Characteristic BOLD signals are detectable in white matter of the spinal cord at rest and after a stimulus.

We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD signals are robustly detectable not only in gray matter (GM) in the brain but also in cerebral WM as well as the GM within the spinal cord, but similar signals in WM of the spinal cord have been overlooked. In this study, we detected BOLD signals in the WM of the spinal cord in squirrel monkeys and studied their relationships with the locations and functions of ascending and descending WM tracts. Tactile sensory stimulus -evoked BOLD signal changes were detected in the ascending tracts of the spinal cord using a general-linear model. Power spectral analysis confirmed that the amplitude at the fundamental frequency of the response to a periodic stimulus was significantly higher in the ascending tracts than the descending ones. Independent component analysis of resting-state signals identified coherent fluctuations from eight WM hubs which correspond closely to the known anatomical locations of the major WM tracts. Resting-state analyses showed that the WM hubs exhibited correlated signal fluctuations across spinal cord segments in reproducible patterns that correspond well with the known neurobiological functions of WM tracts in the spinal cord. Overall, these findings provide evidence of a functional organization of intraspinal WM tracts and confirm that they produce hemodynamic responses similar to GM both at baseline and under stimulus conditions.

Contribution of copy number variations to education, socioeconomic status and cognition from a genome-wide study of 305,401 subjects.

Educational attainment (EA), socioeconomic status (SES) and cognition are phenotypically and genetically linked to health outcomes. However, the role of copy number variations (CNVs) in influencing EA/SES/cognition remains unclear. Using a large-scale (n = 305,401) genome-wide CNV-level association analysis, we discovered 33 CNV loci significantly associated with EA/SES/cognition, 20 of which were novel (deletions at 2p22.2, 2p16.2, 2p12, 3p25.3, 4p15.2, 5p15.33, 5q21.1, 8p21.3, 9p21.1, 11p14.3, 13q12.13, 17q21.31, and 20q13.33, as well as duplications at 3q12.2, 3q23, 7p22.3, 8p23.1, 8p23.2, 17q12 (105 kb), and 19q13.32). The genes identified in gene-level tests were enriched in biological pathways such as neurodegeneration, telomere maintenance and axon guidance. Phenome-wide association studies further identified novel associations of EA/SES/cognition-associated CNVs with mental and physical diseases, such as 6q27 duplication with upper respiratory disease and 17q12 (105 kb) duplication with mood disorders. Our findings provide a genome-wide CNV profile for EA/SES/cognition and bridge their connections to health. The expanded candidate CNVs database and the residing genes would be a valuable resource for future studies aimed at uncovering the biological mechanisms underlying cognitive function and related clinical phenotypes.

fMRI, LFP, and anatomical evidence for hierarchical nociceptive routing pathway between somatosensory and insular cortices.

The directional organization of multiple nociceptive regions, particularly within obscure operculoinsular areas, underlying multidimensional pain processing remains elusive. This study aims to establish the fundamental organization between somatosensory and insular cortices in routing nociceptive information. By employing an integrated multimodal approach of high-field fMRI, intracranial electrophysiology, and transsynaptic viral tracing in rats, we observed a hierarchically organized connection of S1/S2 → posterior insula → anterior insula in routing nociceptive information. The directional nociceptive pathway determined by early fMRI responses was consistent with that examined by early evoked LFP, intrinsic effective connectivity, and anatomical projection, suggesting fMRI could provide a valuable facility to discern directional neural circuits in animals and humans non-invasively. Moreover, our knowledge of the nociceptive hierarchical organization of somatosensory and insular cortices and the interface role of the posterior insula may have implications for the development of targeted pain therapies.

Differential Recovery of Submodality Touch Neurons and Interareal Communication in Sensory Input-Deprived Area 3b and S2 Cortices.

Cortical reactivation and regain of interareal functional connections have been linked to the recovery of hand grasping behavior after loss of sensory inputs in primates. We investigated contributions of neurons in two hierarchically organized somatosensory areas, 3b and S2, by characterizing local field potential (LFP) and multiunit spiking activity in five states (rest, stimulus-on, sustained, stimulus-off, and induced) and interareal communication after grasping behavior of dorsal column lesioned male squirrel monkeys had mostly recovered. Compared with normal cortex, fMRI, LFP, and spiking response magnitudes to step indentations were significantly weaker. The sustained component of the spiking recovered much better than the stimulus-off response. Correlation between overall spiking and γ LFP remained strong within each recovered areas 3b and S2. The interareal correlations of γ LFP were severely disrupted, except in the resting and stimulus-on periods. Interareal correlation of spiking was disrupted in the stimulus-off period only. In summary, submodality of low threshold mechanoreceptive neurons recovered differentially in input-deprived area 3b and S2 when impaired global hand grasping behavior returned. Slow-adapting-like neurons recovered, whereas rapid-adapting-like neurons did not. Interareal communications were also severely compromised. We propose that slow-adapting-like neurons and afferents in recovered area 3b and S2 mediate recovery of impaired grasping behavior after dorsal column tract lesion.SIGNIFICANCE STATEMENT Sensory feedback is essential for execution of hand grasping behavior in primates. Reactivations of somatosensory cortices have been attributed to recovery of such behavior after loss of sensory inputs via largely unknown mechanisms. In input-deprived area 3b and S2 cortex, after hand grasping behavior mostly recovered, we found slow-adapting-like neurons were greatly recovered, whereas rapid-adapting-like neurons did not. Communications between area 3b and S2 neurons were severely compromised. We suggest that recovery of slow-adapting-like neurons in input-deprived area 3b and S2 may mediate the recovery of hand grasping behavior.

Detection of laser-associated heating in the brain during simultaneous fMRI and optogenetic stimulation.

PURPOSE: To calculate temperatures from T2 *-weighted images collected during optogenetic fMRI based on proton resonance frequency (PRF) shift thermometry, to monitor confounding heating effects and determine appropriate light parameters for optogenetic stimulation. METHODS: fMRI is mainly based on long-TE gradient-recalled echo acquisitions that are also suitable for measuring small temperature changes via the PRF shift. A motion- and respiration-robust processing pipeline was developed to calculate temperature changes based on the PRF shift directly from the T2 *-weighted images collected for fMRI with a two-shot 2D gradient-recalled echo-EPI sequence at 9.4T. Optogenetic fMRI protocols which differed in stimulation durations (3, 6 and 9 s) within a total block duration of 30 s were applied in a squirrel monkey to validate the methods with blue and green light (20 Hz, 30 mW) delivery interleaved between periods. General linear modeling was performed on the resulting time series temperature maps to verify if light delivery with each protocol resulted in significant heating in the brain around the optical fiber. RESULTS: The temperature SD was 0.05°C with the proposed imaging protocol and processing. Statistical analysis showed that the optogenetic stimulation protocol with a 3 s stimulation duration did not result in significant temperature rises. Significant temperature rises up to 0.13°C (p < 0. 05) were observed with 6 and 9 s stimulation durations for blue and green light. CONCLUSION: The proposed processing pipeline can be useful for the design of optogenetic stimulation protocols and for monitoring confounding heating effects.

First Report of Fusarium asiaticum Causing Sheath Rot of Zizania latifolia in China.

Zizania latifolia is perennial plant, belonging to the rice tribe (Oryzeae) of the grass family Poaceae (Xu et al. 2020), which is also called jiaobai in China and commonly consumed as a vegetable crop. In 2022, a sheath rot occurred on Z. latifolia plants in Lishui, the Zhejiang Province of China. Symptoms occurred on the leaf sheath and initially showed as water-soaked chlorotic spots, later enlarging to irregular, elliptic, and elongated dark brown necrotic lesions. Later, lesions fused and extended to most of the leaf sheath leading to wilting. Almost 60% of the surveyed Z. latifolia plants in 100 hectare were affected. Diseased samples were collected for pathogen isolation. Symptomatic tissues were taken from the edge of lesions, sterilized for 10 s in 70% ethanol, then 2 min in 1% NaClO, washed three times with sterile distilled water, and placed on potato dextrose agar (PDA) at 26 °C in the dark. Fungal colonies displaying similar morphology were picked and purified by single spore isolation. In total, 8 isolates were obtained from 8 plant samples. When cultured on PDA, fungal colonies were white, gradually turning pale yellow with time. Macroconidia only were produced on Carnation leaf agar (CLA) and were hyaline, slender, falcate with single foot cells, 3 to 5 septate, and measured 29 to 50 µm × 3.75 to 5.0 µm. Chlamydospores were globose to subglobose and measured 6.8 to 16.5 µm. These morphological features were consistent with the description of Fusarium asiaticum (Leslie and Summerell 2006). For molecular identification, the partial translation elongation factor 1 alpha (TEF1-α) gene and RNA polymerase II second largest subunit (RPB2) gene of three representative isolates were amplified and sequenced (O'Donnell et al. 1998). These sequences were identical to each other, and one representative, Z-3-1, was deposited in GenBank (Accession No. OQ129437 and OQ858619, respectively). Analysis of the TEF1-α and RPB2 sequences of Z-3-1 showed that they were 99.85% (688/689) and 100% (945/945) identical to F. asiaticum strain Daya350-3 (KT380124) and MRC 1976 (MH582121), respectively, in NCBI, and had 99.38% and 100% identity to F. asiaticum strain CBS 110257 (AF212451 and JX171573) in Fusarium-ID. A combined phylogenetic tree based on the TEF1-α and RPB2 sequences showed that Z-3-1 was clustered with F. asiaticum using the neighbor-joining algorithm. Pathogenicity testing was conducted by inoculating potted Z. latifolia plants with a 1×105 conidial suspension of isolate Z-3-1, which was prepared by culturing the fungal strain in PDB at 26°C for 4 days in a shaker incubator. Conidial suspensions (1 mL) were dropped onto sheaths of potted Z. latifolia plants with sterile water serving as controls. All inoculated plants were covered with plastic bags and maintained in a humid growth chamber at 26°C with a photoperiod of 16 h. The inoculation experiment was repeated twice with 5 replicates per test. Four days later, the sheaths of potted inoculated plants displayed symptoms similar to those observed in the field. No symptoms were observed on control plants. Fusarium asiaticum was re-isolated specifically from the symptomatic inoculated Z. latifolia plants and confirmed by morphological and molecular methods, thus fulfilling Koch's postulates. Fusarium asiaticum has been reported to be a pathogen of other plants in China, such as Ligusticum (Zhu et al. 2022) and Setaria italica (Kong et al. 2022). To our knowledge, this is the first report of F. asiaticum causing sheath rot of Z. latifolia in China. The identification of the pathogen is the first step in developing appropriate field management strategies for this new disease.

Graph theory analysis identified two hubs that connect sensorimotor and cognitive and cortical and subcortical nociceptive networks in the non-human primate.

Pain perception involves multiple brain regions and networks. Understanding how these brain networks work together is fundamental for appreciating network-wise changes reported in patients with chronic pain disorders. Parcellating pain related networks and understanding their causal relationships is the first step to understand how painful information is processed, integrated, and modulated, and it requires direct manipulation of specific brain regions. Nonhuman primates (NHP) offer an ideal model system to achieve these goals because cortical and subcortical regions in the NHP brain are established based on a variety of different types of data collected in a way that is not feasible or, at least, extremely difficult in humans (i.e., histology data, tract-tracing, intracerebral recordings). In addition, different methodological techniques can also help characterize and further understand these brain cortical and subcortical regions over the course of development. Here we used a heat nociceptive stimulation that is proven to elicit activity of nociceptive neurons in the cortex to refine and parcellate the whole brain nociceptive functional networks, to identify key network hubs, and to characterize network-wise temporal dynamic signatures using high-resolution fMRI. We first functionally localized 24 cortical and subcortical regions that responded to heat nociceptive stimuli (somatosensory area 1/2, area 3a/3b, S2, posterior insula (pIns), anterior insula, area 7b, posterior parietal cortex, anterior cingulate cortex (ACC), prefrontal cortex, caudate, and mediodorsal (MD) and ventral posterior lateral (VPL) thalamic nuclei) and used them as seeds in resting state fMRI (rsfMRI) data analysis. We applied both hierarchical clustering and graph-theory analyses of the pairwise rsfMRI correlation metrics and identified five cortical and one subcortical sub-networks: strong resting state functional connectivity (rsFC) between ACC and prefrontal regions, parietal cortex and area 7b, S2 and posterior insula, areas 3a/3b and 1/2 within the S1 cortex, and thalamic MD and caudate nuclei. The rsFC strengths between cortical areas within each subnetwork were significantly stronger than those between subcortical regions. Regions within each sub-network also exhibited highly correlated temporal dynamics at rest, but the overall dynamic patterns varied drastically across sub-networks. Graph-theory analysis identified the MD nucleus as a hub that connects subcortical and cortical nociceptive sub-networks. The S2-pIns connection joins the sensory and affective/cognitive sub-networks.

A novel prognostic index for sporadic Burkitt lymphoma in adult patients: a real-word multicenter study.

BACKGROUND: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. METHODS: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan-Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm. RESULTS AND CONCLUSIONS: Univariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell's concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.

Circular RNA circ_GLIS2 suppresses hepatocellular carcinoma growth and metastasis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the leading causes of tumour-related death. Here, we investigated the molecular mechanism of HCC by studying the function of circ_GLIS2. METHODS: Human HCC specimens and cell lines were used. Sanger sequencing, actinomycin D and RNase R treatment were performed to validate circular RNA features of circ_GLIS2. qRT-PCR, western blotting, immunostaining, and IHC were employed to examine levels of circ_GLIS2, GLIS2 mRNA, and EMT-related markers. CCK-8, colony formation, flow cytometry, wound healing assay, and transwell assays were performed to evaluate cancer cell proliferation, apoptosis, migration, and invasion. RIP and RNA pull-down assay were used to validate EIF4A3/GLIS2 mRNA interaction. MSP was performed to measure the methylation status of GLIS2 promoter. Nude mouse xenograft model was used to examine tumour growth and metastasis in vivo. RESULTS: Circ_GLIS2 and linear GLIS2 mRNA were reduced in human HCC tissues and cells. Their low levels correlated with a poor survival rate of HCC patients. Overexpression of circ_GLIS2 and GLIS2 suppressed HCC cell proliferation, migration, and invasion but promoted cell apoptosis. GLIS2 promoter region was hypermethylated in HCC cells. EIF4A3 was directly bound with GLIS2 mRNA and promoted circ_GLIS2/GLIS2 expression. Moreover, overexpression of circ_GLIS2 restrained HCC tumour growth and metastasis in vivo. CONCLUSION: Circ_GLIS2 suppresses HCC growth and metastasis by inhibiting cell proliferation, migration, and invasion, but promoting cell apoptosis. These findings provide molecular insights into the mechanism of HCC and indicate that circ_GLIS2 could serve as a diagnosis marker or therapeutic target for HCC.

Comparative biochemical and transcriptome analyses in tomato and eggplant reveal their differential responses to Tuta absoluta infestation.

Tomato is more prone to Tuta absoluta invasion and damages as compared to other host plants but the mechanism behind this preference has not been elucidated. Here, two contrasting host preference plants, tomato and eggplant, were used to investigate biochemical and transcriptomic modifications induced by T. absoluta infestation. Biochemical analysis at 0-72 h post T. absoluta infestation revealed significantly reduced concentrations of amino acid, fructose, sucrose, jasmonic acid, salicylic acid, and total phenols in tomato compared to eggplant, mainly at 48 h post T. absoluta infestation. Transcriptome analysis showed higher transcript changes in infested eggplant than tomato. Signaling genes had significant contributions to mediate plant immunity against T. absoluta, specifically genes associated with salicylic acid in eggplant. Genes from PR1b1, NPR1, NPR3, MAPKs, and ANP1 families play important roles to mitigate T. absoluta infestation. Our results will facilitate the development of control strategies against T. absoluta for sustainable tomato production.