Threshold current density for diffusion-controlled stability of electrolytic surface nanobubbles.

Understanding the stability mechanism of surface micro/nanobubbles adhered to gas-evolving electrodes is essential for improving the efficiency of water electrolysis, which is known to be hindered by the bubble coverage on electrodes. Using molecular simulations, the diffusion-controlled evolution of single electrolytic nanobubbles on wettability-patterned nanoelectrodes is investigated. These nanoelectrodes feature hydrophobic islands as preferential nucleation sites and allow the growth of nanobubbles in the pinning mode. In these simulations, a threshold current density distinguishing stable nanobubbles from unstable nanobubbles is found. When the current density remains below the threshold value, nucleated nanobubbles grow to their equilibrium states, maintaining their nanoscopic size. However, for the current density above the threshold value, nanobubbles undergo unlimited growth and can eventually detach due to buoyancy. Increasing the pinning length of nanobubbles increases the degree of nanobubble instability. By connecting the current density with the local gas oversaturation, an extension of the stability theory for surface nanobubbles [Lohse and Zhang, Phys. Rev. E 91, 031003(R) (2015)] accurately predicts the nanobubble behavior found in molecular simulations, including equilibrium contact angles and the threshold current density. For larger systems that are not accessible to molecular simulations, continuum numerical simulations with the finite difference method combined with the immersed boundary method are performed, again demonstrating good agreement between numerics and theories.

The human cell count and size distribution.

Cell size and cell count are adaptively regulated and intimately linked to growth and function. Yet, despite their widespread relevance, the relation between cell size and count has never been formally examined over the whole human body. Here, we compile a comprehensive dataset of cell size and count over all major cell types, with data drawn from >1,500 published sources. We consider the body of a representative male (70 kg), which allows further estimates of a female (60 kg) and 10-y-old child (32 kg). We build a hierarchical interface for the cellular organization of the body, giving easy access to data, methods, and sources (https://humancelltreemap.mis.mpg.de/). In total, we estimate total body counts of ≈36 trillion cells in the male, ≈28 trillion in the female, and ≈17 trillion in the child. These data reveal a surprising inverse relation between cell size and count, implying a trade-off between these variables, such that all cells within a given logarithmic size class contribute an equal fraction to the body's total cellular biomass. We also find that the coefficient of variation is approximately independent of mean cell size, implying the existence of cell-size regulation across cell types. Our data serve to establish a holistic quantitative framework for the cells of the human body, and highlight large-scale patterns in cell biology.

Generation of single-round infectious rotavirus with a mutation in the intermediate capsid protein VP6.

Rotavirus causes severe diarrhea in infants. Although live attenuated rotavirus vaccines are available, vaccine-derived infections have been reported, which warrants development of next-generation rotavirus vaccines. A single-round infectious virus is a promising vaccine platform; however, this platform has not been studied extensively in the context of rotavirus. Here, we aimed to develop a single-round infectious rotavirus by impairing the function of the viral intermediate capsid protein VP6. Recombinant rotaviruses harboring mutations in VP6 were rescued using a reverse genetics system. Mutations were targeted at VP6 residues involved in virion assembly. Although the VP6-mutated rotavirus expressed viral proteins, it did not produce progeny virions in wild-type cells; however, the virus did produce progeny virions in VP6-expressing cells. This indicates that the VP6-mutated rotavirus is a single-round infectious rotavirus. Insertion of a foreign gene, and replacement of the VP7 gene segment with that of human rotavirus clinical isolates, was successful. No infectious virions were detected in mice infected with the single-round infectious rotavirus. Immunizing mice with the single-round infectious rotavirus induced neutralizing antibody titers as high as those induced by wild-type rotavirus. Taken together, the data suggest that this single-round infectious rotavirus has potential as a safe and effective rotavirus vaccine. This system is also applicable for generation of safe and orally administrable viral vectors.IMPORTANCERotavirus, a leading cause of acute gastroenteritis in infants, causes an annual estimated 128,500 infant deaths worldwide. Although live attenuated rotavirus vaccines are available, they are replicable and may cause vaccine-derived infections. Thus, development of safe and effective rotavirus vaccine is important. In this study, we report the development of a single-round infectious rotavirus that can replicate only in cells expressing viral VP6 protein. We demonstrated that (1) the single-round infectious rotavirus did not replicate in wild-type cells or in mice; (2) insertion of foreign genes and replacement of the outer capsid gene were possible; and (3) it was as immunogenic as the wild-type virus. Thus, the mutated virus shows promise as a next-generation rotavirus vaccine. The system is also applicable to orally administrable viral vectors, facilitating development of vaccines against other enteric pathogens.

Myelination potential and injury susceptibility of grey versus white matter human oligodendrocytes.

Increasing evidence indicates heterogeneity in functional and molecular properties of oligodendrocyte lineage cells both during development and under pathologic conditions. In multiple sclerosis, remyelination of grey matter lesions exceeds that in white matter. Here we used cells derived from grey matter versus white matter regions of surgically resected human brain tissue samples, to compare the capacities of human A2B5-positive progenitor cells and mature oligodendrocytes to ensheath synthetic nanofibers, and relate differences to the molecular profiles of these cells. For both cell types, the percentage of ensheathing cells was greater for grey matter versus white matter cells. For both grey matter and white matter samples, the percentage of cells ensheathing nanofibers was greater for A2B5-positive cells versus mature oligodendrocytes. Grey matter A2B5-positive cells were more susceptible than white matter A2B5-positive cells to injury induced by metabolic insults. Bulk RNA sequencing indicated that separation by cell type (A2B5-positive vs mature oligodendrocytes) is more significant than by region but segregation for each cell type by region is apparent. Molecular features of grey matter versus white matter derived A2B5-positive and mature oligodendrocytes were lower expression of mature oligodendrocyte genes and increased expression of early oligodendrocyte lineage genes. Genes and pathways with increased expression in grey matter derived cells with relevance for myelination included those related to responses to external environment, cell-cell communication, cell migration, and cell adhesion. Immune and cell death related genes were up-regulated in grey matter derived cells. We observed a significant number of up-regulated genes shared between the stress/injury and myelination processes, providing a basis for these features. In contrast to oligodendrocyte lineage cells, no functional or molecular heterogeneity was detected in microglia maintained in vitro, likely reflecting the plasticity of these cells ex vivo. The combined functional and molecular data indicate that grey matter human oligodendrocytes have increased intrinsic capacity to myelinate but also increased injury susceptibility, in part reflecting their being at a stage earlier in the oligodendrocyte lineage.

MerTK is a mediator of alpha-synuclein fibril uptake by human microglia.

Mer tyrosine kinase (MerTK) is a receptor tyrosine kinase that mediates non-inflammatory, homeostatic phagocytosis of diverse types of cellular debris. Highly expressed on the surface of microglial cells, MerTK is of importance in brain development, homeostasis, plasticity and disease. Yet, involvement of this receptor in the clearance of protein aggregates that accumulate with ageing and in neurodegenerative diseases has yet to be defined. The current study explored the function of MerTK in the microglial uptake of alpha-synuclein fibrils which play a causative role in the pathobiology of synucleinopathies. Using human primary and induced pluripotent stem cell-derived microglia, the MerTK-dependence of alpha-synuclein fibril internalization was investigated in vitro. Relevance of this pathway in synucleinopathies was assessed through burden analysis of MERTK variants and analysis of MerTK expression in patient-derived cells and tissues. Pharmacological inhibition of MerTK and siRNA-mediated MERTK knockdown both caused a decreased rate of alpha-synuclein fibril internalization by human microglia. Consistent with the non-inflammatory nature of MerTK-mediated phagocytosis, alpha-synuclein fibril internalization was not observed to induce secretion of pro-inflammatory cytokines such as IL-6 or TNF, and downmodulated IL-1ß secretion from microglia. Burden analysis in two independent patient cohorts revealed a significant association between rare functionally deleterious MERTK variants and Parkinson's disease in one of the cohorts (P = 0.002). Despite a small upregulation in MERTK mRNA expression in nigral microglia from Parkinson's disease/Lewy body dementia patients compared to those from non-neurological control donors in a single-nuclei RNA-sequencing dataset (P = 5.08 × 10-21), no significant upregulation in MerTK protein expression was observed in human cortex and substantia nigra lysates from Lewy body dementia patients compared to controls. Taken together, our findings define a novel role for MerTK in mediating the uptake of alpha-synuclein fibrils by human microglia, with possible involvement in limiting alpha-synuclein spread in synucleinopathies such as Parkinson's disease. Upregulation of this pathway in synucleinopathies could have therapeutic values in enhancing alpha-synuclein fibril clearance in the brain.

Publisher Correction: DNA sequencing at 40: past, present and future.

In this Review, the year of publication of reference 54 should be 2005, not 2015. In Box 2, "1982: GenBank ( https://www.ncbi.nlm.nih.gov/genbank/statistics/ )" should read "1982: Genbank/ENA/DDBJ" and "2007: NCBI Short Read Archive" should read "2007: NCBI and ENA Short Read Archives"; this is because the launches of these American, European and Japanese databases were coordinated. These errors have not been corrected.

Performance Enhancement of Electrocatalytic Hydrogen Evolution through Coalescence-Induced Bubble Dynamics.

The evolution of electrogenerated gas bubbles during water electrolysis can significantly hamper the overall process efficiency. Promoting the departure of electrochemically generated bubbles during (water) electrolysis is therefore beneficial. For a single bubble, a departure from the electrode surface occurs when buoyancy wins over the downward-acting forces (e.g., contact, Marangoni, and electric forces). In this work, the dynamics of a pair of H2 bubbles produced during the hydrogen evolution reaction in 0.5 M H2SO4 using a dual platinum microelectrode system is systematically studied by varying the electrode distance and the cathodic potential. By combining high-speed imaging and electrochemical analysis, we demonstrate the importance of bubble-bubble interactions in the departure process. We show that bubble coalescence may lead to substantially earlier bubble departure as compared to buoyancy effects alone, resulting in considerably higher reaction rates at a constant potential. However, due to continued mass input and conservation of momentum, repeated coalescence events with bubbles close to the electrode may drive departed bubbles back to the surface beyond a critical current, which increases with the electrode spacing. The latter leads to the resumption of bubble growth near the electrode surface, followed by buoyancy-driven departure. While less favorable at small electrode spacing, this configuration proves to be very beneficial at larger separations, increasing the mean current up to 2.4 times compared to a single electrode under the conditions explored in this study.

Reversible female contraceptives: historical, current, and future perspectives†.

Contraception is a practice with extensive and complicated social and scientific histories. From cycle tracking, to the very first prescription contraceptive pill, to now having over-the-counter contraceptives on demand, family planning is an aspect of healthcare that has undergone and will continue to undergo several transformations through time. This review provides a comprehensive overview of current reversible hormonal and non-hormonal birth control methods as well as their mechanism of action, safety, and effectiveness specifically for individuals who can become pregnant. Additionally, we discuss the latest Food and Drug Administration (FDA)-approved hormonal method containing estetrol and drospirenone that has not yet been used worldwide as well as the first FDA-approved hormonal over-the-counter progestin-only pills. We also review available data on novel hormonal delivery through microchip, microneedle, and the latest FDA-approved non-hormonal methods such as vaginal pH regulators. Finally, this review will assist in advancing female contraceptive method development by underlining constructive directions for future pursuits. Information was gathered from the NCBI and Google Scholars databases using English and included publications from 1900 to present. Search terms included contraceptive names as well as efficacy, safety, and mechanism of action. In summary, we suggest that investigators consider the side effects and acceptability together with the efficacy of contraceptive candidate towards their development.

Characterization of Sialic Acid-Independent Simian Rotavirus Mutants in Viral Infection and Pathogenesis.

Rotaviruses (RVs) are nonenveloped viruses that cause gastroenteritis in infants and young children. Sialic acid is an initial receptor, especially for animal RVs, including rhesus RV. Sialic acid binds to the VP8* subunit, a part of the outer capsid protein VP4 of RV. Although interactions between virus and glycan receptors influence tissue and host tropism and viral pathogenicity, research has long been limited to biochemical and structural studies due to the unavailability of an RV reverse genetics system. Here, we examined the importance of sialic acid in RV infections using recombinant RVs harboring mutations in sialic acid-binding sites in VP4 via a simian RV strain SA11-based reverse genetics system. RV VP4 mutants that could not bind to sialic acid had replicated to decreased viral titer in MA104 cells. Wild-type virus infectivity was reduced, while that of VP4 mutants was not affected in sialic acid-deficient cells. Unexpectedly, in vivo experiments demonstrated that VP4 mutants suppressed mouse pups' weight gain and exacerbated diarrhea symptoms compared to wild-type viruses. Intestinal contents enhanced VP4 mutants' infectivity. Thus, possibly via interactions with other unknown receptors and/or intestinal contents, VP4 mutants are more likely than wild-type viruses to proliferate in the murine intestine, causing diarrhea and weight loss. These results suggest that RVs binding sialic acid notably affect viral infection in vitro and viral pathogenesis in vivo. IMPORTANCE Various studies have been conducted on the binding of VP8* and glycans, and the direct interaction between purified VP8* and glycans has been investigated by crystalline structure analyses. Here, we used a reverse genetics system to generate rotaviruses (RVs) with various VP4 mutants. The generated mutant strains clarified the importance of glycan binding in vitro and in vivo. Moreover, even when VP4 mutants could not bind to sialic acid, they were able to bind to an unknown receptor. As RVs evolve, pathogenicity can also be modified by easily altering the glycans to which VP4 binds.

N-Glycosylation of Rotavirus NSP4 Protein Affects Viral Replication and Pathogenesis.

Rotavirus (RV), the most common cause of gastroenteritis in children, carries a high economic and health burden worldwide. RV encodes six structural proteins and six nonstructural proteins (NSPs) that play different roles in viral replication. NSP4, a multifunctional protein involved in various viral replication processes, has two conserved N-glycosylation sites; however, the role of glycans remains elusive. Here, we used recombinant viruses generated by a reverse genetics system to determine the role of NSP4 N-glycosylation during viral replication and pathogenesis. The growth rate of recombinant viruses that lost one glycosylation site was as high as that of the wild-type virus. However, a recombinant virus that lost both glycosylation sites (glycosylation-defective virus) showed attenuated replication in cultured cell lines. Specifically, replications of glycosylation-defective virus in MA104 and HT29 cells were 10- and 100,000-fold lower, respectively, than that of the wild-type, suggesting that N-glycosylation of NSP4 plays a critical role in RV replication. The glycosylation-defective virus showed NSP4 mislocalization, delay of cytosolic Ca2+ elevation, and less viroplasm formation in MA104 cells; however, these impairments were not observed in HT29 cells. Further analysis revealed that assembly of glycosylation-defective virus was severely impaired in HT29 cells but not in MA104 cells, suggesting that RV replication mechanism is highly cell type dependent. In vivo mouse experiments also showed that the glycosylation-defective virus was less pathogenic than the wild-type virus. Taken together, the data suggest that N-glycosylation of NSP4 plays a vital role in viral replication and pathogenicity. IMPORTANCE Rotavirus is the main cause of gastroenteritis in young children and infants worldwide, contributing to 128,500 deaths each year. Here, we used a reverse genetics approach to examine the role of NSP4 N-glycosylation. An N-glycosylation-defective virus showed attenuated and cell-type-dependent replication in vitro. In addition, mice infected with the N-glycosylation-defective virus had less severe diarrhea than mice infected with the wild type. These results suggest that N-glycosylation affects viral replication and pathogenesis. Considering the reduced pathogenicity in vivo and the high propagation rate in MA104 cells, this glycosylation-defective virus could be an ideal live attenuated vaccine candidate.

Tissue Contamination Challenges the Credibility of Machine Learning Models in Real World Digital Pathology.

Machine learning (ML) models are poised to transform surgical pathology practice. The most successful use attention mechanisms to examine whole slides, identify which areas of tissue are diagnostic, and use them to guide diagnosis. Tissue contaminants, such as floaters, represent unexpected tissue. Although human pathologists are extensively trained to consider and detect tissue contaminants, we examined their impact on ML models. We trained 4 whole-slide models. Three operate in placenta for the following functions: (1) detection of decidual arteriopathy, (2) estimation of gestational age, and (3) classification of macroscopic placental lesions. We also developed a model to detect prostate cancer in needle biopsies. We designed experiments wherein patches of contaminant tissue are randomly sampled from known slides and digitally added to patient slides and measured model performance. We measured the proportion of attention given to contaminants and examined the impact of contaminants in the t-distributed stochastic neighbor embedding feature space. Every model showed performance degradation in response to one or more tissue contaminants. Decidual arteriopathy detection--balanced accuracy decreased from 0.74 to 0.69 ± 0.01 with addition of 1 patch of prostate tissue for every 100 patches of placenta (1% contaminant). Bladder, added at 10% contaminant, raised the mean absolute error in estimating gestational age from 1.626 weeks to 2.371 ± 0.003 weeks. Blood, incorporated into placental sections, induced false-negative diagnoses of intervillous thrombi. Addition of bladder to prostate cancer needle biopsies induced false positives, a selection of high-attention patches, representing 0.033 mm2, and resulted in a 97% false-positive rate when added to needle biopsies. Contaminant patches received attention at or above the rate of the average patch of patient tissue. Tissue contaminants induce errors in modern ML models. The high level of attention given to contaminants indicates a failure to encode biological phenomena. Practitioners should move to quantify and ameliorate this problem.

Tuning the Reactivity of Copper(II)-Nitrite Core Towards Nitric Oxide Generation.

Insights into the molecular mechanism and factors affecting nitrite-to-NO transformation at transition metal sites are essential for developing sustainable technologies relevant to NO-based therapeutics, waste water treatment, and agriculture. A set of copper(II)-nitrite complexes 1-4 have been isolated employing tridentate pincer-type ligands (quL, pyL, ClArOL-, PhOL-) featuring systematically varied donors. Although the X-ray crystal structures of the copper(II)-nitrite cores in 1-4 are comparable, electrochemical studies on complexes 1-4 reveal that redox properties of these complexes differ due to the changes in the s-donor abilities of the phenolate / N-heterocycle based donor sites. Reactivity of these nitrite complexes with oxygen-atom-transfer (OAT) reagent (e.g. triphenyl phosphine Ph3P) and H+/e- donor reagent (e.g. substituted phenols ArOH) show the reduction of nitrite to NO gas. Detailed kinetic investigations including kinetic isotope effect (KIE), Eyring analyses for determining the activation parameters unfold that reduction of nitrite at copper(II) by Ph3P or ArOH are influenced by the CuII/CuI redox potential. Finally, this study allows mechanism driven development of catalytic nitrite reduction by ArOH in the presence of 10 mol% copper complex (1).

Adsorption at Nanoconfined Solid-Water Interfaces.

Reactions at solid-water interfaces play a foundational role in water treatment systems, catalysis, and chemical separations, and in predicting chemical fate and transport in the environment. Over the last century, experimental measurements and computational models have made tremendous progress in capturing reactions at solid surfaces. The interfacial reactivity of a solid surface, however, can change dramatically and unexpectedly when it is confined to the nanoscale. Nanoconfinement can arise in different geometries such as pores/cages (3D confinement), channels (2D confinement), and slits (1D confinement). Therefore, measurements on unconfined surfaces, and molecular models parameterized based on these measurements, fail to capture chemical behaviors under nanoconfinement. This review evaluates recent experimental and theoretical advances, with a focus on adsorption at solid-water interfaces. We review how nanoconfinement alters the physico-chemical properties of water, and how the structure and dynamics of nanoconfined water dictate energetics, pathways, and products of adsorption in nanopores. Finally, the implications of these findings and future research directions are discussed.

Diffusiophoretic Behavior of Polyelectrolyte-Coated Particles.

Diffusiophoresis, the movement of particles under a solute concentration gradient, has practical implications in a number of applications, such as particle sorting, focusing, and sensing. For diffusiophoresis in an electrolyte solution, the particle velocity is described by the electrolyte relative concentration gradient and the diffusiophoretic mobility of the particle. The electrolyte concentration, which typically varies throughout the system in space and time, can also influence the zeta potential of particles in space and time. This variation affects the diffusiophoretic behavior, especially when the zeta potential is highly dependent on the electrolyte concentration. In this work, we show that adsorbing a single bilayer (or 4 bilayers) of a polyelectrolyte pair (PDADMAC/PSS) on the surface of microparticles resulted in effectively constant zeta potential values with respect to salt concentration throughout the experimental range of salt concentrations. This allowed a constant potential model for diffusiophoretic transport to describe the experimental observations, which was not the case for uncoated particles in the same electrolyte system. This work highlights the use of simple polyelectrolyte pairs to tune the zeta potential and maintain constant values for precise control of diffusiophoretic transport.

Life beyond Fritz: On the Detachment of Electrolytic Bubbles.

We present an experimental study on detachment characteristics of hydrogen bubbles during electrolysis. Using a transparent (Pt or Ni) electrode enables us to directly observe the bubble contact line and bubble size. Based on these quantities we determine other parameters such as the contact angle and volume through solutions of the Young-Laplace equation. We observe bubbles without ("pinned bubbles") and with ("spreading bubbles") contact line spreading and find that the latter mode becomes more prevalent if the concentration of HClO4 is ≥0.1 M. The departure radius for spreading bubbles is found to drastically exceed the value predicted by the well-known formula of W. Fritz [Phys. Z. 1935, 36, 379-384] for this case. We show that this is related to the contact line hysteresis, which leads to pinning of the contact line after an initial spreading phase at the receding contact angle. The departure mode is then similar to a pinned bubble and occurs once the contact angle reaches the advancing contact angle of the surface. A prediction for the departure radius based on these findings is found to be consistent with the experimental data.

Continuous Focusing of Particles by AC-Electroosmosis and Induced Dipole Interactions.

Continuous particle focusing by using microfluidics is an effective method for separating particles, cells, or droplets for analytical purposes. Previously, it was shown that an alternating current across rectangular microchannels with slightly deformed side walls results in vortex flow patterns caused by alternating current electroosmosis (AC-EOF) and could lead to particle focusing. In this work, we explore this mechanism by experimentally studying the particle focusing behavior for various fluid flow velocities through a microchannel. Since it is unlikely that the particles are kept in their focused position solely by convection, a theoretical force balance between the hydrodynamic and the induced dipole force was determined. In our experiments, it was found that there is no substantial effect of the pressure-driven fluid velocity on the particle focusing velocity within the studied range. From the theoretical force balance calculations, it was determined that while the addition of the induced dipole force can still not completely describe the experimentally observed particle focusing, the induced dipole can be strong enough to overcome the hydrodynamic force. Finally, it is hypothesized that under specific circumstances, including a repulsive electrostatic force between a particle and electrode wall can complete the theoretical particle focusing force balance. Alternative phenomena that could also play a role in particle focusing are proposed.

Organocatalytic Asymmetric Conjugate Addition of Fluorooxindoles to Quinone Methides.

Fluorooxindoles undergo asymmetric Michael addition to para-quinone methides under phase-transfer conditions with 10 mol% of a readily available cinchona alkaloid ammonium catalyst. This reaction affords sterically encumbered, multifunctional fluorinated organic compounds displaying two adjacent chirality centers with high yields, ee's and dr's.

Pain screening in youth with sickle cell disease: A quality improvement study.

BACKGROUND: Youth with sickle cell disease (SCD) face several challenges as they age, including increased pain frequency, duration, and interference. The purpose of this study was to (i) determine the feasibility of routine pain screening; (ii) identify and describe various clinical pain presentations; and (iii) understand preferences/resources related to engaging in integrative health and medicine (IHM) modalities within an outpatient pediatric SCD clinic. METHODS: During routine outpatient visits, patients aged 8-18 completed measures of pain frequency, duration, and chronic pain risk (Pediatric Pain Screening Tool [PPST]). Participants screening positive for (i) persistent or chronic pain or (ii) medium or high risk for persistent symptoms and disability on the PPST were asked to complete measures of pain interference, pain catastrophizing, and interest in/resources for engaging in IHM modalities. RESULTS: Between March 2022 and May 2023, 104/141 (73.8%) patients who attended at least one outpatient visit were screened. Of these 104 (mean age 12.46, 53.8% female, 63.5% HbSS), 34 (32.7%) reported persistent or chronic pain, and 48 (46.2%) reported medium or high risk for persistent symptoms and disability. Patients completing subsequent pain screening measures reported a mean pain interference T-score of 53.2 ± 8.8 and a mean pain catastrophizing total score of 24.3 ± 10.2. Patients expressed highest interest in music (55.6%) and art therapy (51.9%) and preferred in-person (81.5%) over virtual programming (22.2%). CONCLUSIONS: Comprehensive pain screening is feasible within pediatric SCD care. Classifying patients by PPST risk may provide a means of triaging patients to appropriate services to address pain-related psychosocial factors.

Complex forelimb movements and cortical topography evoked by intracortical microstimulation in male and female mice.

The motor cortex is crucial for the voluntary control of skilled movement in mammals and is topographically organized into representations of the body (motor maps). Intracortical microstimulation of the motor cortex with long-duration pulse trains (LD-ICMS; ~500 ms) evokes complex movements, occurring in multiple joints or axial muscles, with characteristic movement postures and cortical topography across a variety of mammalian species. Although the laboratory mouse is extensively used in basic and pre-clinical research, high-resolution motor maps elicited with electrical LD-ICMS in both sexes of the adult mouse has yet to be reported. To address this knowledge gap, we performed LD-ICMS of the forelimb motor cortex in both male (n = 10) and naturally cycling female (n = 8) C57/BL6J mice under light ketamine-xylazine anesthesia. Complex and simple movements were evoked from historically defined caudal (CFA) and rostral (RFA) forelimb areas. Four complex forelimb movements were identified consisting of Elevate, Advance, Dig, and Retract postures with characteristic movement sequences and endpoints. Furthermore, evoked complex forelimb movements and cortical topography in mice were organized within the CFA in a unique manner relative to a qualitative comparison with the rat.

The left inferior frontal gyrus is causally linked to vocal feedback control: evidence from high-definition transcranial alternating current stimulation.

Current models of speech motor control propose a role for the left inferior frontal gyrus (IFG) in feedforward control of speech production. There is evidence, however, that has implicated the functional relevance of the left IFG for the neuromotor processing of vocal feedback errors. The present event-related potential (ERP) study examined whether the left IFG is causally linked to auditory feedback control of vocal production with high-definition transcranial alternating current stimulation (HD-tACS). After receiving active or sham HD-tACS over the left IFG at 6 or 70 Hz, 20 healthy adults vocalized the vowel sounds while hearing their voice unexpectedly pitch-shifted by ±200 cents. The results showed that 6 or 70 Hz HD-tACS over the left IFG led to larger magnitudes and longer latencies of vocal compensations for pitch perturbations paralleled by larger ERP P2 responses than sham HD-tACS. Moreover, there was a lack of frequency specificity that showed no significant differences between 6 and 70 Hz HD-tACS. These findings provide first causal evidence linking the left IFG to vocal pitch regulation, suggesting that the left IFG is an important part of the feedback control network that mediates vocal compensations for auditory feedback errors.