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Non-invasive transcranial brain stimulation (NTBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial current stimulation (TCS) are important tools in human systems and cognitive neuroscience because they are able to reveal the relevance of certain brain structures or neuronal activity patterns for a given brain function. It is nowadays feasible to combine NTBS, either consecutively or concurrently, with a variety of neuroimaging and electrophysiological techniques. Here we discuss what kind of information can be gained from combined approaches, which often are technically demanding. We argue that the benefit from this combination is twofold. Firstly, neuroimaging and electrophysiology can inform subsequent NTBS, providing the required information to optimize where, when, and how to stimulate the brain. Information can be achieved both before and during the NTBS experiment, requiring consecutive and concurrent applications, respectively. Secondly, neuroimaging and electrophysiology can provide the readout for neural changes induced by NTBS. Again, using either concurrent or consecutive applications, both “online” NTBS effects immediately following the stimulation and “offline” NTBS effects outlasting plasticity-inducing NTBS protocols can be assessed. Finally, both strategies can be combined to close the loop between measuring and modulating brain activity by means of closed-loop brain state-dependent NTBS. In this paper, we will provide a conceptual framework, emphasizing principal strategies and highlighting promising future directions to exploit the benefits of combining NTBS with neuroimaging or electrophysiology. •A conceptual framework for combining NTBS and functional brain mapping•Neuroimaging and electrophysiology inform about where, when and how to apply NTBS.•Neuroimaging and electrophysiology provide readouts of NTBS-induced neuronal effects.•Informed open-loop NTBS allows to characterize (e.g. oscillatory) brain states.•Closed-loop NTBS allows to target and manipulate specific brain states.

Pseudomonas aeruginosa is an opportunistic pathogen that synthesizes and secretes a wide range of virulence factors. P. aeruginosa poses a potential threat to human health worldwide due to its omnipresent nature, robust host accumulation, high virulence, and significant resistance to multiple antibiotics. The pathogenicity of P. aeruginosa, which is associated with acute and chronic infections, is linked with multiple virulence factors and associated secretion systems, such as the ability to form and utilize a biofilm, pili, flagella, alginate, pyocyanin, proteases, and toxins. Two-component systems (TCSs) of P. aeruginosa perform an essential role in controlling virulence factors in response to internal and external stimuli. Therefore, understanding the mechanism of TCSs to perceive and respond to signals from the environment and control the production of virulence factors during infection is essential to understanding the diseases caused by P. aeruginosa infection and further develop new antibiotics to treat this pathogen. This review discusses the important virulence factors of P. aeruginosa and the understanding of their regulation through TCSs by focusing on biofilm, motility, pyocyanin, and cytotoxins.

Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint on the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS). •We provide a method for optimizing the configuration of multifocal tDCS.•Optimization cortical target maps are based on fMRI, PET or other data.•Algorithm optimizes electrode currents and locations subject to safety constraints.•We highlight clinical applications in stroke and depression.•We discuss the generalization of these methods to tACS.

Małe, regulatorowe RNA (sRNA) wraz z dwuskładnikowymi systemami transdukcji sygnału (TCS) wchodzą w skład rozbudowanych sieci kontroli ekspresji genów bakteryjnych. Oddziałując ze sobą wzajemnie, zapewniają niezwykle szybką, jak również precyzyjną odpowiedź bakterii na zmieniające się warunki bytowania. Kontrolując wiele procesów wpływają na stan fizjologiczny komórki, skład proteomu osłon komórkowych czy zdolność do wzrostu w postaci biofilmu. Niezwykle często sRNA stanowią brakujące ogniwa, w odpowiedzi na złożone bodźce środowiskowe, pomiędzy dwuskładnikowymi systemami transdukcji sygnału, a genami docelowymi czy innymi systemami regulatorowymi. Współdziałanie TCS-sRNA wydaje się globalną cechą regulacyjną u wielu organizmów prokariotycznych. Zdobywanie wiedzy na temat tych mechanizmów kontroli toruje drogę do opracowania nowych strategii walki z drobnoustrojami patogennymi.

Abstract When the rate of production of metabolites in bacteria exceeds the amounts needed for cell growth, excess metabolites are secreted into the extracellular environment. Upon entry into poor nutrient conditions, overflowed exometabolites are reused to continue cell growth and survival. At present, however, the genetic system for utilization of exometabolites is poorly understood even for the best-characterized model prokaryote Escherichia coli. A two-component system YpdAB of E. coli K-12 was predicted to participate in regulation of this process, and the yhjX gene encoding the MFS-family transporter with an as yet unidentified function was identified as a single regulatory target of YpdB. Using gSELEX screening in vitro, however, we have identified up to eight regulatory targets, including the yhjX gene. The predicted regulatory targets were all confirmed to be under the direct control of YpdB by gel shift assay in vitro and reporter assay in vivo. For induction of YpdAB function, the major exometabolite pyruvate in growing E. coli K-12 was identified as the inducer. We then propose to rename YpdAB as PyrSR (regulator of pyruvate reutilization). One unique feature of PyrSR is its cross-talk with another pyruvate-sensing BtsSR at the TCS stage 1 for fine-tuning of pyruvate reutilization. The poorly characterized two-component PyrSR (YpdAB) system of Escherichia coli K-12 was found to monitor high concentrations of the major exometabolite pyruvate and regulates a set of the genes for reutilization of pyruvate.

This paper, the second of two parts, presents an analytical model of motion artifacts (MA) in measured pulse signals by a tactile sensor, which contains a deformable microstructure sitting on a substrate. While the tissue-contact-sensor (TCS) stack and the sensor are both treated as a 1DOF (degree-of-freedom) system, tissue–sensor contact joins their mass together to form a 1DOF system with springs and dampers on both sides. MA on the sensor substrate causes baseline drift and time-varying system parameters (TVSP) of the TCS stack simultaneously. An analytical model is developed to mathematically relate baseline drift and TVSP to a measured pulse signal. The numerical calculation is conducted in MATLAB. Baseline drift in a measured pulse signal is much lower than the actual MA in its measurement. As compared to baseline drift, TVSP generates relatively abrupt, small distortion (e.g., 0.2% variation in heart rate and <5% change in pulse amplitude), but it rides on each harmonic of the true pulse signal. Sensor design alters both the deviation of the amplitude and waveform of a measured pulse signal from the true pulse signal and the influence of MA on it.

The number of multidrug-resistant bacteria is rapidly spreading worldwide. Among the various mechanisms determining resistance to antimicrobial agents, multidrug efflux pumps play a noteworthy role because they export extraneous and noxious substrates from the inside to the outside environment of the bacterial cell contributing to multidrug resistance (MDR) and, consequently, to the failure of anti-infective therapies. The expression of multidrug efflux pumps can be under the control of transcriptional regulators and two-component systems (TCS). TCS are a major mechanism by which microorganisms sense and reply to external and/or intramembrane stimuli by coordinating the expression of genes involved not only in pathogenic pathways but also in antibiotic resistance. In this review, we describe the influence of TCS on multidrug efflux pump expression and activity in some Gram-negative and Gram-positive bacteria. Taking into account the strict correlation between TCS and multidrug efflux pumps, the development of drugs targeting TCS, alone or together with already discovered efflux pump inhibitors, may represent a beneficial strategy to contribute to the fight against growing antibiotic resistance.

Surgical site infections (SSIs) contribute to increased health care costs and morbidity after procedures as well as prolonged length of stay. Perioperative personnel can use a variety of interventions to help reduce SSI incidence; however, all strategies are not effective for all patients (eg, antibiotic prophylaxis). Results of randomized controlled trials show that some SSI reduction strategies are generally effective, including preoperative skin antisepsis with an alcohol‐based agent, closing surgical wounds with triclosan‐coated suture, and applying a negative pressure wound therapy device to open and closed wounds. Study results do not show that irrigating clean wounds with crystalloid solutions containing antibiotics or routinely using plastic drapes with or without impregnated iodophor or silver nylon–impregnated dressings significantly reduces SSI incidence. Perioperative leaders should support the implementation of strategies to prevent SSIs and work with interdisciplinary team members to develop an SSI prevention bundle that will meet the needs of their patients.

[This corrects the article DOI: 10.3389/fcimb.2023.1270667.].

Telocytes are a recently described stromal cell type widely distributed in various organs including the female and male reproductive systems. This study was aimed to investigate for the first time the existence, distribution and characteristics of telocytes in normal human testis by an integrated morphological approach (immunohistochemistry, immunofluorescence and transmission electron microscopy). We found that telocytes displaying typical long and moniliform prolongations and coexpressing CD34 and PDGFRα formed networks in the outer layer of peritubular tissue and around Leydig cells and vessels in the intertubular stroma. Testicular telocytes were immunophenotypically negative for CD31, c-kit/CD117 as well as α-SMA, thus making them clearly distinguishable from myoid cells/myofibroblasts located in the inner layer of peritubular tissue. Transmission electron microscopy confirmed the presence of cells ultrastructurally identifiable as telocytes ( i.e . cells with telopodes alternating podomers and podoms) in the aforementioned locations. Intercellular contacts between neighboring telocytes and telopodes were observed throughout the testicular stromal compartment. Telopodes intimately surrounded and often established close contacts with peritubular myoid cells/myofibroblasts, Leydig cells and vessels. Extracellular vesicles were also frequently detected near telopodes. In summary, we demonstrated that telocytes are a previously neglected stromal component of human testis with potential implications in tissue homeostasis deserving further investigation.