Cardiac Transverse Tubules in Physiology and Heart Failure

In mammalian cardiac myocytes, the plasma membrane includes the surface sarcolemma but also a network of membrane invaginations called transverse (t-) tubules. These structures carry the action potential deep into the cell interior, allowing efficient triggering of Ca2+ release and initiation of contraction. Once thought to serve as rather static enablers of excitation-contraction coupling, recent work has provided a newfound appreciation of the plasticity of the t-tubule network's structure and function. Indeed, t-tubules are now understood to support dynamic regulation of the heartbeat across a range of timescales, during all stages of life, in both health and disease. This review article aims to summarize these concepts, with consideration given to emerging t-tubule regulators and their targeting in future therapies. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The Genes Encoding Small Leucine-Rich Proteoglycans Undergo Differential Expression Alterations in Colorectal Cancer, Depending on Tumor Location

Small leucine-rich proteoglycans (SLRPs) regulate different processes and undergo significant alterations in various diseases. Colon carcinomas (CCs) are heterogeneous pathologies with important clinical and molecular differences depending on their location, which makes it interesting to analyze the alterations in SLRPs in right- and left-sided tumors (RS- and LSCCs). SLRP transcription levels were studied in 32 CCs using qPCR compared to healthy colon mucosae samples from the same patients, 20 of them from LSCCs and the remaining 12 from RSCCs. Protein expression of genes with significant differences in their transcriptions was analyzed by immunohistochemistry. The alterations observed were related to survival data. The arrangement of transcription of SLRPs was quite similar in ascending and descending colon, but RS- and LSCCs displayed different patterns of alteration, with a greater number of deregulations occurring in the latter. The analysis of protein expression also indicated changes in the location of these molecules, largely moving to the cell interior. While podocan underexpression showed a trend toward better outcomes, no differences were observed in terms of overall survival. In vitro studies using the HT29 tumor cell line suggest that deregulation of SLRPs could affect cell proliferation. SLRPs constitute new differential markers of RS- and LSCCs, showing differences dependent on the anatomical location of the tumor.

TRPV Protein Family—From Mechanosensing to Cancer Invasion

Biophysical cues from the cellular microenvironment are detected by mechanosensitive machineries that translate physical signals into biochemical signaling cascades. At the crossroads of extracellular space and cell interior are located several ion channel families, including TRP family proteins, that are triggered by mechanical stimuli and drive intracellular signaling pathways through spatio-temporally controlled Ca2+-influx. Mechanosensitive Ca2+-channels, therefore, act as critical components in the rapid transmission of physical signals into biologically compatible information to impact crucial processes during development, morphogenesis and regeneration. Given the mechanosensitive nature of many of the TRP family channels, they must also respond to the biophysical changes along the development of several pathophysiological conditions and have also been linked to cancer progression. In this review, we will focus on the TRPV, vanilloid family of TRP proteins, and their connection to cancer progression through their mechanosensitive nature.

New species of benthic marine diatoms (Bacillariophyta) from the Western Pacific islands of Guam and Yap

In the course of preparation of a major checklist for Yap and ongoing investigations into the benthic marine diatom flora of Micronesia, thirteen new araphid and raphid pennate diatom species have been recognized and are described here. Plagiogramma subatomus is even smaller than P. atomus and the pseudoseptum forms a box with only a small opening toward the cell interior. Licmophora romuli is similar in size and spathulate shape to L. remulus, but the majority of the striae in the lamina lack vimines. L. graphis is exceedingly delicate, pencil-shaped, with apical striae 60–70 in 10 µm. Divergita biformis and D. decipiens are straight species with striae biseriate on the margin, uniseriate on the valve face, differing in the shape and prominence of the sternum and the shape of the valve-face areolae. D. macinnisii (from Marshall Islands, but included here for comparison) is curved, again with the decussate areolar pattern on the mantle, but with single extended areolae along each side of the linear sternum. These characters slightly amend the diagnosis of the genus. Thalassionema baculum is a very short member of the genus, linear and isopolar. Climaconeis tarangensis is curved and differs from C. riddleae in stria density and areola shape; C. minaegensis is straight, without a stauros or craticular bars, of intermediate length, 228–247 µm. First SEM observations of Climaconeis lorenzii are presented and an updated key to Climaconeis is appended. Parlibellus paschalis is a tube-dwelling species differing from P. delognei is lacking cuniculi and pores in the central area. P. waabensis is a relatively large species, possibly tube-dwelling, that differs from P. delognei in shape and spacing of central striae and from P. berkeleyi in width and stria density. Pleurosigma simulacrum differs in ultrastructural details from P. intermedium. Lastly, Nitzschia tarangensis is a conopeate species, spathulate in profile with ribs along the edge of the valve depression and bordering the raphe, and with pores in the peri-raphe zone.

Modeling the quiet Sun cell and network emission with ALMA

Observations of the Sun at millimeter wavelengths with the Atacama Large Millimeter/submillimeter Array (ALMA) offer a unique opportunity to investigate the temperature structure of the solar chromosphere. In this article we expand our previous work on modeling the chromospheric temperature of the quiet Sun, by including measurements of the brightness temperature in the network and cell interiors, from high-resolution ALMA images at 3 mm (Band 3) and 1.26 mm (Band 6). We also examine the absolute calibration of ALMA full-disk images. We suggest that the brightness temperature at the center of the solar disk in Band 6 is ∼440 K above the value recommended by White et al. (2017, Sol. Phys., 292, 88). In addition, we give improved results for the electron temperature variation of the average quiet Sun with optical depth and the derived spectrum at the center of the disk. We found that the electron temperature in the network is considerably lower than predicted by model F of Fontenla et al. (1993, ApJ, 406, 319) and that of the cell interior considerably higher than predicted by model A. Depending on the network/cell segregation scheme, the electron temperature difference between network and cell at τ = 1 (100 GHz) ranges from ∼660 K to ∼1550 K, compared to ∼3280 K predicted by the models; similarly, the electron temperature, Te ratio ranges from ∼1.10 to 1.24, compared to ∼1.55 of the model prediction. We also found that the network/cell Te(τ) curves diverge as τ decreases, indicating an increase of contrast with height and possibly a steeper temperature rise in the network than in the cell interior.

A Cellular Automaton Model as a First Model-Based Assessment of Interacting Mechanisms for Insulin Granule Transport in Beta Cells

In this paper a first model is derived and applied which describes the transport of insulin granules through the cell interior and at the membrane of a beta cell. A special role is assigned to the actin network, which significantly influences the transport. For this purpose, microscopically measured actin networks are characterized and then further ones are artificially generated. In a Cellular Automaton model, phenomenological laws for granule movement are formulated and implemented. Simulation results are compared with experiments, primarily using TIRF images and secretion rates. In this respect, good similarities are already apparent. The model is a first useful approach to describe complex granule transport processes in beta cells, and offers great potential for future extensions. Furthermore, the model can be used as a tool to validate hypotheses and associated mechanisms regarding their effect on exocytosis or other processes. For this purpose, the source code for the model is provided online.

Long-Range and Directional Allostery of Actin Filaments Plays Important Roles in Various Cellular Activities

A wide variety of uniquely localized actin-binding proteins (ABPs) are involved in various cellular activities, such as cytokinesis, migration, adhesion, morphogenesis, and intracellular transport. In a micrometer-scale space such as the inside of cells, protein molecules diffuse throughout the cell interior within seconds. In this condition, how can ABPs selectively bind to particular actin filaments when there is an abundance of actin filaments in the cytoplasm? In recent years, several ABPs have been reported to induce cooperative conformational changes to actin filaments allowing structural changes to propagate along the filament cables uni- or bidirectionally, thereby regulating the subsequent binding of ABPs. Such propagation of ABP-induced cooperative conformational changes in actin filaments may be advantageous for the elaborate regulation of cellular activities driven by actin-based machineries in the intracellular space, which is dominated by diffusion. In this review, we focus on long-range allosteric regulation driven by cooperative conformational changes of actin filaments that are evoked by binding of ABPs, and discuss roles of allostery of actin filaments in narrow intracellular spaces.

Optical trapping of nucleolus reveals viscoelastic properties of nucleoplasm inside mouse germinal vesicle oocytes

ABSTRACTWe propose a technique of controlled manipulation with mammalian intracellular bodies by means of optical trapping in order to reveal viscoelastic properties of cell interior. Near infrared laser in the spectral range of tissue transparency was applied to study dynamics of the nucleolus-chromatin complex inside the thermodynamically non-equilibrium system of a mouse oocyte. A nucleolus of germinal vesicle (GV) oocyte as spherical probe was displaced from the equilibrium and its relaxation dynamics was observed. We developed software for subdiffraction tracking of a nucleolus position with lateral resolution up to 3 nm and applied it for different GV-oocyte chromatin configurations. We showed differences in viscoelastic properties within nucleoplasm of NSN-oocytes, visualized by Hoechst 33342 staining. Also, we demonstrate that in germ cells basic biophysical properties of nucleoplasm can be obtained by using optical trapping without disruption and modification of cellular interior.