An interesting concept in the organization of cellular membranes is the proposed existence of lipid rafts. Membranes of eukaryotic cells organize signal transduction proteins into membrane rafts or ...lipid rafts that are enriched in particular lipids such as cholesterol and are important for the correct functionality of diverse cellular processes. The assembly of lipid rafts in eukaryotes has been considered a fundamental step during the evolution of cellular complexity, suggesting that bacteria and archaea were organisms too simple to require such a sophisticated organization of their cellular membranes. However, it was recently discovered that bacteria organize many signal transduction, protein secretion, and transport processes in functional membrane microdomains, which are equivalent to the lipid rafts of eukaryotic cells. This review contains the most significant advances during the last 4 years in understanding the structural and biological role of lipid rafts in bacteria. Furthermore, this review shows a detailed description of a number of molecular and genetic approaches related to the discovery of bacterial lipid rafts as well as an overview of the group of tentative lipid-protein and protein-protein interactions that give consistency to these sophisticated signaling platforms. Additional data suggesting that lipid rafts are widely distributed in bacteria are presented in this review. Therefore, we discuss the available techniques and optimized protocols for the purification and analysis of raft-associated proteins in various bacterial species to aid in the study of bacterial lipid rafts in other laboratories that could be interested in this topic. Overall, the discovery of lipid rafts in bacteria reveals a new level of sophistication in signal transduction and membrane organization that was unexpected for bacteria and shows that bacteria are more complex than previously appreciated.
Spinal muscular atrophy (SMA) is a severe neuromuscular autosomal recessive disorder affecting 1/10,000 live births. Most SMA patients present homozygous deletion of SMN1, while the vast majority of ...SMA carriers present only a single SMN1 copy. The sequence similarity between SMN1 and SMN2, and the complexity of the SMN locus makes the estimation of the SMN1 copy‐number by next‐generation sequencing (NGS) very difficult. Here, we present SMAca, the first python tool to detect SMA carriers and estimate the absolute SMN1 copy‐number using NGS data. Moreover, SMAca takes advantage of the knowledge of certain variants specific to SMN1 duplication to also identify silent carriers. This tool has been validated with a cohort of 326 samples from the Navarra 1000 Genomes Project (NAGEN1000). SMAca was developed with a focus on execution speed and easy installation. This combination makes it especially suitable to be integrated into production NGS pipelines. Source code and documentation are available at https://www.github.com/babelomics/SMAca.
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The soil-dwelling bacterium Bacillus subtilis differentiates into distinct subpopulations of specialized cells that coexist within highly structured communities. The coordination and interplay ...between these cell types requires extensive extracellular communication driven mostly by sensing self-generated secreted signals. These extracellular signals activate a set of sensor kinases, which respond by phosphorylating three major regulatory proteins, Spo0A, DegU and ComA. Each phosphorylated regulator triggers a specific differentiation program while at the same time repressing other differentiation programs. This allows a cell to differentiate in response to a specific cue, even in the presence of other, possibly conflicting, signals. The sensor kinases involved respond to an eclectic group of extracellular signals, such as quorum-sensing molecules, natural products, temperature, pH or scarcity of nutrients. This article reviews the cascades of cell differentiation pathways that are triggered by sensing extracellular signals. We also present a tentative developmental model in which the diverse cell types sequentially differentiate to achieve the proper development of the bacterial community.
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A cross-sectional area (CSA) and thickness reduction of the abductor hallucis (AbH) is shown in subjects with hallux valgus (HV). To date, other soft-tissue structures have not been researched in ...relation with HV. The aim of this study was to compare the CSA and thickness of the intrinsic plantar muscles and fascia (PF) between feet with and without HV. Therefore, a cross-sectional and case-control study was performed using B-mode with an iU22 Philips ultrasound system and a 5 to 17-MHz transducer. The CSA and thickness were measured for the AbH, flexor digitorum brevis (FDB) and flexor hallucis brevis (FHB), and also the thickness for the anterior, middle, and posterior PF portions. A convenience sample of 40 feet, 20 with HV and 20 without HV, was recruited from a clinical and research center. A multivariate regression analysis using linear regression was performed to evaluate the ultrasound imaging measurements (α = 0.05). Consequently, statistically significant differences were observed between the groups (P < 0.05) for the AbH and FHB thickness, and CSA reduction, and also the plantar fascia thickness increase in favor of the HV group. On the contrary, the FDB thickness and CSA did not show statistically significant differences (P ≥ 0.05). In conclusion, the CSA and thickness of the AbH and FHB intrinsic plantar muscles are reduced, whereas the thickness of the anterior, middle, and posterior PF portions are increased, in subjects with HV compared with those without HV.
Programmable Integrated Photonics is a recent area of research that aims to integrate a very-large scale of reconfigurable photonic components to enable flexible and versatile photonic integrated ...circuits. In this paper, we review the state of the art of general-purpose waveguide mesh arrangements with a special focus on those that allow the synthesis of optical feedback loops. Moreover, we propose for the first time, a new design approach to generate waveguide mesh patterns with equally-oriented components. This innovation is of special relevance to improve performance and to mitigate one of the main scalability limitations, the integration density. The paper finalizes with an introduction to control algorithms for waveguide mesh arrangements based on derivative methods and non-derivative methods. These control methods provide a proof for the self-reconfiguration of large-scale waveguide mesh arrangements. In particular, we apply the computational optimization algorithms to program a hexagonal waveguide mesh to emulate a 1 × 8 beamforming network and an optical filter based on an unbalanced MZI design. All in all, the paper comprises recipes to achieve truly practical software-defined photonic integrated circuits.
The androgen receptor (AR) has been shown to be a key determinant in the pathogenesis of castration‐resistant prostate cancer (CRPC). The current standard of care therapies targets the ligand‐binding ...domain of the receptor and can afford improvements to life expectancy often only in the order of months before resistance occurs. Emerging preclinical and clinical compounds that inhibit receptor activity via differentiated mechanisms of action which are orthogonal to current antiandrogens show promise for overcoming treatment resistance. In this review, we present an authoritative summary of molecules that noncompetitively target the AR. Emerging small molecule strategies for targeting alternative domains of the AR represent a promising area of research that shows significant potential for future therapies. The overall quality of lead candidates in the area of noncompetitive AR inhibition is discussed, and it identifies the key chemotypes and associated properties which are likely to be, or are currently, positioned to be first in human applications.
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8.
Biofilms López, Daniel; Vlamakis, Hera; Kolter, Roberto
Cold Spring Harbor perspectives in biology
2, Issue:
7
Journal Article
Peer reviewed
Open access
The ability to form biofilms is a universal attribute of bacteria. Biofilms are multicellular communities held together by a self-produced extracellular matrix. The mechanisms that different bacteria ...employ to form biofilms vary, frequently depending on environmental conditions and specific strain attributes. In this review, we emphasize four well-studied model systems to give an overview of how several organisms form biofilms: Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus. Using these bacteria as examples, we discuss the key features of biofilms as well as mechanisms by which extracellular signals trigger biofilm formation.
Mechanical oscillators are present in almost every electronic device. They mainly consist of a resonating element providing an oscillating output with a specific frequency. Their ability to maintain ...a determined frequency in a specified period of time is the most important parameter limiting their implementation. Historically, quartz crystals have almost exclusively been used as the resonating element, but micromechanical resonators are increasingly being considered to replace them. These resonators are easier to miniaturize and allow for monolithic integration with electronics. However, as their dimensions shrink to the microscale, most mechanical resonators exhibit nonlinearities that considerably degrade the frequency stability of the oscillator. Here we demonstrate that, by coupling two different vibrational modes through an internal resonance, it is possible to stabilize the oscillation frequency of nonlinear self-sustaining micromechanical resonators. Our findings provide a new strategy for engineering low-frequency noise oscillators capitalizing on the intrinsic nonlinear phenomena of micromechanical resonators.
Nonspecific low back pain (LBP) is the most prevalent musculoskeletal condition in various age ranges and is associated with depression. The aim of this study was to determine the Beck Depression ...Inventory (BDI) scores in participants with nonspecific LBP and no-pain by age distribution.
A case-control study was carried out following the Strengthening the Reporting of Observational Studies in Epidemiology criteria. A sample of 332 participants, divided into the following age categories: 19-24 (n=11), 25-39 (n=66), 40-64 (n=90), 65-79 (n=124), and ≥80 (n=41) years was recruited from domiciliary visits and an outpatient clinic. The BDI scores were self-reported in participants with nonspecific acute or subacute (≤3 months) LBP (n=166) and no-pain (n=166).
The BDI scores, mean ± standard deviation, showed statistically significant differences (
<0.001) between participants with nonspecific acute or subacute LBP (9.590±6.370) and no-pain (5.825±5.113). Significantly higher BDI scores were obtained from participants with nonspecific acute and subacute LBP in those aged 40-64 years (
<0.001; 9.140±6.074 vs 4.700±3.777) and 65-79 years (
<0.001; 10.672±6.126 vs 6.210±5.052). Differences were not significant in younger patients aged 19-24 (
=0.494; 5.000±2.646 vs 8.250±7.498), 25-39 (
=0.138; 5.440±5.245 vs 3.634±4.397), and in those aged ≥80 years (
=0.094; 13.625±6.1331 vs 10.440±5.591).
Participants with nonspecific acute and subacute LBP present higher BDI depression scores, influenced by age distribution. Specifically, patients in the age range from 40 to 80 years with LBP could require more psychological care in addition to any medical or physical therapy. Nevertheless, physical factors, different outcomes, and larger sample size should be considered in future studies.
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