Toward Multiplexed Optogenetic Circuits

Owing to its ubiquity and easy availability in nature, light has been widely employed to control complex cellular behaviors. Light-sensitive proteins are the foundation to such diverse and multilevel adaptive regulations in a large range of organisms. Due to their remarkable properties and potential applications in engineered systems, exploration and engineering of natural light-sensitive proteins have significantly contributed to expand optogenetic toolboxes with tailor-made performances in synthetic genetic circuits. Progressively, more complex systems have been designed in which multiple photoreceptors, each sensing its dedicated wavelength, are combined to simultaneously coordinate cellular responses in a single cell. In this review, we highlight recent works and challenges on multiplexed optogenetic circuits in natural and engineered systems for a dynamic regulation breakthrough in biotechnological applications.

STRUCTURI MODULARE DE COMANDĂ ȘI CONTROL ȘI ORGANIZAREA FORȚEI UTILIZABILE ÎN OPERAȚII LA ALTITUDINI MARI

Abordarea anumitor provocări în zone de operații situate la altitudini mari necesită existența unor capabilități specifice de comandă și control. C2 bazat pe comanda prin misiune trebuie adaptat cerințelor actuale, generate de conflictele cu geometrie variabilă, conflicte de tip mozaic, compozit, multifațetat, multistratificat, multidomeniu. Sistemele de comandă și control ar trebui să dispună de flexibilitate arhitecturală, de platforme digitalizate inteligente, iar modulele sale să fie perfect interoperabile funcțional și acțional (bazate pe autosuficiență ‒ capabilitate extinsă de funcționare în timp). Considerăm că, la altitudini mari, arhitectura unui sistem de comandă și control complex trebuie să fie modulară și concepută ca un integrator coerent de senzori, decidenți, executanţi și capabilități de sprijin, interconectați în subsisteme care să asigure planificarea, pregătirea, executarea și evaluarea cu eficiență a acţiunilor militare. În condiţiile diversificării riscurilor și ameninţărilor în mediul operațional multidimensional, arhitectura sistemelor de comandă și control trebuie adaptată permanent astfel încât să asigure comunicarea în timp real, pe orizontală și pe verticală, între forţe, structurile de sprijin și structurile de comandă-control.

Mitochondrial antiviral-signalling protein is a client of the BAG6 protein quality control complex

ABSTRACTThe heterotrimeric BAG6 complex coordinates the direct handover of newly synthesised tail-anchored (TA) membrane proteins from an SGTA-bound preloading complex to the endoplasmic reticulum (ER) delivery component TRC40. In contrast, defective precursors, including aberrant TA proteins, form a stable complex with this cytosolic protein quality control factor, enabling such clients to be either productively re-routed or selectively degraded. We identify the mitochondrial TA protein MAVS (mitochondrial antiviral-signalling protein) as an endogenous client of both SGTA and the BAG6 complex. Our data suggest that the BAG6 complex binds to a cytosolic pool of MAVS before its misinsertion into the ER membrane, from where it can subsequently be removed via ATP13A1-mediated dislocation. This BAG6- associated fraction of MAVS is dynamic and responds to the activation of an innate immune response, suggesting that BAG6 may modulate the pool of MAVS that is available for coordinating the cellular response to viral infection.SUMMARY STATEMENTMitochondrial antiviral-signalling (MAVS) protein is a favoured client of the cytosolic BAG6 complex. We discuss how this dynamic interaction may modulate MAVS biogenesis at signalling membranes.

Non-Coding Genome, Transcription Factors, and Sex Determination

In vertebrates, gonadal sex determination is the process by which transcription factors drive the choice between the testicular and ovarian identity of undifferentiated somatic progenitors through activation of 2 different transcriptional programs. Studies in animal models suggest that sex determination always involves sex-specific transcription factors that activate or repress sex-specific genes. These transcription factors control their target genes by recognizing their regulatory elements in the non-coding genome and their binding motifs within their DNA sequence. In the last 20 years, the development of genomic approaches that allow identifying all the genomic targets of a transcription factor in eukaryotic cells gave the opportunity to globally understand the function of the nuclear proteins that control complex genetic programs. Here, the major transcription factors involved in male and female vertebrate sex determination and the genomic profiling data of mouse gonads that contributed to deciphering their transcriptional regulation role will be reviewed.

Neuronally Produced Betaine Acts via a Novel Ligand Gated Ion Channel to Control Behavioural States

Trimethyl glycine, or betaine, is an amino acid derivative found in diverse organisms, from bacteria to plants and animals. It can function as an osmolyte to protect cells against osmotic stress, and building evidence suggests betaine may also play important functional roles in the nervous system. However, despite growing interest in betaine's roles in the nervous system, few molecular mechanisms have been elucidated. Here we identify the expression of betaine synthesis pathway genes in the nervous system of the nematode worm, C. elegans. We show that betaine, produced in a single pair of interneurons, the RIMs, can control complex behavioural states. Moreover, we also identify and characterise a new betaine-gated inhibitory ligand gated ion channel, LGC-41, which is required for betaine related behavioural changes. Intriguingly we observed expression of LGC-41 in punctate structures across several sensory and interneurons, including those synaptically connected to the RIMs. Our data presents a neuronal molecular mechanism for the action of betaine, via a specific receptor, in the control of complex behaviour within the nervous system of C. elegans. This may suggest a much broader role for betaine in the regulation of animal nervous systems than previously recognised.

AIR TRAFFIC CONTROL BASICS

The concept of flight safety is considered, the features and purpose of the air traffic control system, the air traffic control complex, the capabilities of the system that ensure flight safety are presented.

Optimization of the configurations of the control complex of the integrated navigation bridge of the ship by the method of multiprogramming

In the concept of development of E-navigation, large control systems for navigation, navigation safety, optimization of ship operation, and cargo operations are being developed. The vector of the direction of this development leads to fully automatic management of the maritime industry and individual segments, such as navigation and terminal operations, with the transfer of unified databases to “cloud” technologies. In modern control systems, a significant number of programs for processing information flows and databases are required from external sources. The method of addressing “cloud” technologies and external storage devices, which are updated in real-time, and a complete transition from analog, analog-digital, only to digital media and information processing systems, is adopted. The method of addressing “cloud” technologies and external storage devices, which are updated in real-time, and a complete transition from analog, analog-digital, only to digital media and information processing systems, is adopted. Modern computer systems for helping the navigator in making decisions are shifting to the area of deep integration of control actions and information processing in real perception and optimization of a verified and safe algorithm of actions. The time of work with such complexes depends on the efficiency in organizing data exchange in the “man-machine” system. In the study, an algorithm was developed for deep optimization of the control complex of the ship, to minimize and create a control shell of the “man-machine” system, using the multiprogramming method to stabilize the route passage.

Human-machine system as a control shell in the implementation of mooring operations

Mooring is a complex and responsible process for a boat master, so modern trends determine the need to create automated and automatic systems for mooring vessels to minimize the human factor. The study researched the vessel ergatic control complex and the towing group with the use of mathematical apparatus in the implementation of mooring operations. The human-machine or “ergatic” system is the control shell under the active influences of the bridge complexes and is an auxiliary tool for the watchman on the navigation bridge. This is the essence – a human, as a controlling and observing link, is an integral part of the human-machine complex. Automation, even in systems with artificial intelligence, will not soon replace the flexibility of the human brain, despite possible and sometimes very serious human mistakes. Taking into account the fact that the automated mooring system applies all kinds of monitoring sensors to prevent docking impact, the control and responsibility for the mooring process still lie with the navigator operator.

RNA nucleotide repeats induce mitochondrial dysfunction and the ribosome associated quality control

Nucleotide repeat sequences are prevalent in the genome and expansion of these sequences is associated with more than 40 neuromuscular disorders. To understand the pathogenic mechanisms underlying RNA-repeat toxicity, we performed a genetic screen in a Caenorhabditis elegans model expressing an expanded CUG repeat specifically in the muscle. Here, we show that expression of this RNA repeat impairs motility by mitochondrial dysfunction, disrupting mitochondrial morphology and respiration. The phenotype is dependent on the RNA-binding factor MBL-1 and requires factors from the ribosome associated protein quality control complex. Furthermore, Coenzyme Q supplementation rescued the motility impairment and all of the mitochondrial phenotypes. Together, our data reveal the importance of mitochondrial dysfunction in the molecular pathogenesis of RNA repeat expansion disorders.