It is 30 years since human T-cell leukemia virus type 1 (HTLV-1) was identified as the first human retrovirus. To assess the implications of the virus for human health it is very important to know ...the past and present prevalence. Most of the estimates of HTLV-1 prevalence are based on serological screening of blood donors, pregnant women and other selected population groups. The widely cited estimate that the number of HTLV-1 carriers in Japan is 1.2 million was calculated from data that are now more than 25 years old. Here I summarize previous reports of prevalence studies in the world and Japan. Then, a recent analysis of seroprevalence of healthy blood donors in Japan will be described in comparison with that of 1988. A decrease in the number of HTLV-1 carriers in Japan was demonstrated, however, it is still more than one million. The number has increased in the metropolitan areas, probably reflecting the migration of Japanese population. I conclude that there is a paucity of general population data in countries where HTLV-1 is endemic, and re-evaluation of HTLV-1 infection is required to understand the virus burden on the human health.
Mt. Ontake is an active volcano in central Japan where phreatic eruption activity is prominent. A shallow subsurface structure in the summit region of this volcano has been scarcely studied despite ...its importance. Our study examines the structure from three seismic analyses: a typical P-wave velocity from the semblance of the vertical propagation of intermediate-depth earthquakes (IDEs), a layered velocity model from P- and S-wave arrival times of shallow volcanic earthquakes, and a pseudoreflection profile from the autocorrelation functions of the IDEs. Our results consistently indicate the presence of three layers, which are interpreted as younger (> 0.1 Ma) and older (0.39–0.78 Ma) eruptive deposits and the basement. A comparison of the structure with hypocentres and deformation sources suggests fluid migration controlled by the structure.
Graphical Abstract
HTLV-1 is an oncovirus causing ATL and other inflammatory diseases such as HAM/TSP and HU in about 5% of infected individuals. It is also known that HTLV-1-infected cells maintain a disease-free, ...immortalized, latent state throughout the lifetimes of about 95% of infected individuals. We believe that the stable maintenance of disease-free infected cells in the carrier is an intrinsic characteristic of HTLV-1 that has been acquired during its evolution in the human life cycle. We speculate that the pathogenesis of the virus is ruled by the orchestrated functions of viral proteins. In particular, the regulation of Rex, the conductor of viral replication rate, is expected to be closely related to the viral program in the early active viral replication followed by the stable latency in HTLV-1 infected T cells. HTLV-1 and HIV-1 belong to the family
Retroviridae
and share the same tropism, e.g., human CD4
+
T cells. These viruses show significant similarities in the viral genomic structure and the molecular mechanism of the replication cycle. However, HTLV-1 and HIV-1 infected T cells show different phenotypes, especially in the level of virion production. We speculate that how the activity of HTLV-1 Rex and its counterpart HIV-1 Rev are regulated may be closely related to the properties of respective infected T cells. In this review, we compare various pathological aspects of HTLV-1 and HIV-1. In particular, we investigated the presence or absence of a virally encoded “regulatory valve” for HTLV-1 Rex or HIV-1 Rev to explore its importance in the regulation of viral particle production in infected T cells. Finally, wereaffirm Rex as the key conductor for viral replication and viral pathogenesis based on our recent study on the novel functional aspects of Rex. Since the activity of Rex is closely related to the viral replication rate, we hypothesize that the “regulatory valve” on the Rex activity may have been selectively evolved to achieve the “scenario” with early viral particle production and the subsequent long, stable deep latency in HTLV-1 infected cells.
Autocorrelation functions (ACFs) of vertically incident seismic waves are used to image subsurface reflectors. However, the reflection responses derived from ACFs usually contain many false signals. ...We present a method to quantify the errors in ACFs and extract true reflectors with high reliability. We estimated the errors for each earthquake at each station as follows. We calculated the amplitude of the observed waveform within the noise window and generated 1000 random noise traces that have this amplitude. By subtracting the random noise traces from the observed waveform, we created 1000 candidate earthquake waveforms. We computed the ACF for each of the 1000 waveforms and calculated the ensemble average and standard deviation of the 1000 different ACF amplitudes at each lag time. Then, we applied weighted stacking to the ACFs of many earthquakes to obtain the reflection response at the station. We calculated the standard deviation of the weighted stack to estimate errors in the reflection response. We evaluated the method by applying it to seismic data from the metropolitan area of Japan. The subsurface structure of the study area has been studied extensively and consists of a strong velocity discontinuity between sedimentary and basement layers. Following our method, the discontinuity was imaged as a clear reflector with an amplitude that was substantially greater than three times the standard deviation, which corresponds to statistical significance at the 99% confidence level. At other depths where reflectors are not expected to be present, the amplitudes of the peaks were less than or close to three times the standard deviation. The signal of the discontinuity was clearly visible at frequencies below 10 Hz and was less prominent at higher frequencies.
Graphical Abstract
Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) that develops through a multistep carcinogenesis process involving 5 or more ...genetic events. We provide a comprehensive overview of recently uncovered information on the molecular basis of leukemogenesis in ATL. Broadly, the landscape of genetic abnormalities in ATL that include alterations highly enriched in genes for T-cell receptor–NF-κB signaling such as PLCG1, PRKCB, and CARD11 and gain-of function mutations in CCR4 and CCR7. Conversely, the epigenetic landscape of ATL can be summarized as polycomb repressive complex 2 hyperactivation with genome-wide H3K27 me3 accumulation as the basis of the unique transcriptome of ATL cells. Expression of H3K27 methyltransferase enhancer of zeste 2 was shown to be induced by HTLV-1 Tax and NF-κB. Furthermore, provirus integration site analysis with high-throughput sequencing enabled the analysis of clonal composition and cell number of each clone in vivo, whereas multicolor flow cytometric analysis with CD7 and cell adhesion molecule 1 enabled the identification of HTLV-1–infected CD4+ T cells in vivo. Sorted immortalized but untransformed cells displayed epigenetic changes closely overlapping those observed in terminally transformed ATL cells, suggesting that epigenetic abnormalities are likely earlier events in leukemogenesis. These new findings broaden the scope of conceptualization of the molecular mechanisms of leukemogenesis, dissecting them into immortalization and clonal progression. These recent findings also open a new direction of drug development for ATL prevention and treatment because epigenetic marks can be reprogrammed. Mechanisms underlying initial immortalization and progressive accumulation of these abnormalities remain to be elucidated.
We applied a novel method of passive seismic reflection imaging to actual local earthquake data collected by a dense seismic network in the Kanto region, Japan. This method, which implements reverse ...time migration (RTM), is based on the cross-correlation of wavefields that are extrapolated forward and backward in time from receiver locations using passively observed seismic records. Using multiple reflections between the Earth’s surface and subsurface boundaries, internal structures are imaged using many earthquakes without well-defined source information. The objective of this case study is to evaluate the possibility of acquiring seismic reflection images of the deep crustal structure by applying the RTM-based method using P-wave reflections in the earthquake data collected by a dense seismic network. The P-wave reflection profile along a 191-km-long pseudo-survey line down to a 100 km depth is obtained using the seismic records of hundreds of local earthquakes observed at 72 receiver stations. A P-wave velocity model for RTM imaging is extracted from an existing 3D model obtained by seismic tomography in a previous study. The resulting image shows several continuous reflectors at depths of 15–70 km. These reflectors correspond to the spatially variable velocity and suggest deep structures related to dual plate subduction in this region. Two eastward-dipping reflectors imaged at depths of 15–50 km are likely the top and bottom surfaces of the crust of the Philippine Sea slab, and the westward-dipping reflector at depths of 50–70 km implies the top surface of the Pacific slab. The en-échelon reflectors at depths of 15–20 km may be reflective boundaries between the upper and lower crust in the overlying Okhotsk plate. Our case study results confirm the possibility of obtaining profiles at higher resolutions than are typically obtained by earthquake-based seismic tomography and of imaging at depths beyond the limits of artificially controlled-source seismic surveys. Further implementation of the RTM-based imaging method will improve its potential use for subsurface imaging and monitoring from dense passive seismic data.
Graphical Abstract
The crack initiation and propagation under the application of opening load were analyzed in situ using nondestructive synchrotron radiation X-ray computed tomography (nanoscopic SR X-CT) with a ...spatial resolution of ~50 nm. The results show that the voids and cracks initiation are not only the result of local stresses but also are due to two competing nanoscale mechanisms, that is, fiber/plastic interface debonding and in-resin crack initiation. In the “thin” epoxy region in which the resin thickness between the adjacent carbon fibers is small, cracks propagate mainly by debonding along the carbon fiber/epoxy interface. In the “thick” epoxy region in which the resin thickness between the carbon fibers is large, cracks propagate through the extensive plastic deformation of the epoxy resin, and the propagation mechanism largely depends on the resin thickness, which affects the plastic deformation behavior of the epoxy around the crack tip. Voids (sub-μm) often form in front of the crack tip and merge with the propagating cracks. Nanoscopic SR X-CT provides indispensable information on these nanoscale mechanisms, which cannot be obtained with traditional methods, including macroscopic observations and mechanical theory. These nanoscale mechanisms are essential for the mechanical modeling and analysis at multi-scales.
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•Crack initiation and propagation in CFRP was observed non-destructively in situ.•The 3D nanoscale image datasets were acquired using X-ray computed tomography.•Two datasets of reconstructed and segmented images were captured.•The data provides a valuable and unique insight for the future design of CFRPs.
Abstract
Subclonal genetic heterogeneity and their diverse gene expression impose serious problems in understanding the behavior of cancers and contemplating therapeutic strategies. Here we develop ...and utilize a capture-based sequencing panel, which covers host hotspot genes and the full-length genome of human T-cell leukemia virus type-1 (HTLV-1), to investigate the clonal architecture of adult T-cell leukemia-lymphoma (ATL). For chronologically collected specimens from patients with ATL or pre-onset individuals, we integrate deep DNA sequencing and single-cell RNA sequencing to detect the somatic mutations and virus directly and characterize the transcriptional readouts in respective subclones. Characteristic genomic and transcriptomic patterns are associated with subclonal expansion and switches during the clinical timeline. Multistep mutations in the T-cell receptor (TCR), STAT3, and NOTCH pathways establish clone-specific transcriptomic abnormalities and further accelerate their proliferative potential to develop highly malignant clones, leading to disease onset and progression. Early detection and characterization of newly expanded subclones through the integrative analytical platform will be valuable for the development of an in-depth understanding of this disease.
Nanoscale fracture mechanism in CFRPs is still debated owing to the considerable difficulty in determining the three-dimensional mechanism of fracture using conventional techniques such as optical ...and/or electron microscopy relying on side-surface- and fracture-surface-based observation. In this study, microscopic damages such as fiber/matrix debonding and microcracks under mixed-mode (mode I + II) loading are characterized in situ using nondestructive nanoscopic synchrotron radiation X-ray computed tomography (nanoscopic SR X-CT). It is clearly shown that crack formation proceeds in three steps: (i) initiation at the carbon fiber/epoxy matrix interface, (ii) propagation into the epoxy, and (iii) formation of microcracks (hackles) in the resin matrix, and the resulting microstructures of cracks at the nanoscale are largely affected by the local fiber geometrical distributions. A sharp and straight interfacial crack initiates at the “thin” epoxy-resin region (thickness < half the diameter of the carbon fiber (dCF)) and propagates along the carbon fiber/epoxy interface. The sharp cracks propagate into the epoxy at the “thick” epoxy-region (thickness > ∼1/2 dCF) and hackles are formed in the resin matrix perpendicular to the local principal tensile stress direction. Nanoscopic SR X-CT provides information on three-dimensional mechanisms at the nanoscale during deformation, which is indispensable for understanding heterogenous materials such as CFRPs.
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•Nanoscopic in situ observation of cracking in CFRPs under mixed-mode loading.•The failure mechanism largely depends on local fiber geometrical distribution.•The first initiation or debonding at the carbon fiber/epoxy matrix interface.•The second propagation into the epoxy matrix.•The final formation of hackles in resin matrix at the “thick” epoxy-resin region.
T cells infected with human T-cell leukemia virus type 1 (HTLV-1) acquire various abnormalities during a long latent period and transform into highly malignant adult T-cell leukemia-lymphoma (ATL) ...cells. This can be described as "clonal evolution", in which a single clone evolves into ATL cells after overcoming various selective pressures in the body of the infected individuals. Many studies have shown that the genome and epigenome contain a variety of abnormalities, which are reflected in gene expression patterns and define the characteristics of the disease. The latest research findings suggest that epigenomic disorders are thought to begin forming early in infection and evolve into ATL through further changes and accentuation as they progress. Genomic abnormalities profoundly affect clonal dominance and tumor cell characteristics in later events. ATL harbors both genomic and epigenomic abnormalities, and an accurate understanding of these can be expected to provide therapeutic opportunities.
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