Biology subjects

Chen, K.-H.

Publications and source records attributed to Chen, K.-H..

18 recordsLinked to original sources

bioRxiv2026

An operon encoding two secreted nucleases mediates virulence in Methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen that colonizes a significant proportion of humans, contains numerous virulence factors promoting infection, and continues to threaten human lives and burden healthcare systems globally. Many MRSA virulence factors are known to be either secreted or anchored on the outer leaflet of the cell surface. Although many virulence factors have been studied intensively in MRSA, there remains a significant proportion of secreted and surface proteins that are unstudied for their potential as virulence factors. We began with identifying proteins secreted from MRSA in axenic culture using an unbiased mass-spectrometry based approach. 2 secreted proteins thus identified mapped to an operon of 6 genes, SAUSA300_1739 to SAUSA300_1744. Mutation of each of the individual genes in the operon resulted in attenuation in a mouse model of subcutaneous infection. We demonstrate that two genes in the operon, SAUSA300_1739, and SAUSA300_1740, encode nucleases with DNase activity. Genetic analysis of the SAUSA300_1739 to SAUSA300_1744 operon across several Staphylococcus aureus strains indicate that the operon is highly conserved, highlighting its importance for virulence.

microbiology↗

bioRxiv2025

Tracking White Matter Changes After Stereotaxic Radiosurgery inMiniature Pigs Using structural MRI, DTI, and FDG-PET

Stereotaxic radiosurgery (SRS) non-invasively and precisely ablates brain tumors or glioma located in the location where is surgically inaccessible with the aid of three- dimensional coordination system. This technique can also treat functional or psychiatric disorders, yet its dosimetry and curative mechanism remain to be elucidated. In this study, a miniature pig model was utilized to verify the effect of stereotaxic radiosurgery on a white matter tract with various doses delivered by CyberKnife. As porcine brain bears high resemblance to that of human in size and structure, the potential irradiation- induced change in structures and metabolism was monitored by conventional tools in clinical, including anatomical magnetic resonance image (MRI), diffusion tensor image (DTI) and 18F-Fluoro-D-Glucose positron emission tomography (FDG-PET). The right internal capsule was selected as the surgical target, and a one-year longitudinal study was conducted with whole brain images obtained once per three months. The results indicate that a dose equal to or higher than 60 Gy led to a late-onset radionecrosis which took a period close to 180 d to develop edema and breakage in the blood-brain barrier. In the meanwhile, DTI indices and differential tractography further illustrate a dose- and distance-dependent white matter injury along the tract of internal capsule. In contrast, doses of 40 Gy and below did not result in any discernible harm to the brain structure, but a sustained local inhibition in brain metabolism was observed in some pigs. The modulatory effect of low dose radiation awaits a comprehensive assessment throughout the whole brain in combination with behavioral or cognitive tasks built on pigs. This study showing the dose- and time-dependent changes will improve the understanding of the SRS dosimetry on the white matter and help investigators to decide an optimal window for brain imaging or behavioral assessment to take place on patients.

neuroscience↗

bioRxiv2025

Epinephrine Enhanced Fear Conditioning under Pentobarbital or Dexmedetomidine Anesthesia in Rats

This study examined effects of epinephrine injected in learning under anesthesia on awake memory of three fear conditioning tasks. Epinephrine given after training at various doses did not affect conditioned freezing acquired in an awake state or under 50 mg/kg pentobarbital; however, 0.1 mg/kg epinephrine caused saving in re-learning. For conditioned-fear potentiation of startle acquired in an awake state, epinephrine at 0.01 or 0.1 mg/kg enhanced 1-trial learning but at 1.0 mg/kg impaired 5-trial learning. For this task trained under pentobarbital, epinephrine enhanced 1-trial learning at 1.0 mg/kg and 5-trial learning at 0.1 or 1.0 mg/kg. Under infusion of dexmedetomidine (0.1 mg/kg/hr), learning of this task at a 0.63 mA foot shock yielded poor memory, which was improved by 0.1 mg/kg epinephrine; yet epinephrine had no effect on the better memory yielded by 1.25 mA foot shock. In an inhibitory avoidance task, rats in an awake state explored the apparatus and then received foot shocks under anesthesia of dexmedetomidine, injections of 0.1 mg/kg epinephrine before each shock training session enhanced memory. Deleting the awake exploration abolished the epinephrine effect. These results, taken together, suggest that epinephrine could enhance learning in three conditioning tasks under two anesthetics when the fear memory was assessed indirectly through its modification of an innate or learned behavioral tendency.

animal behavior and cognition↗

bioRxiv2025

Dioecy in a wind-pollinated herb explained by disruptive selection on sex allocation

O_LIThe evolution of dioecy from hermaphroditism is widely thought to be a response to disruptive selection favouring males and females, driven by advantages of inbreeding avoidance, sexual specialization, or both. It has hitherto been difficult to uncouple the importance of these two hypotheses. C_LIO_LIWe use phenotypes produced by experimental evolution to test the inbreeding avoidance hypothesis in populations from which sexual specialization can be effectively ruled out. We estimate the selfing rate and the shape of fitness gain curves under scenarios with and without inbreeding depression in experimental populations of wind-pollinated Mercurialis annua with high variation in sex allocation. C_LIO_LIWe confirm a phenotypic trade-off between male and female allocation in M. annua. Individual selfing rates increased with pollen production. This dependence gave rise to strong disruptive selection on sex allocation due to its interaction with the mating system under the scenario of high inbreeding depression, especially for plants of medium and large sizes. C_LIO_LITaken together, we demonstrate that inbreeding avoidance on its own can lead to disruptive selection on sex allocation, favouring the selection and maintenance of dioecy under wind pollination without associated benefits of sexual specialization. C_LI

evolutionary biology↗

bioRxiv2024

Mapping fitness landscapes to interpret sex allocation in hermaphrodites

Sex allocation theory predicts sex ratios of dioecious organisms, but it has been poor at explaining sex allocation in hermaphrodites in which the assumed trade-off between male and female functions is often obscure. Here, we apply sex-allocation theory to hermaphrodites by mapping components of seasonal reproductive success onto a fitness landscape defined by potentially independent measures of allocation to male and female functions on orthogonal axes. We find that peaks of reproductive success in a perennial hermaphroditic plant reflect the interactive effect of both male and female allocations on self-fertilization and the effects of inbreeding depression. The rugged landscape corresponds well to the complex pattern of sex allocation observed in natural populations in which individuals produce a mix of male and bisexual flowers and express a type of gender diphasy. Our approach may help to interpret common complexities of sex allocation in hermaphroditic plants and animals.

evolutionary biology↗

bioRxiv2024

Effects of floral sex allocation and phenology on the within-flower selfing rate and female reproductive success in Pulsatilla alpina, a perennial herb with strong inbreeding depression

O_LIWithin-flower self-pollination should be the major source of self-fertilization in mixed-mating species presenting single or few flowers simultaneously. It is also an often unmeasured source of selfing in species with many flowers open simultaneously. In general, the rate of within-flower selfing is expected to depend on the number of pistils and stamens, the timing of flowering, and subsidiary floral traits in self-compatible species in which pistil and stamen numbers vary. Accordingly, the intensity and direction of selection on these traits should depend on the level of inbreeding depression. C_LIO_LIHere, we measured the dependence of the within-flower selfing rate on floral sex allocation, phenology, petal length, and floral stalk height in a population of the perennial herb Pulsatilla alpina (Ranunculaceae) in which most individuals had single flowers. We estimated inbreeding depression in the population by comparing inbreeding coefficients between parents and seed progeny using microsatellite markers. We then estimated selection on the measured traits via female reproductive success at the flower level and compared our estimates with a hypothetical scenario in which inbreeding depression was assumed to be absent. C_LIO_LIWe estimated inbreeding depression to be 0.93. The within-flower selfing rate varied widely among flowers and depended positively on stamen number and negatively on pistil number and flowering date, supporting the predictions of a mass-action model. The dependence of the selfing rate on the measured floral traits consistently predicted (non-linear) patterns of selection under high inbreeding depression that were distinct from those under a hypothetical scenario of no inbreeding depression. C_LIO_LISynthesis: While previous research has emphasized the importance of mass-action mating on selfing among flowers of plants with large floral displays, our results demonstrate its importance for selfing within individual flowers. They also demonstrate the importance of accounting for both the selfing rate and inbreeding depression when inferring selection on floral and other traits via female fitness. C_LI

evolutionary biology↗

bioRxiv2024

MicroFisher: Fungal taxonomic classification for metatranscriptomic and metagenomic data using multiple short hypervariable markers

Profiling the taxonomic and functional composition of microbes using metagenomic (MG) and metatranscriptomic (MT) sequencing is advancing our understanding of microbial functions. However, the sensitivity and accuracy of microbial classification using genome- or core protein-based approaches, especially the classification of eukaryotic organisms, is limited by the availability of genomes and the resolution of sequence databases. To address this, we propose the MicroFisher, a novel approach that applies multiple hypervariable marker genes to profile fungal communities from MGs and MTs. This approach utilizes the hypervariable regions of ITS and large subunit (LSU) rRNA genes for fungal identification with high sensitivity and resolution. Simultaneously, we propose a computational pipeline (MicroFisher) to optimize and integrate the results from classifications using multiple hypervariable markers. To test the performance of our method, we applied MicroFisher to the synthetic community profiling and found high performance in fungal prediction and abundance estimation. In addition, we also used MGs from forest soil and MTs of root eukaryotic microbes to test our method and the results showed that MicroFisher provided more accurate profiling of environmental microbiomes compared to other classification tools. Overall, MicroFisher serves as a novel pipeline for classification of fungal communities from MGs and MTs.

bioinformatics↗

bioRxiv2024

Contrasting Phyllosphere Mycobiome in two Lycopodiaceae Plant Species: Unraveling Potential HupA-Producing Fungi and Fungal Interactions

BackgroundHuperzine A (HupA) is a natural lycopodium alkaloid renowned for its efficacy in treating neurodegenerative diseases such as Alzheimers disease. It specifically occurs in the Huperzioideae subfamily of Lycopodiaceae. Fungi associated with Huperzioideae species are potential contributors to HupA biosynthesis, offering promising prospects for HupA production. However, limited knowledge of fungal diversity in lycophytes, coupled with decreased HupA production over time of fungal strains, has impeded the discovery and applications of HupA-producing fungi. Here, we investigated huperzine concentrations and the mycobiome across various tissues of two Lycopodiaceae species, Huperzia asiatica (a HupA producer) and Diphasiastrum complanatum (a non-HupA producer). Our objectives across the tissues of the two species are to unveil the distribution of potential HupA-producing fungi and elucidate fungal interactions within the mycobiome, aiming to uncover the role of HupA-producing fungi and pinpoint their potential fungal facilitators. ResultsAmong the tissues, H. asiatica exhibited the highest HupA concentration in apical shoots (360.27 g/ml) whereas D. complanatum showed no HupA presence in any tissue. We obtained 441 Amplicon Sequence Variants (ASVs) from H. asiatica and 497 ASVs from D. complanatum. The fungal communities in bulbils and apical shoots of H. asiatica were low in diversity and dominated by Sordariomycetes, a fungal class harboring the majority of reported HupA-producing fungi. Integrating bioinformatics with published experimental reports, we identified 27 potential HupA-producing fungal ASVs, primarily in H. asiatica, with 12 ASVs identified as hubs in the fungal interaction network, underscoring their pivotal roles in mycobiome stability. Members of certain fungal genera, such as Penicillium, Trichoderma, Dioszegia, Exobasidium, Lycoperdon and Cladosporium exhibited strong connections with the potential HupA producers in H. asiaticas network rather than in D. complanatums, implying their prospects as fungal facilitators in enhancing HupA production. ConclusionsThis study advances our knowledge of fungal diversity in Lycopodiaceae and provides insights into the search for potential HupA-producing fungi and fungal facilitators. It highlights the importance of exploring young tissues, and emphasizes the ecological interactions that promote the fungi-mediated production of complex bioactive compounds, offering new directions for research in fungal ecology and secondary metabolite production.

microbiology↗

bioRxiv2023

Efficacy of Drpitor1a, a Dynamin-Related Protein 1 inhibitor, in Pulmonary Arterial Hypertension

RationaleDynamin-related protein 1 (Drp1), a large GTPase, mediates mitochondrial fission. Increased Drp1-mediated fission permits accelerated mitosis, contributing to hyperproliferation of pulmonary artery smooth muscle cells (PASMC), which characterizes pulmonary arterial hypertension (PAH). We developed a Drp1 inhibitor, Drpitor1a, and tested its ability to regress PAH. ObjectivesAssess Drpitor1as efficacy and toxicity in: a)normal and PAH human PASMC (hPASMC); b)normal rats versus rats with established monocrotaline (MCT)-induced PAH. MethodsDrpitor1as effects on recombinant and endogenous Drp1-GTPase activity, mitochondrial fission, and cell proliferation were studied in hPASMCs (normal=3; PAH=5). Drpitor1as pharmacokinetics and tissue concentrations were measured (n=3 rats/sex). In a pilot study (n=3-4/sex/dose), Drpitor1a (1mg/kg/48-hours, intravenous) reduced adverse PA remodeling only in females. Consequently, we compared Drpitor1a to vehicle in normal (n=6 versus 8) and MCT-PAH (n=9 and 11) females, respectively. Drpitor1a treatment began 17-days post-MCT with echocardiography and cardiac catheterization performed 28-29 days post-MCT. ResultsDrpitor1a inhibited recombinant and endogenous Drp1 GTPase activity, which was increased in PAH hPASMC. Drpitor1a inhibited mitochondrial fission and proliferation and induced apoptosis, in PAH hPASMC but not normal hPASMC. Drpitor1a tissue levels were higher in female versus male RVs. In MCT-PAH females, Drpitor1a regressed PA obstruction, lowered pulmonary vascular resistance, and improved RV function, without hematologic, renal, or hepatic toxicity. ConclusionsDrpitor1a inhibits Drp1 GTPase, reduces mitochondrial fission, and inhibits cell proliferation in PAH hPASMC. Drpitor1a caused no toxicity in MCT-PAH and had no significant effect on normal rats or hPASMCs. Drpitor1a is a potential PAH therapeutic which displays an interesting therapeutic sexual dimorphism.

pharmacology and toxicology↗

bioRxiv2023

Size-dependent sex allocation and the expression of andromonoecy in a protogynous perennial herb: both size and timing matter

The optimal life history and sex allocation of perennial hermaphrodites should depend on both their size and the relative costs and benefits of reproducing through male versus female functions. Theory predicts that insect-pollinated perennials should increase their allocation to female function with size, while the mating environment hypothesis predicts that allocation to male function should track mating opportunities over the course of flowering. We test these two predictions by inferring male and female reproductive success in the protogynous perennial herb Pulsatilla alpina by tracking the patterns and dynamics of sex allocation over time for marked individuals over a range of sizes. We found that small individuals tend to produce only male flowers and that both small and larger individuals produced male flowers at the beginning of the flowering season when mating opportunities were high. By considering within-population variation in life history and phenology jointly rather than separately, and by considering both the tradeoff costs and benefits of allocation to male versus female functions, our results provide new insights into the evolution of both gender diphasy and andromonoecy in perennial plants that are constrained by a dichogamous flowering strategy.

evolutionary biology↗

bioRxiv2022

Epigenetic reprogramming shapes the cellular landscape of schwannoma

Cell state evolution underlies tumor development and response to therapy1, but mechanisms specifying cancer cell states and intratumor heterogeneity are incompletely understood. Schwannomas are the most common tumors of the peripheral nervous system and are treated with surgery and ionizing radiation2-5. Schwannomas can oscillate in size for many years after radiotherapy6,7, suggesting treatment may reprogram schwannoma cells or the tumor microenvironment. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas. We find schwannomas are comprised of 2 molecular groups distinguished by reactivation of neural crest development pathways or misactivation of nerve injury mechanisms that specify cancer cell states and the architecture of the tumor immune microenvironment. Schwannoma molecular groups can arise independently, but ionizing radiation is sufficient for epigenetic reprogramming of neural crest to immune-enriched schwannoma by remodeling chromatin accessibility, gene expression, and metabolism to drive schwannoma cell state evolution and immune cell infiltration. To define functional genomic mechanisms underlying epigenetic reprograming of schwannomas, we develop a technique for simultaneous interrogation of chromatin accessibility and gene expression coupled with genetic and therapeutic perturbations in single-nuclei. Our results elucidate a framework for understanding epigenetic drivers of cancer evolution and establish a paradigm of epigenetic reprograming of cancer in response to radiotherapy.

cancer biology↗

bioRxiv2021

Data-independent acquisition protease-multiplexing enables increased proteome sequence coverage across multiple fragmentation modes

The use of multiple proteases has been shown to increase protein sequence coverage in proteomics experiments, however due to the additional analysis time required, it has not been widely adapted in routine data-dependent acquisition (DDA) proteomic workflows. Alternatively, data-independent acquisition (DIA) has the potential to analyze multiplexed samples from different protease digests, but has been primarily optimized for fragmenting tryptic peptides. Here we evaluate a DIA multiplexing approach that combines three proteolytic digests (Trypsin, AspN, and GluC) into a single sample. We first optimize data acquisition conditions for each protease individually with both the canonical DIA fragmentation mode (beam type CID), as well as resonance excitation CID, to determine optimal consensus conditions across proteases. Next, we demonstrate that application of these conditions to a protease-multiplexed sample of human peptides results in similar protein identifications and quantitative performance as compared to trypsin alone, but enables up to a 63% increase in peptide detections, and a 27% increase non-redundant amino acid detections. Importantly, this resulted in 100% sequence coverage for numerous proteins, suggesting the utility of this approach in applications where sequence coverage is critical, such as proteoform analysis.

systems biology↗

bioRxiv2021

Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant

Emergence of SARS-CoV-2 variants, including the globally successful B.1.1.7 lineage, suggests viral adaptations to host selective pressures resulting in more efficient transmission. Although much effort has focused on Spike adaptation for viral entry and adaptive immune escape, B.1.1.7 mutations outside Spike likely contribute to enhance transmission. Here we used unbiased abundance proteomics, phosphoproteomics, mRNA sequencing and viral replication assays to show that B.1.1.7 isolates more effectively suppress host innate immune responses in airway epithelial cells. We found that B.1.1.7 isolates have dramatically increased subgenomic RNA and protein levels of Orf9b and Orf6, both known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein required for RNA sensing adaptor MAVS activation, and Orf9b binding and activity was regulated via phosphorylation. We conclude that B.1.1.7 has evolved beyond the Spike coding region to more effectively antagonise host innate immune responses through upregulation of specific subgenomic RNA synthesis and increased protein expression of key innate immune antagonists. We propose that more effective innate immune antagonism increases the likelihood of successful B.1.1.7 transmission, and may increase in vivo replication and duration of infection.

microbiology↗

bioRxiv2021

CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes.

The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis of those functions, remain unknown. Here, we report an atomic model for full-length Nsp2 obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. The resulting structure reveals a highly-conserved zinc ion-binding site, suggesting a role for Nsp2 in RNA binding. Mapping emerging mutations from variants of SARS-CoV-2 on the resulting structure shows potential host-Nsp2 interaction regions. Using structural analysis together with affinity tagged purification mass spectrometry experiments, we identify Nsp2 mutants that are unable to interact with the actin-nucleation-promoting WASH protein complex or with GIGYF2, an inhibitor of translation initiation and modulator of ribosome-associated quality control. Our work suggests a potential role of Nsp2 in linking viral transcription within the viral replication-transcription complexes (RTC) to the translation initiation of the viral message. Collectively, the structure reported here, combined with mutant interaction mapping, provides a foundation for functional studies of this evolutionary conserved coronavirus protein and may assist future drug design.

biophysics↗

bioRxiv2021

Towards comprehensive plasma proteomics by orthogonal protease digestion

Rapid and consistent protein identification across large clinical cohorts is an important goal for clinical proteomics. With the development of data-independent technologies (DIA/SWATH-MS), it is now possible to analyze hundreds of samples with great reproducibility and quantitative accuracy. However, this technology benefits from empirically derived spectral libraries that define the detectable set of peptides and proteins. Here we apply a simple and accessible tip-based workflow for the generation of spectral libraries to provide a comprehensive overview on the plasma proteome in individuals with and without active tuberculosis (TB). To boost protein coverage, we utilized non-conventional proteases such as GluC and AspN together with the gold standard trypsin, identifying more than 30,000 peptides mapping to 3,309 proteins. Application of this library to quantify plasma proteome differences in TB infection recovered more than 400 proteins in 50 minutes of MS-acquisition, including diagnostic Mycobacterium tuberculosis (Mtb) proteins that have previously been detectable primarily by antibody-based assays and intracellular proteins not previously described to be in plasma.

systems biology↗

bioRxiv2020

Categorizing SHR and WKY rats by chi2 algorithm and decision tree

In the past two decades neuroscience has offered many popular methods for the analysis of mental disorder, such as seed-based analysis, ICA, and graph methods. They are widely used in the study of brain network. We offer a new procedure that can simplify the analysis and has a high ROC index over 0.9. This method uses the graph theory to build a connectivity network, which is characterized by degrees and measures the number of effective links for each voxel. When the degree is ranked from low to high, the network equation can be fit by the power-law distribution. It has been proposed that distinct and yet robust exponents of the power law can differentiate human behavior. Using the mentally disordered SHR and WKY rats as samples, we employ chi2 algorithm and Decision Tree to classify different states of mental disorder by analyzing different traits in degree of connectivity.

bioinformatics↗

bioRxiv2018

Structural insights into DNA sequence recognition by Arabidopsis ETHYLENE RESPONSE FACTOR 96

The phytohormone ethylene is widely involved in many developmental processes and is a crucial regulator of defense responses against biotic and abiotic stresses in plants. Ethylene-responsive element binding protein (EREBP), a member of the APETALA2/ethylene response factor (AP2/ERF) superfamily, is a transcription factor that regulates stress-responsive genes by recognizing a specific cis-acting element of target DNA. A previous study showed only the NMR structure of the AP2/ERF domain of AtERF100 in complex with a GCC box DNA motif. In this report, we determined the crystal structure of AtERF96 in complex with a GCC box at atomic resolution. We analyzed the binding residues of the conserved AP2/ERF domain in the DNA recognition sequence. In addition to the AP2/ERF domain, an N-terminal -helix of AtERF96 participates in DNA interaction in the flanking region. We also demonstrated the structure of AtERF96 EDLL motif, a unique conserved motif in the group IX of AP2/ERF family, is critical for the transactivation of defense-related genes. Our study establishes the structural basis of the AtERF96 transcription factor in complex with the GCC box, as well as the DNA binding mechanisms of the N-terminal -helix and AP2/ERF domain.

plant biology↗

bioRxiv2017

The neurobiology of agrammatic sentence comprehension: a lesion study

Brocas area has long been implicated in sentence comprehension. Damage to this region is thought to be the central source of \"agrammatic comprehension\" in which performance is substantially worse (and near chance) on sentences with noncanonical word orders compared to canonical word order sentences (in English). This claim is supported by functional neuroimaging studies demonstrating greater activation in Brocas area for noncanonical versus canonical sentences. However, functional neuroimaging studies also have frequently implicated the anterior temporal lobe (ATL) in sentence processing more broadly, and recent lesion-symptom mapping studies have implicated the ATL and mid temporal regions in agrammatic comprehension. The present study investigates these seemingly conflicting findings in 66 left hemisphere patients with chronic focal cerebral damage. Patients completed two sentence comprehension measures, sentence-picture matching and plausibility judgments. Patients with damage including Brocas area (but excluding the temporal lobe; n=11) on average did not exhibit the expected agrammatic comprehension pattern, e.g. their performance was > 80% on noncanonical sentences in the sentence-picture matching task. Patients with ATL damage (n=18) also did not exhibit an agrammatic comprehension pattern. Across our entire patient sample, the lesions of patients with agrammatic comprehension patterns in either task had maximal overlap in posterior superior temporal and inferior parietal regions. Using voxel-based lesion symptom mapping (VLSM), we find that lower performances on canonical and noncanonical sentences in each task are both associated with damage to a large left superior temporal-inferior parietal network including portions of the ATL, but not Brocas area. Notably however, response bias in plausibility judgments was significantly associated with damage to inferior frontal cortex, including gray and white matter in Brocas area, suggesting that the contribution of Brocas area to sentence comprehension may be related to task-related cognitive demands.

neuroscience↗