bluuebunny/crossref_metadata_2025_split huggingface dataset:
Harnessing Split‐Inteins as a Tool for the Selective Modification of Surface Receptors in Live Cells
Authors: Ray Devin M. , Flood Julia R. , David Yael 
Published: September 2022

AbstractBiochemical studies of integral membrane proteins are often hampered by low purification yields and technical limitations such as aggregation causing in vitro manipulations to be challenging. The ability of controlling proteins in live cells bypasses these limitations while broadening the scope of accessible questions owing to the proteins being in their native environment. Here we take advantage of the intein biorthogonality to mammalian systems, site specificity, fast kinetics, and auto‐processing nature as an attractive option for modifying surface proteins. Using EGFR as a model, we demonstrate that the split‐intein pair AvaN/NpuC can be used to efficiently and specifically modify target membrane proteins with a synthetic adduct for downstream live cell application.
DNA Strand Displacement with Base Pair Stabilizers: Purine‐2,6‐Diamine and 8‐Aza‐7‐Bromo‐7‐Deazapurine‐2,6‐Diamine Oligonucleotides Invade Canonical DNA and New Fluorescent Pyrene Click Sensors Monitor the Reaction
Authors: Zhang Aigui , Kondhare Dasharath , Leonard Peter , Seela Frank 
Published: September 2022

AbstractPurine‐2,6‐diamine and 8‐aza‐7‐deaza‐7‐bromopurine‐2,6‐diamine 2’‐deoxyribonucleosides (1and2) were implemented in isothermal DNA strand displacement reactions. Nucleoside1is a weak stabilizer of dA‐dT base pairs, nucleoside2evokes strong stabilization. Strand displacement reactions used single‐stranded invaders with single and multiple incorporations of stabilizers. Displacement is driven by negative enthalpy changes between target and displaced duplex. Toeholds are not required. Two new environmental sensitive fluorescent pyrene sensors were developed to monitor the progress of displacement reactions. Pyrene was connected to the nucleobase in the invader or to a dendritic linker in the output strand. Both new sensors were constructed by click chemistry; phosphoramidites and oligonucleotides were prepared. Sensors show monomer or excimer emission. Fluorescence intensity changes when the displacement reaction progresses. Our work demonstrates that strand displacement with base pair stabilizers is applicable to DNA, RNA and to related biopolymers with applications in chemical biology, nanotechnology and medicinal diagnostics.
Numerical simulation of fine particle liquid–solid flow in porous media based on LBM‐IBM‐DEM
Authors: Fo Bin , Xu Ruifu , Xi Jianfei , Lu Yang , Song Xianping , Cai Jie , Gu Zhongzhu 
Published: September 2022

AbstractFine particle liquid–solid flow in porous media is involved in many industrial processes such as oil exploitation, geothermal reinjection, and filtration systems. It is of great significance to master the behaviours of the fine particle liquid–solid flow in porous media. At present, there are few studies on the influences of the migration of fine particles on the flow field in porous media, and the effects of the porosity of porous media and inlet fluid velocity on the migration behaviours of fine particles in porous media. In this paper, a liquid–solid flow model was established based on the lattice Boltzmann method (LBM)‐immersed boundary method (IBM)‐distinct element method (DEM) and verified by the classical Drag Kiss Tumble (DKT) phenomena and flow around a cylinder successfully. In this model, the interaction between solid particles is analyzed using the distinct element method, and the interaction between fine particles and flow field is handled by IBM. Then, the migration and blockage of fine particles in porous media was studied using this model. It is found that, in addition to the blockage, a large amount of blocked‐surface sliding‐separation occur in fine particles. At the same time, the decrease in porosity increases the damage degree of fine particles on the permeability. The porosity exerts great influence on the penetration rate and dispersion behaviour of fine particles. The inlet fluid velocity mainly affects the residence time of fine particles and the average velocity of motion in the direction perpendicular to the main flow direction.
Synthesis of Photosensitizers Based on Tetrapyrrolic Macrocycles for Combination with Antibiotics: Dual Inactivation of Bacteria
Authors: Aroso Rafael T. , Piccirillo Giusi , Dias Lucas D. , Pinto Sara M. A. , Arnaut Luís G. , Pereira Mariette M. 
Published: September 2022

AbstractThe combination of photodynamic therapy with antibiotics or antimicrobial peptides for inactivation of bacteria is an area of growing interest due to the synergistic effect already observed by many authors. It has been shown that the efficiency of this dual antimicrobial therapy is highly dependent on the structure of the photosensitizer, being tetrapyrrolic macrocycles the ones with most promising results. There are a few review articles in the recent literature describing the main microbiological results concerning this dual inactivation of bacteria, but none of them focus on the synthetic processes of these photosensitizers and their remarkable chemical versatility. Therefore, herein we present an overview on synthetic methodologies for preparation of tetrapyrrolic macrocycles and their conjugates with antibiotics or antimicrobial peptides, for use in dual inactivation of bacteria. This review will be divided in two sections concerning the physical or covalent combinations of PS with antibiotic/cationic peptides, followed by brief critical analysis on their corresponding antimicrobial outcomes.
Environmental DNA metabarcoding read numbers and their variability predict species abundance, but weakly in non‐dominant species
Authors: Skelton James , Cauvin Allison , Hunter Margaret E. 
Published: September 2022

AbstractMetabarcoding of environmental DNA (eDNA) provides more comprehensive, efficient, and non‐invasive sampling of biological communities than conventional methods. However, limitations of metabarcoding include taxon‐specific biases in amplification and sequencing that distort assessments of community composition. Further, hyper‐abundant species may disproportionately affect community composition assessments and impair the detection of rare species (i.e., “species masking”). In this study, we examine methodological approaches to improve eDNA metabarcoding assessments of community structure using fish community diversity in a pond in south Florida using MiFish primers modified to improve cichlid detection. Mitochondrial 12S eDNA amplicon sequencing via Illumina NovaSeq was analyzed using the DADA2 model‐based exact sequence inference. The fish species and abundances in the system were recorded during piscicide treatment and subsequent native species restocking. Our results demonstrate that (1) ultra‐high‐throughput sequencing on the newer NovaSeq patterned flow cell provided reliable detection of very rare taxa—with detections of a single individual. (2) Read numbers were significantly correlated to the total surface area of the fish population, and numerical abundance to a lesser degree; however, dominant taxa largely drove those correlations, and simulations showed that biases in the most abundant taxa will have disproportionate effects on the strength of the correlation. (3) The read number coefficient of variation for each species across spatially separated replicate samples may provide less biased abundance estimates compared with estimates based on average read counts. Finally, (4) exact sequence inference detected multiple haplotypes and population genetic diversity within a species. Our results demonstrate the real‐world metabarcoding capacity to reveal community structure and reliably detect rare species and unique haplotypes and shows that read numbers can, to a limited degree, be used to infer the size of fish populations. Careful examination of detection biases among dominant taxa and spatial variation among samples are required for rigorous eDNA‐based estimates of community structure. Our results demonstrate the capacity of NovaSeq metabarcoding to reveal freshwater fish community structure and reliably detect rare species and unique haplotypes. Metabarcoding read numbers were significantly correlated to the total surface area of the fish species' populations, allowing for conditional inferences of population sizes. However, dominant taxa largely drove those correlations, and simulations indicated that biases toward the most abundant taxa will have disproportionate effects on the strength of the correlation.
P2X7 is expressed on human innate‐like T lymphocytes and mediates susceptibility to ATP‐induced cell death
Authors: Winzer Riekje , Serracant‐Prat Arnau , Brock Valerie J. , Pinto‐Espinoza Carolina , Rissiek Björn , Amadi Miriam , Eich Niklas , Rissiek Anne , Schneider Enja , Magnus Tim , Guse Andreas H. , Diercks Björn‐Philipp , Koch‐Nolte Friedrich , Tolosa Eva 
Published: September 2022

AbstractExtracellular ATP activates the P2X7 receptor, leading to inflammasome activation and release of pro‐inflammatory cytokines in monocytes. However, a detailed analysis of P2X7 receptor expression and function in the human T cell compartment has not been reported. Here, we used a P2X7‐specific nanobody to assess cell membrane expression and function of P2X7 on peripheral T lymphocyte subsets. The results show that innate‐like T cells, which effectively react to innate stimuli by secreting high amounts of pro‐inflammatory cytokines, have the highest expression of P2X7 in the human T cell compartment. Using Tγδ cells as example for an innate‐like lymphocyte population, we demonstrate that these cells are more sensitive to P2X7 receptor activation than conventional T cells, affecting fundamental cellular mechanisms like calcium signaling and ATP‐induced cell death. The increased susceptibility of innate‐like T cells to P2X7‐mediated cell death provides a mechanism to control their homeostasis under inflammatory conditions. Understanding the expression and function of P2X7 on human immune cells is essential to assume the benefits and consequences of newly developed P2X7‐based therapeutic approaches.
The human posterior cingulate, retrosplenial, and medial parietal cortex effective connectome, and implications for memory and navigation
Authors: Rolls Edmund T. , Wirth Sylvia , Deco Gustavo , Huang Chu‐Chung , Feng Jianfeng 
Published: September 2022

AbstractThe human posterior cingulate, retrosplenial, and medial parietal cortex are involved in memory and navigation. The functional anatomy underlying these cognitive functions was investigated by measuring the effective connectivity of these Posterior Cingulate Division (PCD) regions in the Human Connectome Project‐MMP1 atlas in 171 HCP participants, and complemented with functional connectivity and diffusion tractography. First, the postero‐ventral parts of the PCD (31pd, 31pv, 7m, d23ab, and v23ab) have effective connectivity with the temporal pole, inferior temporal visual cortex, cortex in the superior temporal sulcus implicated in auditory and semantic processing, with the reward‐related vmPFC and pregenual anterior cingulate cortex, with the inferior parietal cortex, and with the hippocampal system. This connectivity implicates it in hippocampal episodic memory, providing routes for “what,” reward and semantic schema‐related information to access the hippocampus. Second, the antero‐dorsal parts of the PCD (especially 31a and 23d, PCV, and also RSC) have connectivity with early visual cortical areas including those that represent spatial scenes, with the superior parietal cortex, with the pregenual anterior cingulate cortex, and with the hippocampal system. This connectivity implicates it in the “where” component for hippocampal episodic memory and for spatial navigation. The dorsal–transitional–visual (DVT) and ProStriate regions where the retrosplenial scene area is located have connectivity from early visual cortical areas to the parahippocampal scene area, providing a ventromedial route for spatial scene information to reach the hippocampus. These connectivities provide important routes for “what,” reward, and “where” scene‐related information for human hippocampal episodic memory and navigation. The midcingulate cortex provides a route from the anterior dorsal parts of the PCD and the supracallosal part of the anterior cingulate cortex to premotor regions.
Clinicogenomic characteristics and synthetic lethal implications of germline homologous recombination‐deficient hepatocellular carcinoma
Authors: An Jihyun , Oh Ji‐Hye , Oh Bora , Oh Yoo‐Jin , Ju Jin‐Sung , Kim Wonkyung , Kang Hyo Jung , Sung Chang Ohk , Shim Ju Hyun 
Published: September 2022

Backgrounds and Aims:
We performed an in‐depth examination of pathogenic germline variants (PGVs) and somatic variants in DNA damage response (DDR) genes in hepatocellular carcinoma (HCC) to explore their clinical and genomic impacts.

Approach and Results:
We used a merged whole‐exome or RNA sequencing data set derived from in‐house (n = 230) and The Cancer Genome Atlas (n = 362) databases of multiethnic HCC samples. We also evaluated synthetic lethal approaches targeting mutations in homologous recombination (HR) genes using HCC cells selected from five genomic databases of cancer cell lines. A total of 110 PGVs in DDR pathways in 96 patients were selected. Of the PGV carriers, 44 were HR‐altered and found to be independently associated with poorer disease‐free survival after hepatectomy. The most frequently altered HR gene in both germline and somatic tissues was POLQ, and this variant was detected in 22.7% (10/44) and 23.8% (5/21) of all the corresponding carriers, respectively. PGVs in HR were significantly associated with upregulation of proliferation and replication‐related genes and familial risk of HCC. Samples harboring PGVs in HR with loss of heterozygosity were most strongly correlated with the genomic footprints of deficient HR, such as mutation burden and denovoSig2 (analogous to Catalogue of Somatic Mutations in Cancer [COSMIC] 3), and poor outcome. Pharmacologic experiments with HCC cells defective in BRCA2 or POLQ suggested that tumors with this phenotype are synthetic lethal with poly(ADP‐ribose) polymerase inhibitors.

Conclusions:
Our findings suggest that germline HR defects in HCC tend to confer a poor prognosis and result in distinctive genomic scarring. Tests of the clinical benefits of HR‐directed treatments in the affected patients are needed.
Flow and heat transfer analysis of MHD third‐grade fluid flow through a vertical microchannel subjected to entropy generation
Authors: Roja A. , Gireesha B. J. 
Published: September 2022

AbstractThis paper analyses the generation of entropy in an electrically conducting third‐grade fluid through a vertical channel considering the variable thermal conductivity. Aspects of radiation, viscous dissipation, porous medium, Joule heating, convective boundary condition, and heat generation are studied. Nonlinear systems of ordinary differential equations are obtained via applying suitable dimensionless variables. After that, the system is solved with the aid of using the Runge–Kutta–Fehlberg method. The numerical solutions are used to characterize the irreversibility and irreversibility ratio. It is established that the entropy is enhanced with accelerating estimations of the third‐grade material parameter, Brinkman number, magnetism, Biot number, porous parameter, and the impact is decelerated with elevating values of the radiation. The rate of heat transfer is higher for the Brinkman number, and a similar impact on drag force is noticed for magnetic and Grashof numbers. All the parameters on flow, temperature, fluid irreversibility and irreversibility ratio are discussed through graphical illustration.
Inflammatory biomarkers after an exercise intervention in childhood acute lymphoblastic leukemia survivors
Authors: Lähteenmäki Taalas Tuomas , Järvelä Liisa , Niinikoski Harri , Huurre Anu , Harila‐Saari Arja 
Published: September 2022

AbstractCancer survivors show increased risk for non‐communicable diseases and chronic low‐grade inflammation characterizes the development of such diseases. We investigated inflammatory plasma protein profiles of survivors of childhood acute lymphoblastic leukemia (ALL) in comparison to healthy controls and after an intervention with a home‐based exercise program. Survivors of childhood ALL aged 16–30 years (n = 21) with a median age at diagnosis 4.9 (1.6–12.9) years and a median time of 15.9 years from diagnosis, and sex‐ and age‐matched healthy controls (n = 21) were studied. Stored plasma samples were analyzed with Olink's 92‐protein‐wide Inflammation panel in 21 ALL long‐term survivors at baseline, after a previous 16‐week home‐based exercise intervention (n = 17) and in 21 age‐ and sex‐matched controls at baseline. Protein expression levels were compared between the groups. Inflammatory protein levels did not differ between the survivors and controls at baseline. Significantly reduced levels after the intervention were found in 11 proteins related to either vascular inflammation, insulin resistance, or both: tumor necrosis factor superfamily member 14 (TNFSF14), oncostatin M (OSM), monocyte chemoattractant protein 1 (MCP‐1), MCP‐2, fibroblast growth factor 21 (FGF‐21), chemokine (C‐C motif) ligand 4 (CCL4), transforming growth factor alpha (TGF‐α), tumor necrosis factor‐related apoptosis‐inducing ligand 10 (TRAIL), adenosine deaminase (ADA), chemokine (C‐X‐C motif) ligand 6 (CXCL6), and latency‐associated peptide transforming growth factor beta 1 (LAP TGF‐β1). The ALL survivors were not significantly more affected by inflammation than controls at baseline. The survivors’ 16‐week exercise intervention led to significant reduction in inflammatory protein levels. Physical exercise should be promoted for survivors of childhood cancer.
Providing differentiated service delivery to the ageing population of people living with HIV
Authors: Godfrey Catherine , Vallabhaneni Snigdha , Shah Minesh Pradyuman , Grimsrud Anna 
Published: September 2022

AbstractIntroductionDifferentiated service delivery (DSD) models for HIV are a person‐centred approach to providing services across the HIV care cascade; DSD has an increasing policy and implementation support in high‐burden HIV countries. The life‐course approach to DSD for HIV treatment has focused on earlier life phases, childhood and adolescence, families, and supporting sexual and reproductive health during childbearing years. Older adults, defined as those over the age of 50, represent a growing proportion of HIV treatment cohorts with approximately 20% of those supported by PEPFAR in this age band and have specific health needs that differ from younger populations. Despite this, DSD models have not been designed or implemented to address the health needs of older adults.DiscussionOlder adults living with HIV are more likely to have significant co‐morbid medical conditions. In addition to the commonly discussed co‐morbidities of hypertension and diabetes, they are at increased risk of cognitive impairment, frailty and mental health conditions. Age and HIV‐related cognitive impairment may necessitate the development of adapted educational materials. Identifying the optimal package of differentiated services to this population, including the frequency of clinical visits, types and location of services is important as is capacitating the healthcare cadres to adapt to these challenges. Technological advances, which have made remote monitoring of adherence and other aspects of disease management easier for younger populations, may not be as readily available or as familiar to older adults. To date, adaptations to service delivery have not been scaled and are limited to nascent programmes working to integrate treatment of common co‐morbidities.ConclusionsOlder individuals living with HIV may benefit from a DSD approach that adapts care to the specific challenges of ageing with HIV. Models could be developed and validated using outcome measures, such as viral suppression and treatment continuity. DSD models for older adults should consider their specific health needs, such as high rates of co‐morbidities. This may require educational materials, health worker capacity building and outreach designed specifically to treat this age group.
Nuclear localisation sequences of chloride intracellular channels 1 and 4 facilitate nuclear import via interactions with import mediator importin‐α: An empirical and theoretical perspective
Authors: Færch Olga , Worth Roland , Achilonu Ikechukwu , Dirr Heini 
Published: September 2022

AbstractChloride intracellular channel proteins (CLICs) display ubiquitous expression, with each member exhibiting specific subcellular localisation. While all CLICs, except CLIC3, exhibit a highly conserved putative nuclear localisation sequence (NLS), only CLIC1, CLIC3 and CLIC4 exist within the nucleus. The CLIC4 NLS, 199‐KVVAKKYR‐206, appears crucial for nuclear entry and interacts with mouse nuclear import mediator Impα isoform 1, omitting the IBB domain (mImpα1ΔIBB). The essential nature of the basic residues in the CLIC4 NLS has been established by the fact that mutating out these residues inhibits nuclear import, which in turn is linked to cutaneous squamous cell cancer. Given the conservation of the CLIC NLS, CLIC1 likely follows a similar import pathway to CLIC4. Peptides of the CLIC1 (Pep1; Pep1_S C/S mutant) and CLIC4 (Pep4) NLSs were designed to examine binding to human Impα isoform 1, omitting the IBB domain (hImpα1ΔIBB). Molecular docking indicated that the core CLIC NLS region (KKYR) forms a similar binding pattern to both mImpα1ΔIBB and hImpα1ΔIBB. Fluorescence quenching demonstrated that Pep1_S (Kd ≈ 237 μM) and Pep4 (Kd ≈ 317 μM) bind hImpα1ΔIBB weakly. Isothermal titration calorimetry confirmed the weak binding interaction between Pep4 and hImpα1ΔIBB (Kd ≈ 130 μM) and the presence of a proton‐linked effect. This weak interaction may be due to regions distal from the CLIC NLS needed to stabilise and strengthen hImpα1ΔIBB binding. Additionally, this NLS may preferentially bind another hImpα isoform with different flexibility properties.
Proteomics‐based mass spectrometry profiling of SARS‐CoV‐2 infection from human nasopharyngeal samples
Authors: Chatterjee Sayantani , Zaia Joseph 
Published: September 2022

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the cause of the on‐going global pandemic of coronavirus disease 2019 (COVID‐19) that continues to pose a significant threat to public health worldwide. SARS‐CoV‐2 encodes four structural proteins namely membrane, nucleocapsid, spike, and envelope proteins that play essential roles in viral entry, fusion, and attachment to the host cell. Extensively glycosylated spike protein efficiently binds to the host angiotensin‐converting enzyme 2 initiating viral entry and pathogenesis. Reverse transcriptase polymerase chain reaction on nasopharyngeal swab is the preferred method of sample collection and viral detection because it is a rapid, specific, and high‐throughput technique. Alternate strategies such as proteomics and glycoproteomics‐based mass spectrometry enable a more detailed and holistic view of the viral proteins and host–pathogen interactions and help in detection of potential disease markers. In this review, we highlight the use of mass spectrometry methods to profile the SARS‐CoV‐2 proteome from clinical nasopharyngeal swab samples. We also highlight the necessity for a comprehensive glycoproteomics mapping of SARS‐CoV‐2 from biological complex matrices to identify potential COVID‐19 markers.