LOCALIZED EXPRESSION OF HEAT SHOCK PROTEIN IN CELL POPULATION BY MICRO HEATER DEVICE

This paper reports on the localized expression of heat shock proteins (HSPs) in a cell population on a micron-scale. Thermal stimulation was realized by micro heaters on cells in microfluidic channels to investigate cell-cell interactions with precise temperature control of microfluidic channels utilizing temperature sensor

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Computer-Aided Diagnosis Scheme for Determining Histological Classification of Breast Lesions on Ultrasonographic Images Using Convolutional Neural Network

It can be difficult for clinicians to accurately discriminate among histological classifications of breast lesions on ultrasonographic images. The purpose of this study was to develop a computer-aided diagnosis (CADx) scheme for determining histological classifications of breast lesions using a convolutional neural network (CNN). Our database consisted of 578 breast ultrasonographic images. It included 287 malignant (217 invasive carcinomas and 70 noninvasive carcinomas) and 291 benign lesions (111 cysts and 180 fibroadenomas). In this study, the CNN constructed from four convolutional layers, three batch-normalization layers, four pooling layers, and two fully connected layers was employed for distinguishing between the four different types of histological classifications for lesions. The classification accuracies for histological classifications with our CNN model were 83.9–87.6%, which were substantially higher than those with our previous method (55.7–79.3%) using hand-crafted features and a classifier. The area under the curve with our CNN model was 0.976, whereas that with our previous method was 0.939 (p = 0.0001). Our CNN model would be useful in differential diagnoses of breast lesions as a diagnostic aid

Pressure Effects with Incorporated Particle Size Dependency in Graphene Oxide Layers through Observing Spin Crossover Temperature

This research highlights the pressure effects with the particle size dependency incorporated in two-dimensional graphene oxide (GO)/reduced graphene oxide (rGO). GO and rGO composites employing nanorods (NRs) of type [Fe(Htrz)2(trz)](BF4) have been prepared, and their pressure effects in the interlayer spaces through observing the changes of the spin crossover (SCO) temperature (T1/2) have been discussed. The composites show the decrease of interlayer spaces from 8.7 Å to 3.5 Å that is associated with GO to rGO transformation. The shorter interlayer spaces were induced by pressure effects, resulting in the increment of T1/2 from 357 K to 364 K. The pressure effects in the interlayers spaces estimated from the T1/2 value correspond to 24 MPa in pristine [Fe(Htrz)2(trz)](BF4) NRs under hydrostatic pressure. The pressure observed in the composites incorporating NRs (30 × 200 nm) is smaller than that observed in the composite incorporating nanoparticles (NPs) (30 nm). These results clearly demonstrated that the incorporated particle size and shape influenced the pressure effects between the GO/rGO layer

Synthesis of N-beta-brominated alkenyl isothiocyanates via dehydrogenation of alkyl isothiocyanates

This study presents a new dehydrogenative synthesis of alkenyl isothiocyanates, providing compounds with bromo and isothiocyanate groups. These reactive functionalities offer versatility for further transformations. Application in an amine sensor utilizing a coumarin-attached product demonstrates practical utility. This streamlined approach facilitates access to alkenyl isothiocyanates, valuable tools for biological studies

Functionalized polyamine synthesis with photoredox catalysis

Polyamines, such as putrescine and spermidine, are pivotal in various biological processes across living organisms. Despite their significance, structurally modified polyamines offer a less-explored avenue for discovering bioactive compounds. The limitation is attributed to the synthetic difficulty of accessing functionalized polyamines. In this study, we accomplished photoredox-catalyzed functionalization of polyamines to diversify their structure. The rapid functionalization allows attaching fluorophores to the target polyamine, facilitating the development of molecular probes for advancing chemical biology studies