The potential effect of larval condition on adult immunity in holometabolous insects is rarely considered. We show here that larval food composition can impact adult immunity independent from effects ...on general condition of the animal. Rather, our data indicate a plastic allocation of resources to immunity in high-protein environments. Specifically, we found that increasing the nutritional yeast (protein) available to larval Drosophila melanogaster increased the adult's constitutive transcription of two genes encoding defensive antimicrobial peptides. Adult dry weight was not significantly affected by larval food composition, while adult fat content decreased when larval yeast increased. Larval immune activity was unaffected by alterations of larval diet, indicating a lack of covariation in this trait across life-stages. We conclude that the nutritional environment of insect larvae can affect adult immunity by influencing plastic allocation of resources. These influences are less predictable than constraints linked to general condition would be.
The human motor cortex has a tendency to resonant activity at about 20 Hz so stimulation should more readily entrain neuronal populations at this frequency. We investigated whether and how different ...interneuronal circuits contribute to such resonance by using transcranial magnetic stimulation (TMS) during transcranial alternating current stimulation (tACS) at motor (20 Hz) and a nonmotor resonance frequency (7 Hz). We tested different TMS interneuronal protocols and triggered TMS pulses at different tACS phases. The effect of cholinergic short-latency afferent inhibition (SAI) was abolished by 20 Hz tACS, linking cortical beta activity to sensorimotor integration. However, this effect occurred regardless of the tACS phase. In contrast, 20 Hz tACS selectively modulated MEP size according to the phase of tACS during single pulse, GABAAergic short-interval intracortical inhibition (SICI) and glutamatergic intracortical facilitation (ICF). For SICI this phase effect was more marked during 20 Hz stimulation. Phase modulation of SICI also depended on whether or not spontaneous beta activity occurred at ~20 Hz, supporting an interaction effect between tACS and underlying circuit resonances. The present study provides in vivo evidence linking cortical beta activity to sensorimotor integration, and for beta oscillations in motor cortex being promoted by resonance in GABAAergic interneuronal circuits.
This paper intends to provide a critical review of the literature on the technological issues on control and sensorization of hand prostheses interfacing with the Peripheral Nervous System (i.e., ...PNS), and their experimental validation on amputees. The study opens with an in-depth analysis of control solutions and sensorization features of research and commercially available prosthetic hands. Pros and cons of adopted technologies, signal processing techniques and motion control solutions are investigated. Special emphasis is then dedicated to the recent studies on the restoration of tactile perception in amputees through neural interfaces. The paper finally proposes a number of suggestions for designing the prosthetic system able to re-establish a bidirectional communication with the PNS and foster the prosthesis natural control.
•TMS primarily targets the gyri at the hemispheric surface due to limited depth penetration.•The direct response to TMS is complex, involving a mixture of neuronal populations.•Myelinated axon ...terminals of pyramidal cells and inhibitory interneurons in the crown of the gyri constitute low-threshold targets for TMS.•Neuronal excitation propagates along axons and across synapses from the primary stimulation site to connected regions in a state-dependent fashion.•TMS always causes substantial peripheral somatosensory and auditory co-stimulation.
Transcranial (electro)magnetic stimulation (TMS) is currently the method of choice to non-invasively induce neural activity in the human brain. A single transcranial stimulus induces a time-varying electric field in the brain that may evoke action potentials in cortical neurons. The spatial relationship between the locally induced electric field and the stimulated neurons determines axonal depolarization. The induced electric field is influenced by the conductive properties of the tissue compartments and is strongest in the superficial parts of the targeted cortical gyri and underlying white matter. TMS likely targets axons of both excitatory and inhibitory neurons. The propensity of individual axons to fire an action potential in response to TMS depends on their geometry, myelination and spatial relation to the imposed electric field and the physiological state of the neuron. The latter is determined by its transsynaptic dendritic and somatic inputs, intrinsic membrane potential and firing rate. Modeling work suggests that the primary target of TMS is axonal terminals in the crown top and lip regions of cortical gyri. The induced electric field may additionally excite bends of myelinated axons in the juxtacortical white matter below the gyral crown. Neuronal excitation spreads ortho- and antidromically along the stimulated axons and causes secondary excitation of connected neuronal populations within local intracortical microcircuits in the target area. Axonal and transsynaptic spread of excitation also occurs along cortico-cortical and cortico-subcortical connections, impacting on neuronal activity in the targeted network. Both local and remote neural excitation depend critically on the functional state of the stimulated target area and network. TMS also causes substantial direct co-stimulation of the peripheral nervous system. Peripheral co-excitation propagates centrally in auditory and somatosensory networks, but also produces brain responses in other networks subserving multisensory integration, orienting or arousal. The complexity of the response to TMS warrants cautious interpretation of its physiological and behavioural consequences, and a deeper understanding of the mechanistic underpinnings of TMS will be critical for advancing it as a scientific and therapeutic tool.
•An overview of TMS-EEG methodology and neurophysiological derivations.•A comprehensive review of TMS-EEG as a clinical tool to study healthy and disease brain states.•A discussion of current ...challenges in the field of TMS-EEG and recommendations for future studies.
Concurrent transcranial magnetic stimulation and electroencephalography (TMS–EEG) has emerged as a powerful tool to non-invasively probe brain circuits in humans, allowing for the assessment of several cortical properties such as excitability and connectivity. Over the past decade, this technique has been applied to various clinical populations, enabling the characterization and development of potential TMS–EEG predictors and markers of treatments and of the pathophysiology of brain disorders. The objective of this article is to present a comprehensive review of studies that have used TMS–EEG in clinical populations and to discuss potential clinical applications. To provide a technical and theoretical framework, we first give an overview of TMS–EEG methodology and discuss the current state of knowledge regarding the use of TMS–EEG to assess excitability, inhibition, plasticity and connectivity following neuromodulatory techniques in the healthy brain. We then review the insights afforded by TMS–EEG into the pathophysiology and predictors of treatment response in psychiatric and neurological conditions, before presenting recommendations for how to address some of the salient challenges faced in clinical TMS–EEG research. Finally, we conclude by presenting future directions in line with the tremendous potential of TMS–EEG as a clinical tool.
Anonymous service delivery has attracted the interest of research and the industry for many decades. To obtain effective solutions, anonymity should be guaranteed against the service provider itself. ...However, if the full anonymity of users is implemented, no accountability mechanism can be provided. This represents a problem, especially when referring to scenarios in which a user, protected by anonymity, may perform illegally when leveraging the anonymous service. In this paper, we propose a blockchain-based solution to the trade-off between anonymity and accountability. In particular, our solution relies on three independent parties (one of which is the service provider itself) such that only the collaboration of all three actors allows for the disclosure of the real identity of the user. In all other cases, anonymity is guaranteed. To show the feasibility of the proposal, we developed a prototype with user-friendly interfaces that minimize the client-side operations. Our solution is then also effective from the point of view of usability.
Comparative genomics can be an initial step in finding the genetic basis for phenotypic differences among bacterial strains and species. Bacteria belonging to the genus Providencia have been isolated ...from numerous and varied environments. We sequenced, annotated and compared draft genomes of P. rettgeri, P. sneebia, P. alcalifaciens, and P. burhodogranariea. These bacterial species that were all originally isolated as infections of wild Drosophila melanogaster and have been previously shown to vary in virulence to experimentally infected flies.
We found that these Providencia species share a large core genome, but also possess distinct sets of genes that are unique to each isolate. We compared the genomes of these isolates to draft genomes of four Providencia isolated from the human gut and found that the core genome size does not substantially change upon inclusion of the human isolates. We found many adhesion related genes among those genes that were unique to each genome. We also found that each isolate has at least one type 3 secretion system (T3SS), a known virulence factor, though not all identified T3SS belong to the same family nor are they in syntenic genomic locations.
The Providencia species examined here are characterized by high degree of genomic similarity which will likely extend to other species and isolates within this genus. The presence of T3SS islands in all of the genomes reveal that their presence is not sufficient to indicate virulence towards D. melanogaster, since some of the T3SS-bearing isolates are known to cause little mortality. The variation in adhesion genes and the presence of T3SSs indicates that host cell adhesion is likely an important aspect of Providencia virulence.
Commentary: Size matters, at least when it pertains to the trachea and ventilation Lazzaro, Richard S.; Patton, Byron; Inra, Matthew L.
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
January 2022, 2022-01-00, 20220101, Letnik:
163, Številka:
1
Journal Article
Penicillin-resistance among
clinical isolates has been recently associated with overexpression or aminoacidic substitutions in low-affinity PBP4. Ceftobiprole (BPR), a new-generation cephalosporin, ...is a therapeutic option against
Here, we present evidence that
4 gene sequence alterations may influence the expression level of the gene and ceftobiprole binding to PBP4 in
clinical isolates showing remarkable MDR-phenotypes, and how this could interfere with BPR
antibacterial and bactericidal activity. Seven
strains from bloodstream infections were analyzed for their antibiotic and β-lactam resistance. BPR bactericidal activity was assessed by time-kill analysis;
4 genes were sequenced and
4 relative expression levels of transcription were performed by RT-qPCR. Five penicillin-resistant ampicillin-susceptible (PRAS) isolates were detected, 4 of which were also BPR non-susceptible (BPR-NS). In the time-kill experiments, BPR exposure resulted in a potent bactericidal activity (3-5 log
reduction) at the different concentrations tested.
4 gene sequence analysis revealed some mutations that may account for the changes in PBP4 affinity and MIC increase in the 4 BPR-NS strains (MICs 4-16 mg/L): the deletion of an adenine (
A) in the promoter region in all PRAS/BPR-NS strains; 12 different amino acid substitutions, 7 of which were next to the PBP catalytic-sites. The most significant were: T418A, located 6 amino acids (aa) upstream of the catalytic-serine included in the
STFK
I; L475Q, 7 aa upstream of the
SDN
II; V606A and the novel Y605H, 13/14 aa upstream of the
KTGT
III. Taken together, our data showed that elevated BPR MICs were attributable to increased transcription of
4 - associated with a single upstream adenine deletion and PBP4 alterations in the catalytic-site
- which might interfere with the formation of the BPR/PBP4 complex.
4 molecular alterations may account for the changes in PBP4 affinity and MIC increase, without affecting BPR
activity. Indeed, our
dynamic analysis by time-kill assays showed that BPR exerted a bactericidal activity against
clinical isolates, despite their MDR phenotypes.
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