bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein tyrosine phosphatases in skeletal development and diseases
Authors: Yang Huiliang , Wang Lijun , Shigley Christian , Yang Wentian 
Published: January 2022

AbstractSkeletal development and homeostasis in mammals are modulated by finely coordinated processes of migration, proliferation, differentiation, and death of skeletogenic cells originating from the mesoderm and neural crest. Numerous molecular mechanisms are involved in these regulatory processes, one of which is protein posttranslational modifications, particularly protein tyrosine phosphorylation (PYP). PYP occurs mainly through the action of protein tyrosine kinases (PTKs), modifying protein enzymatic activity, changing its cellular localization, and aiding in the assembly or disassembly of protein signaling complexes. Under physiological conditions, PYP is balanced by the coordinated action of PTKs and protein tyrosine phosphatases (PTPs). Dysregulation of PYP can cause genetic, metabolic, developmental, and oncogenic skeletal diseases. Although PYP is a reversible biochemical process, in contrast to PTKs, little is known about how this equilibrium is modulated by PTPs in the skeletal system. Whole-genome sequencing has revealed a large and diverse superfamily of PTP genes (over 100 members) in humans, which can be further divided into cysteine (Cys)-, aspartic acid (Asp)-, and histidine (His)-based PTPs. Here, we review current knowledge about the functions and regulatory mechanisms of 28 PTPs involved in skeletal development and diseases; 27 of them belong to class I and II Cys-based PTPs, and the other is an Asp-based PTP. Recent progress in analyzing animal models that harbor various mutations in these PTPs and future research directions are also discussed. Our literature review indicates that PTPs are as crucial as PTKs in supporting skeletal development and homeostasis.
Pharmacological targeting PIKfyve and tubulin as an effective treatment strategy for double-hit lymphoma
Authors: Feng Liying , Chen Kai , Huang Wei , Jiang Yuelong , Sun Xihuan , Zhou Yong , Li Li , Li Yin , Deng Xianming , Xu Bing 
Published: January 2022

AbstractDouble-hit lymphoma is one of the most aggressive and refractory lymphoma subtypes with recurrent genetic abnormalities of MYC and BCL-2 or BCL6 rearrangement, leading to a poor prognosis in the present clinical practice. Therefore, new therapeutic strategies for eliminating double-hit lymphomas are urgently needed. Here, we reported that HZX-02-059, a novel PIKfyve and tubulin dual-target inhibitor, showed a highly cytotoxic activity against double-hit lymphoma cell lines in vitro and in vivo through a noncanonical caspase-independent cell death, methuosis. Mechanistically, the cytotoxicity triggered by HZX-02-059 was contributed to the PIKfyve/TFEB axis-induced cell death of methuosis, as well as the inhibition of tubulin and mTOR/Myc axis-induced cell cycle arrest. In summary, the present findings suggest that HZX-02-059 represents a good starting point for developing targeted therapeutics against double-hit lymphomas.
Amazon forests capture high levels of atmospheric mercury pollution from artisanal gold mining
Authors: Gerson Jacqueline R. , Szponar Natalie , Zambrano Angelica Almeyda , Bergquist Bridget , Broadbent Eben , Driscoll Charles T. , Erkenswick Gideon , Evers David C. , Fernandez Luis E. , Hsu-Kim Heileen , Inga Giancarlo , Lansdale Kelsey N. , Marchese Melissa J. , Martinez Ari , Moore Caroline , Pan William K. , Purizaca Raúl Pérez , Sánchez Victor , Silman Miles , Ury Emily A. , Vega Claudia , Watsa Mrinalini , Bernhardt Emily S. 
Published: January 2022

AbstractMercury emissions from artisanal and small-scale gold mining throughout the Global South exceed coal combustion as the largest global source of mercury. We examined mercury deposition and storage in an area of the Peruvian Amazon heavily impacted by artisanal gold mining. Intact forests in the Peruvian Amazon near gold mining receive extremely high inputs of mercury and experience elevated total mercury and methylmercury in the atmosphere, canopy foliage, and soils. Here we show for the first time that an intact forest canopy near artisanal gold mining intercepts large amounts of particulate and gaseous mercury, at a rate proportional with total leaf area. We document substantial mercury accumulation in soils, biomass, and resident songbirds in some of the Amazon’s most protected and biodiverse areas, raising important questions about how mercury pollution may constrain modern and future conservation efforts in these tropical ecosystems.
Accumulation of microbial DNAs promotes to islet inflammation and β cell abnormalities in obesity in mice
Authors: Gao Hong , Luo Zhenlong , Ji Yudong , Tang Kechun , Jin Zhongmou , Ly Crystal , Sears Dorothy D. , Mahata Sushil , Ying Wei 
Published: January 2022

AbstractVarious microbial products leaked from gut lumen exacerbate tissue inflammation and metabolic disorders in obesity. Vsig4+ macrophages are key players preventing infiltration of bacteria and their products into host tissues. However, roles of islet Vsig4+ macrophages in the communication between microbiota and β cells in pathogenesis of obesity-associated islet abnormalities are unknown. Here, we find that bacterial DNAs are enriched in β cells of individuals with obesity. Intestinal microbial DNA-containing extracellular vesicles (mEVs) readily pass through obese gut barrier and deliver microbial DNAs into β cells, resulting in elevated inflammation and impaired insulin secretion by triggering cGAS/STING activation. Vsig4+ macrophages prevent mEV infiltration into β cells through a C3-dependent opsonization, whereas loss of Vsig4 leads to microbial DNA enrichment in β cells after mEV treatment. Removal of microbial DNAs blunts mEV effects. Loss of Vsig4+ macrophages leads to microbial DNA accumulation in β cells and subsequently obesity-associated islet abnormalities.
Temperature- and vacancy-concentration-dependence of heat transport in Li3ClO from multi-method numerical simulations
Authors: Pegolo Paolo , Baroni Stefano , Grasselli Federico 
Published: January 2022

AbstractDespite governing heat management in any realistic device, the microscopic mechanisms of heat transport in all-solid-state electrolytes are poorly known: existing calculations, all based on simplistic semi-empirical models, are unreliable for superionic conductors and largely overestimate their thermal conductivity. In this work, we deploy a combination of state-of-the-art methods to calculate the thermal conductivity of a prototypical Li-ion conductor, the Li3ClO antiperovskite. By leveraging ab initio, machine learning, and force-field descriptions of interatomic forces, we are able to reveal the massive role of anharmonic interactions and diffusive defects on the thermal conductivity and its temperature dependence, and to eventually embed their effects into a simple rationale which is likely applicable to a wide class of ionic conductors.
Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis
Authors: Al Khleifat Ahmad , Iacoangeli Alfredo , van Vugt Joke J. F. A. , Bowles Harry , Moisse Matthieu , Zwamborn Ramona A. J. , van der Spek Rick A. A. , Shatunov Aleksey , Cooper-Knock Johnathan , Topp Simon , Byrne Ross , Gellera Cinzia , López Victoria , Jones Ashley R. , Opie-Martin Sarah , Vural Atay , Campos Yolanda , van Rheenen Wouter , Kenna Brendan , Van Eijk Kristel R. , Kenna Kevin , Weber Markus , Smith Bradley , Fogh Isabella , Silani Vincenzo , Morrison Karen E. , Dobson Richard , van Es Michael A. , McLaughlin Russell L. , Vourc’h Patrick , Chio Adriano , Corcia Philippe , de Carvalho Mamede , Gotkine Marc , Panades Monica P. , Mora Jesus S. , Shaw Pamela J. , Landers John E. , Glass Jonathan D. , Shaw Christopher E. , Basak Nazli , Hardiman Orla , Robberecht Wim , Van Damme Philip , van den Berg Leonard H. , Veldink Jan H. , Al-Chalabi Ammar 
Published: January 2022

AbstractThere is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwise unexplained heritability. We therefore investigated association between structural variation in a set of 25 ALS genes, and ALS risk and phenotype. As expected, the repeat expansion in the C9orf72 gene was identified as associated with ALS. Two other ALS-associated structural variants were identified: inversion in the VCP gene and insertion in the ERBB4 gene. All three variants were associated both with increased risk of ALS and specific phenotypic patterns of disease expression. More than 70% of people with respiratory onset ALS harboured ERBB4 insertion compared with 25% of the general population, suggesting respiratory onset ALS may be a distinct genetic subtype.
Oligonucleotide correction of an intronic TIMMDC1 variant in cells of patients with severe neurodegenerative disorder
Authors: Kumar Raman , Corbett Mark A. , Smith Nicholas J. C. , Hock Daniella H. , Kikhtyak Zoya , Semcesen Liana N. , Morimoto Atsushi , Lee Sangmoon , Stroud David A. , Gleeson Joseph G. , Haan Eric A. , Gecz Jozef 
Published: January 2022

AbstractTIMMDC1 encodes the Translocase of Inner Mitochondrial Membrane Domain-Containing protein 1 (TIMMDC1) subunit of complex I of the electron transport chain responsible for ATP production. We studied a consanguineous family with two affected children, now deceased, who presented with failure to thrive in the early postnatal period, poor feeding, hypotonia, peripheral neuropathy and drug-resistant epilepsy. Genome sequencing data revealed a known, deep intronic pathogenic variant TIMMDC1 c.597-1340A>G, also present in gnomAD (~1/5000 frequency), that enhances aberrant splicing. Using RNA and protein analysis we show almost complete loss of TIMMDC1 protein and compromised mitochondrial complex I function. We have designed and applied two different splice-switching antisense oligonucleotides (SSO) to restore normal TIMMDC1 mRNA processing and protein levels in patients’ cells. Quantitative proteomics and real-time metabolic analysis of mitochondrial function on patient fibroblasts treated with SSOs showed restoration of complex I subunit abundance and function. SSO-mediated therapy of this inevitably fatal TIMMDC1 neurologic disorder is an attractive possibility.
Density functional tight binding approach utilized to study X-ray-induced transitions in solid materials
Authors: Lipp Vladimir , Tkachenko Victor , Stransky Michal , Aradi Bálint , Frauenheim Thomas , Ziaja Beata 
Published: January 2022

AbstractIntense X-ray pulses from free-electron lasers can trigger ultrafast electronic, structural and magnetic transitions in solid materials, within a material volume which can be precisely shaped through adjustment of X-ray beam parameters. This opens unique prospects for material processing with X rays. However, any fundamental and applicational studies are in need of computational tools, able to predict material response to X-ray radiation. Here we present a dedicated computational approach developed to study X-ray induced transitions in a broad range of solid materials, including those of high chemical complexity. The latter becomes possible due to the implementation of the versatile density functional tight binding code DFTB+ to follow band structure evolution in irradiated materials. The outstanding performance of the implementation is demonstrated with a comparative study of XUV induced graphitization in diamond.
Digital twin data-driven proactive job-shop scheduling strategy towards asymmetric manufacturing execution decision
Authors: Zhang Fuqiang , Bai Junyan , Yang Dongyu , Wang Qiang 
Published: January 2022

AbstractThe information asymmetry phenomenon widely exists in production management decisions due to the latency of manufacturing data transmissions. Also, stochastic events on the physical production site will result in information asymmetry, which may lead to inconsistency between current execution and previous resource allocation plans. It is meaningful and important for developing an information model based on the Internet of Manufacturing Things to timely and actively adjust the scheduling strategy to meet the symmetry requirements of the production execution process. Based on the digital twin data collected from the workshop, a proactive job-shop scheduling strategy was discussed in this paper. Firstly, the mechanism for the influence of delayed local operations on makespan was deduced. Then, a framework for implementing the proactive job-shop scheduling strategy was proposed. Coordination point was used to determine the adjustment interval of local operations; right-shift rule with delay time constraints was used to adjust the unprocessed operation sequences on machines. Finally, the examples including 6*6 (6 jobs, 6 machines) and 20*40 (20 jobs, 40 machines) were presented to verify the effectiveness and scalability of the proposed method. It can be predicted that the proactive scheduling strategy provides the online decisions for the efficient and smooth execution of the digital twin-driven workshop production.
Liraglutide, a glucagon-like peptide 1 receptor agonist, exerts analgesic, anti-inflammatory and anti-degradative actions in osteoarthritis
Authors: Meurot C. , Martin C. , Sudre L. , Breton J. , Bougault C. , Rattenbach R. , Bismuth K. , Jacques C. , Berenbaum F. 
Published: January 2022

AbstractOsteoarthritis (OA) is a common disabling disease worldwide, with no effective and safe disease-modifying drugs (DMOAD) in the market. However, studies suggest that drugs, such as liraglutide, which possess strong potential in decreasing low-grade systemic inflammation may be effective in treating OA. Therefore, the aim of this study was to examine the anti-inflammatory, analgesic, and anti-degradative effects in OA using in vitro and in vivo experiments. The results showed that intra-articular injection of liraglutide alleviated pain-related behavior in in vivo sodium monoiodoacetate OA mouse model, which was probably driven by the GLP-1R-mediated anti-inflammatory activity of liraglutide. Moreover, liraglutide treatment significantly decreased IL-6, PGE2 and nitric oxide secretion, and the expression of inflammatory genes in vitro in chondrocytes and macrophages in a dose-dependent manner. Additionally, liraglutide shifted polarized macrophage phenotype in vitro from the pro-inflammatory M1 phenotype to the M2 anti-inflammatory phenotype. Furthermore, liraglutide exerted anti-catabolic activity by significantly decreasing the activities of metalloproteinases and aggrecanases, a family of catabolic enzymes involved in cartilage breakdown in vitro. Overall, the findings of this study showed that liraglutide ameliorated OA-associated pain, possess anti-inflammatory and analgesic properties, and could constitute a novel therapeutic candidate for OA treatment.
Physiological responses of Holstein calves to heat stress and dietary supplementation with a postbiotic from Aspergillus oryzae
Authors: Ríus A. G. , Kaufman J. D. , Li M. M. , Hanigan M. D. , Ipharraguerre I. R. 
Published: January 2022

AbstractIncreased ambient temperature causes heat stress in mammals, which affects physiological and molecular functions. We have recently reported that the dietary administration of a postbiotic from Aspergillus oryzae (AO) improves tolerance to heat stress in fruit flies and cattle. Furthermore, heat-induced gut dysfunction and systemic inflammation have been ameliorated in part by nutritional interventions. The objective of this study was to characterize the phenotypic response of growing calves to heat stress compared to thermoneutral ad libitum fed and thermoneutral feed-restricted counterparts and examining the physiologic alterations associated with the administration of the AO postbiotic to heat-stressed calves with emphasis on intestinal permeability. In this report, we expand previous work by first demonstrating that heat stress reduced partial energetic efficiency of growth in control (45%) but not in AO-fed calves (62%) compared to thermoneutral animals (66%). While heat stress increased 20% the permeability of the intestine, AO postbiotic and thermoneutral treatments did not affect this variable. In addition, AO postbiotic reduced fecal water content relative to thermoneutral and heat stress treatments. Heat stress increased plasma concentrations of serum amyloid A, haptoglobin and lipocalin-2, and administration of AO postbiotic did not ameliorate this effect. In summary, our findings indicated that heat stress led to reduced nutrient-use efficiency and increased systemic inflammation. Results suggest that the AO postbiotic improved energy-use efficiency, water absorption, and the intestinal permeability in heat stress-mediated increase in gut permeability but did not reduce heat stress-mediated rise in markers of systemic inflammation.
Dust entrainment in photoevaporative winds: Synthetic observations of transition disks
Authors: Franz R. , Picogna G. , Ercolano B. , Casassus S. , Birnstiel T. , Rab Ch. , Pérez S. 
Published: January 2022

Context. X-ray- and extreme-ultraviolet- (XEUV-) driven photoevaporative winds acting on protoplanetary disks around young T Tauri stars may strongly impact disk evolution, affecting both gas and dust distributions. Small dust grains in the disk are entrained in the outflow and may produce a detectable signal. In this work, we investigate the possibility of detecting dusty outflows from transition disks with an inner cavity.
Aims. We compute dust densities for the wind regions of XEUV-irradiated transition disks and determine whether they can be observed at wavelengths 0.7 ≲ λobs [μm] ≲ 1.8 with current instrumentation.
Methods. We simulated dust trajectories on top of 2D hydrodynamical gas models of two transition disks with inner holes of 20 and 30 AU, irradiated by both X-ray and EUV spectra from a central T Tauri star. The trajectories and two different settling prescriptions for the dust distribution in the underlying disk were used to calculate wind density maps for individual grain sizes. Finally, the resulting dust densities were converted to synthetic observations in scattered and polarised light.
Results. For an XEUV-driven outflow around a M* = 0.7 M⊙ T Tauri star with LX = 2 × 1030 erg s-1, we find dust mass-loss rates Ṁdust ≲ 2.0 × 10−3 Ṁgas, and if we invoke vertical settling, the outflow is quite collimated. The synthesised images exhibit a distinct chimney-like structure. The relative intensity of the chimneys is low, but their detection may still be feasible with current instrumentation under optimal conditions.
Conclusions. Our results motivate observational campaigns aimed at the detection of dusty photoevaporative winds in transition disks using JWST NIRCam and SPHERE IRDIS.
Taking the Green Road Towards Pharmaceutical Manufacturing
Authors: Federsel Hans-Jürgen 
Published: January 2022

AbstractThe introduction of the Green Chemistry Principles in the late 1990s formed the basis for a transition to a greener environment. These Principles have become an integral part in the work on designing chemical processes, especially for large-scale manufacture. The ultimate target is the achievement of a sustainable production method allowing hundreds of tons of valuable materials to be prepared. For this purpose, a holistic view must be applied to the elements constituting a fully-fledged process encompassing layout of the synthetic route, defining starting materials and their origin, output of product and quality features, quantity of effluent streams and waste, recovery and recycling of chemicals involved, and energy consumption. These parameters form a complex matrix where the individual components are in a complicated relationship with each other. This short review addresses these issues and the benefits of life-cycle assessment and metrics commonly used to measure the performance of chemical manufacturing – all from a pharmaceutical industry perspective as experienced by the author.1	Introduction: Facing Severe Challenges2	The Historical Context: Addressing an Image Problem3	Prospects, Drivers and Roadmap for the Green Future4	Living by the Principles: Industrial Perspectives5	Taking the Green Route – Catalysis Leading the Way: Case Stories6	State of the Art: How Green Are We?7	Sending Signals, Creating Impressions: Focus on Communication8	Conclusions
Slow liquid dynamics near solid surfaces: Insights from site-resolved studies of ionic liquids in silica confinement
Authors: Köster Robin , Vogel Michael 
Published: January 2022

We perform molecular dynamics simulations of ionic liquids that are confined between amorphous silica surfaces and composed of 1-butyl-3-methylimidazolium [C4mim] cations and tetrafluoroborate [BF4], hexafluorophosphate [PF6], or bis(trifluoromethylsulfonyl)imide [TFSI] anions. Near the silica surfaces, we observe strong slowdowns of ion dynamics, which involve mainly two layers of ions and amount to about two orders of magnitude, depending on temperature and anion type. For a detailed investigation of the slow interfacial dynamics, we determine the adsorption sites of the various anion species on the amorphous silica surfaces and ascertain the repopulation dynamics of these sites. The analysis reveals that the mean residence times show a broad distribution, where anions stay longer at sites, which provide better opportunities for hydrogen bonding. Furthermore, the mean residence times follow Arrhenius laws, providing access to site-specific activation energies Ei. The distributions G(Ei) have Gaussian shape with mean values from ∼0.40 eV for TFSI to ∼0.48 eV for PF6 and standard deviations of about 0.31 eV. Thus, the amorphous silica surfaces impose static and disordered energy landscapes to the neighboring liquid, which have considerable ruggedness and, in this way, substantially hinder ion rearrangements. We discuss that qualitatively similar situations are expected for all kinds of confined liquids.
Environmental remediation promotes the restoration of biodiversity in the Shenzhen Bay Estuary, South China
Authors: Xu Hualin , Liu Ke , Ning Tianzhu , Huang Gu , Zhang Qianmei , Li Yuelin , Wang Mengqi , Fan Yiming , an Weili , Ji Lingbo , Guo Qinfeng , Ren Hai 
Published: January 2022

ABSTRACT

Background
Rapid urbanization has greatly changed land-use patterns in many estuarine areas around the world, including the Guangdong–Hong Kong–Macao Greater Bay Area (GBA) resulting in serious water pollution and ecosystem degradation. Shenzhen City has conducted comprehensive ecological management and restoration in the Shenzhen Bay since 2007. The natural vegetation consisting of mangroves, semi-mangroves, wetland plants, and terrestrial plants were restored from the bund to the inner bank of the Fengtang River. Rain and sewage flow diversion systems were established. The non-point source and point-source sewage are now treated in municipal sewage treatment plants, then naturally flow through the constructed wetland, and then through a natural wetland, restored natural embankment, and finally through mangrove communities substantially improving water quality.

Result
The restoration of the wetland has increased animal and microbial diversity and has supported the establishment of a complex and stable food web. With water purification and habitat restoration, the number of alien invasive plants in the estuarine ecosystem has decreased, and the diversity of native species of birds, fish, macrobenthos, amphibians, and reptiles has increased.

Conclusion
These improvements indicate that human beings and nature can coexist in support of the sustainable development of Shenzhen City.