bluuebunny/crossref_metadata_2025 huggingface dataset:
Visualizing and Manipulating Biological Processes by Using HaloTag and SNAP‐Tag Technologies
Authors: Hoelzel Conner A. , Zhang Xin
Published: March 2020

Visualizing and manipulating the behavior of proteins is crucial to understanding the physiology of the cell. Methods of biorthogonal protein labeling are important tools to attain this goal. In this review, we discuss advances in probe technology specific for self‐labeling protein tags, focusing mainly on the application of HaloTag and SNAP‐tag systems. We describe the latest developments in small‐molecule probes that enable fluorogenic (no wash) imaging and super‐resolution fluorescence microscopy. In addition, we cover several methodologies that enable the perturbation or manipulation of protein behavior and function towards the control of biological pathways. Thus, current technical advances in the HaloTag and SNAP‐tag systems means that they are becoming powerful tools to enable the visualization and manipulation of biological processes, providing invaluable scientific insights that are difficult to obtain by traditional methodologies. As the multiplex of self‐labeling protein tag systems continues to be developed and expanded, the utility of these protein tags will allow researchers to address previously inaccessible questions at the forefront of biology.
Mechanism and Application of the Catalytic Reaction of [NiFe] Hydrogenase: Recent Developments
Authors: Tai Hulin , Hirota Shun
Published: March 2020

Hydrogenases (H2ase) catalyze the oxidation of dihydrogen and the reduction of protons with remarkable efficiency, thereby attracting considerable attention in the energy field due to their biotechnological potential. For this simple reaction, [NiFe] H2ase has developed a sophisticated but intricate mechanism with the heterolytic cleavage of dihydrogen, where its Ni−Fe active site exhibits various redox states. Recently, new spectroscopic and crystal structure studies of [NiFe] H2ases have been reported, providing significant insights into the catalytic reaction mechanism, hydrophobic gas‐access tunnel, proton‐transfer pathway, and electron‐transfer pathway of [NiFe] H2ases. In addition, [NiFe] H2ases have been shown to play an important role in biofuel cell and solar dihydrogen production. This concept provides an overview of the biocatalytic reaction mechanism and biochemical application of [NiFe] H2ases based on the new findings.
Effects of NIX‐mediated mitophagy on ox‐LDL‐induced macrophage pyroptosis in atherosclerosis
Authors: Peng Xue , Chen Hengmei , Li Yunyun , Huang Dake , Huang Baojun , Sun Dengqun
Published: March 2020

Pyroptosis is a form of cell death that is uniquely dependent on caspase‐1. Pyroptosis involved in oxidized low‐density lipoprotein (ox‐LDL)‐induced human macrophage death through the promotion of caspase‐1 activation is important for the formation of unstable plaques in atherosclerosis. The mitochondrial outer membrane protein NIX directly interacts with microtubule‐associated protein 1 light chain 3 (LC3). Although we previously showed that NIX‐mediated mitochondrial autophagy is involved in the clearance of damaged mitochondria, how NIX contributes to ox‐LDL‐induced macrophage pyroptosis remains unknown. Here, immunoperoxidase staining Nix expression decreased in human atherosclerosis. When we silenced NIX expression in murine macrophage cell, active caspase‐1, and mature interleukin‐1β expression levels were increased and LC3 was reduced. In addition, LDH release and acridine orange and ethidium bromide staining indicated that damage to macrophage cell membranes induced by ox‐LDL was substantially worse. Moreover, intracellular reactive oxygen species and NLRP3 inflammasome levels increased. Taken together, these results demonstrated that NIX inhibits ox‐LDL‐induced macrophage pyroptosis via autophagy in atherosclerosis.
Influence of cardiac arrest and SCAI shock stage on cardiac intensive care unit mortality
Authors: Jentzer Jacob C. , Henry Timothy D. , Barsness Gregory W. , Menon Venu , Baran David A. , Van Diepen Sean
Published: March 2020

Background

Patients with concomitant cardiac arrest (CA) and shock are at increased risk of mortality, even when stratified according to shock severity. We sought to determine whether the presence of ventricular fibrillation (VF) modified the relationship between CA and mortality in cardiac intensive care unit (CICU) patients.

Methods

We retrospectively analyzed unique Mayo Clinic CICU patients admitted between 2007 and 2015. Society for Cardiovascular Angiography and Intervention (SCAI) shock stages A through E were classified at admission. Hospital mortality in each SCAI shock stage was stratified by the presence of CA, VF CA, or non‐VF CA.

Results

We included 9,898 patients with a mean age of 68 years (38% females). CA was present in 12%, including 53% with VF CA and 47% with non‐VF CA. Hospital mortality was higher in patients with CA compared to patients without CA (34% vs. 6%; adjusted odds ratio [OR] = 3.1, 95% CI [2.4, 4.0],p < .001), and patients with non‐VF CA had higher hospital mortality than patients with VF CA (44% vs. 25%; adjusted OR = 2.1, 95% CI [1.4, 3.0],p < .001). After adjustment, patients with any CA or non‐VF CA had higher hospital mortality at each SCAI stage, except stage E (all otherp < .05), whereas patients with VF CA did not (allp > .1).

Conclusions

CA rhythm modifies the relationship between CA and mortality in CICU patients, when accounting for coma, shock, and organ failure. Outcome studies examining CA in patients with cardiogenic shock need to account for important differences such as CA rhythm.
Antithrombotic regimens for percutaneous coronary intervention of the left main coronary artery: The EXCEL trial
Authors: Brener Sorin J. , Lembo Nicholas J. , Kandzari David E. , Sabaté Manel , Gershlick Anthony H. , Banning Adrian P. , Buszman Paweł E. , Kosmidou Ioanna , Simonton Charles A. , Morice Marie‐Claude , Ben‐Yehuda Ori , Dressler Ovidiu , Zhang Zixuan , Sabik Joseph F. , Kappetein Arie Pieter , Serruys Patrick W. , Stone Gregg W.
Published: March 2020

Objectives

We compared the effect of bivalirudin or heparin and use or nonuse of glycoprotein IIb/IIIa inhibitors (GPI) on the outcome of left main coronary artery (LMCA) percutaneous coronary intervention (PCI) in the randomized EXCEL trial.

Background

The optimal antithrombotic regimen to support PCI of the LMCA remains controversial because of low representation of this subset in clinical trials.

Methods

The PCI cohort (n = 928) in EXCEL was divided according to bivalirudin versus heparin antithrombin treatment and compared for the primary composite endpoint of death, myocardial infarction (MI), or stroke at 30 days and 5 years.

RESULTS

Bivalirudin was used in 319 patients (34.4%). The composite endpoint at 30 days occurred in 7.2% versus 3.8% bivalirudin and heparin patients, respectively, p = .02; at 5 years, the composite endpoint occurred in 26.3% versus 19.9% bivalirudin and heparin patients, respectively, p = .02. Major bleeding was more frequent in bivalirudin patients (4.1% versus 1.3%, p = .008). There were no differences in stent thrombosis between the groups. Bivalirudin use was an independent predictor of the 30‐day composite endpoint (OR 2.88, 95% CI 1.28–6.48, p = .01) but not of the 5‐year composite endpoint (OR 1.30, 95% CI 0.84–2.02, p = .23). GPI use was infrequent (n = 67, 7.2%) and was not associated with adverse outcomes.

Conclusion

Among patients undergoing LMCA PCI in the EXCEL trial, procedural use of bivalirudin was associated with greater rates of periprocedural MI and the 30‐day composite endpoint without reducing bleeding complications. Five‐year outcomes were similar. GPIs were used infrequently and were not associated with clinical outcomes.
Role of Cocatalysts on Hematite Photoanodes in Photoelectrocatalytic Water Splitting: Challenges and Future Perspectives
Authors: Bedin Karen C. , Muche Dereck N. F. , Melo Mauricio A. , Freitas Andre L. M. , Gonçalves Renato V. , Souza Flavio L.
Published: March 2020

The efficiency of a nanostructure applied to photo‐electrocatalysis is fundamentally governed by the capability of the nanostructure surface to sustain a reaction without the occurrence of electron trapping or a recombination of the photogenerated holes. This Minireview summarizes the latest progress in the use of cocatalysts on hematite electrodes and their application in water splitting induced by sunlight. The major drawback of hole diffusion through a solid‐liquid interface is addressed through the selection of the best cocatalyst for increasing the efficiency of an iron‐based material. Finally, the most promising modification routes and outstanding materials for enhancing the low kinetics of the oxygen evolution reaction during sunlight‐driven water oxidation reactions in hematite are provided and those materials that may have a significant impact on the overall photoelectrochemical performance are discussed.
Facile Synthesis of a Stable Side‐on Phosphinyne Complex by Redox Driven Intramolecular Cyclisation
Authors: Lange Helge , Schröder Henning , Oberem Elisabeth , Villinger Alexander , Rabeah Jabor , Ludwig Ralf , Neymeyr Klaus , Seidel Wolfram W.
Published: March 2020

Alkyne complexes with vicinal substitution by a Lewis acid and a Lewis base at the coordinated alkyne are prospective frustrated Lewis pairs exhibiting a particular mutual distance and, hence, a specific activation potential. In this contribution, investigations on the generation of a WII alkyne complex bearing a phosphine as Lewis base and a carbenium group as Lewis acid are presented. Independently on potential substrates added, an intramolecular cyclisation product was always isolated. A subsequent deprotonation step led to an unprecedented side‐on λ5‐phosphinyne complex, which is interpreted as highly zwitterionic according to visible absorption spectroscopy supported by TD‐DFT. Low‐temperature 31P NMR and EPR spectroscopic measurements combined with time‐dependent IR‐spectroscopic monitoring provided insights in the mechanism of the cyclisation reaction. Decomposition of the multicomponent IR spectra by multivariate curve resolution and a kinetic hard‐modelling approach allowed the derivation of kinetic parameters. Assignment of the individual IR spectra to potential intermediates was provided by DFT calculations.
First‐Principles Investigation of β‐FeOOH for Hydrogen Evolution: Identifying Reactive Sites and Boosting Surface Reactions
Authors: Huang Zhenxiong , Guan Xiangjiu , Li Mingtao , Guo Liejin
Published: March 2020

Akaganeite (β‐FeOOH) is a widely investigated candidate for photo(electro)catalysis, such as water splitting. Nevertheless, insights into understanding the surface reaction between water and β‐FeOOH, in particular, the hydrogen evolution reaction (HER), are still insufficient. Herein, a set of first‐principles calculations on pristine β‐FeOOH and halogen‐substituted β‐FeOOH are applied to evaluate the HER performance through the computational hydrogen electrode model. The results show that the HER on β‐FeOOH tends to occur at Fe sites on the (010) surface, and palladium and nickel are found to serve as excellent co‐catalysts to boost the HER process, due to the remarkably reduced free energy change of hydrogen adsorption upon loading on the surface of β‐FeOOH, demonstrating great potential for efficient water splitting.
Targeting an Interaction Between Two Disordered Domains by Using a Designed Peptide
Authors: Mayer Guy , Shpilt Zohar , Bressler Shachar , Marcu Orly , Schueler‐Furman Ora , Tshuva Edit Y. , Friedler Assaf
Published: March 2020

Intrinsically disordered regions in proteins (IDRs) mediate many disease‐related protein–protein interactions. However, the unfolded character and continuous conformational changes of IDRs make them difficult to target for therapeutic purposes. Here, we show that a designed peptide based on the disordered p53 linker domain can be used to target a partner IDR from the anti‐apoptotic iASPP protein, promoting apoptosis of cancer cells. The p53 linker forms a hairpin‐like structure with its two termini in close proximity. We designed a peptide derived from the disordered termini without the hairpin, designated as p53 LinkTer. The LinkTer peptide binds the disordered RT loop of iASPP with the same affinity as the parent p53 linker peptide, and inhibits the p53–iASPP interaction in vitro. The LinkTer peptide shows increased stability to proteolysis, penetrates cancer cells, causes nuclei shrinkage, and compromises the viability of cells. We conclude that a designed peptide comprising only the IDR from a peptide sequence can serve as an improved inhibitor since it binds its target protein without the need for pre‐folding, paving the way for therapeutic targeting of IDRs.
Facile Construction of Furanoacenes by a Three‐Step Sequence Going through Disilyl‐exo‐cyclic Dienes
Authors: Minami Yasunori , Furuya Yuki , Hiyama Tamejiro
Published: March 2020

Facile synthesis of various benzonaphthofurans was achieved by intramolecular hydroarylation of 1,4‐disilyl‐2‐aryloxy‐1,3‐enynes followed by cycloaddition with arynes or alkenes and finally desilylaromatization. The three‐step transformation can be operated sequentially in one‐pot, providing with a range of furanoacenes easily and highly effectively.
Sensor Array Based Determination of Edman Degradated Amino Acids Using Poly(p‐phenyleneethynylene)s
Authors: Zhang Hao , Wang Benhua , Seehafer Kai , Bunz Uwe H. F.
Published: March 2020

A cross‐reactive optical sensor array based on poly(p‐phenyleneethynylene)s (PPEs) determines Edman degraded amino acids. We report a sensor array composed of three anionic PPEs P1–P3, and their electrostatic complexes with metal ions (Fe2+, Cu2+, Co2+). We recorded distinct fluorescence intensity response patterns as “fingerprints” of this chemical tongue toward standard phenylthiohydantoin (PTH) amino acids—degradation products of the Edman process. These “fingerprints” were converted into canonical scores by linear discrimination analysis (LDA), which differentiates all of the PTH‐amino acids. This array discriminates PTH‐amino acid residues degraded from an oligopeptide through Edman sequencing. This approach is complementary to chromatography approaches which rely on mass spectrometry; our array offers the advantage of simplicity.
Boosting Conjugate Addition to Nitroolefins Using Lithium Tetraorganozincates: Synthetic Strategies and Structural Insights
Authors: Dell'Aera Marzia , Perna Filippo Maria , Vitale Paola , Altomare Angela , Palmieri Alessandro , Maddock Lewis C. H. , Bole Leonie J. , Kennedy Alan R. , Hevia Eva , Capriati Vito
Published: March 2020

We report the first transition metal catalyst‐ and ligand‐free conjugate addition of lithium tetraorganozincates (R4ZnLi2) to nitroolefins. Displaying enhanced nucleophilicity combined with unique chemoselectivity and functional group tolerance, homoleptic aliphatic and aromatic R4ZnLi2 provide access to valuable nitroalkanes in up to 98 % yield under mild conditions (0 °C) and short reaction time (30 min). This is particularly remarkable when employing β‐nitroacrylates and β‐nitroenones, where despite the presence of other electrophilic groups, selective 1,4 addition to the C=C is preferred. Structural and spectroscopic studies confirmed the formation of tetraorganozincate species in solution, the nature of which has been a long debated issue, and allowed to unveil the key role played by donor additives on the aggregation and structure of these reagents. Thus, while chelating N,N,N’,N’‐tetramethylethylenediamine (TMEDA) and (R,R)‐N,N,N’,N’‐tetramethyl‐1,2‐diaminocyclohexane (TMCDA) favour the formation of contacted‐ion pair zincates, macrocyclic Lewis donor 12‐crown‐4 triggers an immediate disproportionation process of Et4ZnLi2 into equimolar amounts of solvent‐separated Et3ZnLi and EtLi.
Computational Study on the Charge Transport and Optical Spectra of Anthracene Derivatives in Aggregates
Authors: Sun Yajing , Geng Hua , Peng Qian , Shuai Zhigang
Published: March 2020

A recent experiment [Angew. Chem. Int. Ed. 2017, 56, 722–727] found that a (1 : 9) blend film of two anthracene derivatives, 2‐fluorenyl‐2‐anthracene (FlAnt) and 2‐anthryl‐2‐anthracence (2 A), exhibit both efficient white light emission and high hole mobility, thus promising for organic light‐emitting transistors (OLETs). Employing quantum chemistry at the polarizable continuum model (PCM) and the quantum mechanics/molecular mechanics (QM/MM) levels, we investigated the excited‐state structures, optical spectra, band structure and the carrier mobility for FlAnt and 2 A from solution to aggregate phases. We suggest using the ratio of intermolecular excitonic coupling J and intramolecular excited state relaxation energy E to judge the bathochromic shift in optical emission in aggregates. For FlAnt, ρ=J/E is calculated to be less than 0.17, a critical value we identified earlier, and the spectra in solution and aggregate phases present quite similar features (blue emission). However, ρ is ∼0.5 for 2 A systems, and the calculated emission in the aggregate phase exhibits a remarkable bathochromic shift. In addition, the 0–0 emission is strongly suppressed in the herringbone stacking. These observations justify the experimental findings that (i) 2 A is blue emissive in solution but yellow‐green in the aggregate phase, whereas FlAnt is always blue, and (ii) the blend of them show white emission. By using the “quantum nuclear tunneling” model we proposed earlier, we found the hole mobility for FlAnt and 2 A are 0.5 and 4.2 cm2 V−1 s−1, respectively, indicating both are good hole transport materials.
Composite score considers emotional dysregulation in treating ADHD
Authors: Knopf Alison
Published: March 2020

Using a composite score for symptom severity and symptom‐induced impairment of attention‐deficit/hyperactivity disorder (ADHD) and emotional dysregulation is a better indicator of improvement in heterogeneous samples with ADHD than single subscales, researchers have found.
A framework to conceptualize personal recovery from eating disorders: A systematic review and qualitative meta‐synthesis of perspectives from individuals with lived experience
Authors: Wetzler Sara , Hackmann Corinna , Peryer Guy , Clayman Kelsey , Friedman Donna , Saffran Kristina , Silver Jody , Swarbrick Margaret , Magill Elizabeth , van Furth Eric F. , Pike Kathleen M.
Published: March 2020

Background

An extensive literature exists describing treatment interventions and recovery from eating disorders (EDs); however, this body of knowledge is largely symptom‐based and from a clinical perspective and thus limited in capturing perspectives and values of individuals with lived experience of an ED. In this study, we performed a systematic review to coproduce a conceptual framework for personal recovery from an ED based on primary qualitative data available in published literature.

Methods

A systematic review and qualitative meta‐synthesis approach was used. Twenty studies focusing on ED recovery from the perspective of individuals with lived experience were included. The studies were searched for themes describing the components of personal recovery. All themes were analyzed and compared to the established connectedness; hope and optimism about the future; identity; meaning in life; and empowerment (CHIME) and Substance Abuse and Mental Health Services Administration (SAMHSA) frameworks of recovery, which are applicable to all mental disorders. Themes were labeled and organized into a framework outlining key components of the ED personal recovery process.

Results

Supportive relationships, hope, identity, meaning and purpose, empowerment, and self‐compassion emerged as the central components of the recovery process. Symptom recovery and its relationship to the personal recovery process are also significant.

Discussion

Individuals with lived experience of EDs noted six essential elements in the personal ED recovery process. This framework is aligned with several of the key components of the CHIME and SAMHSA frameworks of recovery, incorporating person‐centered elements of the recovery process. Future research should validate these constructs and develop instruments (or tools) that integrate the lived experiences into a measurement of recovery from an ED.
Cryogenic Luminescent Ratiometric Thermometers Based on Tetragonal Na[LnSiO4]·xNaOH (Ln = Gd, Tb, Eu; x ≈ 0.2)
Authors: Ananias Duarte , Mongis Camille M. , Carlos Luís D. , Rocha João
Published: March 2020

The hydrothermal synthesis under mild conditions and structural characterization of Na[LnSiO4]·xNaOH (Ln = Gd, Tb, Eu; x ≈ 0.2) are reported. These materials crystallize in the tetragonal non‐centrosymmetric I4– space group. The crystal phase purity is ascertained by powder X‐ray diffraction and scanning electron microscopy, and further confirmed by photoluminescence spectroscopy and lifetime measurements at 294 and 12 K. Na[(Gd0.82Tb0.14Eu0.04)SiO4]·xNaOH and Na[(Gd0.66Tb0.30Eu0.04)SiO4]·xNaOH perform well as visible ratiometric thermometers, based on the ratio between the Tb3+ and Eu3+ emissions, presenting good relative thermal sensitivities at cryogenic temperature (<100 K) with maxima of 1.9 %K–1 at 14 K and 6.2 %K–1 at 12 K, respectively.
Thin Silica‐Based Microsheets with Controlled Geometry
Authors: Maciel Marta M. , Patrício Sónia G. , Borges João , Levkin Pavel A. , Correia Tiago R. , Mano João F.
Published: March 2020

A high demand for materials with defined geometry and size is required in a wide range of fields. Inorganic compounds, especially silica‐based, arise as a cheap source and chemically flexible for the purpose. Silica display unique properties, like easy functionalization and good optical features making an interesting material to manipulate. In this work, we developed a method to create thin silica microsheets with defined size and high‐fidelity shape using superhydrophobic‐hydrophilic microarrays. These microstructures were produced through sol‐gel process using biomimetic superhydrophobic surfaces decorated with wettable spots. The results confirm the manufacture of porous silica microstructures with defined design (squares and circles) and thickness around 7 µm. The methodology applied in this work enables the high throughput fabrication of shaped silica materials in a single step, unlocking an extensive number of applications in areas that require miniaturization, like microelectronics or in fields like sensing and biomedicine.
Formal Total Syntheses of (+)‐ and (–)‐ar‐Macrocarpene via Rh(I)‐BINAP Catalyzed Conjugate Addition
Authors: Khatua Arindam , Pal Souvik , Bisai Vishnumaya
Published: March 2020

Catalytic asymmetric formal total syntheses of both antipodes of sesquiterpene, (+)‐ar‐macrocarpene (1) and (–)‐ar‐macrocarpene (ent‐1) has been achieved from 5,5‐dimethyl‐(3‐p‐tolyl)cyclohexanone 12. Enantioenriched compound 12 was obtained in excellent yield with 96 % ee by catalytic enantioselective p‐tolylboronic acid addition to 5,5‐dimethyl cyclohexen‐2‐one 13 using Rh(I)‐(S)‐BINAP (L7). Moreover, ent‐12 was achieved in 96 % ee by using Rh(I)‐(R)‐BINAP (ent‐L7).
Deployment of edge servers in 5G cellular networks
Authors: Li Bo , Hou Peng , Wang Keyue , Peng Ziyi , Jin Shicheng , Niu Li
Published: March 2020

With the rapid development of Internet of Things technology and interactive applications, the number of terminal devices in the network is increasing, and the development of interactive applications is hindered by network delay. To solve the network delay, bandwidth, and workload requirements in the new era, edge computing came into being. Edge computing aims to implement computing, storage, communication, and other services at the edge of the network by sinking cloud services from the core network to the edge of the network. Current research studies pay less attention to the impact of edge server location on the system performance, and edge server deployment is one of the key technologies for mobile edge computing. Therefore, we take 5G macrocellular/microcellular cluster as the edge server deployment scenario, propose an equivalent bandwidth‐based deployment strategy, establish a mathematical model for edge server deployment, and contract a task experience function as an evaluation index from two aspects: task time and energy overhead. Based on the analysis of the experimental results, it is verified that the deployment strategy based on equivalent bandwidth is superior to other deployment strategies in terms of terminal device task overhead.
Effects of Chinese medicines on monacolin K production and related genes transcription of Monascus ruber in red mold rice fermentation
Authors: Peng Lin , Ai‐lati Aisikaer , Liu Shuangping , Ji Zhongwei , Mao Jian , Che Xin
Published: March 2020

Monacolin K (MK) is a secondary metabolite synthesized by polyketide synthases of Monascus spp. In this study, the combined supplementation of three medicines, including Citri Reticulatae Pericarpium (CRP), Fructus crataegi (FC), and Radix Angelicae Dahuricae (RAD), were mixed with nonglutinous rice and were optimized by response surface methodology to enhance the production of MK in fermented red mold rice (RMR). Under the optimum condition, MK production achieved 3.60 mg/g, which was 41.18% higher than RMR without medicines. The improved MK production was mainly caused by the up‐regulated transcription level of mokA, mokB, mokF, mokH, mokI, and mplaeA. Meanwhile, the inhibitory effect of Poria cocos (PC) on MK production (only 0.436 mg/g) was caused by significantly down‐regulated transcription of six tested genes. Therefore, this study is beneficial for better understanding of the possible mechanism of enhanced MK production by optimization of fermentation conditions.
Source and origin of Late Paleozoic dropstones from Peninsular Malaysia: First record of Mississippian glaciogenic deposits of Gondwana in Southeast Asia
Authors: Baioumy Hassan , Anuar Mohammad Noor Akmal Bin , Nordin Mohd Nawawi Mohd , Arifin Mohd Hariri , Al‐Kahtany Khaled
Published: March 2020

This study reports several Late Paleozoic dropstone‐bearing formations in Peninsular Malaysia which were not previously investigated. Additionally, the source, formation mechanisms, and correlation to the global Late Paleozoic Ice Age (LPIA) of these dropstones are discussed. Dropstones occur as subrounded to rounded single clasts ranging in size from 0.5 to 20 cm, scattered in red mudstone, black shales, sandstones and shales, and are composed of granite, quartzite, and sandstone. Occurrence of dropstones as rounded, single clasts, and soft‐sediment deformation of the host rock with striations in the dropstones suggest a glaciomarine origin. Precambrian basement rocks and Cambrian–Ordovician quartzite and sandstones are the main sources of the dropstones. Dropstones hosted by shallow‐marine sediments are formed by dropping of clasts from icebergs, while, dropstones present in deep‐marine sediments are formed by dropping of clasts from an ice sheet. The oldest glaciomarine rocks of the Rebak and Chepor members (Singa Formation) can be correlated to the Early Carboniferous global glaciation of the LPIA episode of Gondwana. These sediments are considered as the first record of Lower Carboniferous (Mississippian) glaciomarine rocks in Southeast Asia. However, the glaciomarine deposits of the Kentut and Bukit Raja members (Singa and Kubang Pasu formations, respectively) are correlated with the global Middle Carboniferous glaciation. In addition, the glaciomarine deposits of the “undifferentiated” member (Kubang Pasu Formation), Ulang and Selang members (Singa Formation), as well as the Kenny Hill Formation, are correlative to the Late Carboniferous‐Early Permian glaciation episode known as the apex of the LPIA. These results confirm the paleomagnetic and paleontological data which suggest that the Sibumasu Terrane initially was attached to the Late Paleozoic Gondwana.
Molecular mechanisms of K+ clearance and extracellular space shrinkage—Glia cells as the stars
Authors: MacAulay Nanna
Published: March 2020

Neuronal signaling in the central nervous system (CNS) associates with release of K+ into the extracellular space resulting in transient increases in [K+]o. This elevated K+ is swiftly removed, in part, via uptake by neighboring glia cells. This process occurs in parallel to the [K+]o elevation and glia cells thus act as K+ sinks during the neuronal activity, while releasing it at the termination of the pulse. The molecular transport mechanisms governing this glial K+ absorption remain a point of debate. Passive distribution of K+ via Kir4.1‐mediated spatial buffering of K+ has become a favorite within the glial field, although evidence for a quantitatively significant contribution from this ion channel to K+ clearance from the extracellular space is sparse. The Na+/K+‐ATPase, but not the Na+/K+/Cl− cotransporter, NKCC1, shapes the activity‐evoked K+ transient. The different isoform combinations of the Na+/K+‐ATPase expressed in glia cells and neurons display different kinetic characteristics and are thereby distinctly geared toward their temporal and quantitative contribution to K+ clearance. The glia cell swelling occurring with the K+ transient was long assumed to be directly associated with K+ uptake and/or AQP4, although accumulating evidence suggests that they are not. Rather, activation of bicarbonate‐ and lactate transporters appear to lead to glial cell swelling via the activity‐evoked alkaline transient, K+‐mediated glial depolarization, and metabolic demand. This review covers evidence, or lack thereof, accumulated over the last half century on the molecular mechanisms supporting activity‐evoked K+ and extracellular space dynamics.
Nurr1Cd11bcreconditional knockout mice display inflammatory injury to nigrostriatal dopaminergic neurons
Authors: Dong Jie , Liu Xinyao , Wang Yuanyuan , Cai Huaibin , Le Weidong
Published: March 2020

Nuclear receptor‐related 1 protein (NURR1) is essential for the development and maintenance of midbrain dopaminergic (DAergic) neurons. NURR1 also protects DAergic neurons against neuroinflammation. However, it remains to be determined to what extent does NURR1 exerts its protective function through acting autonomously in the microglia. Using Cre/lox gene targeting system, we deletedNurr1in the microglia ofNurr1Cd11bcreconditional knockout (cKO) mice. TheNurr1Cd11bcrecKO mice displayed age‐dependent motor abnormalities and increased microglial activation, but with no obvious DAergic neurodegeneration. To boost the inflammatory injury, we systemically administered endotoxin lipopolysaccharide (LPS) toNurr1Cd11bcremice. As expected, LPS treatment exacerbated the motor phenotypes and inflammatory reactions inNurr1Cd11bcrecKO mice. More importantly, LPS administration caused DAergic neuron loss and α‐synuclein aggregation, two pathological hallmarks of Parkinson's disease (PD). Therefore, our findings provide in vivo evidence supporting a critical protective role of NURR1 in the microglia against inflammation‐induced degeneration of DAergic neurons in PD.
Spatiotemporal and spectral dynamics of multi‐item working memory as revealed by the n‐back task using MEG
Authors: Costers Lars , Van Schependom Jeroen , Laton Jorne , Baijot Johan , Sjøgård Martin , Wens Vincent , De Tiège Xavier , Goldman Serge , D'Haeseleer Miguel , D'hooghe Marie Beatrice , Woolrich Mark , Nagels Guy
Published: March 2020

Multi‐item working memory (WM) is a complex cognitive function thought to arise from specific frequency band oscillations and their interactions. While some theories and consistent findings have been established, there is still a lot of unclarity about the sources, temporal dynamics, and roles of event‐related fields (ERFs) and theta, alpha, and beta oscillations during WM activity. In this study, we performed an extensive whole‐brain ERF and time‐frequency analysis on n‐back magnetoencephalography data from 38 healthy controls. We identified the previously unknown sources of the n‐back M300, the right inferior temporal and parahippocampal gyrus and left inferior temporal gyrus, and frontal theta power increase, the orbitofrontal cortex. We shed new light on the role of the precuneus during n‐back activity, based on an early ERF and theta power increase, and suggest it to be a crucial link between lower‐level and higher‐level information processing. In addition, we provide strong evidence for the central role of the hippocampus in multi‐item WM behavior through the dynamics of theta and alpha oscillatory changes. Almost simultaneous alpha power decreases observed in the hippocampus and occipital fusiform gyri, regions known to be involved in letter processing, suggest that these regions together enable letter recognition, encoding and storage in WM. In summary, this study offers an extensive investigation into the spatial, temporal, and spectral characteristics of n‐back multi‐item WM activity.
The effectiveness of long‐acting injectable antipsychotics versus oral antipsychotics in the maintenance treatment of outpatients with chronic schizophrenia
Authors: Fang Su‐Chen , Liao Ding‐Lieh , Huang Cheng‐Yi , Hsu Chun‐Chi , Cheng Shu‐Li , Shao Yu‐Hsuan J.
Published: March 2020

Objective

To compare the psychiatric service utilization between patients who only received long‐acting injectable antipsychotics (LAIAs) and those who only received oral antipsychotics (OAPs) in the maintenance treatment of chronic schizophrenia.

Methods

We constructed a cohort of chronic schizophrenia patients who underwent maintenance treatment from the Taiwan National Health Insurance Research Database in 2011 and followed these patients for 12 months. We included patients who had been diagnosed with schizophrenia for at least 3 years, were not hospitalized in 2011, and had received 1 year of maintenance treatment. Inverse probability of treatment weighting logistic, linear, and negative binomial regression models were used to estimate associated psychiatric services utilization and adjust for covariate imbalances between the LAIAs and OAPs groups.

Results

Among 40,194 patients, 948 (2.36%) received only LAIAs and 39,246 (97.64%) received only OAPs. Compared with those who received only OAPs, the sole LAIAs users were associated with a lower percentage of psychiatric hospitalization (8.4% and 5.8%, respectively; odds ratio: 0.63, p < .01), shorter lengths of hospitalization days (82.8 and 65.9, respectively; coefficient [b]: −16.87, p = .03), and fewer emergency room visits (2.3 and 1.8, respectively; b: −0.24, p < .01) per patient.

Conclusions

Chronic schizophrenia patients who received only LAIs had a lower risk of disease relapse and a reduction in psychiatric service utilization than those receiving only OAPs.
Excessive ADAM17 activation occurs in uremic patients and may contribute to their immunocompromised status
Authors: Yashiro Mitsuru , Ohya Masaki , Mima Toru , Nakashima Yuri , Kawakami Kazuki , Sonou Tomohiro , Tatsuta Koichi , Yamano Yukiko , Negi Shigeo , Shigematsu Takashi
Published: March 2020

Introduction

We previously reported that fibroblast growth factor 23 (FGF23)‐klotho signaling plays a role in B cell immunity. Despite high serum levels of FGF23, a decline in immunity is frequently observed in patients on hemodialysis (HD); thus, abnormalities in the FGF23‐klotho signaling pathway in immune cells may occur in these patients.

Methods

We analyzed the number of klotho‐positive cells in peripheral blood mononuclear cells from 10 male and 6 female patients on HD and 5 healthy male subjects using flow cytometry. We analyzed the abundance of cleaved klotho protein in the murine B cell line, A20, and in the serum of HD patients and healthy subjects (HS) using flow cytometry and Western blotting. The serum level of A disintegrin and metalloprotease 17 (ADAM17) was measured in HD patients and HS using enzyme‐linked immunosorbent assay.

Results

The number of klotho‐positive B cells was reduced in HD patients. Serum ADAM17 was responsible for the reduction in klotho, as a specific ADAM17 inhibitor reversed this change. The total serum levels of ADAM17 were similar in HD patients and HS; however, activated ADAM17 was increased in the serum of HD patients.

Conclusions

We concluded that abnormal ADAM17 activation could contribute to the immunocompromised status in patients on HD, in line with the reported role of ADAM17 as an anti‐inflammatory and immunosuppressive factor.
MicroRNA‐34a‐mediated death of acute myeloid leukemia stem cells through apoptosis induction and exosome shedding inhibition via histone deacetylase 2 targeting
Authors: Hu Yanning , Ma Xiaotang , Wu Zhimei , Nong Qingwei , Liu Feng , Wang Yue , Dong Min
Published: March 2020

We investigated the role of leukemia stem cells in chemoresistance and recurrence of acute myeloid leukemia. Total RNA was isolated from cells or tissues using TRIzol reagent. Cell viability was assessed with the tetrazolium assay. MicroRNA‐34a (miR‐34a), which acts on cell death regulation pathways, was noticeably downregulated in non‐M3 acute myeloid leukemia stem cells compared with normal hematopoietic stem cells. Furthermore, inhibition of miR‐34a‐mediated suppression in leukemia stem cells was associated with poor clinical outcomes and impaired treatment efficacy in acute myeloid leukemia. Transfection with a miR‐34a mimic triggered leukemia stem cell death and prevented leukemia. Bioinformatics analysis and a dual‐luciferase reporter assay showed that miR‐34a targeted the 3′‐untranslated region of histone deacetylase 2, and the reinforced expression of miR‐34a remarkably stimulated the expression of histone deacetylase 2 in leukemia stem cells. Ectopic miR‐34a expression triggered death of leukemia stem cells via pathways involving the Janus kinase 1‐signal transducer and activator of transcription 2‐p53 axis. Targeting leukemia stem cells to trigger cell death through upregulation of miR‐34a expression could be used to diagnose and treat acute myeloid leukemia.
Conjugating homogenized liver‐extracellular matrix into decellularized hepatic scaffold for liver tissue engineering
Authors: Saleh Tarek , Ahmed Ebtehal , Yu Lina , Song Su‐Hyeon , Park Kyung‐Mee , Kwak Ho‐Hyun , Woo Heung‐Myong
Published: March 2020

The generation of a transplantable liver scaffold is crucial for the treatment of end‐stage liver failure. Unfortunately, decellularized liver scaffolds suffer from lack of bioactive molecules and functionality. In this study, we conjugated homogenized liver‐extracellular matrix (ECM) into a decellularized liver in a rat model to improve its structural and functional properties. The homogenized ECM was prepared, characterized, and subsequently perfused into ethyl carbodiimide hydrochloride (EDC)/N‐hydroxysuccinimide (NHS) activated liver scaffolds. Various techniques were performed to confirm the improvements that were accomplished through the conjugation process; these included micro/ultra‐structural analyses, biochemical analysis of ECM components, DNA quantification, swelling ratio, structural stability, calcification properties, platelet activation study, static and dynamic seeding with EAhy926 endothelial cells and HepG2 hepatocarcinoma cells, subcutaneous implantation and intrahepatic transplantation. The results showed that the conjugated scaffolds have superior micro‐ and ultrastructural and biochemical characteristics. In addition, DNA contents, swelling ratios, calcification properties, platelet reactions, and host inflammatory reactions were not altered with the conjugation process. The conjugated scaffolds revealed better cellular spreading and popularity compared to the non‐conjugated scaffolds. Intrahepatic transplantation showed that the conjugated scaffold had higher popularity of hepatic regenerative cells with better angiogenesis. The conjugation of the decellularized liver scaffold with homogenized liver‐ECM is a promising tool to improve the quality of the generated scaffold for further transplantation.
Cell–cell interaction in a coculture system consisting of CRISPR/Cas9 mediated GFP knock‐in HUVECs and MG‐63 cells in alginate‐GelMA based nanocomposites hydrogel as a 3D scaffold
Authors: Shahabipour Fahimeh , Oskuee Reza K. , Dehghani Hesam , Shokrgozar Mohammad A. , Aninwene George E. , Bonakdar Shahin
Published: March 2020

The interaction between osteogenic and angiogenic cells through a coculturing system in biocompatible materials has been considered for successfully engineering vascularized bone tissue equivalents. In this study, we developed a hydrogel‐blended scaffold consisted of gelatin methacryloyl (GelMA) and alginate enriched with hydroxyapatite nanoparticles (HAP) to model an in vitro prevascularized bone construct. The hydrogel‐based scaffold revealed a higher mechanical stiffness than those of pure (GelMA), alginate, and (GelMA+ HAP) hydrogels. In the present study, we generated a green fluorescent protein (GFP) knock‐in umbilical vein endothelial cells (HUVECs) cell line using the CRISPR/Cas9 technology. The GFP was inserted into the human‐like ROSA locus of HUVECs genome. HUVECs expressing GFP were cocultured with OB‐like cells (MG‐63) within three‐dimensionally (3D) fabricated hydrogel to investigate the response of cocultured osteoblasts and endothelial cells in a 3D structure. Cell viability under the 3D cocultured gel was higher than the 3D monocultured. Compared to the 3D monocultured condition, the cells were aligned and developed into the vessel‐like structures. During 14 days of culture periods, the cells displayed actin protrusions by the formation of spike‐like filopodia in the 3D cocultured model. Angiogenic and osteogenic‐related genes such as CD31, vWF, and osteocalcin showed higher expression in the cocultured versus the monocultured. These results have collectively indicated that the 3D cocultured hydrogel facilitates interaction among cells, thereby having a greater effect on angiogenic and osteogenic properties in the absence of induction media.
RUNX1 and RUNX2 transcription factors function in opposing roles to regulate breast cancer stem cells
Authors: Fritz Andrew J. , Hong Deli , Boyd Joseph , Kost Jason , Finstaad Kristiaan H. , Fitzgerald Mark P. , Hanna Sebastian , Abuarqoub Alqassem H. , Malik Miles , Bushweller John , Tye Coralee , Ghule Prachi , Gordon Jonathan , Frietze Seth , Zaidi Sayyed K. , Lian Jane B. , Stein Janet L. , Stein Gary S.
Published: March 2020

Breast cancer stem cells (BCSCs) are competent to initiate tumor formation and growth and refractory to conventional therapies. Consequently BCSCs are implicated in tumor recurrence. Many signaling cascades associated with BCSCs are critical for epithelial‐to‐mesenchymal transition (EMT). We developed a model system to mechanistically examine BCSCs in basal‐like breast cancer using MCF10AT1 FACS sorted for CD24 (negative/low in BCSCs) and CD44 (positive/high in BCSCs). Ingenuity Pathway Analysis comparing RNA‐seq on the CD24−/low versus CD24+/high MCF10AT1 indicates that the top activated upstream regulators include TWIST1, TGFβ1, OCT4, and other factors known to be increased in BCSCs and during EMT. The top inhibited upstream regulators include ESR1, TP63, and FAS. Consistent with our results, many genes previously demonstrated to be regulated by RUNX factors are altered in BCSCs. The RUNX2 interaction network is the top significant pathway altered between CD24−/low and CD24+/high MCF10AT1. RUNX1 is higher in expression at the RNA level than RUNX2. RUNX3 is not expressed. While, human‐specific quantitative polymerase chain reaction primers demonstrate that RUNX1 and CDH1 decrease in human MCF10CA1a cells that have grown tumors within the murine mammary fat pad microenvironment, RUNX2 and VIM increase. Treatment with an inhibitor of RUNX binding to CBFβ for 5 days followed by a 7‐day recovery period results in EMT suggesting that loss of RUNX1, rather than increase in RUNX2, is a driver of EMT in early stage breast cancer. Increased understanding of RUNX regulation on BCSCs and EMT will provide novel insight into therapeutic strategies to prevent recurrence.
A guideline for homology modeling of the proteins from newly discovered betacoronavirus, 2019 novel coronavirus (2019‐nCoV)
Authors: Dong Shengjie , Sun Jiachen , Mao Zhuo , Wang Lu , Lu Yi‐Lin , Li Jiesen
Published: March 2020

During an outbreak of respiratory diseases including atypical pneumonia in Wuhan, a previously unknown β‐coronavirus was detected in patients. The newly discovered coronavirus is similar to some β‐coronaviruses found in bats but different from previously known SARS‐CoV and MERS‐CoV. High sequence identities and similarities between 2019‐nCoV and SARS‐CoV were found. In this study, we searched the homologous templates of all nonstructural and structural proteins of 2019‐nCoV. Among the nonstructural proteins, the leader protein (nsp1), the papain‐like protease (nsp3), the nsp4, the 3C‐like protease (nsp5), the nsp7, the nsp8, the nsp9, the nsp10, the RNA‐directed RNA polymerase (nsp12), the helicase (nsp13), the guanine‐N7 methyltransferase (nsp14), the uridylate‐specific endoribonuclease (nsp15), the 2'‐O‐methyltransferase (nsp16), and the ORF7a protein could be built on the basis of homology templates. Among the structural proteins, the spike protein (S‐protein), the envelope protein (E‐protein), and the nucleocapsid protein (N‐protein) can be constructed based on the crystal structures of the proteins from SARS‐CoV. It is known that PL‐Pro, 3CL‐Pro, and RdRp are important targets for design antiviral drugs against 2019‐nCoV. And S protein is a critical target candidate for inhibitor screening or vaccine design against 2019‐nCoV because coronavirus replication is initiated by the binding of S protein to cell surface receptors. It is believed that these proteins should be useful for further structure‐based virtual screening and related computer‐aided drug development and vaccine design.
Development of hepatic pathology in GBV‐B‐infected red‐bellied tamarins (Saguinus labiatus)
Authors: Dale Jessica M. , Hood Simon P. , Bowen Ori , Bright Helen , Cutler Keith L. , Berry Neil , Almond Neil , Goldin Robert , Karayiannis Peter , Rose Nicola J.
Published: March 2020

GB virus B (GBV‐B) is a new world monkey‐associated flavivirus used to model acute hepatitis C virus (HCV) infection. Critical for evaluation of antiviral or vaccine approaches is an understanding of the effect of HCV on the liver at different stages of infection. In the absence of longitudinal human tissue samples at defined time points, we have characterized changes in tamarins. As early as 2 weeks post‐infection histological changes were noticeable, and these were established in all animals by 6 weeks. Despite high levels of liver‐associated viral RNA, there was reversal of hepatic damage on clearance of peripheral virus though fibrosis was demonstrated in four tamarins. Notably, viral RNA burden in the liver dropped to near undetectable or background levels in all animals which underwent a second viral challenge, highlighting the efficacy of the immune response in removing foci of replication in the liver. These data add to the knowledge of GBV‐B infection in New World primates which can offer attractive systems for the testing of prophylactic and therapeutic treatments and the evaluation of their utility in preventing or reversing liver pathology.