bluuebunny/crossref_metadata_2025 huggingface dataset:
Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract
Authors: Maddala Rupalatha , Gao Junyuan , Mathias Richard T. , Lewis Tylor R. , Arshavsky Vadim Y. , Levine Adriana , Backer Jonathan M. , Bresnick Anne R. , Rao Ponugoti V.
Published: January 2021

S100A4, a member of the S100 family of multifunctional calcium-binding proteins, participates in several physiological and pathological processes. In this study, we demonstrate that S100A4 expression is robustly induced in differentiating fiber cells of the ocular lens and that S100A4(−/−) knockout mice develop late-onset cortical cataracts. Transcriptome profiling of lenses from S100A4(−/−) mice revealed a robust increase in the expression of multiple photoreceptor- and Müller glia-specific genes, as well as the olfactory sensory neuron-specific gene, S100A5. This aberrant transcriptional profile is characterized by corresponding increases in the levels of proteins encoded by the aberrantly upregulated genes. Ingenuity pathway network and curated pathway analyses of differentially expressed genes in S100A4(−/−) lenses identified Crx and Nrl transcription factors as the most significant upstream regulators, and revealed that many of the upregulated genes possess promoters containing a high-density of CpG islands bearing trimethylation marks at histone H3K27 and/or H3K4, respectively. In support of this finding, we further documented that S100A4(−/−) knockout lenses have altered levels of trimethylated H3K27 and H3K4. Taken together, our findings suggest that S100A4 suppresses the expression of retinal genes during lens differentiation plausibly via a mechanism involving changes in histone methylation.
Motor cortical excitability predicts cognitive phenotypes in amyotrophic lateral sclerosis
Authors: Agarwal Smriti , Highton-Williamson Elizabeth , Caga Jashelle , Howells James , Dharmadasa Thanuja , Matamala José M. , Ma Yan , Shibuya Kazumoto , Hodges John R. , Ahmed Rebekah M. , Vucic Steve , Kiernan Matthew C.
Published: January 2021

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are well-recognised as an extended disease spectrum. This study hypothesised that cortical hyperexcitability, an early pathophysiological abnormality in ALS, would distinguish cognitive phenotypes, as a surrogate marker of pathological disease burden. 61 patients with ALS, matched for disease duration (pure motor ALS, n = 39; ALS with coexistent FTD, ALS-FTD, n = 12; ALS with cognitive/behavioural abnormalities not meeting FTD criteria, ALS-Cog, n = 10) and 30 age-matched healthy controls. Cognitive function on the Addenbrooke’s cognitive examination (ACE) scale, behavioural function on the motor neuron disease behavior scale (MiND-B) and cortical excitability using transcranial magnetic stimulation (TMS) were documented. Cortical resting motor threshold (RMT), lower threshold indicating hyperexcitability, was lower in ALS-FTD (50.2 ± 6.9) compared to controls (64.3 ± 12.6, p < 0.005), while ALS-Cog (63.3 ± 12.7) and ALS (60.8 ± 13.9, not significant) were similar to controls. Short interval intracortical inhibition (SICI) was reduced across all ALS groups compared to controls, indicating hyperexcitability. On receiver operating characteristic curve analysis, RMT differentiated ALS-FTD from ALS (area under the curve AUC = 0.745, p = 0.011). The present study has identified a distinct pattern of cortical excitability across cognitive phenotypes in ALS. As such, assessment of cortical physiology may provide more precise clinical prognostication in ALS.
Direct current stimulation enhances neuronal alpha-synuclein degradation in vitro
Authors: Sala Gessica , Bocci Tommaso , Borzì Valentina , Parazzini Marta , Priori Alberto , Ferrarese Carlo
Published: January 2021

Despite transcranial Direct Current Stimulation (DCS) is currently proposed as a symptomatic treatment in Parkinson’s disease, the intracellular and molecular mechanisms elicited by this technique are still unknown, and its disease-modifying potential unexplored. Aim of this study was to elucidate the on-line and off-line effects of DCS on the expression, aggregation and degradation of alpha-synuclein (asyn) in a human neuroblastoma cell line under basal conditions and in presence of pharmachologically-induced increased asyn levels. Following DCS, gene and protein expression of asyn and its main autophagic catabolic pathways were assessed by real-time PCR and Western blot, extracellular asyn levels by Dot blot. We found that, under standard conditions, DCS increased monomeric and reduced oligomeric asyn forms, with a concomitant down-regulation of both macroautophagy and chaperone-mediated autophagy. Differently, in presence of rotenone-induced increased asyn, DCS efficiently counteracted asyn accumulation, not acting on its gene transcription, but potentiating its degradation. DCS also reduced intracellular and extracellular asyn levels, increased following lysosomal inhibition, independently from autophagic degradation, suggesting that other mechanisms are also involved. Collectively, these findings suggest that DCS exerts on-line and off-line effects on the expression, aggregation and autophagic degradation of asyn, indicating a till unknown neuroprotective role of tDCS.
Identification and development of novel salt-responsive candidate gene based SSRs (cg-SSRs) and MIR gene based SSRs (mir-SSRs) in bread wheat (Triticum aestivum)
Authors: Mehta Geetika , Muthusamy Senthilkumar K. , Singh G. P. , Sharma Pradeep
Published: January 2021

Salt stress adversely affects the global wheat production and productivity. To improve salinity tolerance of crops, identification of robust molecular markers is highly imperative for development of salt-tolerant cultivars to mimic yield losses under saline conditions. In this study, we mined 171 salt-responsive genes (including 10 miRNAs) from bread wheat genome using the sequence information of functionally validated salt-responsive rice genes. Salt-stress, tissue and developmental stage-specific expression analysis of RNA-seq datasets revealed the constitutive as well as the inductive response of salt-responsive genes in different tissues of wheat. Fifty-four genotypes were phenotyped for salt stress tolerance. The stress tolerance index of the genotypes ranged from 0.30 to 3.18. In order to understand the genetic diversity, candidate gene based SSRs (cg-SSRs) and MIR gene based SSRs (miR-SSRs) were mined from 171 members of salt-responsive genes of wheat and validated among the contrasting panels of 54 tolerant as well as susceptible wheat genotypes. Among 53 SSR markers screened, 10 cg-SSRs and 8 miR-SSRs were found to be polymorphic. Polymorphic information content between the wheat genotypes ranged from 0.07 to 0.67, indicating the extant of wide genetic variation among the salt tolerant and susceptible genotypes at the DNA level. The genetic diversity analysis based on the allelic data grouped the wheat genotypes into three separate clusters of which single group encompassing most of the salt susceptible genotypes and two of them containing salt tolerance and moderately salt tolerance wheat genotypes were in congruence with penotypic data. Our study showed that both salt-responsive genes and miRNAs based SSRs were more diverse and can be effectively used for diversity analysis. This study reports the first extensive survey on genome-wide analysis, identification, development and validation of salt-responsive cg-SSRs and miR-SSRs in wheat. The information generated in the present study on genetic divergence among genotypes having a differential response to salt will help in the selection of suitable lines as parents for developing salt tolerant cultivars in wheat.
Interspecific interactions within a vector-borne complex are influenced by a co-occurring pathosystem
Authors: Cruzado-Gutiérrez Regina K. , Sadeghi Rohollah , Prager Sean M. , Casteel Clare L. , Parker Jessica , Wenninger Erik J. , Price William J. , Bosque-Pérez Nilsa A. , Karasev Alexander V. , Rashed Arash
Published: January 2021

Potato virus Y (PVY) and zebra chip (ZC) disease are major threats to solanaceous crop production in North America. PVY can be spread by aphid vectors and through vegetative propagation in potatoes. ZC is associated with “Candidatus Liberibacter solanacearum” (Lso), which is transmitted by the tomato/potato psyllid, Bactericera cockerelli Šulc (Hemiptera: Triozidae). As these two pathosystems may co-occur, we studied whether the presence of one virus strain, PVY°, affected the host preference, oviposition, and egg hatch rate of Lso-free or Lso-carrying psyllids in tomato plants. We also examined whether PVY infection influenced Lso transmission success by psyllids, Lso titer and plant chemistry (amino acids, sugars, and phytohormones). Lso-carrying psyllids showed a preference toward healthy hosts, whereas the Lso-free psyllids preferentially settled on the PVY-infected tomatoes. Oviposition of the Lso-carrying psyllids was lower on PVY-infected than healthy tomatoes, but Lso transmission, titer, and psyllid egg hatch were not significantly affected by PVY. The induction of salicylic acid and its related responses, and not nutritional losses, may explain the reduced attractiveness of the PVY-infected host to the Lso-carrying psyllids. Although our study demonstrated that pre-existing PVY infection can reduce oviposition by the Lso-carrying vector, the preference of the Lso-carrying psyllids to settle on healthy hosts could contribute to Lso spread to healthy plants in the presence of PVY infection in a field.
Bayesian analysis of depth resolved OCT attenuation coefficients
Authors: Fiske Lionel D. , Aalders Maurice C. G. , Almasian Mitra , van Leeuwen Ton G. , Katsaggelos Aggelos K. , Cossairt Oliver , Faber Dirk J.
Published: January 2021

Optical coherence tomography (OCT) is an optical technique which allows for volumetric visualization of the internal structures of translucent materials. Additional information can be gained by measuring the rate of signal attenuation in depth. Techniques have been developed to estimate the rate of attenuation on a voxel by voxel basis. This depth resolved attenuation analysis gives insight into tissue structure and organization in a spatially resolved way. However, the presence of speckle in the OCT measurement causes the attenuation coefficient image to contain unrealistic fluctuations and makes the reliability of these images at the voxel level poor. While the distribution of speckle in OCT images has appeared in literature, the resulting voxelwise corruption of the attenuation analysis has not. In this work, the estimated depth resolved attenuation coefficient from OCT data with speckle is shown to be approximately exponentially distributed. After this, a prior distribution for the depth resolved attenuation coefficient is derived for a simple system using statistical mechanics. Finally, given a set of depth resolved estimates which were made from OCT data in the presence of speckle, a posterior probability distribution for the true voxelwise attenuation coefficient is derived and a Bayesian voxelwise estimator for the coefficient is given. These results are demonstrated in simulation and validated experimentally.
In vivo silencing of amphiregulin by a novel effective Self-Assembled-Micelle inhibitory RNA ameliorates renal fibrosis via inhibition of EGFR signals
Authors: Son Seung Seob , Hwang Soohyun , Park Jun Hong , Ko Youngho , Yun Sung-Il , Lee Ji-Hye , Son Beomseok , Kim Tae Rim , Park Han-Oh , Lee Eun Young
Published: January 2021

Amphiregulin (AREG) is a transmembrane glycoprotein recently implicated in kidney fibrosis. Previously, we reported that the AREG-targeting Self-Assembled-Micelle inhibitory RNA (SAMiRNA-AREG) alleviated fibrosis by stably silencing the AREG gene, and reduced the side effects of conventional siRNA treatment of pulmonary fibrosis. However, the therapeutic effect of SAMiRNA-AREG in renal fibrosis has not been studied until now. We used two animal models of renal fibrosis generated by a unilateral ureteral obstruction (UUO) and an adenine diet (AD) to investigate whether SAMiRNA-AREG inhibited renal fibrosis. To investigate the delivery of SAMiRNA-AREG to the kidney, Cy5-labeled SAMiRNA-AREG was injected into UUO- and AD-induced renal fibrosis models. In both kidney disease models, SAMiRNA-AREG was delivered primarily to the damaged kidney. We also confirmed the protective effect of SAMiRNA-AREG in renal fibrosis models. SAMiRNA-AREG markedly decreased the UUO- and AD-induced AREG mRNA expression. Furthermore, the mRNA expression of fibrosis markers, including α-smooth muscle actin, fibronectin, α1(I) collagen, and α1(III) collagen in the UUO and AD-induced kidneys, was diminished in the SAMiRNA-AREG-treated mice. The transcription of inflammatory markers (tumor necrosis factor-α and monocyte chemoattractant protein-1) and adhesion markers (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1) was attenuated. The hematoxylin and eosin, Masson’s trichrome, and immunohistochemical staining results showed that SAMiRNA-AREG decreased renal fibrosis, AREG expression, and epidermal growth factor receptor (EGFR) phosphorylation in the UUO- and AD-induced models. Moreover, we studied the effects of SAMiRNA-AREG in response to TGF-β1 in mouse and human proximal tubule cells, and mouse fibroblasts. TGF-β1-induced extracellular matrix production and myofibroblast differentiation were attenuated by SAMiRNA-AREG. Finally, we confirmed that upregulated AREG in the UUO or AD models was mainly localized in the distal tubules. In conclusion, SAMiRNA-AREG represents a novel siRNA therapeutic for renal fibrosis by suppressing EGFR signals.
Simulating thoughts to measure and study internal attention in mental health
Authors: Amir Iftach , Ruimi Liad , Bernstein Amit
Published: January 2021

Our mind’s eye and the role of internal attention in mental life and suffering has intrigued scholars for centuries. Yet, experimental study of internal attention has been elusive due to our limited capacity to control the timing and content of internal stimuli. We thus developed the Simulated Thoughts Paradigm (STP) to experimentally deliver own-voice thought stimuli that simulate the content and experience of thinking and thereby experimental study of internal attentional processes. In independent experiments (N = 122) integrating STP into established cognitive-experimental tasks, we found and replicated evidence that emotional reactivity to negative thoughts predicts difficulty disengaging internal attention from, as well as biased selective internal attention of, those thoughts; these internal attention processes predict cognitive vulnerability (e.g., negative repetitive thinking) which thereby predict anxiety and depression. Proposed methods and findings may have implications for the study of information processing and attention in mental health broadly and models of internal attentional (dys)control in cognitive vulnerability and mental health more specifically.
Longitudinal touchscreen use across early development is associated with faster exogenous and reduced endogenous attention control
Authors: Portugal Ana Maria , Bedford Rachael , Cheung Celeste H. M. , Mason Luke , Smith Tim J.
Published: January 2021

Childhood screen time is associated with both attentional difficulties (for television viewing) and benefits (in action video gamers), but few studies have investigated today’s pervasive touchscreen devices (e.g. smartphones and tablets), which combine salient features, interactive content, and accessibility from toddlerhood (a peak period of cognitive development). We tested exogenous and endogenous attention, following forty children who were stable high (HU) or low (LU) touchscreen users from toddlerhood to pre-school. HUs were slower to disengage attention, relative to their faster baseline orienting ability. In an infant anti-saccade task, HUs displayed more of a corrective strategy of orienting faster to distractors before anticipating the target. Results suggest that long-term high exposure to touchscreen devices is associated with faster exogenous attention and concomitant decreases in endogenous attention control. Future work is required to demonstrate causality, dissociate variants of use, and investigate how attention behaviours found in screen-based contexts translate to real-world settings.
Relevance of ddRADseq method for species and population delimitation of closely related and widely distributed wolf spiders (Araneae, Lycosidae)
Authors: Ivanov Vladislav , Marusik Yuri , Pétillon Julien , Mutanen Marko
Published: January 2021

Although species delimitation is often controversial, emerging DNA-based and classical morphology-based methods are rarely compared using large-scale samplings, even less in the case of widely distributed species that have distant, allopatric populations. In the current study, we examined species boundaries within two wolf spider species of the genusPardosa(Araneae, Lycosidae),P. ripariaandP. palustris. Wolf spiders constitute an excellent model for testing the relevance of traditional vs. modern methods in species and population delimitation because several closely related species are distributed over cross-continental geographic ranges. Allopatric populations of the twoPardosaspecies were sampled across Europe to Far East Russia (latitudinal range > 150°) and several dozen individuals were studied using morphological characters (morphometry of three measures for both sexes, plus five in males only and two in females only), DNA barcoding (COI sequencing) and double-digest restriction site associated DNA sequencing (ddRADseq). The results obtained allow for changing the taxonomic status of two Far East Russian populations to subspecies and ddRADseq proved to be a powerful tool for taxonomic research despite scarce sampling and inherent subjectivity of species delimitation in allopatry. Overall, this study pleads for both multi-criteria and more population-based studies in taxonomy.
The role of tides in bottom water export from the western Ross Sea
Authors: Bowen Melissa M. , Fernandez Denise , Forcen-Vazquez Aitana , Gordon Arnold L. , Huber Bruce , Castagno Pasquale , Falco Pierpaolo
Published: January 2021

Approximately 25% of Antarctic Bottom Water has its origin as dense water exiting the western Ross Sea, but little is known about what controls the release of dense water plumes from the Drygalski Trough. We deployed two moorings on the slope to investigate the water properties of the bottom water exiting the region at Cape Adare. Salinity of the bottom water has increased in 2018 from the previous measurements in 2008–2010, consistent with the observed salinity increase in the Ross Sea. We find High Salinity Shelf Water from the Drygalski Trough contributes to two pulses of dense water at Cape Adare. The timing and magnitude of the pulses is largely explained by an inverse relationship with the tidal velocity in the Ross Sea. We suggest that the diurnal and low frequency tides in the western Ross Sea may control the magnitude and timing of the dense water outflow.
Fructosamine is a valuable marker for glycemic control and predicting adverse outcomes following total hip arthroplasty: a prospective multi-institutional investigation
Authors: Shohat Noam , Goswami Karan , Breckenridge Leigham , Held Michael B. , Malkani Arthur L. , Shah Roshan P. , Schwarzkopf Ran , Parvizi Javad
Published: January 2021

Recently, fructosamine has shown promising results in predicting adverse outcomes following total knee arthroplasty. The purpose of this study was to assess the utility of fructosamine to predict adverse outcomes following total hip arthroplasty (THA). A prospective multi-center study involving four institutions was conducted. All primary THA were evaluated for glycemic control using fructosamine levels prior to surgery. Adverse outcomes were assessed at a minimum 1 year from surgery. Primary outcome of interest was periprosthetic joint infection (PJI) based on the International Consensus Meeting (ICM) criteria. Secondary outcomes assessed were superficial infections, readmissions and death. Based on previous studies on the subject, fructosamine levels above 293 µmol/L were used to define inadequate glycemic control. Overall 1212 patients were enrolled in the present study and were available for follow up at a minimum 1 year from surgery. Of those, 54 patients (4.5%) had elevated fructosamine levels (> 293 µmol/L) and these patients were 6.7 times more likely to develop PJI compared to patients with fructosamine levels below 293 µmol/L (p = 0.002). Patients with elevated fructosamine were also associated with more readmissions (16.7% vs. 4.4%, p < 0.007) and a higher mortality rate (3.7% vs. 0.6%, p = 0.057). These associations remained statistically significant in a multi-regression analysis after adjusting for age, comorbidities and length of stay; Adjusted odds ratio were 6.37 (95% confidence interval 1.98–20.49, p = 0.002) for PJI and 2.68 (95% confidence interval 1.14–6.29, p = 0.023) for readmissions. Fructosamine is a good predictor of adverse outcomes in patients undergoing THA and should be used routinely to mitigate morbidity and mortality risk.
The cyclic expansion and contraction characteristics of a loess slope and implications for slope stability
Authors: Lan Hengxing , Zhao Xiaoxia , Macciotta Renato , Peng Jianbing , Li Langping , Wu Yuming , Zhu Yanbo , Liu Xin , Zhang Ning , Liu Shijie , Zhou Chenghu , Clague John J.
Published: January 2021

Loess covers approximately 6.6% of China and forms thick extensive deposits in the northern and northwestern parts of the country. Natural erosional processes and human modification of thick loess deposits have produced abundant, potentially unstable steep slopes in this region. Slope deformation monitoring aimed at evaluating the mechanical behavior of a loess slope has shown a cyclic pattern of contraction and expansion. Such cyclic strain change on the slope materials can damage the loess and contribute to slope instability. The site showing this behavior is a 70-m high loess slope near Yan’an city in Shanxi Province, northwest China. A Ground-Based Synthetic Aperture Radar (GB-SAR) sensor and a displacement meter were used to monitor this cyclic deformation of the slope over a one-year period from September 2018 to August 2019. It is postulated that this cyclic behavior corresponds to thermal and moisture fluctuations, following energy conservation laws. To investigate the validity of this mechanism, physical models of soil temperature and moisture measured by hygrothermographs were used to simulate the observed cyclic deformations. We found good correlations between the models based on the proposed mechanism and the exhibited daily and annual cyclic contraction and expansion. The slope absorbed energy from the time of maximum contraction to the time of maximum expansion, and released energy from the time of maximum expansion to the time of maximum contraction. Recoverable cyclic deformations suggest stresses in the loess are within the elastic range, and non-recoverable cyclic deformations suggest damage of the loess material (breakage of bonds between soil grains), which could lead to instability. Based on these observations and the models, we developed a quantitative relationship between weather cycles and thermal deformation of the slope. Given the current climate change projections of temperature increases of up to 3.5 °C by 2100, the model estimates the loess slope to expand about 0.35 mm in average, which would be in addition to the current cyclic “breathing” behavior experienced by the slope.
Long-term cyclic use of a sample collector for toilet-based urine analysis
Authors: Temirel Mikail , Yenilmez Bekir , Tasoglu Savas
Published: January 2021

Urine analysis via a toilet-based device can enable continuous health monitoring, a transformation away from hospital-based care towards more proactive medicine. To enable reliable sample collection for a toilet-attached analyzer, here a novel sample collector is proposed. The applicability of the proposed sample collector is validated for long-term use. Geometric parameters of the 3D-printed sample collector are optimized. The collected and leftover volumes are quantified for a range of urination speeds and design parameters. For long-term cyclic use, the protein concentrations of samples are quantified and the effectiveness of washing the sample collector is assessed.
Large-scale preparation of Co nanoparticles as an additive in carbon fiber for microwave absorption enhancement in C band
Authors: Zhu Y. X. , Wang S. F. , Zhang Y. S. , Wu Z. G. , Zhong B. , Li D. R. , Wang F. Y. , Feng J. J. , Tang J. , Zhuo R. F. , Yan P. X.
Published: January 2021

Recent studies have found that the core–shell structured metal nanoparticles and porous carbon nanofibers (PCNF) are combined into a microwave absorbing material through electrospinning, which exhibits excellent microwave absorption performance. In this study, the core–shell structure Co nanoparticles prepared by the self-developed HEIBE process (production rate of > 50 g/h) were combined with porous carbon fibers, and their absorbing properties were greatly improved. The morphology of Co/PCNF demonstrated that CoNPs are randomly dispersed in the porous carbon nanofibers and carbon nanofiber form complex conductive network which enhances the dielectric loss of the materials. Meanwhile, the Co/PCNF has a low graphitization and shows a significant improvement in permittivity due to the combination of CoNPs and high conductivity of carbon material. The maximum reflection loss (RL) of Co/PCNF reaches − 63.69 dB at 5.28 GHz with a thickness of 5.21 mm and the absorption bandwidth (RL ≤  − 10.0 dB) is 12.92 GHz. In terms of 5.60 mm and 6.61 mm absorber, there are two absorption peaks of − 47.64 dB and − 48.30 dB appear around 12.50 GHz and 14.10 GHz, respectively. The results presented in this paper may pave a way for promising applications of lightweight and high-efficiency microwave absorbing materials (MAMs).
Modality-specific improvements in sensory processing among baseball players
Authors: Yamashiro Koya , Yamazaki Yudai , Siiya Kanako , Ikarashi Koyuki , Baba Yasuhiro , Otsuru Naofumi , Onishi Hideaki , Sato Daisuke
Published: January 2021

Long-term skills training is known to induce neuroplastic alterations, but it is still debated whether these changes are always modality-specific or can be supramodal components. To address this issue, we compared finger-targeted somatosensory-evoked and auditory-evoked potentials under both Go (response) and Nogo (response inhibition) conditions between 10 baseball players, who require fine hand/digit skills and response inhibition, to 12 matched track and field (T&F) athletes. Electroencephalograms were obtained at nine cortical electrode positions. Go potentials, Nogo potentials, and Go/Nogo reaction time (Go/Nogo RT) were measured during equiprobable somatosensory and auditory Go/Nogo paradigms. Nogo potentials were obtained by subtracting Go trial from Nogo trial responses. Somatosensory Go P100 latency and Go/Nogo RT were significantly shorter in the baseball group than the T&F group, while auditory Go N100 latency and Go/Nogo RT did not differ between groups. Additionally, somatosensory subtracted Nogo N2 latency was significantly shorter in the baseball group than the T&F group. Furthermore, there were significant positive correlations between somatosensory Go/Nogo RT and both Go P100 latency and subtracted Nogo N2 latency, but no significant correlations among auditory responses. We speculate that long-term skills training induce predominantly modality-specific neuroplastic changes that can improve both execution and response inhibition.
Clonal hematopoiesis in adult pure red cell aplasia
Authors: Fujishima Naohito , Kohmaru Junki , Koyota Souichi , Kuba Keiji , Saga Tomoo , Omokawa Ayumi , Moritoki Yuki , Ueki Shigeharu , Ishida Fumihiro , Nakao Shinji , Matsuda Akira , Ohta Akiko , Tohyama Kaoru , Yamasaki Hiroshi , Usuki Kensuke , Nakashima Yasuhiro , Sato Shinya , Miyazaki Yasushi , Nannya Yasuhito , Ogawa Seishi , Sawada Kenichi , Mitani Kinuko , Hirokawa Makoto
Published: January 2021

Idiopathic pure red cell aplasia (PRCA) and secondary PRCA associated with thymoma and large granular lymphocyte leukemia are generally considered to be immune-mediated. The PRCA2004/2006 study showed that poor responses to immunosuppression and anemia relapse were associated with death. PRCA may represent the prodrome to MDS. Thus, clonal hematopoiesis may be responsible for treatment failure. We investigated gene mutations in myeloid neoplasm-associated genes in acquired PRCA. We identified 21 mutations affecting amino acid sequences in 11 of the 38 adult PRCA patients (28.9%) using stringent filtering of the error-prone sequences and SNPs. Four PRCA patients showed 7 driver mutations in TET2, DNMT3A and KDM6A, and 2 PRCA patients carried multiple mutations in TET2. Five PRCA patients had mutations with high VAFs exceeding 0.3. These results suggest that clonal hematopoiesis by stem/progenitor cells might be related to the pathophysiology of chronic PRCA in certain adult patients.
Monthly mobility inferred from isoscapes and laser ablation strontium isotope ratios in caprine tooth enamel
Authors: Lazzerini N. , Balter V. , Coulon A. , Tacail T. , Marchina C. , Lemoine M. , Bayarkhuu N. , Turbat Ts. , Lepetz S. , Zazzo A.
Published: January 2021

Strontium isotopic analysis of sequentially formed tissues, such as tooth enamel, is commonly used to study provenance and mobility of humans and animals. However, the potential of 87Sr/86Sr in tooth enamel to track high-frequency movements has not yet been established, in part due to the lack of data on modern animals of known movement and predictive model of isotope variation across the landscape. To tackle this issue, we measured the 87Sr/86Sr in plant samples taken from a 2000 km2 area in the Altai Mountains (Mongolia), and the 87Sr/86Sr in tooth enamel of domestic caprines whose mobility was monitored using GPS tracking. We show that high-resolution, sequential profiles of strontium isotope composition of tooth enamel reliably reflect the high-frequency mobility of domestic livestock and that short-term residency of about 45 days can be resolved. This offers new perspectives in various disciplines, including forensics, ecology, palaeoanthropology, and bioarchaeology.
Breast-conserving surgery with 3D-printed surgical guide: a single-center, prospective clinical study
Authors: Wu Zhen-Yu , Kim Hee Jeong , Lee Jongwon , Chung Il Yong , Kim Jisun , Lee Saebyeol , Son Byung Ho , Ahn Sei-Hyun , Kim Hak Hee , Seo Joon Beom , Jeong Jae Ho , Gong Gyungyub , Kim Namkug , Ko BeomSeok
Published: January 2021

To facilitate precise tumor resection at the time of breast-conserving surgery (BCS), we developed and implemented a magnetic resonance imaging (MRI)-based three-dimensional-printed (3DP) breast surgical guide (BSG). This prospective cohort study was conducted at a single institution from July 2017 to February 2019 on women with breast cancer who underwent partial breast resection using patient-specific 3DP BSGs. Eighty-eight patients with invasive cancer were enrolled, of whom 1 patient had bilateral breast cancer. The mean size of the tumor long-axis on MRI before surgery was 2.8 ± 0.9 cm, and multiple tumors were observed in 34 patients. In 16 cases (18.0%), the resection margin was tumor-positive according to intraoperative frozen biopsy; all of these tumors were ductal carcinoma in situ and were re-excised intraoperatively. In 93.3% of the cases, the resection margin was tumor-free in the permanent pathology. The mean pathological tumor size was 1.7 ± 1.0 cm, and the mean distance from the tumor to the border was 1.5 ± 1.0 cm. This exploratory study showed that the tumor area on the MRI could be directly displayed on the breast when using a 3DP BSG for BCS, thereby allowing precise surgery and safe tumor removal.

Trial Registration Clinical Research Information Service (CRIS) Identifier (No. KCT0002375, KCT0003043).
Identifying metastatic ability of prostate cancer cell lines using native fluorescence spectroscopy and machine learning methods
Authors: Xue Jianpeng , Pu Yang , Smith Jason , Gao Xin , Wang Chun , Wu Binlin
Published: January 2021

Metastasis is the leading cause of mortalities in cancer patients due to the spreading of cancer cells to various organs. Detecting cancer and identifying its metastatic potential at the early stage is important. This may be achieved based on the quantification of the key biomolecular components within tissues and cells using recent optical spectroscopic techniques. The aim of this study was to develop a noninvasive label-free optical biopsy technique to retrieve the characteristic molecular information for detecting different metastatic potentials of prostate cancer cells. Herein we report using native fluorescence (NFL) spectroscopy along with machine learning (ML) to differentiate prostate cancer cells with different metastatic abilities. The ML algorithms including principal component analysis (PCA) and nonnegative matrix factorization (NMF) were used for dimension reduction and feature detection. The characteristic component spectra were used to identify the key biomolecules that are correlated with metastatic potentials. The relative concentrations of the molecular spectral components were retrieved and used to classify the cancer cells with different metastatic potentials. A multi-class classification was performed using support vector machines (SVMs). The NFL spectral data were collected from three prostate cancer cell lines with different levels of metastatic potentials. The key biomolecules in the prostate cancer cells were identified to be tryptophan, reduced nicotinamide adenine dinucleotide (NADH) and hypothetically lactate as well. The cancer cells with different metastatic potentials were classified with high accuracy using the relative concentrations of the key molecular components. The results suggest that the changes in the relative concentrations of these key fluorophores retrieved from NFL spectra may present potential criteria for detecting prostate cancer cells of different metastatic abilities.
Bioinformatics analysis of DNMT1 expression and its role in head and neck squamous cell carcinoma prognosis
Authors: Cui Jili , Zheng Lian , Zhang Yuanyuan , Xue Miaomiao
Published: January 2021

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of malignancy in the world. DNA cytosine-5-methyltransferase 1 (DNMT1) play key roles in carcinogenesis and regulation of the immune micro-environment, but the gene expression and the role of DNMT1 in HNSCC is unknown. In this study, we utilized online tools and databases for pan-cancer and HNSCC analysis of DNMT1 expression and its association with clinical cancer characteristics. We also identified genes that positively and negatively correlated with DNMT1 expression and identified eight hub genes based on protein–protein interaction (PPI) network analysis. Enrichment analyses were performed to explore the biological functions related with of DNMT1. The Tumor Immune Estimation Resource (TIMER) database was performed to explore the relationship between DNMT1 expression and immune-cell infiltration. We demonstrated that DNMT1 gene expression was upregulated in HNSCC and associated with poor prognosis. Based on analysis of the eight hub genes, we determined that DNMT1 may be involved in cell cycle, proliferation and metabolic related pathways. We also found that significant difference of B cells infiltration based on TP 53 mutation. These findings suggest that DNMT1 related epigenetic alterations have close relationship with HNSCC progression, and DNMT1 could be a novel diagnostic biomarker and a promising therapeutic target for HNSCC.
Changes in telomere length and senescence markers during human ovarian tissue cryopreservation
Authors: Kim Boram , Ryu Ki-Jin , Lee Sanghoon , Kim Tak
Published: January 2021

Ovarian tissue cryopreservation is considered as a useful option to preserve fertility for cancer patients. This study purposed to evaluate the change of telomere length and senescence markers during human ovarian tissue cryopreservation. Ovarian tissues were obtained from women who underwent benign ovarian surgery in the gynecology research unit of a university hospital with prior consent and IRB approval. DNA was extracted from the ovarian tissues using a DNeasy tissue kit and telomere lengths in the DNA samples were determined by real time PCR before and after cryopreservation. All tissues were stained with hematoxylin–eosin and subjected to immunohistochemistry and TUNEL assays. Other senescence markers, including p53, p16, p21, and phospho-pRb proteins, were evaluated using western blot analysis. Ovarian tissues were collected from ten patients and prepared for slow freezing with the same size of diameter 4 mm and 1 mm thickness. Mean age of patients was 26.7 ± 6.2 years (range, 16–34 years), and ovarian tissues were cryopreserved and thawed 4 weeks after cryopreservation. The mean telomere length was significantly decreased after cryopreservation (9.57 ± 1.47 bp vs. 8.34 ± 1.83 bp, p = 0.001). Western blot analysis revealed that p53, p16, and p21 proteins increased and phospho-pRb protein expression decreased after ovarian tissue cryopreservation. Ovarian tissue cryopreservation and transplantation is regarded as one of promising options for fertility preservation. However, clinicians and researchers should be aware of possible irreversible DNA changes such as shortening of telomere length and alterations of other senescence markers in human ovarian tissues.
Proteome-wide profiling and mapping of post translational modifications in human hearts
Authors: Bagwan Navratan , El Ali Henrik H. , Lundby Alicia
Published: January 2021

Post translational modifications (PTMs) are covalent modifications of proteins that can range from small chemical modifications to addition of entire proteins. PTMs contribute to regulation of protein function and thereby greatly increase the functional diversity of the proteome. In the heart, a few well-studied PTMs, such as phosphorylation and glycosylation, are known to play essential roles for cardiac function. Yet, only a fraction of the ~ 300 known PTMs have been studied in a cardiac context. Here we investigated the proteome-wide map of PTMs present in human hearts by utilizing high-resolution mass spectrometry measurements and a suite of PTM identification algorithms. Our approach led to identification of more than 150 different PTMs across three of the chambers in human hearts. This finding underscores that decoration of cardiac proteins by PTMs is much more diverse than hitherto appreciated and provides insights in cardiac protein PTMs not yet studied. The results presented serve as a catalogue of which PTMs are present in human hearts and outlines the particular protein and the specific amino acid modified, and thereby provides a detail-rich resource for exploring protein modifications in human hearts beyond the most studied PTMs.
Relationship of back muscle and knee extensors with the compensatory mechanism of sagittal alignment in a community-dwelling elderly population
Authors: Takahashi Shinji , Hoshino Masatoshi , Ohyama Shoichiro , Hori Yusuke , Yabu Akito , Kobayashi Akio , Tsujio Tadao , Kotake Shiro , Nakamura Hiroaki
Published: January 2021

Compensatory mechanisms, such as a decrease in thoracic spine kyphosis and posterior tilting or rotation of the pelvis, aim to achieve optimal alignment of the spine. However, the effect of muscle strength on these compensatory mechanisms has not been elucidated. This study aimed to investigate the impact of back muscle and lower extremity strength on compensatory mechanisms in elderly people. Overall, 409 community-dwelling elderly participants (164 men, 245 women) were included. Age, disc degeneration, and 2 or more vertebral fractures showed a significant increase of risk for sagittal vertical axis (SVA) deterioration. Conversely, stronger back, hip flexor, and knee extensor muscles reduced the risk for SVA deterioration. To investigate the association of each muscle’s strength with compensatory mechanisms, 162 subjects with pelvic incidence-lumbar lordosis > 10° were selected. The linear regression model for thoracic kyphosis demonstrated a negative correlation with back muscle strength and positive correlation with vertebral fracture. The regression analysis for pelvic tilt demonstrated a positive correlation with knee extensor strength. Back, hip flexor, and knee extensor muscle strength were associated with sagittal spinal alignment. Back muscle strength was important for the decrease in thoracic kyphosis, and knee extensor strength was associated with pelvic tilt.
Mash-based analyses of Escherichia coli genomes reveal 14 distinct phylogroups
Authors: Abram Kaleb , Udaondo Zulema , Bleker Carissa , Wanchai Visanu , Wassenaar Trudy M. , Robeson Michael S. , Ussery David W.
Published: January 2021

In this study, more than one hundred thousand Escherichia coli and Shigella genomes were examined and classified. This is, to our knowledge, the largest E. coli genome dataset analyzed to date. A Mash-based analysis of a cleaned set of 10,667 E. coli genomes from GenBank revealed 14 distinct phylogroups. A representative genome or medoid identified for each phylogroup was used as a proxy to classify 95,525 unassembled genomes from the Sequence Read Archive (SRA). We find that most of the sequenced E. coli genomes belong to four phylogroups (A, C, B1 and E2(O157)). Authenticity of the 14 phylogroups is supported by several different lines of evidence: phylogroup-specific core genes, a phylogenetic tree constructed with 2613 single copy core genes, and differences in the rates of gene gain/loss/duplication. The methodology used in this work is able to reproduce known phylogroups, as well as to identify previously uncharacterized phylogroups in E. coli species.
Circulating extracellular vesicles release oncogenic miR-424 in experimental models and patients with aggressive prostate cancer
Authors: Albino Domenico , Falcione Martina , Uboldi Valeria , Temilola Dada Oluwaseyi , Sandrini Giada , Merulla Jessica , Civenni Gianluca , Kokanovic Aleksandra , Stürchler Alessandra , Shinde Dheeraj , Garofalo Mariangela , Mestre Ricardo Pereira , Constâncio Vera , Wium Martha , Burrello Jacopo , Baranzini Nicolò , Grimaldi Annalisa , Theurillat Jean-Philippe , Bossi Daniela , Barile Lucio , Henrique Rui M. , Jeronimo Carmen , Zerbini Luiz Fernando , Catapano Carlo V. , Carbone Giuseppina M.
Published: January 2021

Extracellular vesicles (EVs) are relevant means for transferring signals across cells and facilitate propagation of oncogenic stimuli promoting disease evolution and metastatic spread in cancer patients. Here, we investigated the release of miR-424 in circulating small EVs or exosomes from prostate cancer patients and assessed the functional implications in multiple experimental models. We found higher frequency of circulating miR-424 positive EVs in patients with metastatic prostate cancer compared to patients with primary tumors and BPH. Release of miR-424 in small EVs was enhanced in cell lines (LNCaPabl), transgenic mice (Pb-Cre4;Ptenflox/flox;Rosa26ERG/ERG) and patient-derived xenograft (PDX) models of aggressive disease. EVs containing miR-424 promoted stem-like traits and tumor-initiating properties in normal prostate epithelial cells while enhanced tumorigenesis in transformed prostate epithelial cells. Intravenous administration of miR-424 positive EVs to mice, mimicking blood circulation, promoted miR-424 transfer and tumor growth in xenograft models. Circulating miR-424 positive EVs from patients with aggressive primary and metastatic tumors induced stem-like features when supplemented to prostate epithelial cells. This study establishes that EVs-mediated transfer of miR-424 across heterogeneous cell populations is an important mechanism of tumor self-sustenance, disease recurrence and progression. These findings might indicate novel approaches for the management and therapy of prostate cancer.
Sonic-spray introduction of liquid samples to hand-held Ion mobility spectrometry analyzers
Authors: Pevzner Alexander , Feldheim Gil , Zaltsman Amalia , Elisha Shmuel , Heleg-Shabtai Vered , Ron Izhar
Published: January 2021

Sonic spray vaporization of liquid samples for introduction to hand-held ion mobility spectrometry vapor analyzers.
Block copolymer micelles enable facile synthesis of organic–inorganic perovskite nanostructures with tailored architecture
Authors: Nah Yoonseo , Jang Dohyub , Kim Dong Ha
Published: January 2021

We report a distinct method for the production of organic–inorganic hybrid perovskite (OIHP) nanostructures using block copolymer micelles as scaffolds.
Facile synthesis of 3D covalent organic frameworks via a two-in-one strategy
Authors: Yan Xiaoli , Li Hui , Shang Pengna , Liu Huan , Liu Jingjuan , Zhang Ting , Xing Guolong , Fang Qianrong , Chen Long
Published: January 2021

A new 3D imine-linked COF (3D-Flu-COF) was readily prepared via a “two-in-one” strategy for the first time which featured high stability and excellent acidichromic sensing properties.
Distinct structure assembly driven by metal–ligand binding in Au23 nanoclusters and its relation to photocatalysis
Authors: Li Shuohao , Sun Yongnan , Wu Chenyang , Hu Weigang , Li Wei , Liu Xu , Chen Mingyang , Zhu Yan
Published: January 2021

Au23(SR)4(PPh3)9 constructed from Au4 tetrahedron assembly exhibits higher photocatalytic activity than Au23(SR′)16 from shell-by-shell assembly.
Sandwich-like low-sensitive nitroamine explosives stabilized by hydrogen bonds and π–π stacking interactions
Authors: Cheng Yanfei , Chen Xiang , Yang Na , Zhang Yazhou , Ma Haixia , Guo Zhaoqi
Published: January 2021

Sandwich-like low-sensitive nitroamine explosives were developed which expand the structural category of low-sensitive energetic materials and could give references to the design of new low-sensitive energetic materials.
Theoretical prediction by DFT and experimental observation of heterocation-doping effects on hydrogen adsorption and migration over the CeO2(111) surface
Authors: Murakami Kota , Mizutani Yuta , Sampei Hiroshi , Ishikawa Atsushi , Tanaka Yuta , Hayashi Sasuga , Doi Sae , Higo Takuma , Tsuneki Hideaki , Nakai Hiromi , Sekine Yasushi
Published: January 2021

The addition of dopants with a small ionic radius led to strong binding of H atoms, and the balance of H+ reactivity (mobility) and H+ coverage was fundamentally important for high H+ conductivity and catalysis involving surface protonics.
Collective structural properties of embedded molecular motors in functionalized metal–organic frameworks
Authors: Kolodzeiski Elena , Amirjalayer Saeed
Published: January 2021

A theoretical protocol has been developed to investigate the collective structural properties of molecular motors embedded in metal–organic frameworks.
Investigating the role of halogen-bonded complexes in microsolvated Y−(H2O)n + CH3I SN2 reactions
Authors: Ji Xiaoyan , Zhao Chongyang , Xie Jing
Published: January 2021

A halogen-bonded complex pathway is computed for Y−(H2O)n + CH3I (Y = HO, F, Cl, Br, and I) ion–molecule nucleophilic substitution reactions and is compared with back-side and front-side attack pathways.
Unconventional singlet fission materials
Authors: Ullrich Tobias , Munz Dominik , Guldi Dirk M.
Published: January 2021

Singlet fission (SF) is a photophysical downconversion pathway, in which a singlet excitation transforms into two triplet excited states.
Efficient non-noble Ni–Cu based catalysts for the valorization of palmitic acid through a decarboxylation reaction
Authors: Ferraz Camila P. , Kiméné Anouchka , Silva Vargas Karen , Heyte Svetlana , Durlin Claire , Simon Olivier , Dumeignil Franck , Paul Sébastien , Wojcieszak Robert
Published: January 2021

The synergistic effect Ni–Cu in the bimetallic catalyst Ni–Cu/C improved the stability and reduction temperature as well as enhanced the catalytic activity for the decarboxylation of palmitic acid.