DOUBLING CONDITIONS FOR HARMONIC MEASURE IN JOHN DOMAINS

We introduce new classes of domains, i.e., semi-uniform domains and inner emi-uniform domains. Both of them are intermediate between the class of John domains nd the class of uniform domains. Under the capacity density condition, we show that the armonic measure of a John domain D satisfies certain doubling conditions if and only if is a semi-uniform domain or an inner semi-uniform domain

Discovery of a lectin domain that regulates enzyme activity in mouse N-acetylglucosaminyltransferase-IVa (MGAT4A)

N-Glycosylation is a common post-translational modification, and the number of GlcNAc branches in N-glycans impacts glycoprotein functions. N-Acetylglucosaminyltransferase-IVa (GnT-IVa, also designated as MGAT4A) forms a β1-4 GlcNAc branch on the α1-3 mannose arm in N-glycans. Downregulation or loss of GnT-IVa causes diabetic phenotypes by dysregulating glucose transporter-2 in pancreatic β-cells. Despite the physiological importance of GnT-IVa, its structure and catalytic mechanism are poorly understood. Here, we identify the lectin domain in mouse GnT-IVa’s C-terminal region. The crystal structure of the lectin domain shows structural similarity to a bacterial GlcNAc-binding lectin. Comprehensive glycan binding assay using 157 glycans and solution NMR reveal that the GnT-IVa lectin domain selectively interacts with the product N-glycans having a β1-4 GlcNAc branch. Point mutation of the residue critical to sugar recognition impairs the enzymatic activity, suggesting that the lectin domain is a regulatory subunit for efficient catalytic reaction. Our findings provide insights into how branching structures of N-glycans are biosynthesized

CYP1B1 promotes tumorigenesis via altered expression of CDC20 and DAPK1 genes in renal cell carcinoma.

BackgroundCytochrome P450 1B1 (CYP1B1) has been shown to be up-regulated in many types of cancer including renal cell carcinoma (RCC). Several reports have shown that CYP1B1 can influence the regulation of tumor development; however, its role in RCC has not been well investigated. The aim of the present study was to determine the functional effects of CYP1B1 gene on tumorigenesis in RCC.MethodsExpression of CYP1B1 was determined in RCC cell lines, and tissue microarrays of 96 RCC and 25 normal tissues. To determine the biological significance of CYP1B1 in RCC progression, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses.ResultsFirst, we confirmed that CYP1B1 protein expression was significantly higher in RCC cell lines compared to normal kidney tissue. This trend was also observed in RCC samples (p < 0.01). Interestingly, CYP1B1 expression was associated with tumor grade and stage. Next, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses to determine the biological significance of CYP1B1 in RCC progression. Inhibition of CYP1B1 expression resulted in decreased cell proliferation, migration and invasion of RCC cells. In addition, reduction of CYP1B1 induced cellular apoptosis in Caki-1. We also found that these anti-tumor effects on RCC cells caused by CYP1B1 depletion may be due to alteration of CDC20 and DAPK1 expression based on gene microarray and confirmed by real-time PCR. Interestingly, CYP1B1 expression was associated with CDC20 and DAPK1 expression in clinical samples.ConclusionsCYP1B1 may promote RCC development by inducing CDC20 expression and inhibiting apoptosis through the down-regulation of DAPK1. Our results demonstrate that CYP1B1 can be a potential tumor biomarker and a target for anticancer therapy in RCC

Masked diabetes insipidus in pituitary metastasis from breast cancer after thalamic biopsy: a case report

Hashimoto H., Maruo T., Nakamura M., et al. Masked diabetes insipidus in pituitary metastasis from breast cancer after thalamic biopsy: a case report. Journal of Medical Case Reports 16, 12 (2022); https://doi.org/10.1186/s13256-021-03229-y.Background: Symptomatic pituitary metastasis is rare; furthermore, it can result in diabetes insipidus and panhypopituitarism. Since diabetes insipidus is masked by concurrent panhypopituitarism, it can impede the diagnosis of pituitary dysfunction. Case presentation: A 68-year-old Japanese female suffering from pituitary and thalamic metastases caused by untreated breast cancer, underwent a biopsy targeting the thalamus, not the pituitary. She lacked prebiopsy pituitary dysfunction symptoms; however, these symptoms unexpectedly occurred after biopsy. Diabetes insipidus was masked by corticosteroid insufficiency, and she showed normal urinary output and plasma sodium levels. Upon commencement of glucocorticoid replacement therapy, the symptoms of diabetes insipidus appeared. Conclusions: In this case, thalamic biopsy, as opposed to pituitary biopsy, was performed to preserve pituitary function. However, pituitary dysfunction could not be avoided. Caution is necessary for asymptomatic patients with pituitary metastases as invasive interventions, such as surgery, may induce pituitary dysfunction. Moreover, with respect to masked diabetes insipidus, there is a need to carefully consider pituitary dysfunction to avoid misdiagnosis and delayed treatment

Non-invasive detection of language-related prefrontal high gamma band activity with beamforming MEG

Hashimoto H., Hasegawa Y., Araki T., et al. Non-invasive detection of language-related prefrontal high gamma band activity with beamforming MEG. Scientific Reports 7, 14262 (2017); https://doi.org/10.1038/s41598-017-14452-3.High gamma band (>50 Hz) activity is a key oscillatory phenomenon of brain activation. However, there has not been a non-invasive method established to detect language-related high gamma band activity. We used a 160-channel whole-head magnetoencephalography (MEG) system equipped with superconducting quantum interference device (SQUID) gradiometers to non-invasively investigate neuromagnetic activities during silent reading and verb generation tasks in 15 healthy participants. Individual data were divided into alpha (8-13 Hz), beta (13-25 Hz), low gamma (25-50 Hz), and high gamma (50-100 Hz) bands and analysed with the beamformer method. The time window was consecutively moved. Group analysis was performed to delineate common areas of brain activation. In the verb generation task, transient power increases in the high gamma band appeared in the left middle frontal gyrus (MFG) at the 550-750 ms post-stimulus window. We set a virtual sensor on the left MFG for time-frequency analysis, and high gamma event-related synchronization (ERS) induced by a verb generation task was demonstrated at 650 ms. In contrast, ERS in the high gamma band was not detected in the silent reading task. Thus, our study successfully non-invasively measured language-related prefrontal high gamma band activity

Peri-Renal Fat and Adiponectin

Background: The interactions of adipose tissue with the kidney are hypothesized to affect kidney function. Also, excessive peri-renal fat may increase the risk of cardiometabolic risk. However, the role(s) of peri-renal fat adipocytokine has never been evaluated. Objectives: To elucidate levels of adiponectin expression in peri-renal and subcutaneous adipose tissue and its determinants in human biopsied samples. Methods: A pair of subcutaneous and perirenal fat tissue samples were collected from 80 patients (men: 54; women: 26) who underwent urological operations. Subcutaneous adipose tissue (SAT) area, visceral adipose tissue (VAT) area and peri-renal adipose tissue (RAT) volume were quantified on abdominal computed tomography. Cytokine/adipocytokine expression was evaluated by real-time semi-quantitative polymerase chain reaction (qPCR). Probability was considered significant if P < 0.05. Results: Current study evaluated determinants of plasma adiponectin levels and expression levels of adiponectin in SAT and RAT in human samples. We found that: first, plasma adiponectin levels were correlated with VAT area but not with BMI, waist circumference, SAT area, and RAT volume; second, expression levels of adiponectin in SAT were correlated with BMI, waist circumference, and SAT area but not with VAT area and RAT volume; and third, expression levels of adiponectin in RAT were correlated with all adiposity indices including BMI, waist circumference, SAT area, VAT area, and RAT volume. Conclusion: This study evaluated levels of adiponectin expression in RAT and SAT and its determinants in patients who underwent urological operation. Levels of adiponectin mRNA in RAT were negatively correlated with remote fat mass in SAT and VAT and also with local fat mass in RAT, while level of adiponectin in SAT was not correlated with RAT volume. Further studies are warranted to evaluate roles of peri-renal fat mass accumulation and its pathophysiological machineries

Coupling between infraslow activities and high-frequency oscillations precedes seizure onset

Hashimoto H., Khoo H.M., Yanagisawa T., et al. Coupling between infraslow activities and high-frequency oscillations precedes seizure onset. Epilepsia Open 5, 501 (2020); https://doi.org/10.1002/epi4.12425.Infraslow activities and high-frequency oscillations (HFOs) are observed in seizure-onset zones. However, the relation between them remains unclear. In this study, we investigated phase-amplitude coupling between infraslow phase (0.016-1 Hz) and HFOs' amplitude of focal impaired awareness seizures followed by focal to bilateral tonic-clonic seizures, in a 28-year-old right-handed man with a dysembryoplastic neuroepithelial tumor. We recorded five habitual seizures. After the time of seizure onset, a significant increase in the power of HFOs was observed, and the power was significantly coupled with θ (4-8 Hz) phase. In contrast, coupling of infraslow activities and HFOs surged a few minutes before the seizure-onset time, and ictal HFOs discharged after that. Collectively, our results show that coupling of infraslow activities and HFOs precedes the seizure-onset time. We infer that such coupling may be a potential biomarker for seizure prediction

Phase-amplitude coupling between infraslow and high-frequency activities well discriminates between the preictal and interictal states

Hashimoto H., Khoo H.M., Yanagisawa T., et al. Phase-amplitude coupling between infraslow and high-frequency activities well discriminates between the preictal and interictal states. Scientific Reports 11, 17405 (2021); https://doi.org/10.1038/s41598-021-96479-1.Infraslow activity (ISA) and high-frequency activity (HFA) are key biomarkers for studying epileptic seizures. We aimed to elucidate the relationship between ISA and HFA around seizure onset. We enrolled seven patients with drug-resistant focal epilepsy who underwent intracranial electrode placement. We comparatively analyzed the ISA, HFA, and ISA-HFA phase-amplitude coupling (PAC) in the seizure onset zone (SOZ) or non-SOZ (nSOZ) in the interictal, preictal, and ictal states. We recorded 15 seizures. HFA and ISA were larger in the ictal states than in the interictal or preictal state. During seizures, the HFA and ISA of the SOZ were larger and occurred earlier than those of nSOZ. In the preictal state, the ISA-HFA PAC of the SOZ was larger than that of the interictal state, and it began increasing at approximately 87 s before the seizure onset. The receiver-operating characteristic curve revealed that the ISA-HFA PAC of the SOZ showed the highest discrimination performance in the preictal and interictal states, with an area under the curve of 0.926. This study demonstrated the novel insight that ISA-HFA PAC increases before the onset of seizures. Our findings indicate that ISA-HFA PAC could be a useful biomarker for discriminating between the preictal and interictal states