A new algorithm for wavelet-based heart rate variability analysis

One of the most promising non-invasive markers of the activity of the autonomic nervous system is heart rate variability (HRV). HRV analysis toolkits often provide spectral analysis techniques using the Fourier transform, which assumes that the heart rate series is stationary. To overcome this issue, the Short Time Fourier Transform (STFT) is often used. However, the wavelet transform is thought to be a more suitable tool for analyzing non-stationary signals than the STFT. Given the lack of support for wavelet-based analysis in HRV toolkits, such analysis must be implemented by the researcher. This has made this technique underutilized.This paper presents a new algorithm to perform HRV power spectrum analysis based on the Maximal Overlap Discrete Wavelet Packet Transform (MODWPT). The algorithm calculates the power in any spectral band with a given tolerance for the band's boundaries. The MODWPT decomposition tree is pruned to avoid calculating unnecessary wavelet coefficients, thereby optimizing execution time. The center of energy shift correction is applied to achieve optimum alignment of the wavelet coefficients. This algorithm has been implemented in RHRV, an open-source package for HRV analysis. To the best of our knowledge, RHRV is the first HRV toolkit with support for wavelet-based spectral analysis.     

Light supports cell-integrity and growth rates of taxonomically diverse coastal photoheterotrophs

Despite the widespread distribution of proteorhodopsin (PR)-containing bacteria in the oceans, the use of light-derived energy to promote bacterial growth has only been shown in a few bacterial isolates, and there is a paucity of data describing the metabolic effects of light on environmental photoheterotrophic taxa. Here, we assessed the effects of light on the taxonomic composition, cell integrity and growth responses of microbial communities in monthly incubations between spring and autumn under different environmental conditions. The photoheterotrophs expressing PR in situ were dominated by Pelagibacterales and SAR116 in July and November, while members of Euryarchaeota, Gammaproteobacteria and Bacteroidetes dominated the PR expression in spring. Cell-membrane integrity decreased under dark conditions throughout most of the assessment, with maximal effects in summer, under low-nutrient conditions. A positive effect of light on growth was observed in one incubation (out of nine), coinciding with a declining phytoplankton bloom. Light-enhanced growth was found in Gammaproteobacteria (Alteromonadales) and Bacteroidetes (Polaribacter and Tenacibaculum). Unexpectedly, some Pelagibacterales also exhibited higher growth rates under light conditions. We propose that the energy harvested by PRs helps to maintain cell viability in dominant coastal photoheterotrophic oligotrophs while promoting the growth of some widespread taxa benefiting from the decline of phytoplankton blooms.     

Immunosuppression-Independent Role of Regulatory T Cells against Hypertension-Driven Renal Dysfunctions

Hypertension-associated cardiorenal diseases represent one of the heaviest burdens for current health systems. In addition to hemodynamic damage, recent results have revealed that hematopoietic cells contribute to the development of these diseases by generating proinflammatory and profibrotic environments in the heart and kidney. However, the cell subtypes involved remain poorly characterized. Here we report that CD39⁺ regulatory T (T_REG) cells utilize an immunosuppression-independent mechanism to counteract renal and possibly cardiac damage during angiotensin II (AngII)-dependent hypertension. This mechanism relies on the direct apoptosis of tissue-resident neutrophils by the ecto-ATP diphosphohydrolase activity of CD39. In agreement with this, experimental and genetic alterations in T_REG/T_H cell ratios have a direct impact on tissue-resident neutrophil numbers, cardiomyocyte hypertrophy, cardiorenal fibrosis, and, to a lesser extent, arterial pressure elevation during AngII-driven hypertension. These results indicate that T_REG cells constitute a first protective barrier against hypertension-driven tissue fibrosis and, in addition, suggest new therapeutic avenues to prevent hypertension-linked cardiorenal diseases.     

Temporomandibular Disorders: The Habitual Chewing Side Syndrome

Background

Temporomandibular disorders are the most common cause of chronic orofacial pain, but, except where they occur subsequent to trauma, their cause remains unknown. This cross-sectional study assessed chewing function (habitual chewing side) and the differences of the chewing side and condylar path and lateral anterior guidance angles in participants with chronic unilateral temporomandibular disorder. This is the preliminary report of a randomized trial that aimed to test the effect of a new occlusal adjustment therapy.

Methods

The masticatory function of 21 randomly selected completely dentate participants with chronic temporomandibular disorders (all but one with unilateral symptoms) was assessed by observing them eat almonds, inspecting the lateral horizontal movement of the jaw, with kinesiography, and by means of interview. The condylar path in the sagittal plane and the lateral anterior guidance angles with respect to the Frankfort horizontal plane in the frontal plane were measured on both sides in each individual.

Results

Sixteen of 20 participants with unilateral symptoms chewed on the affected side; the concordance (Fisher’s exact test, P = .003) and the concordance-symmetry level (Kappa coefficient κ = 0.689; 95% confidence interval [CI], 0.38 to 0.99; P = .002) were significant. The mean condylar path angle was steeper (53.47(10.88) degrees versus 46.16(7.25) degrees; P = .001), and the mean lateral anterior guidance angle was flatter (41.63(13.35) degrees versus 48.32(9.53) degrees P = .036) on the symptomatic side.

Discussion

The results of this study support the use of a new term based on etiology, “habitual chewing side syndrome”, instead of the nonspecific symptom-based “temporomandibular joint disorders”; this denomination is characterized in adults by a steeper condylar path, flatter lateral anterior guidance, and habitual chewing on the symptomatic side.     

Vav1 and Rac control chemokine-promoted T lymphocyte adhesion mediated by the integrin alpha4beta1

The chemokine CXCL12 promotes T lymphocyte adhesion mediated by the integrin alpha4beta1. CXCL12 activates the GTPase Rac, as well as Vav1, a guanine-nucleotide exchange factor for Rac, concomitant with up-regulation of alpha4beta1-dependent adhesion. Inhibition of CXCL12-promoted Rac and Vav1 activation by transfection of dominant negative Rac or Vav1 forms, or by transfection of their siRNA, remarkably impaired the increase in T lymphocyte attachment to alpha4beta1 ligands in response to this chemokine. Importantly, inhibition of Vav1 expression by RNA interference resulted in a blockade of Rac activation in response to CXCL12. Adhesions in flow chambers and soluble binding assays using these transfectants indicated that initial ligand binding and adhesion strengthening mediated by alpha4beta1 were dependent on Vav1 and Rac activation by CXCL12. Finally, CXCL12-promoted T-cell transendothelial migration involving alpha4beta1-mediated adhesion was notably inhibited by expression of dominant negative Vav1 and Rac. These results indicate that activation of Vav1-Rac signaling pathway by CXCL12 represents an important inside-out event controlling efficient up-regulation of alpha4beta1-dependent T lymphocyte adhesion.     

Understanding Rho/Rac biology in T-cells using animal models

Experiments with cell lines have unveiled the implication of the Rho/Rac family of GTPases in cytoskeletal organization, mitogenesis, and cell migration. However, there have not been adequate animal models to investigate the role of these proteins in more physiological settings. This scenario has changed recently in the case of the T-cell lineage after the generation of animal models for Rho/Rac family members, their regulators, and effectors. These studies have revealed the implication of these GTPases on multiple regulatory layers of T-cells, including the coordination of cytoskeletal change, activation of kinase cascades, stimulation of calcium fluxes, and the induction of gene expression. These pathways affect the transition of different T-cell maturation stages, the positive/negative selection of thymocytes, T-cell responses to antigens, and the homeostasis of peripheral T-lymphocytes. Moreover, these animals have revealed interesting cross-talks between Rho/Rac pathways and other signal transduction routes that participate in lymphocyte responses.     

The disease-linked Glu-26-Lys mutant version of Coronin 1A exhibits pleiotropic and pathway-specific signaling defects

Coronin 1A (Coro1A) is involved in cytoskeletal and signaling events, including the regulation of Rac1 GTPase– and myosin II–dependent pathways. Mutations that generate truncated or unstable Coro1A proteins cause immunodeficiencies in both humans and rodents. However, in the case of the peripheral T-cell–deficient (Ptcd) mouse strain, the immunodeficiency is caused by a Glu-26-Lys mutation that targets a surface-exposed residue unlikely to affect the intramolecular architecture and stability of the protein. Here we report that this mutation induces pleiotropic effects in Coro1A protein, including the exacerbation of Coro1A-dependent actin-binding and -bundling activities; the formation of large meshworks of Coro1A^E26K-decorated filaments endowed with unusual organizational, functional, and staining properties; and the elimination of Coro1A functions associated with both Rac1 and myosin II signaling. By contrast, it does not affect the ability of Coro1A to stimulate the nuclear factor of activated T-cells (NF-AT). Coro1A^E26K is not a dominant-negative mutant, indicating that its pathological effects are derived from the inability to rescue the complete loss of the wild-type counterpart in cells. These results indicate that Coro1A^E26K behaves as either a recessive gain-of-function or loss-of-function mutant protein, depending on signaling context and presence of the wild-type counterpart in cells.     

The 90S preribosome is a multimodular structure that is assembled through a hierarchical mechanism

The 90S preribosomal particle is required for the production of the 18S rRNA from a pre-rRNA precursor. Despite the identification of the protein components of this particle, its mechanism of assembly and structural design remain unknown. In this work, we have combined biochemical studies, proteomic techniques, and bioinformatic analyses to shed light into the rules of assembly of the yeast 90S preribosome. Our results indicate that several protein subcomplexes work as discrete assembly subunits that bind in defined steps to the 35S pre-rRNA. The assembly of the t-UTP subunit is an essential step for the engagement of at least five additional subunits in two separate, and mutually independent, assembling routes. One of these routes leads to the formation of an assembly intermediate composed of the U3 snoRNP, the Pwp2p/UTP-B, subunit and the Mpp10p complex. The other assembly route involves the stepwise binding of Rrp5p and the UTP-C subunit. We also report the use of a bioinformatic approach that provides a model for the topological arrangement of protein components within the fully assembled particle. Together, our data identify the mechanism of assembly of the 90S preribosome and offer novel information about its internal architecture.