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Romano, A.

Publications and source records attributed to Romano, A..

At least 19 recordsLinked to original sources

The BEAC, an epigenetic clock for birds

Epigenetic clocks are powerful tools for estimating both chronological and biological age, enabling the integration of age information into population monitoring, demographic modelling, and research on the ecophysiology and evolution of ageing. Most epigenetic clocks so far have been developed for mammals: here, we present the Bird Epigenetic Ageing Clock (BEAC) for estimating chronological age in avian species. BEAC was established based on genome-wide enzymatic methylation sequencing data of known-age king penguins (Aptenodytes patagonicus), and validated in nine other bird species. The BEAC collects age-informative signals into a bisulfite amplicon sequencing panel of 24 primer pairs, providing a highly accurate and cost-effective alternative to sequencing-intensive approaches. It achieved strong predictive performance in independent king penguin training (R{superscript 2}=0.88; MAE=1.7 years, n=78) and testing data (R{superscript 2}=0.79; MAE=2.3 years, n=41), with negligible batch effects, high longitudinal consistency, and resilience to reduced sample size or missing loci. Importantly, cross-species validation across 180 samples showed that BEAC reliably captures age-associated methylation signals in nine additional bird species across seven clades, demonstrating that a single set of loci can be predictive of ageing across multiple different bird species. BEAC offers a flexible, empirically validated tool and a transferable framework for developing epigenetic clocks in avian species, providing a highly valuable resource for eco-evolutionary studies of ageing in wild species.

molecular biology↗

HDAC3 inhibitor RGFP966 acts on the NF-kB pathway and enhances memory persistence in a biphasic manner

Nearly five decades ago, it was first observed that long-term memory consolidation requires waves of transcriptional activity and protein synthesis, with the first two waves occurring within hours after learning. While numerous studies have examined the effects of protein synthesis inhibitors, how specific epigenetic regulators contribute to these waves remains poorly understood. Here, we aimed to determine whether HDAC3, a key modulator of memory, is involved in memory consolidation at these two time points through its potential relationship with the transcription factor NF-kB, one of its deacetylation targets and a critical player in memory formation. Pharmacological inhibition of HDAC3 with RGFP966, either immediately or 6 hours after training, enhanced memory persistence in the NOR task in mice. Conversely, inhibition of NF-kB with BAY 11-7082 impaired memory at the same time points. Moreover, RGFP966 injection increased the nuclear proportion of NF-{kappa}B in the CA1 region of the hippocampus, suggesting that HDAC3 inhibition is associated with changes in NF-kB nuclear localization. To our knowledge, this study provides the first in vivo evidence that HDAC3 inhibition is associated with altered NF-kB localization during memory consolidation, extending previous observations from cell culture and electrophysiological studies in brain slices. Although these findings support a functional association between HDAC3 inhibition and NF-kB signaling during consolidation, further experiments will be required to determine whether this relationship is mechanistically causal.

neuroscience↗

Combinatorial and Inducible CRISPRa/i Enables Canalized hiPSC Forward Programming and Iterative Refinement via Single-Cell Genomics

Synthetic gene-regulation logic is established in immortalized cell lines but remains largely aspirational in human induced pluripotent stem cells (hiPSCs) and derivatives. This gap constrains both mechanistic discovery and translational engineering in physiologically relevant models. We developed CIRI (Combinatorial Inducible CRISPR in IPSCs), an isogenic, safe-harbor-engineered platform in which tetracycline-responsive single guide RNAs (sgR-NAs) carry modular RNA aptamers that recruit RNA-binding proteins and effector domains. This design enables multimodal regulation from a single catalytically inactive Cas9 (dCas9), exemplified by orthogonal CRISPR activation and interference (CRISPRa/i). After optimizing sgRNA-aptamer architectures, we achieved robust CRISPRa and CRISPRi in hiPSCs and hiPSC-derived cardiac organoids. CIRI rapidly channels hiPSC forward programming into skeletal myocytes by activating MYOD1 while repressing NANOG, POU5F1/OCT4, and SOX2. Combinatorial pooled dual-guide single-cell RNA sequencing screens identify ID3 as a road-block and KDM6B and SMARCD3 as synergistic enhancers of myogenic maturation. Together, CIRI establishes a programmable synthetic biology framework in human stem cell models. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/729073v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@18ce445org.highwire.dtl.DTLVardef@de8d94org.highwire.dtl.DTLVardef@1212763org.highwire.dtl.DTLVardef@1a0d83d_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

Ultra-low biomass sequencing workflow (LBV-Seq) enables de novo metagenomic reconstruction of DNA and RNA viral genomes

Genome-resolved virome analysis remains inaccessible for many samples, including those with clinical relevance, because viral nucleic acid recovered after enrichment is often too scarce to support de novo genome assembly. As a result, many analyses are limited to sparse read-level detection, which cannot recover divergent viruses, resolve strains, or interpret gene-level variation. Here, we developed Low Biomass Viral Sequencing (LBV-Seq), a workflow that couples low-input viral sample handling with modified primary template-directed amplification and short- or long-read sequencing to enable de novo reconstruction of DNA and RNA viral genomes from sub-femtogram to nanogram inputs. LBV-Seq reproducibly captures the same relative community composition, amplifies diverse viruses, and achieved broad genome coverage across nearly all targets regardless of viral genome structure, Baltimore class, abundance, or input mass. Short-read assemblies recovered near-complete genomes from femtogram-scale inputs. Long-read sequencing provided orthogonal support for genome structure, with PacBio HiFi reads spanning large portions of viral genomes and, in some cases, complete small viral genomes. Applied to virus-enriched human duodenal biopsy eluates, LBV-Seq provided proof-of-feasibility for recovering both bacteriophage and eukaryotic viral genomes from low-input biopsy-derived material. In the eluates tested, LBV-Seq recovered co-occurring Alphatorquevirus and Betatorquevirus genomes estimated to be present at roughly 10 copies/{micro}L and at viral masses below 0.1 fg/{micro}L. LBV-Seq enables genome-resolved virome analysis in samples previously limited to detection-based viromics, supporting viral discovery and strain-resolved analyses in settings where viral mass is low, including viruses enriched from human tissue biopsies.

genomics↗

Role of ERK2 dimerization in synaptic plasticity and memory

Extensive research has focused on extracellular-signal regulated kinase (ERK) 1/2 phosphorylation across various memory and plasticity models. However, the precise mechanisms linking ERK activity to memory stabilization and restabilization are still poorly understood, and the role of ERK1/2 dimerization remains unexplored. ERK dimerization is essential for the binding and activation of cytoplasmic targets, many of which are involved in memory and plasticity. In this study, we investigated the role of ERK2 dimerization in long-term memory and synaptic plasticity. We found that reactivation of a weak inhibitory avoidance (wIA) memory led to a significant reduction in hippocampal ERK2 dimerization. Furthermore, intrahippocampal infusion of DEL-22379 (DEL), an ERK dimerization inhibitor, following memory reactivation had a bidirectional effect: it blocked the reconsolidation of a strong inhibitory avoidance (sIA) memory but enhanced the reconsolidation of a wIA memory. Moreover, DEL administration blocked hippocampal ERK2 dimerization in vivo and impaired high-frequency stimulation-induced long-term potentiation (LTP) in hippocampal slices. These findings demonstrate that ERK2 dimerization occurs in the intact mouse nervous system and plays a pivotal role in plasticity and memory. While further research is needed, this study highlights the relevance of ERK dimerization in these processes.

neuroscience↗

Habitat partitioning and spatial segregation at multiple scales promotes year-round coexistence in a guild of forest songbirds

O_LIDespite ecological, biological, or genetic similarities, species belonging to the same guild should exhibit some degree of niche differentiation to coexist in the same area. Understanding the mechanisms promoting coexistence among ecologically similar and phylogenetically related species is crucial to improve our understanding of how biodiversity is maintained across broad temporal scales. C_LIO_LIWe examined the mechanisms driving coexistence in a guild of 5 sympatric woodland songbirds (family Paridae) in mixed forests of south-central Europe. We performed interspecific comparisons of habitat and space use considering two different phenological periods (breeding and non-breeding) and two spatial scales (home-range and foraging habitat), as well as spatial segregation of breeding territories. C_LIO_LIBased on broad-scale habitat preferences, two distinct and seasonally consistent species subgroups were identified within the guild, namely broadleaf and conifer species. During breeding, we showed that all species largely overlapped in their use of different foraging micro-habitats within the tree canopy, even within each subgroup. Yet, we detected significant spatial segregation of breeding territories among species. On the contrary, during the non-breeding period, individuals of different species within mixed flocks foraged on different and complementary sectors of the canopy, thus partitioning foraging habitats. C_LIO_LIThis study highlights that coexistence within the south-central European tit guild across different phenological periods is facilitated by a combination of distinct and complementary mechanisms, including spatial segregation of breeding territories, revealing how sympatric closely-related species coexist through both broad- and fine-scale spatial niche differentiation. C_LI

animal behavior and cognition↗

Magnetoencephalography dimensionality reduction informed by dynamic brain states

Complex spontaneous brain dynamics mirror the large number of interactions taking place among regions, supporting higher functions. Such complexity is manifested in the inter-regional dependencies among signals derived from different brain areas, as observed utilising neuroimaging techniques, like magnetoencephalography. The dynamics of this data produce numerous subsets of active regions at any moment as they evolve. Notably, converging evidence shows that these states can be understood in terms of transient coordinated events that spread across the brain over multiple spatial and temporal scales. Those can be used as a proxy of the "effectiveness" of the dynamics, as they become stereotyped or disorganised in neurological diseases. However, given the high dimensional nature of the data, representing them has been challenging thus far. Dimensionality reduction techniques are typically deployed to describe complex interdependencies and improve their interpretability. However, many dimensionality reduction techniques lose information about the sequence of configurations that took place. Here, we leverage a newly described algorithm, PHATE (Potential of Heat-diffusion for Affinity-based Transition Embedding), specifically designed to preserve the dynamics of the system in the low-dimensional embedding space. We analysed source-reconstructed resting-state magnetoencephalography from 18 healthy subjects to represent the dynamics of the configuration in low-dimensional space. After reduction with PHATE, unsupervised clustering via K-means is applied to identify distinct clusters. The topography of the states is described, and the dynamics are represented as a transition matrix. All the results have been checked against null models, providing a parsimonious account of the large-scale, fast, aperiodic dynamics during resting-state.

neuroscience↗

Linking neuronal avalanches with oscillatory and broadband 1/f activities in the resting human brain

ObjectiveNarrowband oscillations (NOs) and Broadband Arrhythmic Activity (BAA) are valuable conceptualizations extensively used to interpret brain data, with NOs linked to communication and synchronization and BAA encompassing scale-free dynamics and neuronal avalanches. Although both frameworks offer critical in-sights into brain function, they have largely evolved in parallel, with limited integration and no unifying mechanistic account of how these dynamics interact to generate transient, Salient Events (SEs). This gap is particularly pressing given recent interest in how SEs--brief ({approx} 100 ms) bursts of activity coordinated across brain regions--relate to large-scale brain function and cognition. To address this, we introduce a signal-level framework that links the Fourier spectral properties (oscillation-domain) of neural signals to the emergence of realistic SEs in the time-domain from NOs and BAA. MethodsOur approach is grounded in a novel concept--Spectral Group Delay Consistency (SGDC)--along with associated measures that quantify the temporal alignment of spectral components and capture the conditions under which Nos and BAA coalesce into transient, burst-like events. Unlike traditional power- or phase-based measures, or higher-order statistical metrics such as kurtosis and cokurtosis, SGDC provides a signal-level mechanistic account of how local and large-scale SEs emerge from the spectral structure of the underlying signals. Empirical validation is provided using source-reconstructed MEG data from a large cohort and a comprehensive array of features characterizing the statistical, spatiotemporal and spectral properties of observed SEs. ResultsWe found that the SEs identified in our empirical MEG dataset can be segregated based on their spectral signature in two main groups having different propagation patterns. Using generative models based on the SGDC mechanism we provide a theoretical framework to interpret these experimental results showing that cluster 2 events are specifically related to the long-range spread of narrowband alpha bursts across the brain network (i.e., SNEs: Salient Network Events), whereas cluster 1 events correspond to more short-lived and spatially localized fluctuations mainly promoted by the BAA (i.e., SLEs: Salient Local Events). We also provide analytical arguments and numerical simulations showing that a) high SGDC in specific narrow frequency bands, b) transient cross-regional coherent NOs and c) BAA, are all key ingredients for the emergence of realistic SNEs. SignificanceWe combine experimental evidence supported by a signal-level analytical framework and numerical simulations based on generative models to demonstrate that transient phase-structured alpha bursts, shaped by the SGDC mechanism, contribute to long-range coordination during rest. This extends the communication-through-coherence hypothesis to the transient domain. Additionally, SGDC links to findings that NOs interact with fast microstates ({approx}100 - 200 ms) and may modulate long-range dependencies across timescales. While previous studies have described SEs within the framework of neuronal avalanches, they often lacked a generative, signal-level account. Here, we bridge that divide by offering a mathematically grounded and empirically validated framework that accounts for oscillatory and aperiodic bursts perspectives on brain activity. HighlightsO_LISalient network events propagating across the brain during spontaneous resting state activity, are highly structured in terms of their spatial, temporal and spectral properties. C_LIO_LIThe spectral group delay consistency framework provides a signal-level mechanism that accounts for transient salient network events emerging from oscillatory components of the brain activity. C_LIO_LINarrowband oscillations and broadband arrhythmic activity interact to shape the timing and spatial extent of salient events. C_LIO_LISpectral group delay consistency, transient cross-regional coherent narrowband oscillations and broadband arrhythmic activity, are all key ingredients for the emergence of realistic salient network events. C_LIO_LISalient network events during rest reflect large-scale spreading of synchronized alpha band activity, which may play a functional role as a long-range interaction mechanism in the human brain. C_LI

neuroscience↗

PARP-1, EpCAM, and FRα as potential targets for intraoperative detection and delineation of endometriosis: a quantitative tissue expression analysis

Endometriosis is a gynecological disease characterized by the presence of endometrial tissue in abnormal locations, leading to severe symptoms, inflammation, pain, organ dysfunction, and infertility. Surgical removal of endometriosis lesions is crucial for improving pain and fertility outcomes, with the goal of complete lesion removal. Incomplete surgery often results in recurring symptoms and the need for additional interventions. This study aims to explore the biological significance of PARP-1, EpCAM, and FR as potential targets for molecular imaging in endometriosis, assessing their suitability for targeted intraoperative imaging. Gene expression analysis was performed using the EndometDB. By immunohistochemistry, we investigated the presence and distribution of PARP-1, EpCAM, and FR in endometriosis foci and adjacent tissue. We also applied an ad hoc platform for the analysis image to perform a quantitative immunolocalization analysis. Additionally, double immunofluorescence analysis was carried out for PARP-1 and EpCAM, as well as PARP-1 and FR, to explore the expression of these combined markers within endometriosis foci and their potential simultaneous utilization in surgical treatment. The analysis of gene expression revealed that PARP-1, EpCAM, and FR exhibit higher levels of expression in endometriotic lesions compared to the peritoneum, used for control tissue. Immunohistochemical analysis also highlighted a significant increase in expression of all three biomarkers in endometriosis foci compared to surrounding tissues, as well as the quantitative analysis of immunolocalization of the signal. Furthermore, the double immunofluorescence analysis consistently revealed nuclear expression of PARP-1 and membrane and cytoplasmatic expression of EpCAM and FR, although relatively weaker. Overall, the three markers demonstrate significant potential for effective imaging of endometriosis. Particularly, the results emphasize the importance of PARP-1 expression as a possible indicator for distinguishing endometriotic lesions from adjacent tissue. PARP-1, as a potential biomarker for endometriosis, offers promising avenues for further investigation in terms of both pathophysiology and diagnostic-therapeutic approaches.

cell biology↗

Intermodal consistency of whole-brain connectivity and signal propagation delays

Measuring the propagation of perturbations across the human brain and their transmission delays is critical for network neuroscience, but it is a challenging problem that still requires cross-validation approaches. Here, we compare results from a recently introduced, non-invasive technique of functional delays estimation from source-reconstructed electro/magnetoencephalography, to the corresponding findings from a large dataset of cortico-cortical evoked potentials estimated from intracerebral stimulations of epileptic pharmaco-resistant patients. The two methods yield significantly similar probabilistic connectivity maps and signal propagation delays. This similarity suggests a correspondence between the mechanisms underpinning the propagation of spontaneously generated scale-free perturbations (i.e. neuronal avalanches observed in resting state activity studied using magnetoencephalography) and the spreading of cortico-cortical evoked potentials. This manuscript provides evidence for the accuracy of a subject-specific estimate of functional delays obtained non-invasively from reconstructed sources. Conversely, our findings show that estimates obtained from externally-induced perturbations capture physiological activities. In conclusion, this manuscript constitutes a cross-validation between two different modalities. Importantly, the capability to measure delays non-invasively (as per MEG) paves the way for the inclusion of functional delays in personalized large-scale brain models as well as in diagnostic and prognostic algorithms.

neuroscience↗

Long-term structural plasticity of hippocampal dendritic spines following contextual fear memory reactivation

Dendritic spines are plastic structures exhibiting a high degree of morphological variability. Certain morphometric parameters, such as volume, positively correlate with the strength of the synapse in which they participate. Memories, too, are subject to change over time and with experiences. In particular, the presence of a reminder of a learning event can trigger the labilization of the memory trace, followed by a re-stabilization process termed reconsolidation. The underlying mechanisms behind the labilization/reconsolidation processes are of great interest, as they are thought of as possible targets for the treatment of post-traumatic stress disorders. Dendritic spines have long been considered the physical sites for memory formation and storage. Our work aimed at studying the long-term spine morphological plasticity associated with labilization/reconsolidation in the dorsal hippocampus, a brain region relevant for the formation of contextual memories. Our results suggest that labilization/reconsolidation does not affect spine density, but rather induces changes in spine morphology. Furthermore, we show that some of these changes are prevented by the inhibition of the transcription factor NF-{kappa}B inhibition. Finally, we found that NF-{kappa}B negative modulation also affects spine morphology in animals that were not exposed to recall but have undergone the training session, suggesting that there may be a late surge of NF-{kappa}B activity resulting from the consolidation itself.

neuroscience↗

Brain fingerprint is based on the aperiodic, scale-free, neuronal activity

The possibility to identify subjects from their brain activity was met enthusiastically, as it bears the possibility to individualize brain analyses. However, the nature of the processes generating subject-specific features remains unknown, as the literature does not point to specific mechanisms. In particular, most of the current literature uses techniques that are based on the assumption of stationarity (e.g. Pearsons correlation), which do not hypothesize any mechanisms, and crashes against a large body of literature showing the complex, highly non-linear nature of brain activity. In this paper, we hypothesize that intermittent moments when large, non-linear perturbations spread across the brain (defined as neuronal avalanches in the context of critical dynamics) are the ones that carry subject-specific information, and that contribute the most to identifiability. To test this hypothesis, we apply the recently-developed avalanche transition matrix (ATM) to source reconstructed magnetoencephalographic data, as to characterize subject-speficic fast dynamics. Then, we perform identifiability analysis based on the ATMs, and compared the performance to more classical ways of estimating large-scale connections (which assume stationareity). We demonstrate that selecting the moments and places where neuronal avalanches spread improves identifiability (p<0.0001, permutation testing), despite the fact that most ot the data (i.e. the linear part) are discarded. Our results show that the non-linear part of the brain signals carries most of the subject-specific information, shading light on the nature of the processes that underlie subject-identifiability. Borrowing from statistical mechanics, a solid branch of physics, we provide a principled way to link emergent large-scale personalized activations to non-observable, microscopic processes.

neuroscience↗

Eco-evolutionary drivers of avian migratory connectivity

Understanding how individuals redistribute after migration assists in the conservation and management of mobile species, yet the eco-evolutionary drivers of migratory connectivity remain unclear. Taking advantage of an exceptionally large (~150,000 individuals, 83 species) and more-than-a-century long dataset of bird ringing encounters, we investigated determinants of avian migratory connectivity on both short- and long-distance migrants. Most species exhibited significant connectivity likely due to the large intraspecific variability in migration strategies, which often led to the identification of distinct migratory populations. Migratory connectivity was strongly predicted by geography, especially migration distance, but it was evolutionary labile and weakly influenced by biological traits due to flexibility in migratory behaviour. By unravelling determinants of migratory connectivity we improve knowledge about the resilience of migrants to ecological perturbations. Also, our population-level analysis provides a critical tool to inform transboundary conservation and management strategies by explicitly considering the large intraspecific variability of avian migration.

ecology↗

Spatial point pattern analysis identifies mechanisms shaping the skin parasite landscape in Leishmania donovani infection

Increasing evidence suggests that infectiousness of hosts carrying parasites of the Leishmania donovani complex, the causative agents of visceral leishmaniasis, is linked to parasite repositories in the host skin. However, a detailed understanding of the dispersal and dispersion of these obligatory-intracellular parasites and their host phagocytes in the skin is lacking. Using endogenously fluorescent parasites as a proxy, we apply image analysis combined with spatial point pattern models borrowed from ecology to characterize dispersion of parasitized myeloid cells (including ManR+ and CD11c+ cells) and predict dispersal mechanisms in a previously described immunodeficient model of L. donovani infection. Our results suggest that after initial seeding of infection in the skin, heavily parasite-infected myeloid cells are found in patches that resemble innate granulomas. Spread of parasites from these initial patches subsequently occurs through infection of recruited myeloid cells, ultimately leading to self-propagating networks of patch clusters. This combination of imaging and ecological pattern analysis to identify mechanisms driving the skin parasite landscape offers new perspectives on myeloid cell behavior following parasitism by L. donovani and may also be applicable to elucidating the behavior of other intracellular tissue-resident pathogens and their host cells.

microbiology↗

Muscle fatigue revisited - Insights from optically pumped magnetometers

Muscle fatigue is well characterized electromyographically, nevertheless only information about summed potential differences is detectable. In contrast, recently developed quantum sensors optically pumped magnetometers (OPMs) offer the advantage of recording both the electrical current propagation in the muscle as well as its geometry, by measuring the magnetic field generated by the muscular action potentials. Magnetomyographic investigation of muscle fatigue is still lacking and it is an open question whether fatigue is characterized similarly in magnetomyography (MMG) compared to electromyography (EMG). Herein, we investigated the muscle fatigue during a 3x1-min strong isometric contraction of the rectus femoris muscle of 12 healthy subjects using simultaneous EMG-MMG (4-channel surface EMG and 4 OPM along the rectus femoris muscle). Both EMG and MMG showed the characteristic frequency decrease in the signal magnitude during isometric contraction, which is typical for muscle fatigue. In addition, it was shown that the main part of this frequency decrease seems to occur in the circular component of the magnetic field around the muscle fibers and less longitudinally along the muscle fibers. Overall, these results show not only that magnetomyography is capable of reproducing the electromyographic standards in identifying muscular fatigue, but it also adds relevant information about the spatial characterization of the signal. Therefore, OPM-MMG offers new insights for the study of muscular activity and might serve as a new, supplementary neurophysiological method.

physiology↗

Interferon-γ-producing CD4+ T cells drive monocyte activation in the bone marrow during experimental Leishmania donovani infection.

Ly6Chi inflammatory monocytes develop in the bone marrow and migrate to the site of infection during inflammation. Upon recruitment, Ly6Chi monocytes can differentiate into dendritic cells or macrophages. According to the tissue environment they can also acquire different functions. Several studies have described pre-activation of Ly6Chi monocytes in the bone marrow during parasitic infection, but whether this process occurs during experimental visceral leishmaniasis and, if so, the mechanisms contributing to their activation are yet to be established. In wild type C57BL/6 (B6) mice infected with Leishmania donovani, the number of bone marrow Ly6Chi monocytes increased over time. Ly6Chi monocytes displayed a highly activated phenotype from 28 days to 5 months post infection (p.i), with >90% expressing MHCII and >20% expressing iNOS. In comparison, in B6.Rag2-/- mice <10% of bone marrow monocytes were MHCII+ at day 28 p.i., an activation deficiency that was reversed by adoptive transfer of CD4+ T cells. Depletion of CD4+ T cells in B6 mice and the use of mixed bone marrow chimeras further indicated that monocyte activation was driven by IFN-{gamma} produced by CD4+ T cells. In B6.Il10-/- mice, L. donovani infection induced a faster but transient activation of bone marrow monocytes, which correlated with the magnitude of CD4+ T cell production of IFN-{gamma} and resolution of the infection. Under all of the above conditions, monocyte activation was associated with greater control of parasite load in the bone marrow. Through reinfection studies in B6.Il10-/- mice and drug (AmBisome) treatment of B6 mice, we also show the dependence of monocyte activation on parasite load. In summary, these data demonstrate that during L. donovani infection, Ly6Chi monocytes are primed in the bone marrow in a process driven by CD4+ T cells and whereby IFN-{gamma} promotes and IL-10 limits monocyte activation and that the presence of parasites/parasite antigen plays a crucial role in maintaining bone marrow monocyte activation.

immunology↗

Ultra-compact Dual-band Smart NEMS Magnetoelectric Antennas for Simultaneous Wireless Energy Harvesting and Magnetic Field Sensing

Ultra-compact wireless implantable medical devices (IMDs) are in great demand for healthcare applications, in particular for neural recording and stimulation. Current implantable technologies based on miniaturized micro-coils suffer from low wireless power transfer efficiency (PTE) and are not always compliant with the specific absorption rate imposed by the Federal Communications Commission, particularly for deep brain implantation where field attenuation and tissue loss are significant. Moreover, current implantable devices are reliant on recordings of voltage or current. This has two major weaknesses: 1) the necessary direct contact between electrode and tissue degrades over time due to electrochemical fouling and tissue reactions, and 2) the necessity for differential recordings across space. Here, we report, for the first time, an ultra-compact dual-band smart nanoelectromechanical systems magnetoelectric (ME) antenna with a size of 250×174 µm2 that can efficiently perform wireless energy harvesting and sense ultra-small magnetic fields such as those arising from neural activities. The proposed smart ME antenna has a wireless PTE 1∼2 orders of magnitude higher than any other reported miniaturized micro-coil, allowing the wireless IMDs to be compliant with the specific absorption rate (SAR) limit and to operate under safe exposure of radio frequency energy. Furthermore, the magnetic sensing capability of the proposed smart ME antenna, with a limit of detection of 300∼500pT at > 200Hz, should allow the IMDs to record neural magnetic fields from the brain without requiring differential recording.Competing Interest StatementThe authors have declared no competing interest.View Full Text

bioengineering↗

Energy dynamics for systemic configurations of virus-host coevolution

Virus cause multiple outbreaks, for which comprehensive tailored therapeutic strategies are still missing. Virus and host cell dynamics are strictly connected, and convey in virion assembly to ensure virus spread in the body. Study of the systemic behavior of virus-host interaction at the single-cell level is a scientific challenge, considering the difficulties of using experimental approaches and the limited knowledge of the behavior of emerging novel virus as a collectivity. This work focuses on positive-sense, single-stranded RNA viruses, like human coronaviruses, in their virus-individual host interaction, studying the changes induced in the host cell bioenergetics. A systems-thinking representation, based on stock-flow diagramming of virus-host interaction at the cellular level, is used here for the first time to simulate the system energy dynamics. We found that reducing the energy flow which fuels virion assembly is the most affordable strategy to limit the virus spread, but its efficacy is mitigated by the contemporary inhibition of other flows relevant for the system.Summary Positive-single-strand ribonucleic acid ((+)ssRNA) viruses can cause multiple outbreaks, for which comprehensive tailored therapeutic strategies are still missing. Virus and host cell dynamics are strictly connected, generating a complex dynamics that conveys in virion assembly to ensure virus spread in the body.This work focuses on (+)ssRNA viruses in their virus-individual host interaction, studying the changes induced in the host cell bioenergetics. A systems-thinking representation, based on stock-flow diagramming of virus-host interaction at the cellular level, is used here for the first time to simulate the energy dynamics of the system.By means of a computational simulator based on the systemic diagramming, we identifid host protein recycling and folded-protein synthesis as possible new leverage points. These also address different strategies depending on time setting of the therapeutic procedures. Reducing the energy flow which fuels virion assembly is addressed as the most affordable strategy to limit the virus spread, but its efficacy is mitigated by the contemporary inhibition of other flows relevant for the system. Counterintuitively, targeting RNA replication or virion budding does not give rise to relevant systemic effects, and can possibly contribute to further virus spread. The tested combinations of multiple systemic targets are less efficient in minimizing the stock of virions than targeting only the virion assembly process, due to the systemic configuration and its evolution overtime. Viral load and early addressing (in the first two days from infection) of leverage points are the most effective strategies on stock dynamics to minimize virion assembly and preserve host-cell bioenergetics.As a whole, our work points out the need for a systemic approach to design effective therapeutic strategies that should take in account the dynamic evolution of the system.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pathology↗