal innervation of primary tumors contributes to the disease's advancement. This study focuses on segmenting individual axons within the prostate tumor microenvironment, which have been challenging to detect and analyze due to their irregular morphologies. We present a novel deep learning-based approach for the automated segmentation of axons, AxonFinder, leveraging a U-Net model with a ResNet-101 encoder, based on a multiplexed imaging approach.

UniFORM: Towards Universal Immunofluorescence Normalization for Multiplex Tissue Imaging.

Multiplexed tissue imaging (MTI) technologies enable high-dimensional spatial analysis of tumor microenvironments but face challenges with technical variability in staining intensities. Existing normalization methods, including z-score, ComBat, and MxNorm, often fail to account for the heterogeneous, right-skewed expression patterns of MTI data, compromising signal alignment and downstream analyses. We present UniFORM, a non-parametric, Python-based pipeline for normalizing both feature- and pixel-level MTI data.

AxonFinder: Automated segmentation of tumor innervating neuronal fibers.

Neurosignaling is increasingly recognized as a critical factor in cancer progression, where neuronal innervation of primary tumors contributes to the disease's advancement. This study focuses on segmenting individual axons within the prostate tumor microenvironment, which have been challenging to detect and analyze due to their irregular morphologies. We present a novel deep learning-based approach for the automated segmentation of axons, AxonFinder, leveraging a U-Net model with a ResNet-101 encoder, based on a multiplexed imaging approach.

Multiplex imaging of localized prostate tumors reveals altered spatial organization of AR-positive cells in the microenvironment.

Mapping the spatial interactions of cancer, immune, and stromal cell states presents novel opportunities for patient stratification and for advancing immunotherapy. While single-cell studies revealed significant molecular heterogeneity in prostate cancer cells, the impact of spatial stromal cell heterogeneity remains poorly understood. Here, we used cyclic immunofluorescent imaging on whole-tissue sections to uncover novel spatial associations between cancer and stromal cells in low- and high-grade prostate tumors and tumor-adjacent normal tissues.

Oligo cyc-DEP: On-chip cyclic immunofluorescence profiling of cell-derived nanoparticles.

We present a follow-on technique for the cyclic-immunofluorescence profiling of suspension particles isolated using dielectrophoresis. The original lab-on-chip technique ("cyc-DEP" [cyclic immunofluorescent imaging on dielectrophoretic chip]) was designed for the multiplex surveillance of circulating biomarkers. Nanoparticles were collected from low-volume liquid biopsies using microfluidic dielectrophoretic chip technology.

cyc-DEP: Cyclic immunofluorescence profiling of particles collected using dielectrophoresis.

Cancer is a highly heterogenous disease that requires precise detection tools and active surveillance methods. Liquid biopsy assays provide an agnostic way to follow the complex trajectory of cancer, providing better patient stratification tools for optimized treatment. Here, we present the development of a low-volume liquid biopsy assay called cyc-DEP (cyclic immunofluorescent imaging on dielectrophoretic chip) to profile biomarkers collected on a dielectrophoretic microfluidic chip platform.

Epigenetic loss of heterogeneity from low to high grade localized prostate tumours.

Identifying precise molecular subtypes attributable to specific stages of localized prostate cancer has proven difficult due to high levels of heterogeneity. Bulk assays represent a population-average, which mask the heterogeneity that exists at the single-cell level. In this work, we sequence the accessible chromatin regions of 14,424 single-cells from 18 flash-frozen prostate tumours.

Does education variability change testicular cancer awareness and testicular self-examination?

Objective: To investigate the awareness about testicular cancer and testicular self examination among medical students and the community.

Methods: The cross-sectional comparative study was conducted from January to April 2019 at Tekirdag, Turkey, and comprised young male medical students aged 18-26 years and an age-matched control group of male high school graduates. Data was collected using face-to-face survey through a 15-question survey form.

Cohesin Is Out for Stalled Replication Fork Restart.

Replication stress underlies many genomic alterations in cancer cells. In this issue of Developmental Cell, Benedict et al. show that WAPL-dependent cohesin removal is needed to restart DNA synthesis at stalled forks and promote survival following replication stress, uncovering an unexpected link between stress and sister chromatid cohesion loss.

A Distalless-responsive enhancer of the Hox gene Sex combs reduced is required for segment- and sex-specific sensory organ development in Drosophila.

Hox genes are involved in the patterning of animal body parts at multiple levels of regulatory hierarchies. Early expression of Hox genes in different domains along the embryonic anterior-posterior (A/P) axis in insects, vertebrates, and other animals establishes segmental or regional identity. However, Hox gene function is also required later in development for the patterning and morphogenesis of limbs and other organs.

PaCaHa inhibits proliferation of human cancer cells in vitro.

Background/aim: The aim of this study was to investigate the antiproliferative and cytotoxic effects of a newly synthesized molecule named paracetamol acetohydroxamic acid (PaCaHa) on human neoplastic cell lines.

Materials And Methods: A549, CRL 2923, HeLa, and ARPE were treated with various concentrations of PaCaHa and DMSO (vehicle control). The cytotoxic/cytostatic effects of PaCaHa were determined after a 24-h incubation period and compared to the DMSO control.

Taenia infestation in the appendix: a case report.

Taenia saginata is a zoonotic cestode causing taeniasis. Taeniasis refers to the intestinal infection with the adult stage of this tapeworm. An association between teaniasis and acute appendicitis is uncommon.

Plasmodium falciparum gametocyte development 1 (Pfgdv1) and gametocytogenesis early gene identification and commitment to sexual development.

Malaria transmission requires the production of male and female gametocytes in the human host followed by fertilization and sporogonic development in the mosquito midgut. Although essential for the spread of malaria through the population, little is known about the initiation of gametocytogenesis in vitro or in vivo. Using a gametocyte-defective parasite line and genetic complementation, we show that Plasmodium falciparumgametocyte development 1 gene (Pfgdv1), encoding a peri-nuclear protein, is critical for early sexual differentiation.

Functional analysis of the exported type IV HSP40 protein PfGECO in Plasmodium falciparum gametocytes.

During Plasmodium falciparum infection, host red blood cell (RBC) remodeling is required for the parasite's survival. Such modifications are mediated by the export of parasite proteins into the RBC that alter the architecture of the RBC membrane and enable cytoadherence. It is probable that some exported proteins also play a protective role against the host defense response.

Protein targeting to the parasitophorous vacuole membrane of Plasmodium falciparum.

Red blood cell (RBC) invasion and parasitophorous vacuole (PV) formation by Plasmodium falciparum are critical for the development and pathogenesis of malaria, a continuing global health problem. Expansion of the PV membrane (PVM) during growth is orchestrated by the parasite. This is particularly important in mature RBCs, which lack internal organelles and no longer actively synthesize membranes.

Malaria parasites form filamentous cell-to-cell connections during reproduction in the mosquito midgut.

Physical contact is important for the interaction between animal cells, but it can represent a major challenge for protists like malaria parasites. Recently, novel filamentous cell-cell contacts have been identified in different types of eukaryotic cells and termed nanotubes due to their morphological appearance. Nanotubes represent small dynamic membranous extensions that consist of F-actin and are considered an ancient feature evolved by eukaryotic cells to establish contact for communication.

Sex- and stage-specific reporter gene expression in Plasmodium falciparum.

For malaria transmission, Plasmodium parasites must successfully complete gametocytogenesis in the vertebrate host. Differentiation into mature male or female Plasmodium falciparum gametocytes takes 9-12 days as the parasites pass through five distinct morphologic stages (I-V). To evaluate the signals controlling the initiation of stage- and/or sex-specific expression, reporter constructs containing the 5'-flanking regions (FR) of seven genes with distinct expression patterns through gametogenesis were developed.

Inhibition of Plasmodium falciparum oocyst production by membrane-permeant cysteine protease inhibitor E64d.

During asexual intraerythrocytic growth, Plasmodium falciparum utilizes hemoglobin obtained from the host red blood cell (RBC) as a nutrient source. Papain-like cysteine proteases, falcipains 2 and 3, have been reported to be involved in hemoglobin digestion and are targets of current antimalarial drug development efforts. However, their expression during gametocytogenesis, which is required for malaria parasite transmission, has not been studied.

Malaria transmission-blocking antigen, Pfs230, mediates human red blood cell binding to exflagellating male parasites and oocyst production.

Malaria transmission requires that the parasites differentiate into gametocytes prior to ingestion by a mosquito during a blood meal. Once in the mosquito midgut the gametocytes emerge from red blood cells (RBCs), fertilize, develop into ookinetes and finally infectious sporozoites. Gamete surface antigen, Pfs230, is an important malaria transmission-blocking vaccine candidate, but its function has remained unclear.

Pfs47, paralog of the male fertility factor Pfs48/45, is a female specific surface protein in Plasmodium falciparum.

The genome of Plasmodium falciparum contains a small gene family that expresses proteins characterized by the presence of 6-cysteine domains. Most of these proteins are expressed on the surface of the parasite and some are known to play a role in cell-cell interactions. Two members of this family, Pfs48/45 and Pfs230, form a complex localized on the surface of gametes and are recognized as important targets for transmission-blocking vaccines.

Identification of a subtelomeric gene family expressed during the asexual-sexual stage transition in Plasmodium falciparum.

For malaria transmission, the parasite must undergo sexual differentiation into mature gametocytes. However, the molecular basis for this critical transition in the parasites life cycle is unknown. Six previously uncharacterized genes, Pfg14.

The DEAD-box RNA helicase Vad1 regulates multiple virulence-associated genes in Cryptococcus neoformans.

The study of fungal regulatory networks is essential to the understanding of how these pathogens respond to host environmental signals with effective virulence-associated traits. In this study, a virulence-associated DEAD-box RNA helicase-encoding gene (VAD1) was isolated from a mutant defective in the virulence factor laccase. A Deltavad1 mutant exhibited a profound reduction in virulence in a mouse model that was restored after reconstitution with WT VAD1.

Targeted disruption of Plasmodium falciparum cysteine protease, falcipain 1, reduces oocyst production, not erythrocytic stage growth.

Cysteine proteases are currently targets for drug development in a number of parasitic diseases, including malaria. In Plasmodium falciparum, the parasite responsible for the most virulent form of human malaria, there are four members of the cathepsin L-like family of cysteine proteases. Three of these (falcipains 2A, 2B and 3) are thought to be primarily involved in haemoglobin digestion, whereas falcipain 1 has recently been linked to erythrocyte invasion.

Male-specific expression of the paralog of malaria transmission-blocking target antigen Pfs230, PfB0400w.

Malaria transmission requires that Plasmodium parasites circulating in the vertebrate host develop into male and female gametocytes, which are then taken up by a mosquito to undergo fertilization and further development into infectious sporozoites. To understand the malaria specific events involved in this process, the gene products involved require identification and characterization. This work demonstrates that antibodies generated against the paralog of malaria transmission-blocking antigen Pfs230, PfB0400w, react only with stage V male gametocytes, not gametes or asexual parasites.

Targeting and sequestration of truncated Pfs230 in an intraerythrocytic compartment during Plasmodium falciparum gametocytogenesis.

For malaria to be transmitted, the Plasmodium falciparum parasite must invade an erythrocyte and undergo gametocytogenesis. When mature intraerythrocytic gametocytes are taken up in a blood meal by a mosquito they emerge as gametes and, once fertilized, continue to differentiate into infectious sporozoites. One of the major proteins associated with the surface of the parasite during gamete differentiation is Pfs230, a 360 kDa member of a family of P.