bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond the COVID-19 pandemic: ‘Learning the hard way’ – adapting long-term IAPT service provision using lessons from past outbreaks
Authors: Skilbeck Lilian , Spanton Christopher , Roylance Ian
Published: August 2020

Infectious disease outbreaks have occurred sporadically over the centuries. The most significant ones of this century, as reported by the World Health Organization, include the EVD epidemic, SARS pandemic, Swine Flu pandemic and MERS pandemic. The long-term mental health consequences of outbreaks are as profound as physical ones and can last for years post-outbreak. This highlights the need for enhancing the preparedness of pragmatic mental health service provision. Due to its magnitude, the novel COVID-19 pandemic has proven to be the most impactful. Compared with previous outbreaks, COVID-19 has also occurred at higher rates in frontline staff in addition to patients. As COVID-19 is more contagious than earlier outbreaks, there is a need to identify infected people quickly and isolate them and their contacts. This is the current context in which mental health services including IAPT have had to operate. Evidently, Improving Access to Psychological Therapies (IAPT) services are a major mental health service provider in the UK that have demonstrated variability in their response to COVID-19. While some IAPT services quickly adapted their existing strengths and resources (e.g. remote working), other services were less prepared. To date, there are no clear unitary guidelines on how IAPT services can use their pre-existing resources to respond to the long-term effects of outbreaks. In light of this, the current paper aims to reflect on the lessons learned from past outbreaks in order to consider how an enhanced remit of IAPT might integrate with other services to meet the long-term needs of patients and staff affected by COVID-19.

Key learning aims

(1)

To understand the development of IAPT within the NHS mental health services.

(2)

To understand the nature of past outbreaks and COVID-19.

(3)

To reflect on lessons from past outbreaks in order to understand how IAPT can respond to the long-term effects of COVID-19.
Effective two-pass herbicide programs to control glyphosate-resistant Palmer amaranth (Amaranthus palmeri) in glyphosate/dicamba-resistant soybean
Authors: Kumar Vipan , Liu Rui , Peterson Dallas E. , Stahlman Phillip W.
Published: August 2020

Field experiments were conducted in 2018 and 2019 at Kansas State University Ashland Bottoms (KSU-AB) research farm near Manhattan, KS, and Kansas State University Agricultural Research Center (KSU-ARC) near Hays, KS, to determine the effectiveness of various PRE-applied herbicide premixes and tank mixtures alone or followed by (fb) an early POST (EPOST) treatment of glyphosate + dicamba for controlling glyphosate-resistant (GR) Palmer amaranth in glyphosate/dicamba-resistant (GDR) soybean. In experiment 1, PRE-applied sulfentrazone + S-metolachlor, saflufenacil + imazethapyr + pyroxasulfone, chlorimuron + flumioxazin + pyroxasulfone, and metribuzin + flumioxazin + imazethapyr provided 85% to 94% end-of-season control of GR Palmer amaranth across both sites. In comparison, Palmer amaranth control ranged from 63% to 87% at final evaluation with PRE-applied pyroxasulfone + sulfentrazone, pyroxasulfone + sulfentrazone plus metribuzin, pyroxasulfone + sulfentrazone plus carfentrazone + sulfentrazone, and sulfentrazone + metribuzin at the KSU-ARC site in experiment 2. All PRE fb EPOST (i.e., two-pass) programs provided near-complete (98% to 100%) control of GR Palmer amaranth at both sites. PRE-alone programs reduced Palmer amaranth shoot biomass by 35% to 76% in experiment 1 at both sites, whereas all two-pass programs prevented Palmer amaranth biomass production. No differences in soybean yields were observed among tested programs in experiment 1 at KSU-ARC site; however, PRE-alone sulfentrazone + S-metolachlor, saflufenacil + imazethapyr + pyroxasulfone, and chlorimuron + flumioxazin + pyroxasulfone had lower grain yield (average, 4,342 kg ha−1) compared with the top yielding (4,832 kg ha−1) treatment at the KSU-AB site. PRE-applied sulfentrazone + metribuzin had a lower soybean yield (1,776 kg ha−1) compared with all other programs in experiment 2 at the KSU-ARC site. These results suggest growers should proactively adopt effective PRE-applied premixes fb EPOST programs evaluated in this study to reduce selection pressure from multiple POST dicamba applications for GR Palmer amaranth control in GDR soybean.
A CRISPR knockout negative screen reveals synergy between CDKs inhibitor and metformin in the treatment of human cancer in vitro and in vivo
Authors: Ma Yarui , Zhu Qing , Liang Junbo , Li Yifei , Li Mo , Zhang Ying , Wang Xiaobing , Zeng Yixin , Jiao Yuchen
Published: August 2020

Laboratory research and pharmacoepidemiology provide support for metformin as a potential antitumor agent. However, the lack of a clear understanding of the indications of metformin limits its efficacy. Here, we performed a genome-wide CRISPR knockout negative screen to identify potential targets that might synergize with metformin. Next-generation sequencing of pooled genomic DNAs isolated from surviving cells after 18 days of metformin treatment (T18) compared to those of the untreated cells at day 0 (T0) yielded candidate genes. Knockdown of a group of cyclin-dependent kinases (CDKs), including CDK1, CDK4, and CDK6, confirmed the results of the screen. Combination treatment of the CDKs inhibitor abemaciclib with metformin profoundly inhibited tumor viability in vitro and in vivo. Although cell cycle parameters were not further altered under the combination treatment, investigation of the metabolome revealed significant changes in cell metabolism, especially with regard to fatty acid oxidation, the tricarboxylic acid cycle and aspartate metabolism. Such changes appeared to be mediated through inhibition of the mTOR pathway. Collectively, our study suggests that the combination of CDKs inhibitor with metformin could be recognized as a potential therapy in future clinical applications.
LXA4-FPR2 signaling regulates radiation-induced pulmonary fibrosis via crosstalk with TGF-β/Smad signaling
Authors: Kim Hyunjung , Park Sung-Hyo , Han Song Yee , Lee Yun-Sil , Cho Jaeho , Kim Jin-Mo
Published: August 2020

Radiation therapy is an important modality in the treatment of lung cancer, but it can lead to radiation pneumonitis, and eventually radiation fibrosis. To date, only few available drugs can effectively manage radiation-induced pulmonary fibrosis. Lipoxins are endogenous molecules exhibit anti-inflammatory and pro-resolving effects. These molecules play a vital role in reducing excessive tissue injury and chronic inflammation; however, their effects on radiation-induced lung injury (RILI) are unknown. In this study, we investigated the effects of lipoxin A4 (LXA4) on RILI using our specialized small-animal model of RILI following focal-ablative lung irradiation (IR). LXA4 significantly inhibited immune-cell recruitment and reduced IR-induced expression of pro-inflammatory cytokines and fibrotic proteins in the lung lesion sites. In addition, micro-CT revealed that LXA4 reduced IR-induced increases in lung consolidation volume. The flexiVentTM assays showed that LXA4 significantly reversed IR-induced lung function damage. Moreover, LXA4 downregulated the activities of NF-κB and the Smad-binding element promoters. The expression of FPR2, an LXA4 receptor, increased during the development of IR-induced pulmonary fibrosis, whereas silencing of endogenous LXA4 using an antagonist (WRW4) or FPR2 siRNA resulted in impaired development of pulmonary fibrosis in response to IR. Collectively, these data suggest that LXA4 could serve as a potent therapeutic agent for alleviating RILI.
MICAL2 is essential for myogenic lineage commitment
Authors: Giarratana Nefele , Conti Filippo , La Rovere Rita , Gijsbers Rik , Carai Paolo , Duelen Robin , Vervliet Tim , Bultynck Geert , Ronzoni Flavio , Piciotti Roberto , Costamagna Domiziana , Fulle Stefania , Barravecchia Ivana , Angeloni Debora , Torrente Yvan , Sampaolesi Maurilio
Published: August 2020

Contractile myofiber units are mainly composed of thick myosin and thin actin (F-actin) filaments. F-Actin interacts with Microtubule Associated Monooxygenase, Calponin And LIM Domain Containing 2 (MICAL2). Indeed, MICAL2 modifies actin subunits and promotes actin filament turnover by severing them and preventing repolymerization. In this study, we found that MICAL2 increases during myogenic differentiation of adult and pluripotent stem cells (PSCs) towards skeletal, smooth and cardiac muscle cells and localizes in the nucleus of acute and chronic regenerating muscle fibers. In vivo delivery of Cas9–Mical2 guide RNA complexes results in muscle actin defects and demonstrates that MICAL2 is essential for skeletal muscle homeostasis and functionality. Conversely, MICAL2 upregulation shows a positive impact on skeletal and cardiac muscle commitments. Taken together these data demonstrate that modulations of MICAL2 have an impact on muscle filament dynamics and its fine-tuned balance is essential for the regeneration of muscle tissues.
Inhibition of HDAC increases BDNF expression and promotes neuronal rewiring and functional recovery after brain injury
Authors: Sada Naoki , Fujita Yuki , Mizuta Nanano , Ueno Masaki , Furukawa Takahisa , Yamashita Toshihide
Published: August 2020

Brain injury causes serious motor, sensory, and cognitive disabilities. Accumulating evidence has demonstrated that histone deacetylase (HDAC) inhibitors exert neuroprotective effects against various insults to the central nervous system (CNS). In this study, we investigated the effects of the HDAC inhibition on the expression of brain-derived neurotrophic factor (BDNF) and functional recovery after traumatic brain injury (TBI) in mice. Administration of class I HDAC inhibitor increased the number of synaptic boutons in rewiring corticospinal fibers and improved the recovery of motor functions after TBI. Immunohistochemistry results showed that HDAC2 is mainly expressed in the neurons of the mouse spinal cord under normal conditions. After TBI, HDAC2 expression was increased in the spinal cord after 35 days, whereas BDNF expression was decreased after 42 days. Administration of CI-994 increased BDNF expression after TBI. Knockdown of HDAC2 elevated H4K5ac enrichment at the BDNF promoter, which was decreased following TBI. Together, our findings suggest that HDAC inhibition increases expression of neurotrophic factors, and promote neuronal rewiring and functional recovery following TBI.
Chlorpromazine eliminates acute myeloid leukemia cells by perturbing subcellular localization of FLT3-ITD and KIT-D816V
Authors: Rai Shinya , Tanaka Hirokazu , Suzuki Mai , Espinoza J. Luis , Kumode Takahiro , Tanimura Akira , Yokota Takafumi , Oritani Kenji , Watanabe Toshio , Kanakura Yuzuru , Matsumura Itaru
Published: August 2020

Mutated receptor tyrosine kinases (MT-RTKs) such as internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3 ITD) and a point mutation KIT D816V are driver mutations for acute myeloid leukemia (AML). Clathrin assembly lymphoid myeloid leukemia protein (CALM) regulates intracellular transport of RTKs, however, the precise role for MT-RTKs remains elusive. We here show that CALM knock down leads to severely impaired FLT3 ITD- or KIT D814V-dependent cell growth compared to marginal influence on wild-type FLT3- or KIT-mediated cell growth. An antipsychotic drug chlorpromazine (CPZ) suppresses the growth of primary AML samples, and human CD34+CD38- AML cells including AML initiating cells with MT-RTKs in vitro and in vivo. Mechanistically, CPZ reduces CALM protein at post transcriptional level and perturbs the intracellular localization of MT-RTKs, thereby blocking their signaling. Our study presents a therapeutic strategy for AML with MT-RTKs by altering the intracellular localization of MT-RTKs using CPZ.
Petahertz non-linear current in a centrosymmetric organic superconductor
Authors: Kawakami Y. , Amano T. , Ohashi H. , Itoh H. , Nakamura Y. , Kishida H. , Sasaki T. , Kawaguchi G. , Yamamoto H. M. , Yamamoto K. , Ishihara S. , Yonemitsu K. , Iwai S.
Published: August 2020

Charge acceleration during an intense light field application to solids attracts much attention as elementary processes in high-harmonic generation and photoelectron emission. For manipulating such attosecond dynamics of charge, carrier-envelope-phase (CEP: relative phase between carrier oscillation of light field and its envelope function) control has been employed in insulators, nanometal and graphene. In superconducting materials, collective control of charge motion is expected because of its strongly coherent nature of quasi-particles. Here we report that, in a layered organic superconductor, a non-linear petahertz current driven by a single-cycle 6 femtosecond near infrared field shows up as second harmonic generation (SHG), which is in contrast to the common belief that even harmonics are forbidden in the centrosymmetric system. The SHG represents a CEP sensitive nature and an enhancement near the superconducting temperature. The result and its quantum many-body analysis indicate that a polarized current is induced by non-linear acceleration of charge, which is amplified by superconducting fluctuations. This will lead to petahertz functions of superconductors and of strongly correlated systems.
Influenza A virus is transmissible via aerosolized fomites
Authors: Asadi Sima , Gaaloul ben Hnia Nassima , Barre Ramya S. , Wexler Anthony S. , Ristenpart William D. , Bouvier Nicole M.
Published: August 2020

Influenza viruses are presumed, but not conclusively known, to spread among humans by several possible routes. We provide evidence of a mode of transmission seldom considered for influenza: airborne virus transport on microscopic particles called “aerosolized fomites.” In the guinea pig model of influenza virus transmission, we show that the airborne particulates produced by infected animals are mainly non-respiratory in origin. Surprisingly, we find that an uninfected, virus-immune guinea pig whose body is contaminated with influenza virus can transmit the virus through the air to a susceptible partner in a separate cage. We further demonstrate that aerosolized fomites can be generated from inanimate objects, such as by manually rubbing a paper tissue contaminated with influenza virus. Our data suggest that aerosolized fomites may contribute to influenza virus transmission in animal models of human influenza, if not among humans themselves, with important but understudied implications for public health.
Natural variation at FLM splicing has pleiotropic effects modulating ecological strategies in Arabidopsis thaliana
Authors: Hanemian Mathieu , Vasseur François , Marchadier Elodie , Gilbault Elodie , Bresson Justine , Gy Isabelle , Violle Cyrille , Loudet Olivier
Published: August 2020

Investigating the evolution of complex phenotypes and the underlying molecular bases of their variation is critical to understand how organisms adapt to their environment. Applying classical quantitative genetics on a segregating population derived from a Can-0xCol-0 cross, we identify the MADS-box transcription factor FLOWERING LOCUS M (FLM) as a player of the phenotypic variation in plant growth and color. We show that allelic variation at FLM modulates plant growth strategy along the leaf economics spectrum, a trade-off between resource acquisition and resource conservation, observable across thousands of plant species. Functional differences at FLM rely on a single intronic substitution, disturbing transcript splicing and leading to the accumulation of non-functional FLM transcripts. Associations between this substitution and phenotypic and climatic data across Arabidopsis natural populations, show how noncoding genetic variation at a single gene might be adaptive through pleiotropic effects.
Femtosecond X-ray emission study of the spin cross-over dynamics in haem proteins
Authors: Kinschel Dominik , Bacellar Camila , Cannelli Oliviero , Sorokin Boris , Katayama Tetsuo , Mancini Giulia F. , Rouxel Jérémy R. , Obara Yuki , Nishitani Junichi , Ito Hironori , Ito Terumasa , Kurahashi Naoya , Higashimura Chika , Kudo Shotaro , Keane Theo , Lima Frederico A. , Gawelda Wojciech , Zalden Peter , Schulz Sebastian , Budarz James M. , Khakhulin Dmitry , Galler Andreas , Bressler Christian , Milne Christopher J. , Penfold Thomas , Yabashi Makina , Suzuki Toshinori , Misawa Kazuhiko , Chergui Majed
Published: August 2020

In haemoglobin the change from the low-spin (LS) hexacoordinated haem to the high spin (HS, S = 2) pentacoordinated domed deoxy-myoglobin (deoxyMb) form upon ligand detachment from the haem and the reverse process upon ligand binding are what ultimately drives the respiratory function. Here we probe them in the case of Myoglobin-NO (MbNO) using element- and spin-sensitive femtosecond Fe Kα and Kβ X-ray emission spectroscopy at an X-ray free-electron laser (FEL). We find that the change from the LS (S = 1/2) MbNO to the HS haem occurs in ~800 fs, and that it proceeds via an intermediate (S = 1) spin state. We also show that upon NO recombination, the return to the planar MbNO ground state is an electronic relaxation from HS to LS taking place in ~30 ps. Thus, the entire ligand dissociation-recombination cycle in MbNO is a spin cross-over followed by a reverse spin cross-over process.
Gene editing and elimination of latent herpes simplex virus in vivo
Authors: Aubert Martine , Strongin Daniel E. , Roychoudhury Pavitra , Loprieno Michelle A. , Haick Anoria K. , Klouser Lindsay M. , Stensland Laurence , Huang Meei-Li , Makhsous Negar , Tait Alexander , De Silva Feelixge Harshana S. , Galetto Roman , Duchateau Philippe , Greninger Alexander L. , Stone Daniel , Jerome Keith R.
Published: August 2020

We evaluate gene editing of HSV in a well-established mouse model, using adeno-associated virus (AAV)-delivered meganucleases, as a potentially curative approach to treat latent HSV infection. Here we show that AAV-delivered meganucleases, but not CRISPR/Cas9, mediate highly efficient gene editing of HSV, eliminating over 90% of latent virus from superior cervical ganglia. Single-cell RNA sequencing demonstrates that both HSV and individual AAV serotypes are non-randomly distributed among neuronal subsets in ganglia, implying that improved delivery to all neuronal subsets may lead to even more complete elimination of HSV. As predicted, delivery of meganucleases using a triple AAV serotype combination results in the greatest decrease in ganglionic HSV loads. The levels of HSV elimination observed in these studies, if translated to humans, would likely significantly reduce HSV reactivation, shedding, and lesions. Further optimization of meganuclease delivery and activity is likely possible, and may offer a pathway to a cure for HSV infection.
High intensity training during spaceflight: results from the NASA Sprint Study
Authors: English Kirk L. , Downs Meghan , Goetchius Elizabeth , Buxton Roxanne , Ryder Jeffrey W. , Ploutz-Snyder Robert , Guilliams Mark , Scott Jessica M. , Ploutz-Snyder Lori L.
Published: August 2020

Historically, International Space Station (ISS) exercise countermeasures have not fully protected astronauts’ musculoskeletal and cardiorespiratory fitness. Although these losses have been reduced on more recent missions, decreasing the time required to perform in-flight exercise would permit reallocation of that time to other tasks. To evaluate the effectiveness of a new training prescription, ISS crewmembers performed either the high intensity/lower volume integrated Sprint resistance (3 d wk−1) and aerobic (interval and continuous workouts, each 3 d wk−1 in alternating fashion) exercise program (n = 9: 8M/1F, 48 ± 7 y, 178 ± 5 cm, 77.7 ± 12.0 kg) or the standard ISS countermeasure consisting of daily resistance and aerobic exercise (n = 17: 14M/3F, 46 ± 6 y, 176 ± 6 cm, 80.6 ± 10.5 kg) during long-duration spaceflight. Bone mineral density (dual energy X-ray absorptiometry (DXA)), muscle strength (isokinetic dynamometry), muscle function (cone agility test), and cardiorespiratory fitness (VO2peak) were assessed pre- and postflight. Mixed-effects modeling was used to analyze dependent measures with alpha set at P < 0.05. After spaceflight, femoral neck bone mineral density (−1.7%), knee extensor peak torque (−5.8%), cone agility test time (+7.4%), and VO2peak (−6.1%) were decreased in both groups (simple main effects of time, all P < 0.05) with a few group × time interaction effects detected for which Sprint experienced either attenuated or no loss compared to control. Although physiologic outcomes were not appreciably different between the two exercise programs, to conserve time and optimally prepare crewmembers for the performance of physically demanding mission tasks, high intensity/lower volume training should be an indispensable component of spaceflight exercise countermeasure prescriptions.
Band gap crossover and insulator–metal transition in the compressed layered CrPS4
Authors: Susilo Resta A. , Jang Bo Gyu , Feng Jiajia , Du Qianheng , Yan Zhipeng , Dong Hongliang , Yuan Mingzhi , Petrovic Cedomir , Shim Ji Hoon , Kim Duck Young , Chen Bin
Published: August 2020

Two-dimensional van der Waals (vdW) magnetic materials have emerged as possible candidates for future ultrathin spintronic devices, and finding a way to tune their physical properties is desirable for wider applications. Owing to the sensitivity and tunability of the physical properties to the variation of interatomic separations, this class of materials is attractive to explore under pressure. Here, we present the observation of direct to indirect band gap crossover and an insulator–metal transition in the vdW antiferromagnetic insulator CrPS4 under pressure through in-situ photoluminescence, optical absorption, and resistivity measurements. Raman spectroscopy experiments revealed no changes in the spectral feature during the band gap crossover whereas the insulator–metal transition is possibly driven by the formation of the high-pressure crystal structure. Theoretical calculations suggest that the band gap crossover is driven by the shrinkage and rearrangement of the CrS6 octahedra under pressure. Such high tunability under pressure demonstrates an interesting interplay between structural, optical and magnetic degrees of freedom in CrPS4, and provides further opportunity for the development of devices based on tunable properties of 2D vdW magnetic materials.
A framework for monitoring the safety of water services: from measurements to security
Authors: Charles Katrina J. , Nowicki Saskia , Bartram Jamie K.
Published: August 2020

The sustainable developments goals (SDGs) introduced monitoring of drinking water quality to the international development agenda. At present, Escherichia coli are the primary measure by which we evaluate the safety of drinking water from an infectious disease perspective. Here, we propose and apply a framework to reflect on the purposes of and approaches to monitoring drinking water safety. To deliver SDG 6.1, universal access to safe drinking water, a new approach to monitoring is needed. At present, we rely heavily on single measures of E. coli contamination to meet a normative definition of safety. Achieving and sustaining universal access to safe drinking water will require monitoring that can inform decision making on whether services are managed to ensure safety and security of access.
Author Correction: Immunofluorescence can assess the efficacy of mTOR pathway therapeutic agent Everolimus in breast cancer models
Authors: Kuo Chun-Ting , Chen Chen-Lin , Li Chih-Chi , Huang Guan-Syuan , Ma Wei-Yuan , Hsu Wei-Fan , Lin Ching-Hung , Lu Yen-Shen , Wo Andrew M.
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Dual-modal magnetic resonance and photoacoustic tracking and outcome of transplanted tendon stem cells in the rat rotator cuff injury model
Authors: Cheng Xueqing , Xu Jinshun , Hu Ziyue , Jiang Jingzhen , Wang Zhigang , Lu Man
Published: August 2020

Stem cells have been used to promote the repair of rotator cuff injury, but their fate after transplantation is not clear. Therefore, contrast agents with good biocompatibility for labeling cell and a reliable technique to track cell are necessary. Here, we developed a micron-sized PLGA/IO MPs to label tendon stem cells (TSCs) and demonstrated that PLGA/IO MPs were safe and efficient for long-term tracking of TSCs by using dual-modal MR and Photoacoustic (PA) imaging both in vitro and in rat rotator cuff injury. Moreover, TSCs improved the repair of injury and the therapeutic effect was not affected by PLGA/IO MPs labeling. We concluded that PLGA/IO particle was a promising dual-modal MR/PA contrast for noninvasive long-term stem cell tracking.
Variational Hilbert Quantitative Phase Imaging
Authors: Trusiak Maciej , Cywińska Maria , Micó Vicente , Picazo-Bueno José Ángel , Zuo Chao , Zdańkowski Piotr , Patorski Krzysztof
Published: August 2020

Utilizing the refractive index as the endogenous contrast agent to noninvasively study transparent cells is a working principle of emerging quantitative phase imaging (QPI). In this contribution, we propose the Variational Hilbert Quantitative Phase Imaging (VHQPI)—end-to-end purely computational add-on module able to improve performance of a QPI-unit without hardware modifications. The VHQPI, deploying unique merger of tailored variational image decomposition and enhanced Hilbert spiral transform, adaptively provides high quality map of sample-induced phase delay, accepting particularly wide range of input single-shot interferograms (from off-axis to quasi on-axis configurations). It especially promotes high space-bandwidth-product QPI configurations alleviating the spectral overlapping problem. The VHQPI is tailored to deal with cumbersome interference patterns related to detailed locally varying biological objects with possibly high dynamic range of phase and relatively low carrier. In post-processing, the slowly varying phase-term associated with the instrumental optical aberrations is eliminated upon variational analysis to further boost the phase-imaging capabilities. The VHQPI is thoroughly studied employing numerical simulations and successfully validated using static and dynamic cells phase-analysis. It compares favorably with other single-shot phase reconstruction techniques based on the Fourier and Hilbert–Huang transforms, both in terms of visual inspection and quantitative evaluation, potentially opening up new possibilities in QPI.
Magma fragmentation and particle size distributions in low intensity mafic explosions: the July/August 2015 Piton de la Fournaise eruption
Authors: Edwards Matthew J. , Pioli Laura , Harris Andrew J. L. , Gurioli Lucia , Thivet Simon
Published: August 2020

Understanding magma fragmentation mechanisms in explosive eruptions is a key requirement for volcanic hazard assessment, eruption management and risk mitigation. This paper focuses on a type case small explosivity eruption (July–August 2015 eruption of Piton de la Fournaise). These eruptions, despite being often overlooked, are exceedingly frequent on local-to-global scales and constitute a significant hazard in vent-proximal areas, which are often populated by guides, tourists and, indeed, volcanologists due to their accessibility. The explosions presented here are ideal cases for the study of the dynamics of magma fragmentation and how it relates to the size distribution of scoria generated at the vent. We documented these events visually and thermally, and characterised the products through sample-return. This allowed us to describe small-scale gas bursts sending ejecta up to 30 m during intermittent lava fountains. Surface tension instabilities and inertial forces played a major role in fragmentation processes and generated particles with coarse-skewed distributions and median diameters ranging from − 8 to − 10 ϕ. However, with time distributions of particles in the most energetic fountains shifted towards more symmetrical shapes as median grains sizes became finer. Analyses of sequences of images demonstrate that the evolution of particle size distributions with time is due to instability of magma droplets and (in-flight) fragmentation.
Rapid repair of human disease-specific single-nucleotide variants by One-SHOT genome editing
Authors: Yokouchi Yuji , Suzuki Shinichi , Ohtsuki Noriko , Yamamoto Kei , Noguchi Satomi , Soejima Yumi , Goto Mizuki , Ishioka Ken , Nakamura Izumi , Suzuki Satoru , Takenoshita Seiichi , Era Takumi
Published: August 2020

Many human diseases ranging from cancer to hereditary disorders are caused by single-nucleotide mutations in critical genes. Repairing these mutations would significantly improve the quality of life for patients with hereditary diseases. However, current procedures for repairing deleterious single-nucleotide mutations are not straightforward, requiring multiple steps and taking several months to complete. In the current study, we aimed to repair pathogenic allele-specific single-nucleotide mutations using a single round of genome editing. Using high-fidelity, site-specific nuclease AsCas12a/Cpf1, we attempted to repair pathogenic single-nucleotide variants (SNVs) in disease-specific induced pluripotent stem cells. As a result, we achieved repair of the Met918Thr SNV in human oncogene RET with the inclusion of a single-nucleotide marker, followed by absolute markerless, scarless repair of the RET SNV with no detected off-target effects. The markerless method was then confirmed in human type VII collagen-encoding gene COL7A1. Thus, using this One-SHOT method, we successfully reduced the number of genetic manipulations required for genome repair from two consecutive events to one, resulting in allele-specific repair that can be completed within 3 weeks, with or without a single-nucleotide marker. Our findings suggest that One-SHOT can be used to repair other types of mutations, with potential beyond human medicine.
Using Relaxation Time to characterize biological effects of different mutagens
Authors: Li Xinglin , Sun Shuguang , Yao Jingxia , Sun Zhengfeng
Published: August 2020

All kinds of mutagenic factors may cause physiological, biochemical and genetic changes of all organisms. To characterize their characteristic biology effects, the concept of Relaxation Time (RT) was introduced for the first time, and the specific process was as follows. After mutation of organisms, the offsprings will be continuingly cultured (or cultivated) to the next generation (Rx). Once a biological effect began to show no significant difference compared to the untreated controls, the Rx was defined as the RT of the effect. In this paper, three kinds of mutagenic factors were selected to treat the seeds or seedlings of Astragalus sinicus L., subsequently, the corresponding RT was calibrated. The results showed that the RT was diverse not only among different biological effects but also among different mutagenic factors. For the RT of chemical mutagens and gamma rays, most of which are concentrated on R1, whereas the heavy ion beams have significant differences among different tracks. Among biological effects, the SOD activity and superoxide anion free radical content in the Peak region are more prominent, and their RT reaches R3 and R4, respectively. Thus, the RT may characterize the characteristic biological effects from differently mutagenic factors.
Seasonal variation of intra-ocular pressure in glaucoma with and without dry eye
Authors: Kuze Manami , Ayaki Masahiko , Yuki Kenya , Kawashima Motoko , Uchino Miki , Tsubota Kazuo , Negishi Kazuno
Published: August 2020

The management of intra-ocular pressure (IOP) is important for glaucoma treatment. IOP is recognized for showing seasonal fluctuation. Glaucoma patients can be at high risk of dry eye disease (DED). We thus evaluated seasonal variation of IOP with and without DED in glaucoma patients. This study enrolled 4,708 patients, with mean age of 55.2 years, who visited our clinics in Japan from Mar 2015 to Feb 2017. We compared the seasonal variation in IOP (mean ± SD) across spring (March–May), summer (June–August), fall (September–November), and winter (December–February). IOP was highest in winter and lowest in summer, at 14.2/13.7 for non-glaucoma without DED group (n = 2,853, P = 0.001), 14.5/13.6 for non-glaucoma with DED group (n = 1,500, P = 0.000), 14.0/13.0 for glaucoma without DED group (n = 240, P = 0.051), and 15.4/12.4 for glaucoma with DED group (n = 115, P = 0.015). Seasonal variation was largest across the seasons in the glaucoma with DED group. IOP was also inversely correlated with corneal staining score (P = 0.000). In conclusion, the seasonal variation was significant in most of study groups and IOP could tend to be low in summer.
Xpert MTB/RIF ultra for rapid diagnosis of extrapulmonary tuberculosis in a high-income low-tuberculosis prevalence setting
Authors: Hoel Ida Marie , Syre Heidi , Skarstein Ingerid , Mustafa Tehmina
Published: August 2020

The diagnosis of extrapulmonary tuberculosis (EPTB) is often challenging due to paucibacillary nature of the disease. Xpert MTB/RIF Ultra (Ultra) has been developed to improve detection of Mycobacterium tuberculosis complex (MTC) in paucibacillary specimens. The objective of the study was to assess the performance of Ultra for the diagnosis of EPTB in a high-income low TB prevalence country. Extrapulmonary samples received for TB diagnostics at two hospitals in Norway between January 2015 and January 2016 were prospectively and consecutively included. Defrosted samples were subjected to Ultra. Culture and routine PCR tests were used as reference standard. A total of 82 samples, 10 culture and/or routine PCR positive (confirmed TB) samples and 72 culture and routine PCR negative samples were included in analysis. The overall sensitivity and specificity of Ultra were 90% (9/10, 95% CI 56–100) and 99% (71/72, 95% CI 93–100), respectively. Ultra was positive in 6/7 smear negative confirmed TB samples. To conclude, Ultra showed a high sensitivity and specificity in extrapulmonary specimens and may contribute to a rapid diagnosis of EPTB in a low TB prevalence setting.
ENaC regulation by phospholipids and DGK explained through mathematical modeling
Authors: Olivença Daniel V. , Voit Eberhard O. , Pinto Francisco R.
Published: August 2020

Cystic fibrosis is a condition caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). It is also thought to increase the activity of epithelial sodium channels (ENaC). The altered function of these ion channels is one of the causes of the thick dehydrated mucus that characterizes the disease and is partially responsible for recurrent pulmonary infections and inflammation events that ultimately destroy the lungs of affected subjects. Phosphoinositides are signaling lipids that regulate numerous cellular processes and membrane proteins, including ENaC. Inhibition of diacylglycerol kinase (DGK), an enzyme of the phosphoinositide pathway, reduces ENaC function. We propose a computational analysis that is based on the combination of two existing mathematical models: one representing the dynamics of phosphoinositides and the other explaining how phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) influences ENaC activity and, consequently, airway surface liquid. This integrated model permits, for the first time, a detailed assessment of the intricate interactions between DGK and ENaC and is consistent with available literature data. In particular, the computational approach allows comparisons of two competing hypotheses regarding the regulation of ENaC. The results strongly suggest that the regulation of ENaC is primarily exerted through the control of PI(4,5)P2 production by type-I phosphatidylinositol-4-phosphate 5-kinase (PIP5KI), which in turn is controlled by phosphatidic acid (PA), the product of the DGK reaction.
Understanding of metals dysregulation in patients with systolic and diastolic dysfunction in ischemic heart disease
Authors: Khan Noman , Hashmi Satwat , Siddiqui Amna Jabbar , Farooq Sabiha , Sami Shahid Ahmed , Basir Nageeb , Bokhari Syeda Saira , Sharif Hasanat , Junejo Sanaullah , El-Seedi Hesham R. , Musharraf Syed Ghulam
Published: August 2020

Ischemic heart disease (IHD) is the leading cause of death and chronic disability in the world. IHD affects both the systolic and diastolic function of the heart which progressively leads to heart failure; a structural and functional impairment of filling or ejection of blood from the heart. In this study, the progression of systolic and diastolic dysfunction characterized according to their echocardiographic parameters including left ventricular ejection fraction (EF), grades of diastolic dysfunction and ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/eʹ), were correlated with differential regulation of various metals in patients sera samples (n = 62) using inductive coupled plasma-mass spectrometry (ICP-MS). Chromium, nickel and selenium were found significant (p < 0.05) in patients having EF < 45% compared with EF > 45%. In patients with systolic dysfunction (EF < 45%), the level of selenium was decreased while the level of chromium and nickel was increased compared to patients with EF > 45%. Selenium level was also decreased significantly (p < 0.05) in grade 1A and 2 patients that are considered as higher grades of diastole dysfunction in comparison to grade 0–1. Overall, selenium deficiency was identified in both systolic and diastolic dysfunctions of IHD patients corresponding to the progression of disease that could be related to many metabolic and translational pathways specifically which involve selenoproteins.
LncRNA and mRNA expression profiles and functional networks of hyposalivation of the submandibular gland in hypertension
Authors: Shen Zhu-Jun , Han Ye-Chen , Wang Yi-Ning , Xie Hong-Zhi
Published: August 2020

Hyposalivation is a complication of hypertension. However, little is known about the role of long non-coding RNAs (lncRNAs) in salivary glands in hypertension. This study aimed to compare the lncRNA and mRNA expression profiles between spontaneous hypertension rats (SHRs) and Wistar-Kyoto (WKY) rats through microarray analysis and apple bioinformatics methods to analyse their potential roles in hyposalivation. The differentially expressed (DE) lncRNAs and mRNAs were confirmed by quantitative real-time PCR (qRT-PCR). Compared with WKY rats, 225 DE lncRNAs and 473 DE mRNAs were identified in the SMG of SHRs. The pathway analyses of DE mRNAs showed that inflammatory mediator regulation of transient receptor potential channels was involved in hyposalivation in SHRs. Ten DE lncRNAs were chosen for further research. A coding-non-coding gene co-expression (CNC) network and competing endogenous RNA (ceRNA) network analysis revealed that the potential functions of these 10 DE lncRNAs were closely connected with the processes of the immune response. This study showed abundant DE lncRNAs and mRNAs in hypertensive SMGs. Furthermore, our results indicated strong associations between the immune response and hyposalivation and showed the potential of immune-related genes as novel and therapeutic targets for hyposalivation.
Implications of back-and-forth motion and powerful propulsion for spirochetal invasion
Authors: Abe Keigo , Kuribayashi Toshiki , Takabe Kyosuke , Nakamura Shuichi
Published: August 2020

The spirochete Leptospira spp. can move in liquid and on a solid surface using two periplasmic flagella (PFs), and its motility is an essential virulence factor for the pathogenic species. Mammals are infected with the spirochete through the wounded dermis, which implies the importance of behaviors on the boundary with such viscoelastic milieu; however, the leptospiral pathogenicity involving motility remains unclear. We used a glass chamber containing a gel area adjoining the leptospiral suspension to resemble host dermis exposed to contaminated water and analyzed the motility of individual cells at the liquid-gel border. Insertion of one end of the cell body to the gel increased switching of the swimming direction. Moreover, the swimming force of Leptospira was also measured by trapping single cells using an optical tweezer. It was found that they can generate $$\sim $$
∼
17 pN of force, which is $$\sim $$
∼
30 times of the swimming force of Escherichia coli. The force-speed relationship suggested the load-dependent force enhancement and showed that the power (the work per unit time) for the propulsion is $$\sim $$
∼
3.1 × 10–16 W, which is two-order of magnitudes larger than the propulsive power of E. coli. The powerful and efficient propulsion of Leptospira using back-and-forth movements could facilitate their invasion.
Dissociation in reactive and proactive inhibitory control in Myoclonus dystonia
Authors: Atkinson-Clement Cyril , Tarrano Clement , Porte Camille-Albane , Wattiez Nicolas , Delorme Cécile , McGovern Eavan M. , Brochard Vanessa , Thobois Stéphane , Tranchant Christine , Grabli David , Degos Bertrand , Corvol Jean-Christophe , Pedespan Jean-Michel , Krystkoviak Pierre , Houeto Jean-Luc , Degardin Adrian , Defebvre Luc , Valabregue Romain , Rosso Charlotte , Apartis Emmanuelle , Vidailhet Marie , Pouget Pierre , Roze Emmanuel , Worbe Yulia
Published: August 2020

Myoclonus-dystonia (MD) is a syndrome characterized by myoclonus of subcortical origin and dystonia, frequently associated with psychiatric comorbidities. The motor and psychiatric phenotypes of this syndrome likely result from cortico-striato-thamalo-cerebellar-cortical pathway dysfunction. We hypothesized that reactive and proactive inhibitory control may be altered in these patients. Using the Stop Signal Task, we assessed reactive and proactive inhibitory control in MD patients with (n = 12) and without (n = 21) deep brain stimulation of the globus pallidus interna and compared their performance to matched healthy controls (n = 24). Reactive inhibition was considered as the ability to stop an already initiated action and measured using the stop signal reaction time. Proactive inhibition was assessed through the influence of several consecutive GO or STOP trials on decreased response time or inhibitory process facilitation. The proactive inhibition was solely impaired in unoperated MD patients. Patients with deep brain stimulation showed impairment in reactive inhibition, independent of presence of obsessive–compulsive disorders. This impairment in reactive inhibitory control correlated with intrinsic severity of myoclonus (i.e. pre-operative score). The results point to a dissociation in reactive and proactive inhibitory control in MD patients with and without deep brain stimulation of the globus pallidus interna.
Paretic knee extensor strength, gait velocity, and fat mass are major determinants of peak aerobic capacity in subacute stroke: observational cohort study
Authors: Kim Ji Hyun , Han Eun Young , Kang Sa-Yoon , Im Sang Hee
Published: August 2020

The purpose of this study is to investigate major determinants of peak aerobic capacity in subacute stroke patients among body composition, balance function, walking capacity, and lower limb muscular strength. This was a retrospective observational cohort study. Eighty-three subacute stroke patients were enrolled and their medical records were retrospectively reviewed in the study (47 males; mean age: 62.95 ± 13.9 years). Gait capacity was assessed by gait velocity (10 m walk velocity:10MWV) and gait endurance (6 min walk distance:6MWD). Balance function was evaluated with Berg Balance Scale (BBS). The isometric muscular strengths of bilateral knee extensors were measured with an isokinetic dynamometer. Cardiovascular fitness was evaluated with an expired gas analyzer. In backward linear regression analyses, paretic isometric extensor strength (p < 0.001), fat mass (p = 0.005) and 10MWV (p < 0.001) are significantly correlated with peak aerobic capacity (adjusted R2 = 0.499) in all patients. Our results confirmed that paretic knee extensor strength, gait velocity, and fat mass were major determinants of peak aerobic capacity in subacute stroke. Therefore, therapeutic approaches should focus on improving gait velocity and paretic knee extensor strength in the early stages of recovery from stroke.
STAT3 inhibition with galiellalactone effectively targets the prostate cancer stem-like cell population
Authors: Canesin Giacomo , Maggio Valentina , Palominos Macarena , Stiehm Anna , Contreras Hector R. , Castellón Enrique A. , Morote Juan , Paciucci Rosanna , Maitland Norman J. , Bjartell Anders , Hellsten Rebecka
Published: August 2020

Cancer stem cells (CSCs) are a small subpopulation of quiescent cells with the potential to differentiate into tumor cells. CSCs are involved in tumor initiation and progression and contribute to treatment failure through their intrinsic resistance to chemo- or radiotherapy, thus representing a substantial concern for cancer treatment. Prostate CSCs’ activity has been shown to be regulated by the transcription factor Signal Transducer and Activator of Transcription 3 (STAT3). Here we investigated the effect of galiellalactone (GL), a direct STAT3 inhibitor, on CSCs derived from prostate cancer patients, on docetaxel-resistant spheres with stem cell characteristics, on CSCs obtained from the DU145 cell line in vitro and on DU145 tumors in vivo. We found that GL significantly reduced the viability of docetaxel-resistant and patient-derived spheres. Moreover, CSCs isolated from DU145 cells were sensitive to low concentrations of GL, and the treatment with GL suppressed their viability and their ability to form colonies and spheres. STAT3 inhibition down regulated transcriptional targets of STAT3 in these cells, indicating STAT3 activity in CSCs. Our results indicate that GL can target the prostate stem cell niche in patient-derived cells, in docetaxel-resistant spheres and in an in vitro model. We conclude that GL represents a promising therapeutic approach for prostate cancer patients, as it reduces the viability of prostate cancer-therapy-resistant cells in both CSCs and non-CSC populations.
Modulation of P2Y6R expression exacerbates pressure overload-induced cardiac remodeling in mice
Authors: Shimoda Kakeru , Nishimura Akiyuki , Sunggip Caroline , Ito Tomoya , Nishiyama Kazuhiro , Kato Yuri , Tanaka Tomohiro , Tozaki-Saitoh Hidetoshi , Tsuda Makoto , Nishida Motohiro
Published: August 2020

Cardiac tissue remodeling caused by hemodynamic overload is a major clinical outcome of heart failure. Uridine-responsive purinergic P2Y6 receptor (P2Y6R) contributes to the progression of cardiovascular remodeling in rodents, but it is not known whether inhibition of P2Y6R prevents or promotes heart failure. We demonstrate that inhibition of P2Y6R promotes pressure overload-induced sudden death and heart failure in mice. In neonatal cardiomyocytes, knockdown of P2Y6R significantly attenuated hypertrophic growth and cell death caused by hypotonic stimulation, indicating the involvement of P2Y6R in mechanical stress-induced myocardial dysfunction. Unexpectedly, compared with wild-type mice, deletion of P2Y6R promoted pressure overload-induced sudden death, as well as cardiac remodeling and dysfunction. Mice with cardiomyocyte-specific overexpression of P2Y6R also exhibited cardiac dysfunction and severe fibrosis. In contrast, P2Y6R deletion had little impact on oxidative stress-mediated cardiac dysfunction induced by doxorubicin treatment. These findings provide overwhelming evidence that systemic inhibition of P2Y6R exacerbates pressure overload-induced heart failure in mice, although P2Y6R in cardiomyocytes contributes to the progression of cardiac fibrosis.
Surface enhanced Raman scattering for robust, sensitive detection and confirmatory identification of dried bloodstains
Authors: Shaine M. L. , Premasiri W. R. , Ingraham H. M. , Andino R. , Lemler P. , Brodeur A. N. , Ziegler L. D.
Published: August 2020

785 nm SERS spectra provide rapid, sensitive confirmatory identification of dried bloodstains due to a ferric, high spin heme moiety.
Pd-catalyzed amidation of 1,3-diketones with CO and azidesviaa nitrene intermediate
Authors: Gu Zheng-Yang , Chen Jie , Xia Ji-Bao
Published: August 2020

An efficient Pd-catalyzed amidation of 1,3-diketones has been developed using carbon monoxide and organic azides.