ARK1 regulates spindle formation during atypical mitosis and forms a divergent chromosomal passenger complex.

Mitosis in spp., the causative agent of malaria, is fundamentally different from model eukaryotes, proceeding via a bipartite microtubule organising centre (MTOC) and lacking canonical regulators such as Polo and Bub1 kinases. During schizogony, asynchronous nuclear replication produces a multinucleate schizont, while rapid male gametogony generates an octaploid nucleus before gamete formation.

Divergent kinases drive MTOC, kinetochore and axoneme organisation in male gametogenesis.

Sexual development and male gamete formation of the malaria parasite in the mosquito midgut are initiated by rapid endomitosis in the activated male gametocyte. This process is highly regulated by protein phosphorylation, specifically by three divergent male-specific protein kinases (PKs): CDPK4, SRPK1, and MAP2. Here, we localise each PK during male gamete formation using live-cell imaging, identify their putative interacting partners by immunoprecipitation, and determine the morphological consequences of their absence using ultrastructure expansion and transmission electron microscopy.

The molecular mechanisms driving Plasmodium cell division.

Malaria, a vector borne disease, is a major global health and socioeconomic problem caused by the apicomplexan protozoan parasite Plasmodium. The parasite alternates between mosquito vector and vertebrate host, with meiosis in the mosquito and proliferative mitotic cell division in both hosts. In the canonical eukaryotic model, cell division is either by open or closed mitosis and karyokinesis is followed by cytokinesis; whereas in Plasmodium closed mitosis is not directly accompanied by concomitant cell division.

DF-dRVFL: A novel deep feature based classifier for breast mass classification.

Amongst all types of cancer, breast cancer has become one of the most common cancers in the UK threatening millions of people's health. Early detection of breast cancer plays a key role in timely treatment for morbidity reduction. Compared to biopsy, which takes tissues from the lesion for further analysis, image-based methods are less time-consuming and pain-free though they are hampered by lower accuracy due to high false positivity rates.

Meiosis in Plasmodium: how does it work?

Meiosis is sexual cell division, a process in eukaryotes whereby haploid gametes are produced. Compared to canonical model eukaryotes, meiosis in apicomplexan parasites appears to diverge from the process with respect to the molecular mechanisms involved; the biology of Plasmodium meiosis, and its regulation by means of post-translational modification, are largely unexplored. Here, we discuss the impact of technological advances in cell biology, evolutionary bioinformatics, and genome-wide functional studies on our understanding of meiosis in the Apicomplexa.

Plasmodium ARK2-EB1 axis drives the unconventional spindle dynamics, scaffold formation and chromosome segregation of sexual transmission stages.

Mechanisms of cell division are remarkably diverse, suggesting the underlying molecular networks among eukaryotes differ extensively. The Aurora family of kinases orchestrates the process of chromosome segregation and cytokinesis during cell division through precise spatiotemporal regulation of their catalytic activities by distinct scaffolds. Plasmodium spp.

ARK2-EB1 axis drives the unconventional spindle dynamics, scaffold formation and chromosome segregation of sexual transmission stages.

Mechanisms of cell division are remarkably diverse, suggesting the underlying molecular networks among eukaryotes differ extensively. The Aurora family of kinases orchestrates the process of chromosome segregation and cytokinesis during cell division through precise spatiotemporal regulation of their catalytic activities by distinct scaffolds. spp.

Genome engineering for estrogen receptor mutations reveals differential responses to anti-estrogens and new prognostic gene signatures for breast cancer.

Mutations in the estrogen receptor (ESR1) gene are common in ER-positive breast cancer patients who progress on endocrine therapies. Most mutations localise to just three residues at, or near, the C-terminal helix 12 of the hormone binding domain, at leucine-536, tyrosine-537 and aspartate-538. To investigate these mutations, we have used CRISPR-Cas9 mediated genome engineering to generate a comprehensive set of isogenic mutant breast cancer cell lines.

Shallow WGS of individual CTCs identifies actionable targets for informing treatment decisions in metastatic breast cancer.

Background: We report copy-number profiling by low-pass WGS (LP-WGS) in individual circulating tumour cells (CTCs) for guiding treatment in patients with metastatic breast cancer (MBC), comparing CTC results with mutations detected in circulating tumour DNA (ctDNA) in the same blood samples.

Methods: Across 10 patients with MBC who were progressing at the time of blood sampling and that had >20 CTCs detected by CellSearch, 63 single cells (50 CTCs and 13 WBCs) and 16 cell pools (8 CTC pools and 8 WBC pools) were recovered from peripheral blood by CellSearch/DEPArray™ and sequenced with Ampli1 LowPass technology (Menarini Silicon Biosystems). Copy-number aberrations were identified using the MSBiosuite software platform, and results were compared with mutations detected in matched plasma cfDNA analysed by targeted next-generation sequencing using the Oncomine™ Breast cfDNA Assay (Thermo Fisher).

Division and Transmission: Malaria Parasite Development in the Mosquito.

The malaria parasite life cycle alternates between two hosts: a vertebrate and the female mosquito vector. Cell division, proliferation, and invasion are essential for parasite development, transmission, and survival. Most research has focused on development in the vertebrate, which causes disease; however, knowledge of malaria parasite development in the mosquito (the sexual and transmission stages) is now rapidly accumulating, gathered largely through investigation of the rodent malaria model, with In this review, we discuss the seminal genome-wide screens that have uncovered key regulators of cell proliferation, invasion, and transmission during sexual development.

PeMNet for Pectoral Muscle Segmentation.

As an important imaging modality, mammography is considered to be the global gold standard for early detection of breast cancer. Computer-Aided (CAD) systems have played a crucial role in facilitating quicker diagnostic procedures, which otherwise could take weeks if only radiologists were involved. In some of these CAD systems, breast pectoral segmentation is required for breast region partition from breast pectoral muscle for specific analysis tasks.

Circulating Tumor DNA Profiling From Breast Cancer Screening Through to Metastatic Disease.

Purpose: We investigated the utility of the Oncomine Breast cfDNA Assay for detecting circulating tumor DNA (ctDNA) in women from a breast screening population, including healthy women with no abnormality detected by mammogram, and women on follow-up through to advanced breast cancer.

Materials And Methods: Blood samples were taken from 373 women (127 healthy controls recruited through breast screening, 28 ductal carcinoma in situ, 60 primary breast cancers, 47 primary breast cancer on follow-up, and 111 metastatic breast cancers [MBC]) to recover plasma and germline DNA for analysis with the Oncomine Breast cfDNA Assay on the Ion S5 platform.

Results: One hundred sixteen of 373 plasma samples had one or more somatic variants detected across eight of the 10 genes and were called ctDNA-positive; MBC had the highest proportion of ctDNA-positive samples (61; 55%) and healthy controls the lowest (20; 15.

Improving ductal carcinoma in situ classification by convolutional neural network with exponential linear unit and rank-based weighted pooling.

Ductal carcinoma in situ (DCIS) is a pre-cancerous lesion in the ducts of the breast, and early diagnosis is crucial for optimal therapeutic intervention. Thermography imaging is a non-invasive imaging tool that can be utilized for detection of DCIS and although it has high accuracy (~ 88%), it is sensitivity can still be improved. Hence, we aimed to develop an automated artificial intelligence-based system for improved detection of DCIS in thermographs.

Protein phosphatase 1 regulates atypical mitotic and meiotic division in Plasmodium sexual stages.

PP1 is a conserved eukaryotic serine/threonine phosphatase that regulates many aspects of mitosis and meiosis, often working in concert with other phosphatases, such as CDC14 and CDC25. The proliferative stages of the malaria parasite life cycle include sexual development within the mosquito vector, with male gamete formation characterized by an atypical rapid mitosis, consisting of three rounds of DNA synthesis, successive spindle formation with clustered kinetochores, and a meiotic stage during zygote to ookinete development following fertilization. It is unclear how PP1 is involved in these unusual processes.

Comparison of two targeted ultra-deep sequencing technologies for analysis of plasma circulating tumour DNA in endocrine-therapy-resistant breast cancer patients.

Purpose: There is growing interest in the application of circulating tumour DNA (ctDNA) as a sensitive tool for monitoring tumour evolution and guiding targeted therapy in patients with cancer. However, robust comparisons of different platform technologies are still required. Here we compared the InVisionSeq™ ctDNA Assay with the Oncomine™ Breast cfDNA Assay to assess their concordance and feasibility for the detection of mutations in plasma at low (< 0.

Patient acceptability of circulating tumour DNA testing in endometrial cancer follow-up.

Objective: Circulating tumour DNA (ctDNA) is emerging as a potential option to detect disease recurrence in many cancer types, however, ensuring patient acceptability of changing clinical practice and the introduction of new technology is paramount.

Methods: Patients enrolled in a non-intervention cohort study determining the ability of ctDNA to detect recurrent endometrial cancer (EC) were invited to participate in a semi-structured interview. Analysis was performed by Template Analysis.

Modeling of diagnosis for metabolic syndrome by integrating symptoms into physiochemical indexes.

Background: Metabolic syndrome (MS) is a major global health concern comprising a cluster of co-occurring conditions that increase the risk of heart disease, stroke and type 2 diabetes. MS is usually diagnosed using a combination of physiochemical indexes (such as BMI, abdominal circumference and blood pressure) but largely ignores clinical symptoms when investigating prevention and treatment of the disease. Exploring predictors of MS using multiple diagnostic indicators may improve early diagnosis and treatment of MS.

A Heuristic Neural Network Structure Relying on Fuzzy Logic for Images Scoring.

Traditional deep learning methods are sub-optimal in classifying ambiguity features, which often arise in noisy and hard to predict categories, especially, to distinguish semantic scoring. Semantic scoring, depending on semantic logic to implement evaluation, inevitably contains fuzzy description and misses some concepts, for example, the ambiguous relationship between normal and probably normal always presents unclear boundaries (normal - more likely normal - probably normal). Thus, human error is common when annotating images.

MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life.

The meiotic recombination 11 protein (MRE11) plays a key role in DNA damage response and maintenance of genome stability. However, little is known about its function during development of the malaria parasite . Here, we present a functional, ultrastructural and transcriptomic analysis of parasites lacking MRE11 during its life cycle in both mammalian and mosquito vector hosts.

DEH is ER-localized and crucial for oocyst mitotic division during malaria transmission.

Cells use fatty acids (FAs) for membrane biosynthesis, energy storage, and the generation of signaling molecules. 3-hydroxyacyl-CoA dehydratase-DEH-is a key component of very long chain fatty acid synthesis. Here, we further characterized in-depth the location and function of DEH, applying in silico analysis, live cell imaging, reverse genetics, and ultrastructure analysis using the mouse malaria model DEH is evolutionarily conserved across eukaryotes, with a single DEH in spp.

Deep Spatio-Temporal Representation and Ensemble Classification for Attention Deficit/Hyperactivity Disorder.

Attention deficit/Hyperactivity disorder (ADHD) is a complex, universal and heterogeneous neurodevelopmental disease. The traditional diagnosis of ADHD relies on the long-term analysis of complex information such as clinical data (electroencephalogram, etc.), patients' behavior and psychological tests by professional doctors.

Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and Progression.

Despite the increasing incidence of endometrial cancer (EC) worldwide and the poor overall survival of patients who recur, no reliable biomarker exists for detecting and monitoring EC recurrence and progression during routine follow-up. Circulating tumor DNA (ctDNA) is a sensitive method for monitoring cancer activity and stratifying patients that are likely to respond to therapy. As a pilot study, we investigated the utility of ctDNA for detecting and monitoring EC recurrence and progression in 13 patients, using targeted next-generation sequencing (tNGS) and personalized ctDNA assays.