bluuebunny/crossref_metadata_2025 huggingface dataset:
Tectonic Controls on Block Rotation and Sheeted Sill Emplacement in the Xigaze Ophiolite (Tibet): The Construction Mode of Slow‐Spreading and Ultraslow‐Spreading Oceanic Crusts
Authors: Liu Tong , Dick Henry J. B. , Liu Chuan‐Zhou , Wu Fu‐Yuan , Ji Wen‐Bin , Zhang Chang , Zhang Wei‐Qi , Zhang Zhen‐Yu , Lin Yin‐Zheng , Zhang Zhen
Published: January 2021

The internal structure of oceanic crusts is not well understood due to the limitation of deep drilling. However, that of ophiolites, i.e., on‐land ancient analogs of oceanic lithosphere, could be precisely mapped and measured. The Xigaze ophiolite in Tibet has been regarded as “peculiar”, due to the sheeted sill complex in its upper crust, and non‐sheeted diabase sills/dikes crosscutting its mantle and lower crust, which are geometrically different from the primarily vertical sheeted dike complex. Based on extensive field observations, here we present petrological and geochemical data for the Xigaze ophiolite to decipher the origin of sheeted sill complex and its implications for the construction of oceanic crusts. Diabases in the Xigaze ophiolite could be subdivided into sheeted sills, Group 1 non‐sheeted dikes, and Group 2 non‐sheeted sills, based on their orientations. These diabases cut other lithologies, and hence belong to the latest‐stage products. Based on petrological, geochemical, and structural data, we highlight the important role of detachment fault in the generation of sheeted and non‐sheeted sills. During the formation of oceanic crust, large block exhumation, multi‐stage rotations, and foundering are argued here as key mechanisms for the generation of Xigaze sheeted and non‐sheeted dikes/sills, all of which are in the evolution of detachment fault systems. These processes are also not uncommon for asymmetrical segments at modern slow‐spreading and ultraslow‐spreading ridges, but are rare at symmetrical segments. Due to the evolution of detachment fault, the internal structures of (ultra)slow‐spreading ridges are more complex than those at fast‐spreading ridges.
Structural Setting, Paleomagnetism, and Magnetic Fabric of Miocene Plutons in a Transpressional Sinistral Shear Zone, Tonalá, Chiapas, Mexico: Evidence of Shortening During Magma Emplacement
Authors: Molina Garza Roberto S. , Geissman John W. , Peña Alonso Tomás , Aranda Gómez Jorge , Wawrzyniec Timothy
Published: January 2021

We studied the structure, paleomagnetism, and magnetic fabric of Miocene granitoids intruded along the left‐lateral, transpressional, Tonalá shear zone in Chiapas, southern Mexico. Magmatic fabrics delineate patterns of regional folding striking parallel to the shear zone, suggesting syn‐magmatic shortening. Magnetic susceptibility fabrics are well developed, and mean magnetic susceptibility averages 18.6 × 10−3 SI. The magnetic fabric of the plutons is controlled primarily by MD and finer PSD magnetite, which also carries the magnetic remanence. The orientations of macroscopic mineral fabrics and magnetic susceptibility fabrics are consistently parallel in protomylonites, but their coincidence is good to poor in granitoids that preserve magmatic fabrics. Most site mean directions are NW‐NE directed of moderate positive inclination (or antipodal), but on a local scale site, mean directions are very discordant. The overall mean direction, omitting highly discordant sites, is of Decl. = 359.6° and Incl. = +41.9° (k = 14.4, α95 = 8.1°, N = 24 sites); it is nearly concordant with the North America reference direction, and the slight difference may indicate a gentle, north‐side down regional tilt. High directional dispersion is interpreted to reflect relative rotation about local vertical to sub‐vertical axes of plutons, or parts of plutons, along the shear zone, with some rotations interpreted to be caused by progressive deformation within the shear zone. Paleomagnetic and AMS data from the protomylonite rocks are interpreted to have been affected by the distortional strain, which accommodated shape and volume change in the rock. We suggest that the introduction of granitic magma into middle crustal levels critically enhanced the crustal response to shortening within the shear zone, possibly due to melt compressibility.
Development of a Brief Primary Care Intervention for PTSD in Adolescents
Authors: Srivastava Akanksha , Miller Alexandria N. , Coles Mandy S. , Brigham Rebecca , Peterson Erin R. , Kreida Ellen , Mueser Kim T. , Ng Lauren C.
Published: January 2021

Objective: Our study aimed to adapt an evidence-based, brief intervention for use in an urban safety net adolescent primary care center with an existing integrated behavioral health team who have not previously treated posttraumatic stress disorder (PTSD) explicitly in the clinic. PTSD is routinely undertreated in adolescent primary care due in part to a lack of evidence-based interventions for PTSD that can be feasibly delivered in primary care. Sustainable PTSD interventions in adolescent medicine clinics must overcome patient-, provider-, and system-level barriers. Method: The Brief Relaxation, Education And Trauma Healing (BREATHE) was selected for adaptation based on a literature review of evidence-based target interventions. Purposeful sampling was used to recruit nine adolescent patients, two parents, and eight clinic staff ( N = 19) for individual qualitative interviews focused on feasibility of implementation of a PTSD intervention delivered in an adolescent medicine primary care clinic that serves diverse patients with high trauma exposure. Audio recordings from these interviews were transcribed and analyzed using inductive and directed a priori approaches related to the central research questions. Results: Participants provided feedback on the format and content of the BREATHE intervention to adapt the existing treatment to be feasible and sustainable in a primary care setting. Overall, participants thought the intervention was helpful and feasible and provided specific feedback for adaptation. Conclusion: This study developed the Primary Care Intervention for PTSD (PCIP) as a resource for improving PTSD care for adolescents in a primary care setting. Further studies will evaluate PCIP efficacy on PTSD symptomology.

Implications for Impact Statement

This study adapted a three-session intervention for posttraumatic stress disorder (PTSD) to be used in an adolescent primary care clinic. The Primary Care Intervention for PTSD is a resource that primary care clinics can implement into their practice as a feasible intervention for patients with PTSD.
Genetic and clinical analyses of psychosis spectrum symptoms in a large multiethnic youth cohort reveal significant link with ADHD
Authors: Olde Loohuis Loes M. , Mennigen Eva , Ori Anil P. S. , Perkins Diana , Robinson Elise , Addington Jean , Cadenhead Kristin S. , Cornblatt Barbara A. , Mathalon Daniel H. , McGlashan Thomas H. , Seidman Larry J. , Keshavan Matcheri S. , Stone William S. , Tsuang Ming T. , Walker Elaine F. , Woods Scott W. , Cannon Tyrone D. , Gur Ruben C. , Gur Raquel E. , Bearden Carrie E. , Ophoff Roel A.
Published: January 2021

Psychotic symptoms are not only an important feature of severe neuropsychiatric disorders, but are also common in the general population, especially in youth. The genetic etiology of psychosis symptoms in youth remains poorly understood. To characterize genetic risk for psychosis spectrum symptoms (PS), we leverage a community-based multiethnic sample of children and adolescents aged 8–22 years, the Philadelphia Neurodevelopmental Cohort (n = 7225, 20% PS). Using an elastic net regression model, we aim to classify PS status using polygenic scores (PGS) based on a range of heritable psychiatric and brain-related traits in a multi-PGS model. We also perform univariate PGS associations and evaluate age-specific effects. The multi-PGS analyses do not improve prediction of PS status over univariate models, but reveal that the attention deficit hyperactivity disorder (ADHD) PGS is robustly and uniquely associated with PS (OR 1.12 (1.05, 1.18) P = 0.0003). This association is driven by subjects of European ancestry (OR = 1.23 (1.14, 1.34), P = 4.15 × 10−7) but is not observed in African American subjects (P = 0.65). We find a significant interaction of ADHD PGS with age (P = 0.01), with a stronger association in younger children. The association is independent of phenotypic overlap between ADHD and PS, not indirectly driven by substance use or childhood trauma, and appears to be specific to PS rather than reflecting general psychopathology in youth. In an independent sample, we replicate an increased ADHD PGS in 328 youth at clinical high risk for psychosis, compared to 216 unaffected controls (OR 1.06, CI(1.01, 1.11), P = 0.02). Our findings suggest that PS in youth may reflect a different genetic etiology than psychotic symptoms in adulthood, one more akin to ADHD, and shed light on how genetic risk can be investigated across early disease trajectories.
The influence of two different cements on remaining cement excess in cement-retained implant-supported zirconia crowns. An in vitro study
Authors: Hidalgo Jazmin , Baghernejad Desirée , Falk Anders , Larsson Christel
Published: January 2021

Aim

To compare the amount of remaining cement excess after cementation of implant-supported zirconia crowns with zinc phosphate or calcium aluminate glass ionomer cement.

MATERIALS AND METHODS

Twenty zirconia crowns were cemented on dental implant abutments using a calcium aluminate glass ionomer cement (n = 10) and zinc phosphate cement (n = 10). After removal of cement excess, remaining cement excess were measured with pixel area calculation method and by weighing. Differences in amount of remaining cement excess were analyzed using Independent Samples t-Test. Level of significance was set at p = 0.05.

Results

Zinc phosphate cement had a significantly greater amount of remaining cement excess than calcium aluminate glass ionomer cement in terms of total number of pixels (p = 0.002) and amount in grams (p = 0.005).

Conclusion

The study suggests that the amount of remaining cement excess can be affected by the type of cement. Calcium aluminate glass ionomer cement may be a more suitable choice for cement-retained dental implant restorations, and possibly reduce the risk of complications related to cement excess such as peri-implant disease. Further studies are needed to verify the results from the present study.
Dental patient reported outcome and oral health-related quality of life measures: protocol for a systematic evidence map of reviews
Authors: Beecher Darragh , James Patrice , Browne John , Di Blasi Zelda , Harding Máiréad , Whelton Helen
Published: January 2021

Aims

This research synthesis protocol addresses the question: what is the evidence concerning measurement properties of dental patient reported outcome measures (dPROMs), and regarding the real-world value of dPROMs, and where are the gaps in this evidence? Evidence mapping will systematically examine reviews of quantitative dPROMs used to assess the impact of oral health on the quality of life of dental patients and research participants. Evidence gaps where future research or systematic reviews are required will be identified.

Materials and methods

This protocol accords with the PRISMA-P guideline. Open Science Framework Registration https://doi.org/10.17605/OSF.IO/RZD3N. Biomedical and grey literature databases will be searched, adapting the same search strategy. Published or unpublished reviews evaluating any dPROM will be considered for inclusion. There will be no restriction by date, setting, or language. AMSTAR2 and ROBIS will evaluate risk of bias. Psychometric criteria will be adapted from COSMIN. Data will be summarised separately for specific populations and conditions.

Discussion

The findings will enable clinicians and researchers to identify methodologically robust dPROMs, appropriate for use with relevant populations and conditions. Implications for real-world practice and research will be discussed.
Extracellular vesicles-released parathyroid hormone-related protein from Lewis lung carcinoma induces lipolysis and adipose tissue browning in cancer cachexia
Authors: Hu Wenjun , Xiong Hairong , Ru Zeyuan , Zhao Yan , Zhou Yali , Xie Kairu , Xiao Wen , Xiong Zhiyong , Wang Cheng , Yuan Changfei , Shi Jian , Du Quansheng , Zhang Xiaoping , Yang Hongmei
Published: January 2021

Cancer cachexia is a metabolic disorder characterized by skeletal muscle wasting and white adipose tissue browning. Specific functions of several hormones, growth factors, and cytokines derived from tumors can trigger cachexia. Moreover, adipose tissue lipolysis might explain weight loss that occurs owing to cachexia. Extracellular vesicles (EVs) are involved in intercellular communication. However, whether EVs participate in lipolysis induced by cancer cachexia has not been thoroughly investigated. Using Lewis lung carcinoma (LLC) cell culture, we tested whether LLC cell-derived EVs can induce lipolysis in 3T3-L1 adipocytes. EVs derived from LLC cells were isolated and characterized biochemically and biophysically. Western blotting and glycerol assay were used to study lipolysis. LLC cell-derived EVs induced lipolysis in vivo and vitro. EVs fused directly with target 3T3-L1 adipocytes and transferred parathyroid hormone-related protein (PTHrP), activating the PKA signaling pathway in 3T3-L1 adipocytes. Blocking PTHrP activity in LLC-EVs using a neutralizing antibody and by knocking down PTHR expression prevented lipolysis in adipocytes. Inhibiting the PKA signaling pathway also prevents the lipolytic effects of EVs. In vivo, suppression of LLC-EVs release by knocking down Rab27A alleviated white adipose tissue browning and lipolysis. Our data showed that LLC cell-derived EVs induced adipocyte lipolysis via the extracellular PTHrP-mediated PKA pathway. Our data demonstrate that LLC-EVs induce lipolysis in vitro and vivo by delivering PTHrP, which interacts with PTHR. The lipolytic effect of LLC-EVs was abrogated by PTHR knockdown and treatment with a neutralizing anti-PTHrP antibody. Together, these data show that LLC-EV-induced lipolysis is mediated by extracellular PTHrP. These findings suggest a novel mechanism of lipid droplet loss and identify a potential therapeutic strategy for cancer cachexia.
Cellular stress signaling activates type-I IFN response through FOXO3-regulated lamin posttranslational modification
Authors: Hwang Inah , Uchida Hiroki , Dai Ziwei , Li Fei , Sanchez Teresa , Locasale Jason W. , Cantley Lewis C. , Zheng Hongwu , Paik Jihye
Published: January 2021

Neural stem/progenitor cells (NSPCs) persist over the lifespan while encountering constant challenges from age or injury related brain environmental changes like elevated oxidative stress. But how oxidative stress regulates NSPC and its neurogenic differentiation is less clear. Here we report that acutely elevated cellular oxidative stress in NSPCs modulates neurogenic differentiation through induction of Forkhead box protein O3 (FOXO3)-mediated cGAS/STING and type I interferon (IFN-I) responses. We show that oxidative stress activates FOXO3 and its transcriptional target glycine-N-methyltransferase (GNMT) whose upregulation triggers depletion of s-adenosylmethionine (SAM), a key co-substrate involved in methyl group transfer reactions. Mechanistically, we demonstrate that reduced intracellular SAM availability disrupts carboxymethylation and maturation of nuclear lamin, which induce cytosolic release of chromatin fragments and subsequent activation of the cGAS/STING-IFN-I cascade to suppress neurogenic differentiation. Together, our findings suggest the FOXO3-GNMT/SAM-lamin-cGAS/STING-IFN-I signaling cascade as a critical stress response program that regulates long-term regenerative potential.
NUPR1 is a critical repressor of ferroptosis
Authors: Liu Jiao , Song Xinxin , Kuang Feimei , Zhang Qiuhong , Xie Yangchun , Kang Rui , Kroemer Guido , Tang Daolin
Published: January 2021

Ferroptosis is a type of iron-dependent regulated cell death, representing an emerging disease-modulatory mechanism. Transcription factors play multiple roles in ferroptosis, although the key regulator for ferroptosis in iron metabolism remains elusive. Using NanoString technology, we identify NUPR1, a stress-inducible transcription factor, as a driver of ferroptosis resistance. Mechanistically, NUPR1-mediated LCN2 expression blocks ferroptotic cell death through diminishing iron accumulation and subsequent oxidative damage. Consequently, LCN2 depletion mimics NUPR1 deficiency with respect to ferroptosis induction, whereas transfection-enforced re-expression of LCN2 restores resistance to ferroptosis in NUPR1-deficient cells. Pharmacological or genetic blockade of the NUPR1-LCN2 pathway (using NUPR1 shRNA, LCN2 shRNA, pancreas-specific Lcn2 conditional knockout mice, or the small molecule ZZW-115) increases the activity of the ferroptosis inducer erastin and worsens pancreatitis, in suitable mouse models. These findings suggest a link between NUPR1-regulated iron metabolism and ferroptosis susceptibility.
Cryptic terrestrial fungus-like fossils of the early Ediacaran Period
Authors: Gan Tian , Luo Taiyi , Pang Ke , Zhou Chuanming , Zhou Guanghong , Wan Bin , Li Gang , Yi Qiru , Czaja Andrew D. , Xiao Shuhai
Published: January 2021

The colonization of land by fungi had a significant impact on the terrestrial ecosystem and biogeochemical cycles on Earth surface systems. Although fungi may have diverged ~1500–900 million years ago (Ma) or even as early as 2400 Ma, it is uncertain when fungi first colonized the land. Here we report pyritized fungus-like microfossils preserved in the basal Ediacaran Doushantuo Formation (~635 Ma) in South China. These micro-organisms colonized and were preserved in cryptic karstic cavities formed via meteoric water dissolution related to deglacial isostatic rebound after the terminal Cryogenian snowball Earth event. They are interpreted as eukaryotes and probable fungi, thus providing direct fossil evidence for the colonization of land by fungi and offering a key constraint on fungal terrestrialization.
Impact of seed color and storage time on the radish seed germination and sprout growth in plasma agriculture
Authors: Attri Pankaj , Ishikawa Kenji , Okumura Takamasa , Koga Kazunori , Shiratani Masaharu , Mildaziene Vida
Published: January 2021

The use of low-temperature plasma for the pre-sowing seed treatment is still in the early stage of research; thus, numerous factors affecting germination percentage, seedling growth, and yield remains unknown. This study aimed to estimate how two critical factors, such as harvest year and seed coat color, affect the percentage of germination and seedling growth after plasma treatment. Radish seeds stored for 2 and 1 year after harvesting (harvested in 2017 and 2018) were sorted into two colors (brown and grey) to investigate the plasma effect on harvest year and seed coat color. We analyzed the amounts of seed phytohormones and antioxidant (γ-tocopherol) were analyzed using mass spectrometry, and physical changes were studied using SEM, EDX, and EPR to understand the mechanism of plasma-induced changes in radish seeds. The obtained results revealed that plasma treatment on seeds affects the germination kinetics, and the maximal germination percentage depends on seed color and the time of seed storage after harvest. Through this study, for the first time, we demonstrated that physical and chemical changes in radish seeds after plasma treatment depends upon the seed color and harvest year. Positive effects of plasma treatment on growth are stronger for sprouts from seeds harvested in 2017 than in 2018. The plasma treatment effect on the sprouts germinated from grey seeds effect was stronger than sprouts from brown radish seeds. The amounts of gibberellin A3 and abscisic acid in control seeds strongly depended on the seed color, and plasma induced changes were better in grey seeds harvested in 2017. Therefore, this study reveals that Air scalar-DBD plasma's reactive oxygen and nitrogen species (RONS) can efficiently accelerate germination and growth in older seeds.
Valerian and valeric acid inhibit growth of breast cancer cells possibly by mediating epigenetic modifications
Authors: Shi Fengqin , Li Ya , Han Rui , Fu Alan , Wang Ronghua , Nusbaum Olivia , Qin Qin , Chen Xinyi , Hou Li , Zhu Yong
Published: January 2021

Valerian root (Valeriana officinalis) is a popular and widely available herbal supplement used to treat sleeping disorders and insomnia. The herb’s ability to ameliorate sleep dysfunction may signify an unexplored anti-tumorigenic effect due to the connection between circadian factors and tumorigenesis. Of particular interest are the structural similarities shared between valeric acid, valerian's active chemical ingredient, and certain histone deacteylase (HDAC) inhibitors, which imply that valerian may play a role in epigenetic gene regulation. In this study, we tested the hypothesis that the circadian-related herb valerian can inhibit breast cancer cell growth and explored epigenetic changes associated with valeric acid treatment. Our results showed that aqueous valerian extract reduced growth of breast cancer cells. In addition, treatment of valeric acid was associated with decreased breast cancer cell proliferation, migration, colony formation and 3D formation in vitro in a dose- and time-dependent manner, as well as reduced HDAC activity and a global DNA hypomethylation. Overall, these findings demonstrate that valeric acid can decrease the breast cancer cell proliferation possibly by mediating epigenetic modifications such as the inhibition of histone deacetylases and alterations of DNA methylation. This study highlights a potential utility of valeric acid as a novel HDAC inhibitor and a therapeutic agent in the treatment of breast cancer.
Clinical pattern of failure after a durable response to immune checkpoint inhibitors in non-small cell lung cancer patients
Authors: Heo Ja Yoon , Yoo Shin Hye , Suh Koung Jin , Kim Se Hyun , Kim Yu Jung , Ock Chan-Young , Kim Miso , Keam Bhumsuk , Kim Tae Min , Kim Dong-Wan , Heo Dae Seog , Lee Jong Seok
Published: January 2021

Although immune checkpoint inhibitors (ICIs) can induce durable responses in non-small-cell lung cancer (NSCLC) patients, a significant proportion of responders still experience progressive disease after a period of response. Limited data are available on the clinical patterns of acquired resistance (AR) to ICIs. Clinical and radiologic data from 125 NSCLC patients treated with anti-PD-1 or PD-L1 antibodies between 2011 and 2018 at two tertiary academic institutions were retrospectively reviewed. Overall, 63 (50.4%) patients experienced AR after ICI treatment in a median of 10.7 months. Among the 13 patients with a partial response with ICI, 12 (32.4%) had only lymph node progression. Most patients (n = 52, 82.5%) had one or two sites with progression (oligo-progression). The median overall survival (OS) after progression was significantly longer in the extrathoracic group than in the thoracic and liver progression groups (30.2 months [95% confidence interval (CI), 13.4 to not reached (NR)], 11.7 months [95% CI, 9.5–21.1], and 5.4 months [95% CI, 2.6-NR], respectively, P < 0.001). Patients with oligo-progression had significantly longer OS after AR than did the multi-progression patients (18.9 months [95% CI, 10.6-NR] vs. 8.8 months [95% CI, 5.7-NR], P = 0.04). No significant difference in progression-free survival was observed between the subsequent chemotherapy and the ICI after AR groups (P = 0.723). Patients with AR after ICI treatment had a unique progression pattern with oligo-progression and high rates of progression only in the lymph nodes. Local treatment and/or continuation of ICIs beyond AR might be an effective option.
The consequences of COVID-19 on social interactions: an online study on face covering
Authors: Calbi Marta , Langiulli Nunzio , Ferroni Francesca , Montalti Martina , Kolesnikov Anna , Gallese Vittorio , Umiltà Maria Alessandra
Published: January 2021

The COVID-19 pandemic has dramatically changed the nature of our social interactions. In order to understand how protective equipment and distancing measures influence the ability to comprehend others’ emotions and, thus, to effectively interact with others, we carried out an online study across the Italian population during the first pandemic peak. Participants were shown static facial expressions (Angry, Happy and Neutral) covered by a sanitary mask or by a scarf. They were asked to evaluate the expressed emotions as well as to assess the degree to which one would adopt physical and social distancing measures for each stimulus. Results demonstrate that, despite the covering of the lower-face, participants correctly recognized the facial expressions of emotions with a polarizing effect on emotional valence ratings found in females. Noticeably, while females’ ratings for physical and social distancing were driven by the emotional content of the stimuli, males were influenced by the “covered” condition. The results also show the impact of the pandemic on anxiety and fear experienced by participants. Taken together, our results offer novel insights on the impact of the COVID-19 pandemic on social interactions, providing a deeper understanding of the way people react to different kinds of protective face covering.
Concomitant improvement in anti-saccade success rate and postural instability gait difficulty after rTMS treatment for Parkinson’s disease
Authors: Okada Ken-ichi , Takahira Mizuki , Mano Tomoo , Uga Taichi , Konaka Kuni , Hosomi Koichi , Saitoh Youichi
Published: January 2021

Parkinson’s disease (PD) is a progressive neurological disorder characterised by motor and non-motor deficits. Repetitive transcranial magnetic stimulation (rTMS) over the bilateral primary motor cortex at a high frequency (5 Hz or higher) is reported to be a potential treatment of PD. We aimed to assess the effect of rTMS on eye movement control in patients with PD in their ‘on’ state. We enrolled 14 patients with PD and assessed motor symptoms (Movement Disorder Society-Sponsored Unified Parkinson’s Disease Rating Scale; MDS-UPDRS) and eye movement performances (visually guided saccades, volitional anti-saccades, and small involuntary saccades during fixation) at baseline and after administering bilateral 10 Hz rTMS on leg region of the motor cortex. We confirmed that rTMS improved the MDS-UPDRS motor scores and found that rTMS improved the anti-saccade success rate, which requires adequate inhibition of the reflexive response. The improvement in anti-saccade success rate was correlated with that of the postural instability gait difficulty (PIGD) sub-scores of MDS-UPDRS and lower baseline Japanese version of the Montreal Cognitive Assessment scores. This result is consistent with previous findings that PIGD and inhibitory control deficits share common brain dysfunctions in PD. rTMS may alleviate dysfunctions of that circuit and have a clinical effect.
Cardiac hypoxic resistance and decreasing lactate during maximum apnea in elite breath hold divers
Authors: Kjeld Thomas , Møller Jakob , Fogh Kristian , Hansen Egon Godthaab , Arendrup Henrik Christian , Isbrand Anders Brenøe , Zerahn Bo , Højberg Jens , Ostenfeld Ellen , Thomsen Henrik , Gormsen Lars Christian , Carlsson Marcus
Published: January 2021

Breath-hold divers (BHD) enduring apnea for more than 4 min are characterized by resistance to release of reactive oxygen species, reduced sensitivity to hypoxia, and low mitochondrial oxygen consumption in their skeletal muscles similar to northern elephant seals. The muscles and myocardium of harbor seals also exhibit metabolic adaptations including increased cardiac lactate-dehydrogenase-activity, exceeding their hypoxic limit. We hypothesized that the myocardium of BHD possesses similar adaptive mechanisms. During maximum apnea 15O-H2O-PET/CT (n = 6) revealed no myocardial perfusion deficits but increased myocardial blood flow (MBF). Cardiac MRI determined blood oxygen level dependence oxygenation (n = 8) after 4 min of apnea was unaltered compared to rest, whereas cine-MRI demonstrated increased left ventricular wall thickness (LVWT). Arterial blood gases were collected after warm-up and maximum apnea in a pool. At the end of the maximum pool apnea (5 min), arterial saturation decreased to 52%, and lactate decreased 20%. Our findings contrast with previous MR studies of BHD, that reported elevated cardiac troponins and decreased myocardial perfusion after 4 min of apnea. In conclusion, we demonstrated for the first time with 15O-H2O-PET/CT and MRI in elite BHD during maximum apnea, that MBF and LVWT increases while lactate decreases, indicating anaerobic/fat-based cardiac-metabolism similar to diving mammals.
A set of simple methods for detection and extraction of laminarinase
Authors: Koteshwara Ananthamurthy , Philip Nancy V. , Aranjani Jesil Mathew , Hariharapura Raghu Chandrashekhar , Volety Mallikarjuna Subrahmanyam
Published: January 2021

A carefully designed ammonium sulfate precipitation will simplify extraction of proteins and is considered to be a gold standard among various precipitation methods. Therefore, optimization of ammonium sulfate precipitation can be an important functional step in protein purification. The presence of high amounts of ammonium sulphate precludes direct detection of many enzymatically active proteins including reducing sugar assays (e.g. Nelson-Somogyi, Reissig and 3,5-dinitrosalicylic acid methods) for assessing carbohydrases (e.g. laminarinase (β (1–3)-glucanohydrolase), cellulases and chitinases). In this study, a simple method was developed using laminarin infused agarose plate for the direct analysis of the ammonium sulphate precipitates from Streptomyces rimosus AFM-1. The developed method is simple and convenient that can give accurate results even in presence of ammonium sulfate in the crude precipitates. Laminarin is a translucent substrate requiring the use of a stain to visualize the zones of hydrolysis in a plate assay. A very low-cost and locally available fluorescent optical fabric brightener Tinopal CBS-X has been used as a stain to detect the zones of hydrolysis. We also report simple methods to prepare colloidal chitin and cell free supernatant in this manuscript.
Assessment of the biological potential of diaryltriazene-derived triazene compounds
Authors: Figueirêdo Patricia de Maria Silva , Sampaio Filho José Costa , Sodré Alzirene de Jesus Sales , de Castro Júnior José Ribamar , Gonçalves Ingrid Santos , Blasques Rodrigo Vieira , S. Correa Rodrigo , Lima Benedicto Augusto Vieira , dos Anjos Marques Larissa , Coutinho Denise Fernandes , de Azevedo dos Santos Ana Paula Silva , Luz Tássio Rômulo Silva Araújo , de Miranda Rita de Cassia Mendonça , dos Santos Julliana Ribeiro Alves , Doriguetto Antonio Carlos , Pividori María Isabel , Hörner Manfredo , Villis Paulo Cesar Mendes
Published: January 2021

In the present study, novel, 1,3-diaryltriazene-derived triazene compounds were synthesized and tested. Triazenes are versatile and belong to a group of alkylating agents with interesting physicochemical properties and proven biological activities. This study describes the synthesis, molecular and crystalline structure, biological activity evaluation, and antifungal and antimicrobial potentials of 1,3-bis(X-methoxy-Y-nitrophenyl)triazenes [X = 2 and 5; Y = 4 and 5]. The antimicrobial and antifungal activities of the compounds were tested by evaluating the sensitivity of bacteria (American Type Culture Collection, ATCC) and clinical isolates to their solutions using standardized microbiological assays, cytotoxicity evaluation, and ecotoxicity tests. The antimicrobial potentials of triazenes were determined according to their minimum inhibitory concentrations (MICs); these compounds were active against gram-positive and gram-negative bacteria, with low MIC values. The most surprising result was obtained for T3 having the effective MIC of 9.937 µg/mL and antifungal activity against Candida albicans ATCC 90028, C. parapsilosis ATCC 22019, and C. tropicallis IC. To the best of our knowledge, this study is the first to report promising activities of triazene compounds against yeast and filamentous fungi. The results showed the potential utility of triazenes as agents affecting selected resistant bacterial and fungal strains.
Development and characterization of patient-derived xenografts from non-small cell lung cancer brain metastases
Authors: Baschnagel Andrew M. , Kaushik Saakshi , Durmaz Arda , Goldstein Steve , Ong Irene M. , Abel Lindsey , Clark Paul A. , Gurel Zafer , Leal Ticiana , Buehler Darya , Iyer Gopal , Scott Jacob G. , Kimple Randall J.
Published: January 2021

Non-small cell lung cancer (NSCLC) brain metastasis cell lines and in vivo models are not widely accessible. Herein we report on a direct-from patient-derived xenograft (PDX) model system of NSCLC brain metastases with genomic annotation useful for translational and mechanistic studies. Both heterotopic and orthotopic intracranial xenografts were established and RNA and DNA sequencing was performed on patient and matching tumors. Morphologically, strong retention of cytoarchitectural features was observed between original patient tumors and PDXs. Transcriptome and mutation analysis revealed high correlation between matched patient and PDX samples with more than more than 95% of variants detected being retained in the matched PDXs. PDXs demonstrated response to radiation, response to selumetinib in tumors harboringKRASG12C mutations and response to savolitinib in a tumor withMETexon 14 skipping mutation. Savolitinib also demonstrated in vivo radiation enhancement in our MET exon 14 mutated PDX. Early passage cell strains showed high consistency between patient and PDX tumors. Together, these data describe a robust human xenograft model system for investigating NSCLC brain metastases. These PDXs and cell lines show strong phenotypic and molecular correlation with the original patient tumors and provide a valuable resource for testing preclinical therapeutics.
Non pharmacological high-intensity ultrasound treatment of human dermal fibroblasts to accelerate wound healing
Authors: Lee Jeong Yu , Min Dae-Jin , Kim Wanil , Bin Bum-Ho , Kim Kyuhan , Cho Eun-Gyung
Published: January 2021

Inspired by the effectiveness of low-intensity ultrasound on tissue regeneration, we investigated the potential effect of short-term high-intensity ultrasound treatment for acceleration of wound healing in an in vitro wound model and dermal equivalent, both comprising human dermal fibroblasts. Short-term ultrasound of various amplitudes significantly increased the proliferation and migration of fibroblasts and subsequently increased the production of the extracellular matrix components fibronectin and collagen type I, both of which are important for wound healing and are secreted by fibroblasts. In addition, ultrasound treatment increased the contraction of a fibroblast-embedded three-dimensional collagen matrix, and the effect was synergistically increased in the presence of TGF-β. RNA-sequencing and bioinformatics analyses revealed changes in gene expression and p38 and ERK1/2 MAPK pathway activation in the ultrasound-stimulated fibroblasts. Our findings suggest that ultrasound as a mechanical stimulus can activate human dermal fibroblasts. Therefore, the activation of fibroblasts using ultrasound may improve the healing of various types of wounds and increase skin regeneration.
Low serum calcium is associated with higher long-term mortality in myocardial infarction patients from a population-based registry
Authors: Schmitz Timo , Thilo Christian , Linseisen Jakob , Heier Margit , Peters Annette , Kuch Bernhard , Meisinger Christa
Published: January 2021

Calcium plays an essential role in physiology of the cardiovascular system. Aberrations from normal serum calcium levels are known to be associated with several cardiovascular diseases. Its possible role as a predictor for long-term mortality after acute myocardial infarction (AMI) is still uncertain. In this study, a total of 3732 patients (aged 25–74 years) with incident AMI surviving at least 28 days after AMI was included. The median follow-up time was 6.0 years. Admission total serum calcium levels were divided into quartiles. The Kaplan–Meier-Curve suggested a division of the follow up time in two different time periods. So, Cox regression models were calculated to assess association between admission serum calcium levels and all-cause long-term mortality with two observation periods: 28–2500 days and > 2500 days. The final model was adjusted for various comorbidities, clinical characteristics, in-hospital treatment and medication. The third quartile (normal-high Calcium levels) served as the reference group. The fully adjusted Cox-regression model shows significantly higher mortality risk for low serum calcium (quartile 1) within the timeframe 28–2500 days after the event (OR 1.53 [1.19–1.98]). The other groups did not differ significantly from each other. In the later observation period (from 2500 days until death or censoring) no more significant differences were seen between the four calcium quartiles. In summary, low serum calcium is an independent predictor of adverse outcome in the first 2500 days (about 7 years) after AMI. On later points in time this effect attenuates, so that no more significant differences can be observed.
Unhealthy life habits associated with self-induced vomiting and laxative misuse in Brazilian adolescents
Authors: de Souza Ana Luiza Gomes , de Almeida Alexandre Aparecido , Noll Priscilla Rayanne E. Silva , Noll Matias
Published: January 2021

Adolescence is a stage in life characterized by important social, cognitive, and physical changes. Adolescents are vulnerable to various psychosocial disorders, including eating disorders. We aimed to investigate the association between unhealthy habits, sociodemographic characteristics, and the practice of self-induced vomiting or laxative misuse in a representative sample of Brazilian adolescent girls and boys. Data from 102,072 students who participated in the National Adolescent School-based Health Survey were analyzed using the dependent variable: presence or absence of self-induced vomiting and/or laxative misuse; independent variables: consumption of unhealthy and high-calorie food items, age during first sexual intercourse, and the use of tobacco, alcohol, and/or illicit drugs. Associations between exposure and outcome were estimated using Poisson’s regression models stratified by sex, and including region, school, age group, and mother's educational history as adjustment variables. Eating ultra-processed foods and age during first sexual intercourse were associated with self-induced vomiting and laxative misuse only for girls; all other variables (consuming unhealthy foods and using legal or illicit substances) were associated with these behaviors for both sexes after applying adjustment variables. Early interventions focusing on changing unhealthy behaviors may prevent development of eating disorders in adolescents. Our findings demonstrate a strong association of many unhealthy habits with laxative misuse and self-induced vomiting practices in Brazilian adolescents.
Construction of a TF–miRNA–gene feed-forward loop network predicts biomarkers and potential drugs for myasthenia gravis
Authors: Bo Chunrui , Zhang Huixue , Cao Yuze , Lu Xiaoyu , Zhang Cong , Li Shuang , Kong Xiaotong , Zhang Xiaoming , Bai Ming , Tian Kuo , Saitgareeva Aigul , Lyaysan Gaysina , Wang Jianjian , Ning Shangwei , Wang Lihua
Published: January 2021

Myasthenia gravis (MG) is an autoimmune disease and the most common type of neuromuscular disease. Genes and miRNAs associated with MG have been widely studied; however, the molecular mechanisms of transcription factors (TFs) and the relationship among them remain unclear. A TF–miRNA–gene network (TMGN) of MG was constructed by extracting six regulatory pairs (TF–miRNA, miRNA–gene, TF–gene, miRNA–TF, gene–gene and miRNA–miRNA). Then, 3/4/5-node regulatory motifs were detected in the TMGN. Then, the motifs with the highest Z-score, occurring as 3/4/5-node composite feed-forward loops (FFLs), were selected as statistically significant motifs. By merging these motifs together, we constructed a 3/4/5-node composite FFL motif-specific subnetwork (CFMSN). Then, pathway and GO enrichment analyses were performed to further elucidate the mechanism of MG. In addition, the genes, TFs and miRNAs in the CFMSN were also utilized to identify potential drugs. Five related genes, 3 TFs and 13 miRNAs, were extracted from the CFMSN. As the most important TF in the CFMSN, MYC was inferred to play a critical role in MG. Pathway enrichment analysis showed that the genes and miRNAs in the CFMSN were mainly enriched in pathways related to cancer and infections. Furthermore, 21 drugs were identified through the CFMSN, of which estradiol, estramustine, raloxifene and tamoxifen have the potential to be novel drugs to treat MG. The present study provides MG-related TFs by constructing the CFMSN for further experimental studies and provides a novel perspective for new biomarkers and potential drugs for MG.
Social isolation enhances cued-reinstatement of sucrose and nicotine seeking, but this is reversed by a return to social housing
Authors: Mastrogiovanni Natalie A. , Wheeler Alice K. , Clemens Kelly J.
Published: January 2021

Physical or perceived (i.e. loneliness) social isolation is increasing in Western cultures. Unfortunately, social isolation is associated with a range of negative physical and mental health outcomes, including increased incidence of obesity and smoking. Here we monitored the impact of social isolation on a range of physical measures, and then tested whether social isolation in adult rats changes how reward-related stimuli motivate sucrose- or nicotine-seeking. Socially isolated rats showed elevated baseline CORT, gained significantly less weight across the study, were more active in response to a novel or familiar environment. Isolated rats also acquired nose-poking for a food pellet more rapidly, and showed increased susceptibility to cue-, but not reward-induced reinstatement. Notably, these effects are partially mitigated by a return to group housing, suggesting that they are not necessarily permanent, and that a return to a social setting can quickly reverse any deficits or changes associated with social isolation. This study advances our understanding of altered reward-processing in socially isolated individuals and reiterates the importance of socialisation in the treatment of disorders such as overeating and addiction.
Development and characterization of GR2E Golden rice introgression lines
Authors: Mallikarjuna Swamy B. P. , Marundan Severino , Samia Mercy , Ordonio Reynante L. , Rebong Democrito B. , Miranda Ronalyn , Alibuyog Anielyn , Rebong Anna Theresa , Tabil Ma. Angela , Suralta Roel R. , Alfonso Antonio A. , Biswas Partha Sarathi , Kader Md. Abdul , Reinke Russell F. , Boncodin Raul , MacKenzie Donald J.
Published: January 2021

Golden Rice with β-carotene in the grain helps to address the problem of vitamin A deficiency. Prior to commercialize Golden Rice, several performance and regulatory checkpoints must be achieved. We report results of marker assisted backcross breeding of the GR2E trait into three popular rice varieties followed by a series of confined field tests of event GR2E introgression lines to assess their agronomic performance and carotenoid expression. Results from confined tests in the Philippines and Bangladesh have shown that GR2E introgression lines matched the performance of the recurrent parents for agronomic and yield performance, and the key components of grain quality. Moreover, no differences were observed in terms of pest and disease reaction. The best performing lines identified in each genetic background had significant amounts of carotenoids in the milled grains. These lines can supply 30–50% of the estimated average requirements of vitamin A.
Correlated flickering of erythrocytes membrane observed with dual time resolved membrane fluctuation spectroscopy under different d-glucose concentrations
Authors: Tapia J. , Vera N. , Aguilar Joao , González M. , Sánchez S. A. , Coelho P. , Saavedra C. , Staforelli J.
Published: January 2021

A correlated human red blood cell membrane fluctuation dependent on d-glucose concentration was found with dual time resolved membrane fluctuation spectroscopy (D-TRMFS). This new technique is a modified version of the dual optical tweezers method that has been adapted to measure the mechanical properties of red blood cells (RBCs) at distant membrane points simultaneously, enabling correlation analysis. Mechanical parameters under different d-glucose concentrations were obtained from direct membrane flickering measurements, complemented with membrane fluidity measurements using Laurdan Generalized Polarization (GP) Microscopy. Our results show an increase in the fluctuation amplitude of the lipid bilayer, and a decline in tension value, bending modulus and fluidity as d-glucose concentration increases. Metabolic mechanisms are proposed as explanations for the results.
A translation enhancer element from black beetle virus engages yeast eIF4G1 to drive cap-independent translation initiation
Authors: Trainor Brandon M. , Ghosh Arnab , Pestov Dimitri G. , Hellen Christopher U. T. , Shcherbik Natalia
Published: January 2021

Cap-independent translation initiation plays crucial roles in fine-tuning gene expression under global translation shutdown conditions. Translation of uncapped or de-capped transcripts can be stimulated by Cap-independent translation enhancer (CITE) elements, but the mechanisms of CITE-mediated translation initiation remain understudied. Here, we characterized a short 5ʹ-UTR RNA sequence from black beetle virus, BBV-seq. Mutational analysis indicates that the entire BBV-seq is required for efficient translation initiation, but this sequence does not operate as an IRES-type module. In yeast cell-free translation extracts, BBV-seq promoted efficient initiation on cap-free mRNA using a scanning mechanism. Moreover, BBV-seq can increase translation efficiency resulting from conventional cap-dependent translation initiation. Using genetic approaches, we found that BBV-seq exploits RNA-binding properties of eIF4G1 to promote initiation. Thus, BBV-seq constitutes a previously uncharacterized short, linear CITE that influences eIF4G1 to initiate 5′ end-dependent, cap-independent translation. These findings bring new insights into CITE-mediated translational control of gene expression.
Influence of levels of automation on the sense of agency during continuous action
Authors: Ueda Sayako , Nakashima Ryoichi , Kumada Takatsune
Published: January 2021

Recent advances in automation technology can lead to unsafe situations where operators lose their sense of agency over the automated equipment. On the other hand, increasing evidence has shown that providing operators with opportunities of continuous operation and helping them improve their performance on tasks through automation can boost their sense of agency. However, it is challenging to ensure that the operator maintains a sense of agency when working with a fully automated tool that removes him/her from the control loop. By demonstrating a tracking task in which participants continuously tracked a moving target through a cursor controlled by a joystick under different levels of automation, we illustrate how the participants’ sense of agency and tracking performance were altered in accordance with the level of automation. The results showed that their sense of agency was enhanced by increasing automation but began to decline when the level of automation exceeded 90%. More generally, this suggests that allowing operators a little contribution to control over the continuous operation of an automated tool may be sufficient to maintain their sense of agency while yielding the maximum improvement in performance.