bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDP-ribitol prodrug treatment ameliorates ISPD-deficient muscular dystrophy mouse model
Authors: Tokuoka Hideki , Imae Rieko , Nakashima Hitomi , Manya Hiroshi , Masuda Chiaki , Hoshino Shunsuke , Kobayashi Kazuhiro , Lefeber Dirk J. , Matsumoto Riki , Okada Takashi , Endo Tamao , Kanagawa Motoi , Toda Tatsushi 
Published: April 2022

AbstractRibitol-phosphate modification is crucial for the functional maturation of α-dystroglycan. Its dysfunction is associated with muscular dystrophy, cardiomyopathy, and central nervous system abnormalities; however, no effective treatments are currently available for diseases caused by ribitol-phosphate defects. In this study, we demonstrate that prodrug treatments can ameliorate muscular dystrophy caused by defects in isoprenoid synthase domain containing (ISPD), which encodes an enzyme that synthesizes CDP-ribitol, a donor substrate for ribitol-phosphate modification. We generated skeletal muscle-selective Ispd conditional knockout mice, leading to a pathogenic reduction in CDP-ribitol levels, abnormal glycosylation of α-dystroglycan, and severe muscular dystrophy. Adeno-associated virus-mediated gene replacement experiments suggested that the recovery of CDP-ribitol levels rescues the ISPD-deficient pathology. As a prodrug treatment strategy, we developed a series of membrane-permeable CDP-ribitol derivatives, among which tetraacetylated CDP-ribitol ameliorated the dystrophic pathology. In addition, the prodrug successfully rescued abnormal α-dystroglycan glycosylation in patient fibroblasts. Consequently, our findings provide proof-of-concept for supplementation therapy with CDP-ribitol and could accelerate the development of therapeutic agents for muscular dystrophy and other diseases caused by glycosylation defects.
Non-metallic T2-MRI agents based on conjugated polymers
Authors: Lin Qinrui , Yang Yuhong , Shao Zhengzhong 
Published: April 2022

AbstractDeveloping non-metallic contrast agents of clinically applied magnetic resonance imaging (MRI) is an alternative strategy to reduce the toxicity of heavy metal elements in current MRI agents. These non-metallic MRI agents usually generate contrasts by unpaired electrons, which are prone to be deactivated by in vivo radical scavenging pathways. Since the unpaired electrons in conjugated polymers exhibit satisfying stability for in vivo imaging, developing conjugated polymers based MRI agents may solve the in vivo stability problem of current non-metallic agents. However, MRI-active properties have not been reported in existing conjugated polymers yet. Herein we report on MRI-active conjugated polymer nanoparticles based on polypyrrole (PPy), which can be used for in vivo imaging. Our method not only introduce a kind of non-metallic MRI agents but extends the applications of conjugated polymers from optical imagings to MRI.
Proteolysis of adaptor protein Mmr1 during budding is necessary for mitochondrial homeostasis in Saccharomyces cerevisiae
Authors: Obara Keisuke , Yoshikawa Taku , Yamaguchi Ryu , Kuwata Keiko , Nakatsukasa Kunio , Nishimura Kohei , Kamura Takumi 
Published: April 2022

AbstractIn yeast, mitochondria are passed on to daughter cells via the actin cable, motor protein Myo2, and adaptor protein Mmr1. They are released from the actin-myosin machinery after reaching the daughter cells. We report that Mmr1 is rapidly degraded by the ubiquitin-proteasome system in Saccharomyces cerevisiae. Redundant ubiquitin ligases Dma1 and Dma2 are responsible for Mmr1 ubiquitination. Dma1/2-mediated Mmr1 ubiquitination requires phosphorylation, most likely at S414 residue by Ste20 and Cla4. These kinases are mostly localized to the growing bud and nearly absent from mother cells, ensuring phosphorylation and ubiquitination of Mmr1 after the mitochondria enter the growing bud. In dma1Δ dma2Δ cells, transported mitochondria are first stacked at the bud-tip and then pulled back to the bud-neck. Stacked mitochondria in dma1Δ dma2Δ cells exhibit abnormal morphology, elevated respiratory activity, and increased level of reactive oxygen species, along with hypersensitivity to oxidative stresses. Collectively, spatiotemporally-regulated Mmr1 turnover guarantees mitochondrial homeostasis.
Differences in RNA polymerase II complexes and their interactions with surrounding chromatin on human and cytomegalovirus genomes
Authors: Spector Benjamin M. , Parida Mrutyunjaya , Li Ming , Ball Christopher B. , Meier Jeffery L. , Luse Donal S. , Price David H. 
Published: April 2022

AbstractInteractions of the RNA polymerase II (Pol II) preinitiation complex (PIC) and paused early elongation complexes with the first downstream (+1) nucleosome are thought to be functionally important. However, current methods are limited for investigating these relationships, both for cellular chromatin and the human cytomegalovirus (HCMV) genome. Digestion with human DNA fragmentation factor (DFF) before immunoprecipitation (DFF-ChIP) precisely revealed both similarities and major differences in PICs driven by TBP on the host genome in comparison with PICs driven by TBP or the viral-specific, late initiation factor UL87 on the viral genome. Host PICs and paused Pol II complexes are frequently found in contact with the +1 nucleosome and paused Pol II can also be found in a complex involved in the initial invasion of the +1 nucleosome. In contrast, viral transcription complexes have very limited nucleosomal interactions, reflecting a relative lack of chromatinization of transcriptionally active regions of HCMV genomes.
Inactivation of various variant types of SARS-CoV-2 by indoor-light-sensitive TiO2-based photocatalyst
Authors: Nakano Ryuichi , Yamaguchi Akira , Sunada Kayano , Nagai Takeshi , Nakano Akiyo , Suzuki Yuki , Yano Hisakazu , Ishiguro Hitoshi , Miyauchi Masahiro 
Published: April 2022

AbstractPhotocatalysts are promising materials for solid-state antiviral coatings to protect against the spread of pandemic coronavirus disease (COVID-19). This paper reports that copper oxide nanoclusters grafted with titanium dioxide (CuxO/TiO2) inactivated the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, including its Delta variant, even under dark condition, and further inactivated it under illumination with a white fluorescent bulb. To investigate its inactivation mechanism, the denaturation of spike proteins of SARS-CoV-2 was examined by sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE) and enzyme-linked immunosorbent assay (ELISA). In addition to spike proteins, fragmentation of ribonucleic acids in SARS-CoV-2 was investigated by real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR). As a result, both spike proteins and RNAs in the SARS-CoV-2 virus were damaged by the CuxO/TiO2 photocatalyst even under dark condition and were further damaged under white fluorescent bulb illumination. Based on the present antiviral mechanism, the CuxO/TiO2 photocatalyst will be effective in inactivating other potential mutant strains of SARS-CoV-2. The CuxO/TiO2 photocatalyst can thus be used to reduce the infectious risk of COVID-19 in an indoor environment, where light illumination is turned on during the day and off during the night.
Rear 4-min Schirmer test, a modified indicator of Schirmer test in diagnosing dry eye
Authors: Wang Xin , Fan Xiaojing , Wu Yaying , Mou Yujie , Min Jinjin , Jin Xiuming 
Published: April 2022

AbstractThis study aims to investigate the reliability and efficacy of rear 4-min Schirmer test, as a supplement indicator, in assessing tear secretion and diagnosing dry eye. 180 participants were enrolled in this study. Schirmer test I without anaesthesia was performed once on both eyes to determine the value of normal Schirmer test. The values of tear secretion were recorded at each minute. Other examinations included the following: the ocular surface disease index (OSDI), the standard patient evaluation of eye dryness (SPEED), fluorescein stain, tear film break-up time (BUT), and Meibomian gland (MG) secretion grading. The participants were divided into dry eye (DE) group and non-dry eye (ND) group. The values of the 2-min Schirmer test, rear 3-min Schirmer test, rear 4-min Schirmer test, and 5-min Schirmer test were 5.36 ± 4.63, 5.57 ± 2.11, 7.21 ± 4.13, and 10.93 ± 6.30, respectively, in the DE group. These indicators were 8.25 ± 6.80, 2.73 ± 2.31, 7.36 ± 3.42, and 11.84 ± 6.16, respectively, in the ND group. The rear 4-min Schirmer test had a significant correlation with OSDI and SPEED in the DE group (r =  − 0.242/ − 0.183) and in the ND group (r =  − 0.316/ − 0.373). Meanwhile, the rear 4-min Schirmer test had a stronger connection with fBUT (r = 0.159) and MG secretion (r =  − 0.162) in the DE group and also had higher accuracy in diagnosing severe DE and borderline DE. In conclusion, the rear 4-min Schirmer test may be a supplement indicator in assessing tear secretion and diagnosing DE.
A new principle of pulse detection based on terahertz wave plethysmography
Authors: Rong Yu , Theofanopoulos Panagiotis C. , Trichopoulos Georgios C. , Bliss Daniel W. 
Published: April 2022

AbstractThis study presents findings in the terahertz (THz) frequency spectrum for non-contact cardiac sensing applications. Cardiac pulse information is simultaneously extracted using THz waves based on the established principles in electronics and optics. The first fundamental principle is micro-Doppler motion effect. This motion based method, primarily using coherent phase information from the radar receiver, has been widely exploited in microwave frequency bands and has recently found popularity in millimeter waves (mmWave) for breathe rate and heart rate detection. The second fundamental principle is reflectance based optical measurement using infrared or visible light. The variation in the light reflection is proportional to the volumetric change of the heart, often referred as photoplethysmography (PPG). Herein, we introduce the concept of terahertz-wave-plethysmography (TPG), which detects blood volume changes in the upper dermis tissue layer by measuring the reflectance of THz waves, similar to the existing remote PPG (rPPG) principle. The TPG principle is justified by scientific deduction, electromagnetic wave simulations and carefully designed experimental demonstrations. Additionally, pulse measurements from various peripheral body parts of interest (BOI), palm, inner elbow, temple, fingertip and forehead, are demonstrated using a wideband THz sensing system developed by the Terahertz Electronics Lab at Arizona State University, Tempe. Among the BOIs under test, it is found that the measurements from forehead BOI gives the best accuracy with mean heart rate (HR) estimation error 1.51 beats per minute (BPM) and standard deviation 1.08 BPM. The results validate the feasibility of TPG for direct pulse monitoring. A comparative study on pulse sensitivity is conducted between TPG and rPPG. The results indicate that the TPG contains more pulsatile information from the forehead BOI than that in the rPPG signals in regular office lighting condition and thus generate better heart rate estimation statistic in the form of empirical cumulative distribution function of HR estimation error. Last but not least, TPG penetrability test for covered skin is demonstrated using two types of garment materials commonly used in daily life.
HiIDDD: a high-throughput imaging pipeline for the quantitative detection of DNA damage in primary human immune cells
Authors: Gallant Kelsey , Bektas Arsun , Kaileh Mary , Lustig Ana , Ferrucci Luigi , Pegoraro Gianluca , Misteli Tom 
Published: April 2022

AbstractDNA damage is a prominent biomarker for numerous diseases, including cancer, as well as for the aging process. Detection of DNA damage routinely relies on traditional microscopy or cytometric methods. However, these techniques are typically of limited throughput and are not ideally suited for large-scale longitudinal and population studies that require analysis of large sample sets. We have developed HiIDDD (High-throughput Immune cell DNA Damage Detection), a robust, quantitative and single-cell assay that measures DNA damage by high-throughput imaging using the two major DNA damage markers 53BP1 and $$\upgamma$$
γ
-H2AX. We demonstrate sensitive detection with low inter-assay variability of DNA damage in various types of freshly isolated and cryopreserved primary human immune cells, including CD4 + and CD8 + T cells, B cells and monocytes. As proof of principle, we demonstrate parallel batch processing of several immune cell types from multiple donors. We find common patterns of DNA damage in multiple immune cell types of donors of varying ages, suggesting that immune cell properties are specific to individuals. These results establish a novel high-throughput assay for the evaluation of DNA damage in large-scale studies.
An activation specific anti-Mac-1 designed ankyrin repeat protein improves survival in a mouse model of acute lung injury
Authors: Siegel Patrick M. , Przewosnik Anne-Sophie , Wrobel Jan , Heidt Timo , Moser Martin , Peter Karlheinz , Bode Christoph , Diehl Philipp , Bojti István 
Published: April 2022

AbstractThe acute respiratory distress syndrome (ARDS) is a life-threatening clinical condition. The number of ARDS cases has risen dramatically recently but specific treatment options are limited. ARDS is associated with an overshooting inflammatory response and neutrophils play a central role in its pathogenesis. Neutrophils express the integrin Mac-1 on their surface which adopts a resting and activated conformation depending on leukocyte activation. The aim of this study was to investigate the anti-inflammatory effects of the unique activation-specific anti-Mac-1 DARPin ‘F7’ in a mouse model of ARDS. ARDS was induced by intratracheal lipopolysaccharide (LPS) instillation and the acute (day 1–4) and chronic phase (day 5–10) were studied. After expression and purification, F7, a control DARPin and PBS, were applied daily via the intraperitoneal route. Survival and weight loss were recorded. Histological analysis of lung sections, flow cytometric leukocyte analysis of blood and bronchioalveolar lavage (BALF) were performed. Moreover, protein concentration and cytokine levels were determined in the BALF. Treatment with F7 improved survival and reduced weight loss significantly compared to treatment with the control DARPin or PBS. Neutrophil count in the BALF and peripheral blood were significantly reduced in mice treated with F7. Histology revealed significantly reduced pulmonary inflammation in the F7 treated group. Treatment with DARPin F7 inhibited neutrophil accumulation, reduced signs of local and systemic inflammation and improved survival in a mouse model of ARDS. F7 may be a novel anti-inflammatory drug candidate for the treatment of severe ARDS.
Combined effects of nucleotide-binding domain-like receptor protein 3 polymorphisms and environmental metals exposure on chronic kidney disease
Authors: Hsueh Yu-Mei , Chen Wei-Jen , Lin Ying-Chin , Huang Ya-Li , Shiue Horng-Sheng , Lin Yuh-Feng , Hsieh Ru-Lan , Chen Hsi-Hsien 
Published: April 2022

AbstractChronic inflammation is the cause of chronic kidney disease (CKD). The nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome plays a vital role in the inflammation process and is associated with the regulatory effects of NLRP3 gene polymorphisms. This study evaluated the association between NLRP3 gene polymorphisms and CKD, and further explored whether the association of environmental metals with CKD varied by the NLRP3 genotypes. A total of 218 CKD patients and 427 age- and sex-matched healthy controls were recruited in this clinic-based case–control study. Patients were identified as having CKD if their estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 and stage 3–5 for at least 3 months. We examined the genotypes of fifteen common ssingle-nucleotide polymorphisms in NLRP3 genes. Concentrations of total urinary arsenic were examined by summing of urinary inorganic arsenic species. Concentrations of selenium, cadmium, and lead were measured from blood samples. Associations between NLRP3 polymorphisms, environmental metals exposure, and CKD were evaluated using multivariable logistic regression while controlling for confounders. We observed that the odds of carrying NLRP3 rs4925650 GA/AA genotypes, NLRP3 rs1539019 CA/AA genotypes, and NLRP3 rs10157379 CT/TT genotypes were significantly higher among CKD cases compared to controls, with the adjusted odds ratio (95% confidence interval) were 1.54 (1.01–2.36), 1.56 (1.04–2.33), and 1.59 (1.05–2.38), respectively. The significant multiplicative interactions were identified between high levels of blood lead and NLRP3 rs4925650 GA/AA genotypes; high levels of blood cadmium or low levels of plasma selenium and the NLRP3 haplotype (rs4925648, rs4925650, rs12048215, and rs10754555) C-A-A-C multiplicatively interacted to increase the risk of CKD. Our results imply that NLRP3 polymorphisms may play an important role in the development of environmental metals exposure related CKD.
Dynamics of laser-induced tunable focusing in silicon
Authors: Shabairou Nadav , Tiferet Maor , Zalevsky Zeev , Sinvani Moshe 
Published: April 2022

AbstractWe report here on focusing of a probe IR (λ = 1.55 μm) laser beam in silicon. The focusing is done by a second pump laser beam, at λ = 0.775 μm and 30 ps pulse width, with a donut shape that is launched collinearly and simultaneously (with some delay time) with the IR beam pulse. The pump beam pulse is absorbed in the silicon and creates, temporally, a free charge carriers (FCCs) donut pattern in the silicon. Following the plasma dispersion effect, the donut FCCs shapes a complex index of refraction pattern in the silicon that serves as a sort of dynamic GRIN lens for the probe beam due to the diffusion of the FCCs towards the donut center. This lens can be tuned to its focal point by the pump-probe delay time to reduce the point spread function (PSF) of the IR probe beam. We start seeing the focusing of the probe beam at pump-probe delay time of $$\mathrm{\Delta t }\approx 100\mathrm{ ps}$$

Δ
t

≈
100
ps

. The best focusing (results in PSF $$< 2\mathrm{ \mu m}$$

<
2

μ
m

) was observed at $$\mathrm{\Delta t}\approx 350\mathrm{ ps}$$

Δ
t

≈
350
ps

and it slowly degrades before the FCCs full recombination at $$\mathrm{\Delta t }\sim 12\mathrm{ ns}$$

Δ
t

∼
12
ns

. We propose this beam shaping method to overcome the diffraction resolution limit in silicon microscopy on and deep under the silicon surface dependent on the pump wavelength and the pulse width. We also proposed this technique for direct measurement of the FCCs dynamics.
Characterisation of the transient mechanical response and the electromyographical activation of lower leg muscles in whole body vibration training
Authors: Rigoni Isotta , Bonci Tecla , Bifulco Paolo , Fratini Antonio 
Published: April 2022

AbstractThe aim of this study is to characterise the transient mechanical response and the neuromuscular activation of lower limb muscles in subjects undergoing Whole Body Vibration (WBV) at different frequencies while holding two static postures, with focus on muscles involved in shaping postural responses. Twenty-five participants underwent WBV at 15, 20, 25 and 30 Hz while in hack squat or on fore feet. Surface electromyography and soft tissue accelerations were collected from Gastrocnemius Lateralis (GL), Soleus (SOL) and Tibialis Anterior (TA) muscles. Estimated displacement at muscle bellies revealed a pattern never highlighted before that differed across frequencies and postures (p < 0.001). After stimulation starts, muscle oscillation peaks, drops and further stabilises, suggesting the occurrence of a neuromuscular activation to reduce the vibration-induced oscillation. The oscillation attenuation at the SOL muscle correlated with its increased activation (rho = 0.29, p < 0.001). Furthermore, only specific WBV settings led to a significant increase in muscle contraction: WBV-induced activation of SOL and GL was maximal in fore-feet (p < 0.05) and in response to higher frequencies (30 Hz vs 15 Hz, p < 0.001). The analysis of the mechanical dynamics of lower leg muscles highlights a resonant response to WBVs, that for the SOL correlates to the increased muscle activation. Despite differing across frequencies and postures, this resonant behaviour seems to discourage the use of dynamic exercises on vibrating platforms. As for the most efficient WBV combination, calf muscle response to WBVs is maximised if those muscles are already pre-contracted and the stimulation frequencies are in the 25–30 Hz range.
Comparison of treatment strategies and survival of early-onset gastric cancer: a population-based study
Authors: Zhang Chunmei , Tang Ruiyi , Zhu Hanlong , Ge Xianxiu , Wang Yue , Wang Xue , Miao Lin 
Published: April 2022

AbstractTreatments for early-onset gastric cancer (EOGC) patients are rarely included in clinical trials, resulting in an unclear impact on survival. This study aimed to investigate the treatment patterns of EOGC patients and their impact on survival. Based on the Surveillance, Epidemiology, and End Results database, we conducted a retrospective analysis of 1639 EOGC patients (< 50 years) diagnosed between 2010 and 2018. Patients with larger tumours, distant metastasis, and AJCC TNM stage in IV were prone to receive nonsurgical treatment. Patients treated with surgery alone had a better prognosis than those receiving SROC or SCRT or nonsurgical treatment. However, analyses stratified by histological type, tumour size and TNM stage showed that patients did not benefit more from SROC and SCRT than from surgery alone. Similar results were observed in the stratified Cox regression risk analysis. Patients who received nonsurgical treatment had the highest risk of overall death [hazard ratio (HR) = 2.443, 95% confidence interval (CI) 1.865–3.200, P < 0.001]. This study indicated that additional radiotherapy, chemotherapy or chemoradiotherapy did not provide a coordinated survival benefit to EOGC patients.
Tumor microenvironment-aware, single-transcriptome prediction of microsatellite instability in colorectal cancer using meta-analysis
Authors: Seo Mi-Kyoung , Kang Hyundeok , Kim Sangwoo 
Published: April 2022

AbstractDetecting microsatellite instability (MSI) in colorectal cancers (CRCs) is essential because it is the determinant of treatment strategies, including immunotherapy and chemotherapy. Yet, no attempt has been made to exploit transcriptomic profile and tumor microenvironment (TME) of it to unveil MSI status in CRC. Hence, we developed a novel TME-aware, single-transcriptome predictor of MSI for CRC, called MAP (Microsatellite instability Absolute single sample Predictor). MAP was developed utilizing recursive feature elimination-random forest with 466 CRC samples from The Cancer Genome Atlas, and its performance was validated in independent cohorts, including 1118 samples. MAP showed robustness and predictive power in predicting MSI status in CRC. Additional advantages for MAP were demonstrated through comparative analysis with existing MSI classifier and other cancer types. Our novel approach will provide access to untouched vast amounts of publicly available transcriptomic data and widen the door for MSI CRC research and be useful for gaining insights to help with translational medicine.