A dynamin superfamily-like pseudoenzyme coordinates with MICOS to promote cristae architecture.

Mitochondrial cristae architecture is crucial for optimal respiratory function of the organelle. Cristae shape is maintained in part by the mitochondrial contact site and cristae organizing system (MICOS) complex. While MICOS is required for normal cristae morphology, the precise mechanistic role of each of the seven human MICOS subunits, and how the complex coordinates with other cristae-shaping factors, has not been fully determined.

A DRP-like pseudoenzyme coordinates with MICOS to promote cristae architecture.

Mitochondrial cristae architecture is crucial for optimal respiratory function of the organelle. Cristae shape is maintained in part by the mitochondrial inner membrane-localized MICOS complex. While MICOS is required for normal cristae morphology, the precise mechanistic role of each of the seven human MICOS subunits, and how the complex coordinates with other cristae shaping factors, has not been fully determined.

Toxoplasma ERK7 protects the apical complex from premature degradation.

Accurate cellular replication balances the biogenesis and turnover of complex structures. In the apicomplexan parasite Toxoplasma gondii, daughter cells form within an intact mother cell, creating additional challenges to ensuring fidelity of division. The apical complex is critical to parasite infectivity and consists of apical secretory organelles and specialized cytoskeletal structures.

Cryo-tomography reveals rigid-body motion and organization of apicomplexan invasion machinery.

The apical complex is a specialized collection of cytoskeletal and secretory machinery in apicomplexan parasites, which include the pathogens that cause malaria and toxoplasmosis. Its structure and mechanism of motion are poorly understood. We used cryo-FIB-milling and cryo-electron tomography to visualize the 3D-structure of the apical complex in its protruded and retracted states.

Not your Mother's MAPKs: Apicomplexan MAPK function in daughter cell budding.

Reversible phosphorylation by protein kinases is one of the core mechanisms by which biological signals are propagated and processed. Mitogen-activated protein kinases, or MAPKs, are conserved throughout eukaryotes where they regulate cell cycle, development, and stress response. Here, we review advances in our understanding of the function and biochemistry of MAPK signaling in apicomplexan parasites.

Divergent kinase WNG1 is regulated by phosphorylation of an atypical activation sub-domain.

Apicomplexan parasites like Toxoplasma gondii grow and replicate within a specialized organelle called the parasitophorous vacuole. The vacuole is decorated with parasite proteins that integrate into the membrane after trafficking through the parasite secretory system as soluble, chaperoned complexes. A regulator of this process is an atypical protein kinase called WNG1.

Multivalent Interactions Drive the AC9:AC10:ERK7 Complex To Concentrate ERK7 in the Apical Cap.

The inner membrane complex (IMC) is a specialized organelle that is crucial for the parasite to establish an intracellular lifestyle and ultimately cause disease. The IMC is composed of both membrane and cytoskeletal components, further delineated into the apical cap, body, and basal subcompartments. The apical cap cytoskeleton was recently demonstrated to govern the stability of the apical complex, which controls parasite motility, invasion, and egress.

SchistoCyte Atlas: A Single-Cell Transcriptome Resource for Adult Schistosomes.

Schistosomes cause untold disease and disability in the developing world. Here, we introduce SchistoCyte Atlas, a web-based platform for exploring gene expression at single-cell resolution in adult Schistosoma mansoni. Similar resources accessible to non-specialists across the globe will expedite our ability to understand the biology of these devastating parasites.

Third-generation sequencing revises the molecular karyotype for and identifies emerging copy number variants in sexual recombinants.

is a useful model for intracellular parasitism given its ease of culture in the laboratory and genomic resources. However, as for many other eukaryotes, the genome contains hundreds of sequence gaps owing to repetitive and/or unclonable sequences that disrupt the assembly process. Here, we use the Oxford Nanopore Minion platform to generate near-complete de novo genome assemblies for multiple strains of and its near relative, We significantly improved genome contiguity (average N50 of ∼6.

Association between cerebrospinal fluid lactate concentration and central nervous system disease in dogs.

Background: Cerebrospinal fluid (CSF) analysis is a sensitive tool for evaluating patients with neurologic diseases but is rarely specific. Biomarkers can be measured from any bodily fluid and can be useful indicators for the presence, severity, and prognosis of diseases.

Objectives: This study was designed to evaluate if CSF lactate can be used as a biomarker in dogs with central nervous system disease.

Loss of the Conserved Alveolate Kinase MAPK2 Decouples Cell Growth from Cell Division.

Mitogen-activated protein kinases (MAPKs) are a conserved family of protein kinases that regulate signal transduction, proliferation, and development throughout eukaryotes. The apicomplexan parasite expresses three MAPKs. Two of these, extracellular signal-regulated kinase 7 (ERK7) and MAPKL1, have been implicated in the regulation of conoid biogenesis and centrosome duplication, respectively.

A single-cell RNA-seq atlas of identifies a key regulator of blood feeding.

Schistosomiasis is a neglected tropical disease that infects 240 million people. With no vaccines and only one drug available, new therapeutic targets are needed. The causative agents, schistosomes, are intravascular flatworm parasites that feed on blood and lay eggs, resulting in pathology.

Naïve CD8 T cell IFNγ responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma gondii ROP5.

Host resistance to Toxoplasma gondii relies on CD8 T cell IFNγ responses, which if modulated by the host or parasite could influence chronic infection and parasite transmission between hosts. Since host-parasite interactions that govern this response are not fully elucidated, we investigated requirements for eliciting naïve CD8 T cell IFNγ responses to a vacuolar resident antigen of T. gondii, TGD057.

Behavior and Performance of Suckling Piglets Provided Three Supplemental Heat Sources.

This study compared water-heated mats (WM) and electric-heated mats (EM) with heat lamps (HL) as supplemental heat sources for suckling piglets. Forty-two litters were studied in 3 trials. In all trials, behavior of piglets was video-recorded on day 1, 3, 7, 14, and 21 postpartum.

Ancient MAPK ERK7 is regulated by an unusual inhibitory scaffold required for apical complex biogenesis.

Apicomplexan parasites use a specialized cilium structure called the apical complex to organize their secretory organelles and invasion machinery. The apical complex is integrally associated with both the parasite plasma membrane and an intermediate filament cytoskeleton called the inner-membrane complex (IMC). While the apical complex is essential to the parasitic lifestyle, little is known about the regulation of apical complex biogenesis.

Loss of a conserved MAPK causes catastrophic failure in assembly of a specialized cilium-like structure in .

Primary cilia are important organizing centers that control diverse cellular processes. Apicomplexan parasites like have a specialized cilium-like structure called the conoid that organizes the secretory and invasion machinery critical for the parasites' lifestyle. The proteins that initiate the biogenesis of this structure are largely unknown.

The assembly of lipid droplets and their roles in challenged cells.

[Image: see text]

Peers Keep It Real: Re-engaging Adults in HIV Care.

Background: After diagnosis, a substantial number of people with HIV disease fall out of care. Effective interventions are needed for this priority population.

Methods: The "Peers Keep It Real" study aimed to help adults who were disengaged from HIV treatment.

Thinking outside of the cell: Secreted protein kinases in bacteria, parasites, and mammals.

Previous decades have seen an explosion in our understanding of protein kinase function in human health and disease. Hundreds of unique kinase structures have been solved, allowing us to create generalized rules for catalysis, assign roles of communities within the catalytic core, and develop specific drugs for targeting various pathways. Although our understanding of intracellular kinases has developed at a fast rate, our exploration into extracellular kinases has just begun.

Divergent kinase regulates membrane ultrastructure of the parasitophorous vacuole.

Apicomplexan parasites replicate within a protective organelle, called the parasitophorous vacuole (PV). The PV is filled with a network of tubulated membranes, which are thought to facilitate trafficking of effectors and nutrients. Despite being critical to parasite virulence, there is scant mechanistic understanding of the network's functions.

In vitro effect of chlorambucil on human glioma cell lines (SF767 and U87-MG), and human microvascular endothelial cell (HMVEC) and endothelial progenitor cells (ECFCs), in the context of plasma chlorambucil concentrations in tumor-bearing dogs.

The objective of this study was to investigate a possible mechanism of action of metronomic chlorambucil on glioma by studying the in vitro cytotoxicity and anti-angiogenic effects on glioma and endothelial cells, respectively. The in vitro LD50 and IC50 of chlorambucil were determined using human SF767 and U87-MG glioma cell lines, human microvascular endothelial cells (HMVECs) and human endothelial colony forming cells (ECFCs). Results were analyzed in the context of chlorambucil concentrations measured in the plasma of tumor-bearing dogs receiving 4 mg m-2 metronomic chlorambucil.

Feasibility trial of an unsupervised, facility-based exercise programme for depressed outpatients.

This pilot study examined feasibility of an unsupervised, facility-based exercise programme for promoting exercise adherence among depressed adult outpatients. The potential effect of adding physical activity counselling on depressive symptoms and physical activity was also explored. Participants were randomly assigned to a 12-week programme comprising an orientation and access to fitness centre resources (control, n = 18) or that programme plus 6 physical activity counselling sessions (intervention, n = 18).

The assembly of lipid droplets and their roles in challenged cells.

Cytoplasmic lipid droplets are important organelles in nearly every eukaryotic and some prokaryotic cells. Storing and providing energy is their main function, but they do not work in isolation. They respond to stimuli initiated either on the cell surface or in the cytoplasm as conditions change.

Ammonia Synthesis at Low Pressure.

Ammonia can be synthesized at low pressure by the use of an ammonia selective absorbent. The process can be driven with wind energy, available locally in areas requiring ammonia for synthetic fertilizer. Such wind energy is often called "stranded," because it is only available far from population centers where it can be directly used.

Clinical and imaging findings, treatments, and outcomes in 27 dogs with imaging diagnosed trigeminal nerve sheath tumors: A multi-center study.

The clinical behavior of canine trigeminal nerve sheath tumors and benefits of previously reported treatments are incompletely defined. Aims of this retrospective, multicenter, observational study were to describe clinical signs, tumor localization characteristics, treatments, and clinical outcomes in a group of dogs with this neoplasm. Databases at four hospitals were reviewed for dogs with a trigeminal nerve sheath tumor diagnosis, magnetic resonance imaging (MRI) studies, and presentation between 2004 and 2014.