Diminazene aceturate-induced cytotoxicity is associated with the deregulation of cell cycle signaling and downregulation of oncogenes Furin, c-MYC, and FOXM1 in human cervical carcinoma Hela cells.

Diminazene aceturate (DIZE) is an FDA-listed small molecule known for the treatment of African sleeping sickness. In vivo studies showed that DIZE may be beneficial for a range of human ailments. However, there is very limited information on the effects of DIZE on human cancer cells.

Author Correction: Retinal progenitor cells release extracellular vesicles containing developmental transcription factors, microRNA and membrane proteins.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Retinal progenitor cells release extracellular vesicles containing developmental transcription factors, microRNA and membrane proteins.

A range of cell types, including embryonic stem cells, neurons and astrocytes have been shown to release extracellular vesicles (EVs) containing molecular cargo. Across cell types, EVs facilitate transfer of mRNA, microRNA and proteins between cells. Here we describe the release kinetics and content of EVs from mouse retinal progenitor cells (mRPCs).

Comparison of Confocal and Super-Resolution Reflectance Imaging of Metal Oxide Nanoparticles.

The potential for human exposure to manufactured nanoparticles (NPs) has increased in recent years, in part through the incorporation of engineered particles into a wide range of commercial goods and medical applications. NP are ideal candidates for use as therapeutic and diagnostic tools within biomedicine, however concern exists regarding their efficacy and safety. Thus, developing techniques for the investigation of NP uptake into cells is critically important.

Understanding liver immunology using intravital microscopy.

The liver has come a long way since it was considered only a metabolic organ attached to the gastrointestinal tract. The simultaneous ascension of immunology and intravital microscopy evidenced the liver as a central axis in the immune system, controlling immune responses to local and systemic agents as well as disease tolerance. The multiple hepatic cell populations are organized in a vascular environment that promotes intimate cellular interactions, including initiation of innate and adaptive immune responses, rapid leukocyte recruitment, pathogen clearance and production of a variety of immune mediators.

Patterns of care in testicular torsion: influence of hospital transfer on testicular outcomes.

Objective: To investigate patterns of care for testicular torsion and influence of hospital transfers on testicular outcomes. Hospital transfer may be a source of treatment delay in a condition where delays increase likelihood of orchiectomy.

Methods: We used a retrospective cohort of Californian males with ICD-9/CPT-defined torsion from inpatient, emergency department (ED), and ambulatory surgery center (ASC) data.

Roles of the nuclear lamina in stable nuclear association and assembly of a herpesviral transactivator complex on viral immediate-early genes.

Unlabelled: Little is known about the mechanisms of gene targeting within the nucleus and its effect on gene expression, but most studies have concluded that genes located near the nuclear periphery are silenced by heterochromatin. In contrast, we found that early herpes simplex virus (HSV) genome complexes localize near the nuclear lamina and that this localization is associated with reduced heterochromatin on the viral genome and increased viral immediate-early (IE) gene transcription. In this study, we examined the mechanism of this effect and found that input virion transactivator protein, virion protein 16 (VP16), targets sites adjacent to the nuclear lamina and is required for targeting of the HSV genome to the nuclear lamina, exclusion of heterochromatin from viral replication compartments, and reduction of heterochromatin on the viral genome.

Human cytomegalovirus UL44 concentrates at the periphery of replication compartments, the site of viral DNA synthesis.

The formation of replication compartments, the subnuclear structures in which the viral DNA genome is replicated, is a hallmark of herpesvirus infections. The localization of proteins and viral DNA within human cytomegalovirus replication compartments is not well characterized. Immunofluorescence analysis demonstrated the accumulation of the viral DNA polymerase subunit UL44 at the periphery of replication compartments and the presence of different populations of UL44 in infected cells.

Herpesviral replication compartments move and coalesce at nuclear speckles to enhance export of viral late mRNA.

The role of the intranuclear movement of chromatin in gene expression is not well-understood. Herpes simplex virus forms replication compartments (RCs) in infected cell nuclei as sites of viral DNA replication and late gene transcription. These structures develop from small compartments that grow in size, move, and coalesce.

The dynamic properties of intermediate filaments during organelle transport.

Intermediate filament (IF) dynamics during organelle transport and their role in organelle movement were studied using Xenopus laevis melanophores. In these cells, pigment granules (melanosomes) move along microtubules and microfilaments, toward and away from the cell periphery in response to alpha-melanocyte stimulating hormone (alpha-MSH) and melatonin, respectively. In this study we show that melanophores possess a complex network of vimentin IFs which interact with melanosomes.

Introducing simulated cellular architecture to the quantitative analysis of fluorescent microscopy.

Biological cells are complex and highly dynamic: many macromolecules are organized in loose assemblies, clusters or highly structured complexes, others exist most of the time as freely diffusing monomers. They move between regions and compartments through diffusion and enzyme-mediated transport, within a heavily crowded cytoplasm. To make sense of this complexity, computational models, and, in turn, quantitative in vivo data are needed.

Role for A-type lamins in herpesviral DNA targeting and heterochromatin modulation.

Posttranslational modification of histones is known to regulate chromatin structure and transcriptional activity, and the nuclear lamina is thought to serve as a site for heterochromatin maintenance and transcriptional silencing. In this report, we show that the nuclear lamina can also play a role in the downregulation of heterochromatin and in gene activation. Herpes simplex virus DNA initiates replication in replication compartments near the inner edge of the nucleus, and histones are excluded from these structures.

The motility and dynamic properties of intermediate filaments and their constituent proteins.

Intermediate filament (IF) proteins exist in multiple structural forms within cells including mature IF, short filaments or 'squiggles', and non-filamentous precursors called particles. These forms are interconvertible and their relative abundance is IF type, cell type- and cell cycle stage-dependent. These structures are often associated with molecular motors, such as kinesin and dynein, and are therefore capable of translocating through the cytoplasm along microtubules.

Assembling an intermediate filament network by dynamic cotranslation.

We have been able to observe the dynamic interactions between a specific messenger RNA (mRNA) and its protein product in vivo by studying the synthesis and assembly of peripherin intermediate filaments (IFs). The results show that peripherin mRNA-containing particles (messenger ribonucleoproteins [mRNPs]) move mainly along microtubules (MT). These mRNPs are translationally silent, initiating translation when they cease moving.

Intermediate filaments mediate cytoskeletal crosstalk.

Intermediate filaments, actin-containing microfilaments and microtubules are the three main cytoskeletal systems of vertebrate and many invertebrate cells. Although these systems are composed of distinctly different proteins, they are in constant and intimate communication with one another. Understanding the molecular basis of this cytoskeletal crosstalk is essential for determining the mechanisms that underlie many cell-biological phenomena.

Intermediate filaments are dynamic and motile elements of cellular architecture.

Recent evidence showing that intermediate filaments (IFs) are dynamic, motile elements of the cytoskeletal repertoire of vertebrate cells has overturned the long-standing view that they simply form static 'space filling' cytoplasmic networks. In fact, many types of IF are now known to engage in a remarkable array of movements that are closely associated with their assembly, disassembly and subcellular organization. Some of these motile properties are intrinsic to IFs and others are attributable to molecular crosstalk with either microtubules or actin-containing microfilaments.

The dynamic and motile properties of intermediate filaments.

For many years, cytoplasmic intermediate filaments (IFs) were considered to be stable cytoskeletal elements contributing primarily to the maintenance of the structural and mechanical integrity of cells. However, recent studies of living cells have revealed that IFs and their precursors possess a remarkably wide array of dynamic and motile properties. These properties are in large part due to interactions with molecular motors such as conventional kinesin, cytoplasmic dynein, and myosin.