Differential Contribution Research Articles

Estimation of Species Abundance Based on the Number of Segregating Sites Using Environmental DNA (eDNA).

The advance of environmental DNA (eDNA) has enabled rapid and non-invasive species detection in aquatic environments. While most studies focus on species detection, recent works explored using eDNA concentration to quantify species abundance. However, the differential individual DNA contribution to eDNA samples could easily obscure the eDNA concentration-species abundance relationship. We propose using the number of segregating sites as a proxy for estimating species abundance. Segregating sites reflect the genetic diversity of the population, which is less sensitive to differential individual DNA contribution than eDNA concentration. We examined the relationship between the number of segregating sites and species abundance in silico, invitro, and insitu experiments, using two brackish goby species, Acanthogobius hasta and Tridentiger bifasciatus. Analyses of the simulated and invitro data with DNA mixed from a known number of individuals showed a strong correlation between the number of segregating sites and species abundance (R2 > 0.9; p < 0.01). In the insitu experiments, we analysed eDNA samples collected from mesocosm. The results further validated that the correlation (R2 = 0.70, p < 0.01) was not affected by biotic factors, including body size and feeding behaviour (p > 0.05). The cross-validation test results also showed that the number of segregating sites predicted species abundance with less bias and variability than the eDNA concentration. Overall, the number of segregating sites is less affected by differential DNA contribution among individuals compared to eDNA concentration. This advancement can significantly enhance the proficiency of estimating species abundance using eDNA.

Differential contributions of microbial necromass to humic acid during composting of organic wastes

Differential contributions of microbial necromass to humic acid during composting of organic wastes

Differential contributions of CA3 and entorhinal cortex inputs to ripple patterns in the hippocampus

Differential contributions of CA3 and entorhinal cortex inputs to ripple patterns in the hippocampus

Direct and indirect genetic effects on early neurodevelopmental traits.

Neurodevelopmental conditions are highly heritable. Recent studies have shown that genomic heritability estimates can be confounded by genetic effects mediated via the environment (indirect genetic effects). However, the relative importance of direct versus indirect genetic effects on early variability in traits related to neurodevelopmental conditions is unknown. The sample included up to 24,692 parent-offspring trios from the Norwegian MoBa cohort. We use Trio-GCTA to estimate latent direct and indirect genetic effects on mother-reported neurodevelopmental traits at age of 3 years (restricted and repetitive behaviors and interests, inattention, hyperactivity, language, social, and motor development). Further, we investigate to what extent direct and indirect effects are attributable to common genetic variants associated with autism, ADHD, developmental dyslexia, educational attainment, and cognitive ability using polygenic scores (PGS) in regression modeling. We find evidence for contributions of direct and indirect latent common genetic effects to inattention (direct: explaining 4.8% of variance, indirect: 6.7%) hyperactivity (direct: 1.3%, indirect: 9.6%), and restricted and repetitive behaviors (direct: 0.8%, indirect: 7.3%). Direct effects best explained variation in social and communication, language, and motor development (5.1%-5.7%). Direct genetic effects on inattention were captured by PGS for ADHD, educational attainment, and cognitive ability, whereas direct genetic effects on language development were captured by cognitive ability, educational attainment, and autism PGS. Indirect genetic effects on neurodevelopmental traits were primarily captured by educational attainment and/or cognitive ability PGS. Results were consistent with differential contributions to neurodevelopmental traits in early childhood from direct and indirect genetic effects. Indirect effects were particularly important for hyperactivity and restricted and repetitive behaviors and interests and may be linked to genetic variation associated with cognition and educational attainment. Our findings illustrate the importance of within-family methods for disentangling genetic processes that influence early neurodevelopmental traits, even when identifiable associations are small.

Human subcutaneous and visceral adipocyte atlases uncover classical and nonclassical adipocytes and depot-specific patterns.

Human adipose depots are functionally distinct. Yet, recent single-nucleus RNA sequencing (snRNA-seq) analyses largely uncovered overlapping or similar cell-type landscapes. We hypothesized that adipocyte subtypes, differentiation trajectories and/or intercellular communication patterns could illuminate this depot similarity-difference gap. For this, we performed snRNA-seq of human subcutaneous or visceral adipose tissues (five or ten samples, respectively). Of 27,665 adipocyte nuclei in both depots, most were 'classical', namely enriched in lipid metabolism pathways. However, we also observed 'nonclassical' adipocyte subtypes, enriched in immune-related, extracellular matrix deposition (fibrosis), vascularization or angiogenesis or ribosomal and mitochondrial processes. Pseudo-temporal analysis showed a developmental trajectory from adipose progenitor cells to classical adipocytes via nonclassical adipocytes, suggesting that the classical state stems from loss, rather than gain, of specialized functions. Last, intercellular communication routes were consistent with the different inflammatory tone of the two depots. Jointly, these findings provide a high-resolution view into the contribution of cellular composition, differentiation and intercellular communication patterns to human fat depot differences.

Un-binding the Umwelt: The Differential Contributions of the Five Classical Senses can be Understood Through Hindu Tantra

Un-binding the Umwelt: The Differential Contributions of the Five Classical Senses can be Understood Through Hindu Tantra

Differential encoding of mammalian proprioception by voltage-gated sodium channels.

Animals requiring purposeful movement for survival are endowed with mechanoreceptors, called proprioceptors, that provide essential sensory feedback from muscles and joints to spinal cord circuits, which modulates motor output. Despite the essential nature of proprioceptive signaling in daily life, the mechanisms governing proprioceptor activity are poorly understood. Here, we identified nonredundant roles for two voltage-gated sodium channels (NaVs), NaV1.1 and NaV1.6, in mammalian proprioception. Deletion of NaV1.6 in somatosensory neurons (NaV1.6cKO mice) causes severe motor deficits accompanied by loss of proprioceptive transmission, which contrasts with our previous findings using similar mouse models to target NaV1.1 (NaV1.1cKO). In NaV1.6cKO animals, we observed impairments in proprioceptor end-organ structure and a marked reduction in skeletal muscle myofiber size that were absent in NaV1.1cKO mice. We attribute the differential contributions of NaV1.1 and NaV1.6 to distinct cellular localization patterns. Collectively, we provide evidence that NaVs uniquely shape neural signaling within a somatosensory modality.

Understanding maladaptive daydreaming from the attachment framework: The intertwining roles of parental care, unresolved attachment, depression/anxiety and obsessive-compulsive symptoms.

Maladaptive Daydreaming (MD) is an excessive absorption in vivid fantasies interfering with individuals' daily functioning, which has been associated with adverse psychological outcomes and adult attachment insecurities. However, no study to date has addressed the relationships between MD, parental care, unresolved attachment, and psychological symptoms (depression/anxiety and obsessive-compulsive disorder; OCD) in a sample of young adults. In this study, 1295 young adults (401 males) completed an online survey including the Parental Bonding Instrument, Maladaptive Daydreaming Scale, Adult Unresolved Attachment Questionnaire, and the DSM-5 Level 1 Cross-Cutting Symptom Measure. The results evidenced the differential contribution of maternal and paternal care on individuals' psychological symptoms; whilst higher maternal care was negatively related to OCD symptoms, higher paternal care was negatively linked to depression/anxiety symptoms. A relationship between unresolved attachment, MD and psychopathological symptoms emerged; specifically, MD mediated the relationships between unresolved attachment and depression/anxiety and OCD symptoms. Overall, paternal and maternal care may have distinct roles in predicting individuals' psychopathological outcomes. In the presence of unresolved attachment, MD may represent a dissociative response that allows individuals to deal with negative experiences through psychopathological symptoms. Understanding the specific pathways that lead to different psychopathological outcomes could have important implications in developing preventive clinical interventions.

The analysis of miR‐133b and miR‐122 in cord blood for eye drop preparations. The differential contribution of platelet‐rich‐plasma and serum

Aims/Purpose: Cord blood (CB) –derived eye drops are safe and effective in many ophthalmological diseases, primarily persistent keratopathy related to severe dry eye disease. MicroRNA (miRNA) fine tune multiple messenger RNAs (mRNAs) and modulate several pathological pathways. This study was aimed at comparing platelet‐rich plasma (PRP) and serum (S) from CB, for expression of miR‐133b and miR‐122, negative regulators of inflammation and neuropathic pain respectively.Methods: PRP and S prepared from the same CB donor (n = 6) were processed for miRNA extraction, subjected to miRNA specific Reverse‐Transcription and Pre‐amplification. MiRNA analysis was performed by Real Time PCR and Digital Droplet PCR, (ddPCR) comparing the two approaches in terms of yield and data comparability. Small nuclear RNA U6 and RNU44 were used as housekeeping genes.Results: PRP samples displayed higher yield in terms of RNA amount and purity than serum (mean RNA concentration: 30 ng/ul vs 8 ng/ul, respectively). The snU6 was more stable among all samples and was selected as housekeeping gene. miR‐133b was 26% lower in S than in PRP, whereas miR‐122 did not show significant differences between CB and S. ddPCR data were comparable with Real Time analysis, displaying higher sensibility also in samples with lower RNA yield.Conclusions: According to our data, CB preparations contain miRNA involved in the modulation of inflammatory process and pain in ocular surface diseases. PRP and S share similar expression levels of miR‐122, whereas miR‐133b is higher in PRP, indicating that PRP is more powerful in terms of anti‐inflammatory function than S, whereas both CB preparations contribute to ameliorating pain in ocular surface diseases. Further investigations are addressed at increasing the CB sample number to dissect the miRNA: mRNA network and validate the miRNA analysis by ddPCR, for a more accurate quantification in view of the therapeutic applications of CB preparations.

Tectonics and climate controlled sedimentary provenance in the teesta basin since mid-holocene

Erosion of the Himalaya Mountain and subsequent deposition of sediments in the flood plains, and distal fans are primarily regulated by tectonics, climates, lithology, and relief of the region. These eroded sediments preserve their chemical and isotopic compositions in their depositional archive, which can be used to trace the erosion processes, assess the relative role of controlling factors and their spatio-temporal variations. The present study have analysed the 87Sr/86Sr and ԐNd of in silicate phase of sediment recovered from a ~ 40 m long sedimentary core representing ~8 ky of sediment accumulation in the Teesta River mega fan. The lithostratigraphy of the core indicates rapid aggradational nature of the Teesta mega fan. The 87Sr/86Sr and ԐNd display large variability with depth, which ranges from 0.75700 to 0.89294 and − 15.1 to −25.0, respectively. The observed 87Sr/86Sr and ԐNd values in the core sediments have been interpreted in terms of differential sediment contribution from the Higher and the Lesser Himalayan lithology. The 87Sr/86Sr and ԐNd isotope profiles and estimated fractional sediment contributions identify the Lesser Himalaya as the major sediment contributor to the Teesta basin since the mid-Holocene, unlike the other Himalayan River basins, dominated by sediments from the Higher Himalaya after the Last Glacial Maximum. The rapid exhumation and erosion of the tectonically active Rangeet window with the focused precipitation and presence of rock types vulnerable to weathering in the Lesser Himalaya of the basin appear to be the major factors resulting the sedimentary budget of the Teesta River basin over at least last 8 ky. Our assessment suggests that tectonic activity and climate have a competitive effect for the observed sedimentary budget, with an additional role of lithology. The study infers a major control of active tectonics, precipitation, and lithology on the sedimentary budget of the Himalayan River basins.

Differential effects of psychological resources on well-being and psychological distress: a one-year longitudinal study during the COVID-19 pandemic

ABSTRACT Extensive research evaluated the protective role of psychological resources (PRs, e.g. optimism, hope, gratitude and wisdom). However, few studies have explored their differential contributions when measured together. This study evaluated the longitudinal relationships between (and among) eight psychological resources, psychological distress (depression and anxiety symptomatology) and well-being (hedonic, eudaimonic, social, and inner well-being), over the first year of the COVID pandemic. Participants (N = 481) reported their levels of PRs, psychological distress, and well-being on two occasions (T0: April 2020; T1: June 2021). Cross-lagged panel analysis of the one-year associations revealed that 1) PRs positively, but differentially, predicted well-being and psychological distress; 2) PRs positively reinforced each other; and 3) well-being and low psychological distress also reinforced PRs, but to a lesser degree. In particular, psychological flexibility appeared to be the most predictive variable in all domains. This study highlights the need to include multiple psychological resources in future research.

MOLECULAR TYPING OF HLA-B*27 SUB-ALLELES REVEALS AN ASSOCIATION WITH ERAP1 AND DISEASE SUBSET OF ANKYLOSING SPONDYLITIS IN NORTH-INDIAN (KASHMIR) POPULATION

Background: Human Leukocyte Antigen(HLA)-B*27 is significantly linked to Ankylosing spondylitis(AS) and its presence aids in the diagnosis of the disease. Identification of HLA-B*27 allele plays an important role in the clinical monitoring,diagnosis and therapy of this spondyloarthropathy because of high HLA polymorphism and differential contribution of alleles and molecules encoded by them. HLA-B*27 is also present in general population 7-8%.We evaluated the presence and correlation of various HLA-B*27 alleles with clinical parameters and ERAP1 (SNPs rs27434, rs27529 and rs26510) of Ankylosing spondylitis in Kashmiri Population. Methods: This study involved total 200 cases (100 Ankylosing Spondylitis patients and 100 healthy controls). Genomic DNA was extracted by phenol-chloroform method. All subjects were genotyped for HLA-B*27 subtyping by Polymerase Chain Reaction(PCR)-Sequence Specific Primer(SSP) method. Result: HLA-B*27 were present in 90% of cases and in 20% of controls OR 36.0(15.91-81.48)P= &lt;0.0001. HLA-B*27:02 OR 9.12(2.63-31.6) p=&lt;0.0001, CAFRW OR 12.61(4.73-33.9)p= &lt;0.0001 and HLA-B*27+CAFRS OR 45.07(2.64-759.4)p=0.0001 were showing significant association with AS disease. Conclusion: The current study indicates that a majority of Kashmiri AS patients are associated with HLA-B*27 alleles. In addition we found that HLA-B*27 associated AS patients presented with more severe axial manifestation.

Differential contributions of the C1 ERP and broadband high-frequency activity to visual processing.

The high-frequency activity (HFA; 80-150 Hz) in human intracranial recordings shows a differential modulation to different degrees in contrast when stimuli are behaviorally relevant, indicating a feedforward process. However, the HFA is also significantly dominated by superficial layers and exhibits a peak before 200 ms, suggesting that it is more likely a feedback signal. Magnetoencephalographic (MEG) recordings are suited to reveal an HFA modulation similar to its modulation in intracranial recordings. This allows for noninvasive, direct comparison of HFA with the C1, an established measure for feedforward input to V1, to test whether HFA represents feedforward or rather feedback. In simultaneous recordings, we used the EEG-C1 event-related potential (ERP) component and MEG-HFA to define feedforward processing in visual cortices. C1 latency preceded the HFA peak modulation, which had a more sustained response. Furthermore, modulation parameters like onset, peak time, and peak amplitude were uncorrelated. Most importantly, the C1 but not HFA distinguished small task-irrelevant contrast differences in visual stimulation. These results highlight the differential roles for the C1 and HFA in visual processing with the C1 measuring feedforward discrimination ability and HFA indexing feedforward and feedback processing.NEW & NOTEWORTHY Whether the broadband high-frequency activity (HFA) represents exclusively feedforward or feedback processing remains unclear. In this study, we compared the response characteristics of the HFA-magnetoencephalographic (MEG) and the C1-EEG component to systematic contrast modulations of task-irrelevant visual stimulation. Our findings reveal that the more sustained HFA follows the C1 component and, unlike the C1, is not modulated by task-irrelevant contrast differences. This timing of the HFA modulation suggests that HFA encompasses both feedforward and feedback processing.

Turbulence modulation in liquid–liquid two-phase Taylor–Couette turbulence

We investigate the coupling effects of the two-phase interface, viscosity ratio and density ratio of the dispersed phase to the continuous phase on the flow statistics in two-phase Taylor–Couette turbulence at a system Reynolds number of $6\times 10^3$ and a system Weber number of 10 using interface-resolved three-dimensional direct numerical simulations with the volume-of-fluid method. Our study focuses on four different scenarios: neutral droplets, low-viscosity droplets, light droplets and low-viscosity light droplets. We find that neutral droplets and low-viscosity droplets primarily contribute to drag enhancement through the two-phase interface, whereas light droplets reduce the system's drag by explicitly reducing Reynolds stress due to the density dependence of Reynolds stress. In addition, low-viscosity light droplets contribute to greater drag reduction by further reducing momentum transport near the inner cylinder and implicitly reducing Reynolds stress. While interfacial tension enhances turbulent kinetic energy (TKE) transport, drag enhancement is not strongly correlated with TKE transport for both neutral droplets and low-viscosity droplets. Light droplets primarily reduce the production term by diminishing Reynolds stress, whereas the density contrast between the phases boosts TKE transport near the inner wall. Therefore, the reduction in the dissipation rate is predominantly attributed to decreased turbulence production, causing drag reduction. For low-viscosity light droplets, the production term diminishes further, primarily due to their greater reduction in Reynolds stress, while reduced viscosity weakens the density difference's contribution to TKE transport near the inner cylinder, resulting in a more pronounced reduction in the dissipation rate and consequently stronger drag reduction. Our findings provide new insights into the physics of turbulence modulation by the dispersed phase in two-phase turbulence systems.

Differential contributions of the gut microbiota and metabolome to pathomechanisms in ulcerative colitis: an in vitro analysis

ABSTRACT The gut microbiota has been implicated in onset and progression of ulcerative colitis (UC). Here, we assess potential causal involvement of the microbiota and -associated fecal water (FW) metabolome in altering key functional parameters of the colonic epithelium. Fecal samples were collected from N = 51 healthy controls (HC), N = 36 patients with active UC (UC-A), and N = 41 subjects in remission N = 41 (UC-R). Using in vitro incubation experiments, the FW metabolome’s impact on butyrate oxidation rates/gene expression and cell death (cytotoxicity) of HT-29 cells, cytokine production by PBMC, and barrier integrity of Caco2 monolayers was evaluated. The FW metabolome from patients and individuals hosting the Bacteroides 2 (Bact2) enterotype (69% of UC-A, 31% of UC-R, 3% of HC), characterized by lower levels of median- and short-chain fatty acids and furan compounds, left butyrate oxidation rates unaltered but affected associated gene expression profiles. UC patients/Bact2-carriers’ FW lowered PBMC IL-8 production and increased IL-1β production. Patients’ FW increased cytotoxicity, associated with sulfide compound levels. Bact2 carriers’ FW, displaying higher levels of bile acids, lowered barrier function upon incubation of monolayers. The FW metabolome of patients and individuals hosting a dysbiotic microbiota could contribute to the disruption of functional processes of the colonic epithelium as observed in UC.

An overview of pathogenesis of metabolic dysfunction-associated steatotic liver disease

Steatotic liver disease (SLD) has been known for a long time, but our understanding of this disease has remained poor until the past decade. Despite extensive research, our ability to comprehend the etiopathogenesis and natural course of SLD is far from the desired level of comprehension. This is required to develop a universally effective novel therapeutic agent. This review aims to concisely elaborate the conceptual approach and advancement in the understanding of global disease burden and etiopathogenic process, identifying the gaps and the pathophysiologic mechanism behind developing novel therapeutic agents. We searched two major databases, PubMed and Google Scholar, to identify publications related to the abovementioned topics. All publications, including original papers, reviews, and commentaries, were reviewed. Findings: Metabolic dysfunction-associated steatotic liver disease (MASLD) is not limited to obese individuals, rather, it may develop in any individual independent of weight. Visceral adiposity is strongly associated with MASLD and subsequent risks of cirrhosis, hepatocellular carcinoma, and cardiovascular disease. MASLD is associated with diabetes mellitus independent of underlying pathogenic mechanisms, and there is a bidirectional connection between MASLD and diabetes mellitus, making the situation quite challenging. Not all patients with MASLD exhibit atherogenic dyslipidemia and thus do not have a higher risk of cardiovascular disease. The overlap of these metabolic risk factors is not straightforward. There is a differential contribution of these risk factors based on age, gender, race, ethnicity, alcohol consumption, and microbiota composition. Poor dietary habits and lifestyle directly affect the microbiota, modulators, and mediators, thereby affecting the final biochemical processes leading to steatosis, steatohepatitis, fibrosis, and oncogenesis. In conclusion, MASLD is a complex and pathogenically heterogeneous disease with significant interpatient variation in the natural course and outcome. Understanding the precise mechanism of variability is the key gap and a limiting factor in the development of a novel therapeutic agent.

Differential contribution of Cu2+ and OH− to the formation of Nε-carboxymethyllysine and Nε-carboxyethyllysine in preserved egg white during pickling

In this study, the relationship between advanced glycosylation end products (AGEs) in preserved egg white (PEW) with protein oxidation and precursors induced by OH− and Cu2+ were performed to clarify the differential contribution of OH− and Cu2+ on the formation of AGEs during pickling. It was found that AGEs were more easily formed in PEW rather than yolk, and the accumulation of Nε-carboxymethyllysine (CML) could be promoted through protein oxidation related to carbonyl compounds, tryptophan induced by Cu2+ at early stage, while carbonyl compounds were more conducive to form Nε-carboxyethyllysine (CEL) under synergistic action of Cu2+ and OH−. At later period, Schiff base promoted the formation of CEL and CML in the presence of Cu2+. Meanwhile, the enrichment of CEL and CML could both be promoted by α-dicarbonyl compounds in presence of Cu2+ and/or OH−. This manuscript will provide theoretical guidance for reducing and limiting hazardous compounds in preserved eggs.

Projection-specific circuits of retrosplenial cortex with differential contributions to spatial cognition.

Retrosplenial cortex (RSC) is a brain region involved in neuropsychiatric and neurodegenerative disorders. It has reciprocal connections with a diverse set of cortical and subcortical brain regions, but the afferent structure and behavioral function of circuits defined by its projection-specific sub-populations have yet to be determined. The corticocortical connections between RSC and secondary motor cortex (M2), as well as corticothalamic connections between RSC and anterodorsal thalamus (AD) have been hypothesized to function as semi-independent, but parallel pathways that impact spatial information processing in distinct ways. We used retrograde and anterograde viral tracers and monosynaptic retrograde rabies virus to quantitatively characterize and compare the afferent and efferent distributions of retrosplenial neuron sub-populations projecting to M2 and AD. AD-projecting and M2-projecting RSC neurons overlap in their collateral projections to other brain regions, but not in their projections to M2 and AD, respectively. Compared with AD-projecting RSC neurons, M2-projecting RSC neurons received much greater afferent input from the dorsal subiculum, AD, lateral dorsal and lateral posterior thalamus, and somatosensory cortex. AD-projecting RSC neurons received greater input from the anterior cingulate cortex and medial septum. We performed chemogenetic inhibition of M2- and AD-projecting RSC neurons and examined its impact on object-location memory, object-recognition, open-field exploration, and place-action association. Our findings indicate that inhibition of M2-projecting RSC neurons impairs object location memory as well as place-action association, while the RSC to AD pathway impacts only object-location memory. The findings indicate that RSC is composed of semi-independent circuits distinguishable by their afferent/efferent distributions and differing in the cognitive functions to which they contribute.

Differential contributions of fetal mononuclear phagocytes to Zika virus neuroinvasion versus neuroprotection during congenital infection.

Fetal immune cell functions during congenital infections are poorly understood. Zika virus (ZIKV) can vertically transmit from mother to fetus, causing nervous system infection and congenital ZIKV syndrome (CZS). We identified differential functional roles for fetal monocyte/macrophage cell types and microglia in ZIKV dissemination versus clearance using mouse models. Trafficking of ZIKV-infected primitive macrophages from the yolk sac allowed initial fetal virus inoculation, while recruited monocytes promoted non-productive neuroinflammation. Conversely, brain-resident differentiated microglia were protective, limiting infection and neuronal death. Single-cell RNA sequencing identified transcriptional profiles linked to the protective versus detrimental contributions of mononuclear phagocyte subsets. In human brain organoids, microglia also promoted neuroprotective transcriptional changes and infection clearance. Thus, microglia are protective before birth, contrasting with the disease-enhancing roles of primitive macrophages and monocytes. Differential modulation of myeloid cell phenotypes by genetically divergent ZIKVs underscores the potential of immune cells to regulate diverse outcomes during fetal infections.

Cortico-thalamic communication for action coordination in a skilled motor sequence.

The coordination of forelimb and orofacial movements to compose an ethological reach-to-consume behavior likely involves neural communication across brain regions. Leveraging wide-field imaging and photo-inhibition to survey across the cortex, we identified a cortical network and a high-order motor area (MOs-c), which coordinate action progression in a mouse reach-and-withdraw-to-drink (RWD) behavior. Electrophysiology and photo-inhibition across multiple projection neuron types within the MOs-c revealed differential contributions of pyramidal tract and corticothalamic (CTMOs) output channels to action progression and hand-mouth coordination. Notably, CTMOs display sustained firing throughout RWD sequence and selectively enhance RWD-relevant activity in postsynaptic thalamus neurons, which also contribute to action coordination. CTMOs receive converging monosynaptic inputs from forelimb and orofacial sensorimotor areas and are reciprocally connected to thalamic neurons, which project back to the cortical network. Therefore, motor cortex corticothalamic channel may selectively amplify the thalamic integration of cortical and subcortical sensorimotor streams to coordinate a skilled motor sequence.