bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclin‐dependent kinase 4 expression alters the number of keratinocyte stem cells in the mouse hair follicle
Authors: Kim Sun Hye , Rodriguez Liliana R. L. , Macias Everardo , Rodriguez‐Puebla Marcelo L.
Published: January 2022

Hair follicles regenerate periodically by spontaneously undergoing cycles of growth, regression, and relative quiescence. During the hair cycle, follicle stem cells residing in a specialized niche remain quiescent, and they are stimulated to proliferate throughout the growth phase of the hair follicle. Although cell cycle regulators play a prominent role during the activation of hair follicle stem cells, the identity and the role of these regulators have not been confirmed. Herein, we reported that stem cells located in the bulge region of the HF (BuSCs) express high levels of cyclin‐dependent kinase 4 (CDK4) through the quiescent phase of the hair cycle. Using gain‐ and loss‐of‐function studies, we have determined that the CDK4 protein level affects the number of BuSCs. Transgenic expression of CDK4 in the bulge region of the hair follicles reduces the number of BuSCs, whereas CDK4 ablation resulted in an increasing number of BuSCs. These results suggest that deregulation of CDK4 protein levels contributes to distorting the self‐renewal/proliferation balance and, in turn, altering the number of BuSCs.
Early‐onset persistent type IIIb endoleak following incraft stent graft implantation in an abdominal aortic aneurysm patient
Authors: Park Jae Hong , Rha Seung‐Woon
Published: January 2022

The type IIIb endoleak a rare complication of endovascular aneurysmal repair caused by endoprosthesis problem leading to deteriorating rupture, which is one of the major reasons for lifelong imaging surveillance. We report a case of an early‐onset type IIIb endoleak from a tear in main body bifurcation (flow divider) area like crotch point tearing of pants following additional intervention to reduce immediate type Ia endoleak. Successful treatment of the endoleak was achieved by surgical conversion.
Predictors of dronedarone plasma drug concentrations and effect on atrial fibrillation/atrial flutter recurrence: Analyses from the EURIDIS and ADONIS studies
Authors: Thind Munveer , McKindley David S. , Reiffel James A. , Naccarelli Gerald V. , Stewart John , Kowey Peter R.
Published: January 2022

Background

In this post hoc analysis, we assessed patient characteristics as predictors of dronedarone trough concentrations and characterized the relationship of trough concentrations of dronedarone with its efficacy and safety.

Hypothesis

Dronedarone is recommended as a 400 mg twice daily dose taken orally with meals. We hypothesize that drug concentration/bioavailability of dronedarone, measured as above‐ and below‐median trough concentrations, does not impact the efficacy outcomes.

Methods

Average trough concentrations (Ctrough_avg) across multiple timepoints were calculated for each patient, and patient Ctrough_avg values were categorized as below‐median or above‐median concentrations. The effect of patient baseline characteristics on dronedarone Ctrough_avg was assessed in the below‐median versus above‐median groups. The effect of dronedarone in each Ctrough_avg group versus placebo on risk of first atrial fibrillation/atrial flutter (AF/AFL) recurrence and safety was also evaluated.

Results

Overall, 1795 plasma samples were available from 507 dronedarone‐treated patients. An above‐median Ctrough_avg was associated with age ≥75 years, female sex, lower weight, higher pacemaker use, and higher oral anticoagulant use. The risk of adjudicated first AF/AFL recurrence was significantly lower with dronedarone versus placebo in the below‐median (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.56–0.91; p = .0054) and above‐median groups (HR: 0.63; 95% CI: 0.50–0.81; p = .0002). No difference in risk of AF/AFL recurrence was observed between the above‐ and below‐median groups. Safety and tolerability of dronedarone were similar between groups.

Conclusion

Significant reduction in AF/AFL recurrence was observed in patients treated with dronedarone versus placebo, regardless of dronedarone concentrations above or below the median value.
Value of M2BP in predicting in‐stent restenosis in patients after coronary drug‐eluting stent implantation
Authors: Yang Le , Zhu Haijun , Sun Yuanyuan , Yan Pengcheng , Song Xiaoning , Xu Fayun , Yuan Haitao , Chen Liming
Published: January 2022

Objective

We evaluated the association between plasma levels of mac‐2 binding protein (M2BP) with the risk of in‐stent restenosis (ISR) after percutaneous coronary intervention (PCI).

Methods

Plasma M2BP levels were compared between 258 patients who experienced ISR at 12‐months post‐PCI and 258 patients, matched for age and sex, without angiographic evidence of ISR.

Results

The plasma M2BP level was significantly higher in the ISR than in the non‐ISR group. On multivariate analysis, adjusted for potential clinical, biochemical, and angiography characteristics, M2BP remained as an independent significant predictor of ISR.

Conclusions

M2BP may be an important predictive biomarker of ISR and may be useful in identifying at‐risk patients.
Effects of Psychoactive Pharmaceuticals in Wastewater on Electricity Generation in Microbial Fuel Cells
Authors: Akagunduz Dilan , Cebecioglu Rumeysa , Ozen Fatih , Ozdemir Murat , Bermek Hakan , Tarhan Nevzat , Arslan Ayla , Catal Tunc
Published: January 2022

Antidepressants accumulate in the aquatic environment due to human wastes. “Here, microbial fuel cell (MFC) technology is investigated as a candidate for elimination of antidepressants introduced into environment via human wastewaters.” Human urine containing selective serotonin reuptake inhibitors (paroxetine) and serotonin‐norepinephrine reuptake inhibitors (venlafaxine, O‐desmethylvenlafaxine (ODV)) are used as substrates in MFCs. Electricity production by the MFCs is monitored while simultaneous drug degradation is analyzed using liquid chromatography‐tandem mass spectrometry. When the human urine samples containing drugs (10 or 50 ng drug per mL) are treated in MFCs, electricity production decreases in response to increasing drug concentrations. Upon addition of drugs‐containing urine, chemical oxygen demand removal capacity of MFCs decreases from 54% to 37%. Mass spectrometry results show that drugs are degraded at a rate of 10 ng mL−1 per hour for paroxetine, 11 ng mL−1 per hour for venlafaxine, and 16 ng mL−1 per hour for ODV, i.e., 94% of paroxetine, 66% of venlafaxine, and 48% of ODV is cleared in 9 h of treatment. In conclusion, MFC exhibits great potential in elimination of paroxetine, venlafaxine, and ODV from wastewater. These results can help to develop sustainable strategies to combat antidepressant pollution.
Mapping the Binding Sites of UDP and Prostaglandin E2 Glyceryl Ester in the Nucleotide Receptor P2Y6
Authors: Zimmermann Anne , Vu Oanh , Brüser Antje , Sliwoski Gregory , Marnett Lawrence J. , Meiler Jens , Schöneberg Torsten
Published: January 2022

Cyclooxygenase‐2 catalyzes the biosynthesis of prostaglandins from arachidonic acid and the biosynthesis of prostaglandin glycerol esters (PG‐Gs) from 2‐arachidonoylglycerol. PG‐Gs are mediators of several biological actions such as macrophage activation, hyperalgesia, synaptic plasticity, and intraocular pressure. Recently, the human UDP receptor P2Y6 was identified as a target for the prostaglandin E2 glycerol ester (PGE2‐G). Here, we show that UDP and PGE2‐G are evolutionary conserved endogenous agonists at vertebrate P2Y6 orthologs. Using sequence comparison of P2Y6 orthologs, homology modeling, and ligand docking studies, we proposed several receptor positions participating in agonist binding. Site‐directed mutagenesis and functional analysis of these P2Y6 mutants revealed that both UDP and PGE2‐G share in parts one ligand‐binding site. Thus, the convergent signaling of these two chemically very different agonists has already been manifested in the evolutionary design of the ligand‐binding pocket.
Investigating Membrane‐Mediated Antimicrobial Peptide Interactions with Synchrotron Radiation Far‐Infrared Spectroscopy
Authors: Hornemann Andrea , Eichert Diane M. , Hoehl Arne , Tiersch Brigitte , Ulm Gerhard , Ryadnov Maxim G. , Beckhoff Burkhard
Published: January 2022

Synchrotron radiation‐based Fourier transform infrared spectroscopy enables access to vibrational information from mid over far infrared to even terahertz domains. This information may prove critical for the elucidation of fundamental bio‐molecular phenomena including folding‐mediated innate host defence mechanisms. Antimicrobial peptides (AMPs) represent one of such phenomena. These are major effector molecules of the innate immune system, which favour attack on microbial membranes. AMPs recognise and bind to the membranes whereupon they assemble into pores or channels destabilising the membranes leading to cell death. However, specific molecular interactions responsible for antimicrobial activities have yet to be fully understood. Herein we probe such interactions by assessing molecular specific variations in the near‐THz 400–40 cm−1range for defined helical AMP templates in reconstituted phospholipid membranes. In particular, we show that a temperature‐dependent spectroscopic analysis, supported by 2D correlative tools, provides direct evidence for the membrane‐induced and folding‐mediated activity of AMPs. The far‐FTIR study offers a direct and information‐rich probe of membrane‐related antimicrobial interactions.
Secondary Structure Transitions for a Family of Amyloidogenic, Antimicrobial Uperin 3 Peptides in Contact with Sodium Dodecyl Sulfate
Authors: Prasad Anup K. , Tiwari Chandni , Ray Sourav , Holden Stephanie , Armstrong David A. , Rosengren K. Johan , Rodger Alison , Panwar Ajay S. , Martin Lisandra L.
Published: January 2022

Secondary structure changes are an inherent part of antimicrobial (AMP) and amyloidogenic peptide activity, especially in close proximity to membranes, and impact the peptides’ function and dysfunction roles. The formation, and stability of α‐helical components are regarded as essential ‘intermediates’ for both these functions. To illuminate the conformational transitions leading to amyloid formation we use short cationic AMPs, from an Australian toadlet, Uperoleia mjobergii, (Uperin 3 family, U3) and assess the impact on secondary structural elements in the presence of a membrane mimetic surfactant, sodium dodecyl sulfate (SDS). Specifically, Uperin 3.x, where x=4, 5, 6 wild‐type peptides and position seven variants for each, R7A or K7A, were investigated using a combination of experimental and simulation approaches. In water, U3 peptides remain largely unstructured as random coils, with the addition of salts initiating structural transitions leading to assembly towards amyloid. Solution NMR data show that an unstructured U3.5 wt peptide transitions in the presence of SDS to a well‐defined α‐helical structure that spans nearly the entire sequence. Circular dichroism (CD) and ThT fluorescence studies show that all six U3 peptides aggregate in solution, albeit with vastly varying rates, and a dynamic equilibrium between soluble aggregates rich in either α‐helices or β‐sheets may exist in solution. However, the addition of SDS leads to a rapid disaggregation for all peptides and stabilisation of predominantly α‐helical content in all the U3 peptides. Molecular dynamics (MD) simulations show that the adsorption of U3.5 wt/R7A peptides onto the SDS micelle is driven by Coulombic attraction between peptide cationic residues and the negatively charged sulfate head‐groups on SDS. Simulating the interactions of various kinds of β‐sheet dimers (of both U3.5 wt and its variant U3.5 R7A) with SDS micelles confirmed β‐sheet content decreases in the dimers after their attachment to the SDS micelle. Adsorbed peptides interact favourably with the hydrophobic core of the micelle, promoting intramolecular hydrogen bonds leading to stabilisation of the α‐helical structure in peptides, and resulting in a corresponding decrease in intermolecular hydrogen bonds responsible for β‐sheets.
Aptamer‐Functionalized Fractal Nanoplasmonics‐Assisted Laser Desorption/Ionization Mass Spectrometry for Metabolite Detection
Authors: Wang Xiwei , Yan Lu , Yu Zijing , Chen Qiaoji , Xiao Mingshu , Liu Xiaohui , Li Li , Pei Hao
Published: January 2022

Abstract: Accurate profiling of metabolites in biofluids provides a feasible approach to disease diagnosis and therapeutic evaluation in clinics. However, current material‐based analytical platforms for in vitro metabolite detection often requires tedious sample pretreatment. To address this issue, herein, we report an aptamer‐functionalized fractal gold nanoflower (Apt‐AuNF)‐based sensing platform for metabolite analysis. A series of fractal AuNFs with tunable nanoshell structures was synthesized using DNA‐engineered strategy, and optimized Apt‐AuNFs were demonstrated to enable efficient trap of target analytes with ∼5‐fold enhanced enrichment, thus achieving selective analysis of metabolites in complex biofluids without requirement of pre‐enrichment and purification. We applied Apt‐AuNF‐assisted laser desorption/ionization mass spectrometry for disease diagnosis, identifying diabetic patients through daily monitoring and glucose quantification in serum. This work provides a guideline to design materials for high‐performance metabolic analysis and precise disease diagnosis.
Comparison of water flow capacity in leaves among sweet corn genotypes as basis for plant transpiration rate sensitivity to vapor pressure deficit
Authors: Jafarikouhini Nahid , Sinclair Thomas R. , Resende Marcio F.
Published: January 2022

Genotypes in crop species have been identified that initiate partial stomata closure at elevated atmospheric vapor pressure deficit (VPD), which results in conserved soil water for crop use during subsequent water‐deficit episodes and thereby allowing for possible yield increase. In sweet corn (Zea mays L), 17 genotypes have been previously identified with the VPD‐responsive trait, although the VPD value at the initiation of stomata closure varied among genotypes. A hypothesis to explain variation in transpiration response to VPD is that water flow capacity in the leaves differs among genotypes. To gauge water flow capacity in leaves, the rate of stomata opening was observed visually after stomata closure was induced by 3 kPa VPD. The stomata opening time was rapid and varied among genotypes from 90 to 179 s. However, there was no correlation between opening time and the VPD at which partial stomata closure was initiated in intact plants. An additional set of experiments was done to examine whether genotypic differences in a subpopulation of silver‐inhibited aquaporins might contribute to differences in leaf water flow. There was a correlation among genotypes between slow opening time of the stomata and greater inhibition of transpiration rate following feeding leaves with silver ion. However, the response to the silver treatment did not correlate with the VPD at which transpiration decrease of intact plants was initiated. These results indicate that the differences observed in the water flow capacity in sweet corn leaves were not major factors accounting for the genotypic differences in whole‐plant transpiration response to elevated VPD.
Geographic variation and thermal plasticity shape salamander metabolic rates under current and future climates
Authors: Muñoz David , Miller David , Schilder Rudolf , Campbell Grant Evan H.
Published: January 2022

Predicted changes in global temperature are expected to increase extinction risk for ectotherms, primarily through increased metabolic rates. Higher metabolic rates generate increased maintenance energy costs which are a major component of energy budgets. Organisms often employ plastic or evolutionary (e.g., local adaptation) mechanisms to optimize metabolic rate with respect to their environment. We examined relationships between temperature and standard metabolic rate across four populations of a widespread amphibian species to determine if populations vary in metabolic response and if their metabolic rates are plastic to seasonal thermal cues. Populations from warmer climates lowered metabolic rates when acclimating to summer temperatures as compared to spring temperatures. This may act as an energy saving mechanism during the warmest time of the year. No such plasticity was evident in populations from cooler climates. Both juvenile and adult salamanders exhibited metabolic plasticity. Although some populations responded to historic climate thermal cues, no populations showed plastic metabolic rate responses to future climate temperatures, indicating there are constraints on plastic responses. We postulate that impacts of warming will likely impact the energy budgets of salamanders, potentially affecting key demographic rates, such as individual growth and investment in reproduction.
Density and habitat use of one of the last jaguar populations of the Brazilian Atlantic Forest: Is there still hope?
Authors: Azevedo Fernando Cesar Cascelli de , Pasa Juliana Benck , Arrais Ricardo Corassa , Massara Rodrigo Lima , Widmer Cynthia Elisa
Published: January 2022

The jaguar (Panthera onca) plays an important role in maintaining biodiversity and ecological processes. We evaluated the status of a jaguar population in one of the last stronghold habitats for its conservation in the Atlantic Forest, the Rio Doce State Park (RDSP). We used a random survey design from 2016/17 to estimate jaguar abundance and density as well as its occupancy and detection probabilities in the entire Park's area. To monitor for temporal fluctuations in density and abundance, we used a systematic survey design in the southern portion of the Park where jaguars were more recorded when using the random approach. We then conducted two surveys in 2017/18 and 2020. Our 2016/17 random survey revealed that jaguar density (0.11 ± SE 0.28 individuals/100 km2) was the lowest obtained for the species across the Atlantic Forest. We noticed that jaguar density increased three times from 2017/18 (0.55 ± SE 0.45 individuals/100 km2) to 2020 (1.61 ± SE 0.6 individuals/100 km2). Jaguar occupancy and detection probability were 0.40 and 0.08, respectively. The low jaguar occupancy probability was positively associated with smaller distances from lakes and records of potential prey. The detection probability was positively associated with prey detection, the rainy season, and smaller distances from lakes. Our work contributes to a growing awareness of the potential conservation value of a protected area in a human‐dominated landscape as one of the last strongholds for jaguars across the Atlantic Forest.
Current biogeographical roles of the Kunlun Mountains
Authors: Du Weibo , Jia Peng , Du Guozhen
Published: January 2022

Large‐scale patterns of biodiversity and formation have garnered increasing attention in biogeography and macroecology. The Qinghai‐Tibet Plateau (QTP) is an ideal area for exploring these issues. However, the QTP consists of multiple geographic subunits, which are understudied. The Kunlun Mountains is a geographical subunit situated in the northern edge of the QTP, in northwest China. The diversity pattern, community phylogenetic structures, and biogeographical roles of the current flora of the Kunlun Mountains were analyzed by collecting and integrating plant distribution, regional geological evolution, and phylogeography. A total of 1911 species, 397 genera, and 75 families present on the Kunlun Mountains, of which 29.8% of the seed plants were endemic to China. The mean divergence time (MDT) of the Kunlun Mountains flora was in the early Miocene (19.40 Ma). Analysis of plant diversity and MDT indicated that the eastern regions of the Kunlun Mountains were the center of species richness, endemic taxa, and ancient taxa. Geographical origins analysis showed that the Kunlun Mountains flora was diverse and that numerous clades were from East Asia and Tethyan. Analysis of geographical origins and geological history together highlighted that the extant biodiversity on the Kunlun Mountains appeared through species recolonization after climatic fluctuations and glaciations during the Quaternary. The nearest taxon index speculated that habitat filtering was the most important driving force for biodiversity patterns. These results suggest that the biogeographical roles of the Kunlun Mountains are corridor and sink, and the corresponding key processes are species extinction and immigration. The Kunlun Mountains also form a barrier, representing a boundary among multiple floras, and convert the Qinghai‐Tibet Plateau into a relatively closed geographical unit.
Outcomes after heart transplantation in patients with cardiac sarcoidosis
Authors: Asleh Rabea , Briasoulis Alexandros , Doulamis Ilias , Alnsasra Hilmi , Tzani Aspasia , Alvarez Paulino , Kuno Toshiki , Kampaktsis Polydoros , Kushwaha Sudhir
Published: January 2022

Background

The number of patients with sarcoidosis requiring heart transplantation (HT) is increasing. The aim of this study was to evaluate outcomes of isolated HT in patients with sarcoid cardiomyopathy and compare them to recipients with non‐ischaemic restrictive or dilated cardiomyopathy.

Methods and results

Adult HT recipients were identified in the UNOS Registry between 1990 and 2020. Patients were grouped according to diagnosis. The cumulative incidences for the all‐cause mortality and rejection were compared using Fine and Gray model analysis, accounting for re‐transplantation as a competing risk. Rejection was evaluated using logistic regression analysis. We also reviewed characteristics and outcomes of all HT recipients with previous diagnosis of sarcoid cardiomyopathy from a single centre. A total of 30 160 HT recipients were included in the present study (n = 239 sarcoidosis, n = 1411 non‐ischaemic restrictive cardiomyopathy, and n = 28 510 non‐ischaemic dilated cardiomyopathy). During a total of 194 733 patient‐years, all‐cause mortality at the latest follow‐up was not significantly different when comparing sarcoidosis to non‐ischaemic dilated cardiomyopathy [adjusted subhazard ratio (aSHR) 1.46, 95% confidence intervals (CIs): 0.9–2.4, P = 0.12] or restrictive cardiomyopathy (aSHR 1.12, 95% CI: 0.65–1.95, P = 0.67). Accordingly, multivariable analysis suggested that 1 year mortality was not significantly different between sarcoidosis and non‐ischaemic dilated cardiomyopathy (aSHR 1.56, 95% CI: 0.9–2.7, P = 0.12) or restrictive cardiomyopathy (aSHR 1.15, 95% CI: 0.61–2.18, P = 0.66). No differences were observed regarding 30 day mortality, treated and hospitalized acute rejection, and 30 day death from graft failure after HT. Thirty‐day mortality did not improve significantly in more recent HT eras whereas there was a trend towards improved 1 year mortality in the latest HT era (P = 0.06). Data from the single‐centre case review showed excellent long‐term outcomes with sirolimus‐based immunosuppression.

Conclusions

Short‐term and long‐term post HT outcomes among patients with sarcoid cardiomyopathy are similar to those with common types of non‐ischaemic cardiomyopathy.
Simple Synthesis of 2D Molybdenum Carbide Nanosheets and Their Application in the Hydrogen Evolution Reaction
Authors: Chithaiah Pallellappa , Binwal Devesh Chandra , Rao C. N. R.
Published: January 2022

We have synthesized two phases of 2D molybdenum carbides (α‐MoC1‐x, β‐Mo2C) in nanosheets form and use them as electrocatalysts for the hydrogen evolution reaction. The procedure involves the preparation of hexadecylamine intercalated molybdenum oxide (MoO3‐HDA) nanosheets at room temperature, followed by heating at a high temperature for different duration (900 °C) in nitrogen atmosphere. α‐MoC1‐x and β‐Mo2C nanosheets have been characterized by scanning electron microscopy (SEM), X‐ray photoelectron spectroscopy (XPS) and other techniques. α‐MoC1‐x exhibits good HER electrocatalytic performance and is chemically stable for a longer time in acidic conditions.
Proposal for the Updating of the ISO 29841 Liquid Chromatographic Method for the Determination of Chlorophyll a and a′ Degradation Products in Virgin Olive Oil
Authors: Kritiktsi Evmorfia , Tsimidou Maria Z. , Nenadis Nikolaos
Published: January 2022

Pyropheophytin a (PPPa) found in minute amounts in virgin olive oil under good manufacturing practice conditions and increasing as a function of storage temperature and length, has attracted the interest of scientists as a marker of quality. Certain bodies developing olive oil standards have adopted its content (% PPPamax < 17 throughout the shelf‐life of a product) as a quality criterion. The analytical protocol to examine product compliance is the ISO 29841 method. In the present work, green improvements are proposed through the use of a short column and vacuum in the solid‐phase sample extraction step. The preparation of handmade cartridges that can be reused without pretreatment at least six times reduces further the cost of analysis. The proposed protocol is repeatable and robust. In case fluorescence detection is used, selection of λex = 407 nm/λem = 672 nm instead of λex = 430 nm/λem = 670 nm increases detection sensitivity of the target compounds by 1.5‐ to 2.6‐fold. Fluorescence detection results in higher %PPPa values by 2% on average compared to those obtained with a diode array detector set at 410 nm. Present proposals and observations are expected to be of interest for the next edition of the ISO 29841:2009/AMD1:2016.

Practical applications: The proposals made in the present study expedite significantly the analysis, thus, increasing the sample throughput even compared to other alternative fast approaches in the literature. The reduction of the use of chemicals adds to the modification of the ISO 29841 method to an analytical tool that abides by green and sustainable chemistry which is considered critical for “beyond the 2020 process.” The proposed chromatographic column updates the method as its effective use in an HPLC instrument provides comparable efficiency to a UHPLC one, and makes method transfer to the latter without adjustments. In this way, method adoption may be wider by analytical laboratories involved in virgin olive oil quality control. Finally, the identification of quantitative differences using different detection means (visible, fluorescence) for the first time, when addressed by the ISO committee, may assist the effective quality control and facilitate the virgin olive oil international trade.
Synthesis of 3‐Acyl‐Isoxazoles via Radical 5‐endo trig Cyclization of β,γ‐Unsaturated Ketones with NaNO2
Authors: Jiang Ping , Wang Yaming , Chen Dengfeng , Zheng Yu , Huang Shenlin
Published: January 2022

Here we report a facile cyclization reaction of β,γ‐unsaturated ketones with NaNO2 under mild conditions to construct 3‐acyl‐isoxazoles. This transformation is realized via nitrosation of the activated methylene, radical 5‐endo trig cyclization, and then aromatization, according to some control experiments. Further, this protocol provided an efficient access to a variety of isoxazoles from readily available allyl ketones.
Exploitation of the ribosomal protein L10 R98S mutation to enhance recombinant protein production in mammalian cells
Authors: Verbelen Benno , Girardi Tiziana , Sulima Sergey O. , Vereecke Stijn , Verstraete Paulien , Verbeeck Jelle , Royaert Jonathan , Cinque Sonia , Montanaro Lorenzo , Penzo Marianna , Imbrechts Maya , Geukens Nick , Geuens Thomas , Dierckx Koen , Pepe Daniele , Kampen Kim , De Keersmaecker Kim
Published: January 2022

Mammalian cells are commonly used to produce recombinant protein therapeutics, but suffer from a high cost per mg of protein produced. There is therefore great interest in improving protein yields to reduce production cost. We present an entirely novel approach to reach this goal through direct engineering of the cellular translation machinery by introducing the R98S point mutation in the catalytically essential ribosomal protein L10 (RPL10‐R98S). Our data support that RPL10‐R98S enhances translation levels and fidelity and reduces proteasomal activity in lymphoid Ba/F3 and Jurkat cell models. In HEK293T cells cultured in chemically defined medium, knock‐in of RPL10‐R98S was associated with a 1.7‐ to 2.5‐fold increased production of four transiently expressed recombinant proteins and 1.7‐fold for one out of two stably expressed proteins. In CHO‐S cells, eGFP reached a 2‐fold increased expression under stable but not transient conditions, but there was no production benefit for monoclonal antibodies. The RPL10‐R98S associated production gain thus depends on culture conditions, cell type, and the nature of the expressed protein. Our study demonstrates the potential for using a ribosomal protein mutation for pharmaceutical protein production gains, and further research on how various factors influence RPL10‐R98S phenotypes can maximize its exploitability for the mammalian protein production industry.
Seven decades of shoreline changes along a muddy mangrove coastline of the Upper Gulf of Thailand
Authors: Sok Kimhuy , Bidorn Butsawan , Burnett William C. , Sasaki Jun , Sola Phachirarat
Published: January 2022

This study evaluates the historical coastal change and development along the eastern coastline of the Upper Gulf of Thailand between 1953 and 2019 based on a series of aerial photographs and satellite images. Long‐term (~70 years) and short‐term (~10 years) shoreline movement rates were analysed using the Digital Shoreline Analysis System (DSAS). Results of this analysis indicate that the shoreline along the western coast (WBK) of the Bang Pakong River mouth has undergone severe coastal degradation, with a land loss of about 980 ha over the last seven decades. Meanwhile, the eastern coastline (EBK) has developed continuously over this time span, resulting in a land growth of about 552 ha. Based on historical shorelines recorded since 1954, the shoreline recession along the WBK coast accelerated over five decades. The average shoreline change rate reached approximately −9 m/year in 2002 and is shown to be related to land subsidence, which was due to groundwater withdrawals. The WBK coastline stabilized in 2009 and became an accretionary coast after 2016 due to the introduction of engineered coastal protection measures. In addition, the construction of major dams on the Chao Phraya and Bang Pakong rivers did not result in severe shoreline recession along the WBK coast. A significant reduction in sediment supply to the coastal zone due to damming was not observed. In contrast, the EBK coastline has advanced continuously since 1953, with average growth rates between 0.5 and 7.6 m/year over 50 years as a result of increased riverine sediment supply. Our results also indicate that mangrove deforestation was not a major factor causing shoreline retreat, and mangrove reforestation was not a successful coastal protection approach in this coast.
Nurturing the marriages of single atoms with atomic clusters and nanoparticles for better heterogeneous electrocatalysis
Authors: Zhang Lei , Zhu Jiawei , Li Xin , Mu Shichun , Verpoort Francis , Xue Junmin , Kou Zongkui , Wang John
Published: January 2022

Single‐atom catalysts, featuring some of the most unique activities, selectivity, and high metal utilization, have been extensively studied over the past decade. Given their high activity, selectivity, especially towards small molecules or key intermediate conversions, they can be synergized together with other active species (typically other single atoms, atomic clusters, or nanoparticles) in either tandem or parallel or both, leading to much better performance in complex catalytic processes. Although there have been reports on effectively combining the multiple components into one single catalytic entity, the combination and synergy between single atoms and other active species have not been reviewed and examined in a systematic manner. Herein, in this overview, the key synergistic interactions, binary complementary effects, and the bifunctional functions of single atoms with other active species are defined and discussed in detail. The integration functions of their marriages are investigated with particular emphasis on the homogeneous and heterogeneous combinations, spatial distribution, synthetic strategies, and the thus‐derived outstanding catalytic performance, together with new light shined on the catalytic mechanisms by zooming in several case studies. The dynamic nature of each of the active species and in particular their interactions in such new catalytic entities in the heterogeneous electrocatalytic processes are visited, on the basis of the in situ/operando evidence. Last, we feature the current challenges and future perspectives of these integrated catalytic entities that can offer guidance for advanced catalyst design by the rational combination and synergy of binary or multiple active species.
Curcumin attenuates isoniazid‐induced hepatotoxicity by upregulating the SIRT1/PGC‐1α/NRF1 pathway
Authors: Li Yun , Luo Wen‐wen , Cheng Xuan , Xiang Huai‐rong , He Bei , Zhang Qi‐zhi , Peng Wen‐xing
Published: January 2022

As a serious infectious disease, tuberculosis threatens global public health. Isoniazid is the first‐line drug not only in active tuberculosis but also in its prevention. Severe hepatotoxicity greatly limits its use. Curcumin, extracted from turmeric, has been found to relieve isoniazid‐induced hepatotoxicity. However, the mechanism of isoniazid‐induced hepatotoxicity and the protective effects of curcumin are not yet understood completely. We established both cell and animal models about isoniazid‐induced hepatotoxicity and investigated the new mechanism of curcumin against isoniazid‐induced liver injury. The experimental data in our study demonstrated that curcumin ameliorated isoniazid‐mediated liver oxidative stress. The protective effects of curcumin were demonstrated and confirmed to be correlated with upregulating SIRT1/PGC‐1α/NRF1 pathway. Western blot revealed that while inhibiting SIRT1 by the siRNA1 (a SIRT1 inhibitor), the expressions of SIRT1, PGC‐1α/Ac‐PGC‐1α, and NRF1 decreased, and the protective effect that curcumin exerted on isoniazid‐treated L‐02 cells was significantly attenuated. Furthermore, curcumin improved liver functions and reduced necrosis of the isoniazid‐treated BALB/c mice, accompanied by downregulating oxidative stress and inflammation in liver. Western blot revealed that curcumin treatment activates the SIRT1/PGC‐1α/NRF1 pathway in the isoniazid‐treated BALB/c mice. In conclusion, we found one mechanism of isoniazid‐induced hepatotoxicity downregulating the SIRT1/PGC‐1α/NRF1 pathway, and curcumin attenuated this hepatotoxicity by activating it. Our study provided a novel approach and mechanism for the treatment of isoniazid‐induced hepatotoxicity.
Using meditation in a control vs. acceptance context: A preliminary evaluation of relations with anxiety, depression, and indices of well‐being
Authors: Tifft Eric D. , Underwood Shannon B. , Roberts Max Z. , Forsyth John P.
Published: January 2022

Background and Objectives

Meditation practices have been marketed broadly to ameliorate human suffering. As such, individuals may seek out and use meditation to control or manage unpleasant thoughts and emotions. Emotion and thought control research suggest that meditation used in this way may potentiate unpleasant private experiences and contribute to negative outcomes. We aimed to evaluate the function or purpose guiding meditation and its relations with anxiety, depression, and other indices of well‐being.

Design and Methods

In a cross‐sectional design, undergraduate meditators (N = 98) reported intentions guiding their meditation practice (i.e., experiential/emotional control or acceptance/openness) and completed an assessment battery.

Results

Most participants (58.2%) indicated using meditation to manage, control, or avoid difficult experiences. Participants using meditation with control‐based intentions reported greater worry, anxiety, depression, negative affect, and lower mindfulness relative to their acceptance‐guided counterparts. After controlling for level of anxiety, viewing anxiety as a problem increased the likelihood of using meditation with control‐based intentions. Similar relations were observed between viewing stress as a problem and the likelihood of using meditation for experiential control.

Conclusions

Findings suggest that (a) how people meditate is significantly related to psychological distress and (b) highlight the importance of evaluating intentions guiding meditative practices, particularly in individuals struggling with unpleasant emotional or psychological experiences.
What relates to length of stay in a sober living home among women with histories of victimization and addiction? A longitudinal analysis
Authors: Edwards Katie M. , Ullman Sarah E. , Siller Laura , Murphy Sharon B. , Harvey Ronald , Wheeler Lorey
Published: January 2022

Despite preliminary research suggesting that length of stay in sober living homes (SLHs) is related to sustained sobriety, little research has examined factors that relate to length of stay in SLHs. The purpose of the proposed exploratory study was to prospectively examine baseline characteristics of women with histories of addiction and victimization as correlates of length of stay in a trauma‐informed, gender‐responsive SLH. Participants (N = 45) were surveyed three times over a 1‐year period. Women were invited to participate within a week of their arrival to the SLH. Nearly two‐thirds (62.2%, n = 28) of women stayed under 3 months, and 37.8% (n = 17) of women stayed over 3 months. Whereas older age and greater financial worries were associated with staying over 3 months at the SLH, other variables (e.g., demographics, mental health, recent victimization, recent substance use) were unrelated. Findings indicate that efforts may be needed to ensure that younger women as well as women with less financial worries, who may be less likely to stay for longer periods of times at SLHs, have adequate support for sobriety.
Generating youth dialogue through the literary arts: A citywide youth health collaboration in the U.S.
Authors: Golden Tasha L. , Sima Richard , Roebuck Grace , Gupta Sonakshi , Magsamen Susan
Published: January 2022

A process and outcomes evaluation was conducted of a citywide literary‐arts initiative designed to reduce stigma, amplify underrepresented narratives, and generate dialogue about violence. Over 4 months, students in 85 middle schools read a novel addressing mental health and violence‐related themes. As a collaboration between a public school district and public library system, the program's classroom activities emphasized dialogue, while coordinated library events supported community engagement. Students completed pre/postsurveys (total n = 1487); school program leaders (n = 39) and public librarians (n = 14) completed postsurveys. Half of student respondents reported personal encounters with violence. Most said the novel influenced their thinking; students with personal experiences of violence reported greater influence than those without. Highest rates of dialogue were seen among students who read the novel in full, and over half of postsurvey respondents wanted more dialogue opportunities. Leaders and librarians indicated that the program was smoothly integrated with existing curricula, but also offered recommendations for improved processes. Findings suggest that this intervention was effective at stimulating dialogue while providing assets‐based opportunities for youth to share experiences and concerns. Current program processes indicate promise for further engagement and impact, with some modifications. To this end, authors draw upon evaluation findings and youth development literature to offer recommendations for program development and replication in other regions.
Cascade testing for inherited arrhythmia conditions: Experiences and attitudes of family communication approaches for a Canadian cohort
Authors: Ho Amy , Leach Emma , Virani Alice , Arbour Laura , Bartels Kirsten , Wong Eugene K.
Published: January 2022

Inherited arrhythmia conditions (IAC) can lead to sudden cardiac death at any age, and relatives of an affected person have up to a 50% chance of inheriting the condition and are at risk for developing features. Cascade testing is a stepwise approach for identifying relatives at risk for IACs through clinical screening and genetic testing. Early detection can reduce morbidity and mortality for affected individuals and determine potential risk mitigation strategies for relatives. However, cardiovascular genetic studies have reported an incomplete uptake of cascade testing in at‐risk relatives. We explored patient perspectives on cascade testing for IACs and alternative approaches to family communication. Twelve semi‐structured phone interviews were conducted with probands of the British Columbia Inherited Arrhythmia Program confirmed to carry a pathogenic or likely pathogenic variant in a gene associated with an IAC. Thematic analysis of transcripts through an iterative coding process revealed five main themes: (a) a stepwise approach is followed in disclosing risk to relatives, (b) relatives’ autonomy in cascade testing is supported, (c) lived experience with the condition influences disclosure and uptake of cascade testing, (d) collaborative approach to informing relatives reduces negative impact of disclosure, and (e) direct contact from a healthcare provider is viewed as acceptable. The findings highlight this patient cohort's experiences and opinions with approaches to disclosure and demonstrate their understanding and acceptance of their relatives’ approaches to cascade testing. In addition, while the notion of direct contact was generally accepted, a collaborative approach to contacting relatives between the proband and provider may be most effective.
lncRNA MALAT1 promotes osteogenic differentiation through the miR‐217/AKT3 axis: A possible strategy to alleviate osteoporosis
Authors: Song Chenyang , Guo Yu , Chen Fenyong , Liu Wenge
Published: January 2022

Background

Accumulating evidence demonstrates that long non‐coding RNAs (lncRNAs) are associated with the development of osteoporosis. The present study aimed to investigate the effect of metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) on osteogenic differentiation in osteoporosis.

Methods

MALAT1 levels were detected by a real‐time polymerase chain reaction (RT‐qPCR). Moreover, the levels of osteogenic differentiation‐related factors (Bmp4, Col1a1 and Spp1) were measured by a RT‐qPCR and western blotting. Alkaline phosphatase (ALP) activity was detected using an ALP staining assay.

Results

MALAT1 levels were downregulated in hindlimb unloading mice and simulated in microgravity (MG) treated MC3T3‐E1 cells. Moreover, MG treatment induced the downregulation of the expression of ALP, BMP4, Col1a1 and Spp1, whereas overexpression of MALAT1 abolished the downregulation. MG also inhibited ALP activity, whereas MALAT1 reversed the effect. Furthermore, miR‐217 was identified as a target of MALAT1, and AKT3 was verified as a target of miR‐217. Overexpression of miR‐217 rescued the promotion of osteogenic differentiation induced by MALAT1 in MG treated cells. Knockdown of AKT3 abolished the facilitation of osteogenic differentiation induced by downregulation of miR‐217.

Conclusions

MALAT1 promotes osteogenic differentiation through regulating miR‐217/AKT3 axis, suggesting that MALAT1 is a potential target with respect to alleviating osteoporosis.
Brain and visceral gene editing of mucopolysaccharidosis I mice by nasal delivery of the CRISPR/Cas9 system
Authors: Vera Luisa Natalia Pimentel , Schuh Roselena Silvestri , Fachel Flavia Nathielly Silveira , Poletto Edina , Piovesan Eduarda , Kubaski Francyne , Couto Eduarda , Brum Bruna , Rodrigues Graziella , Souza Hallana , Giugliani Roberto , Matte Ursula , Baldo Guilherme , Teixeira Helder F.
Published: January 2022

Background

Mucopolysaccharidosis type I (MPS I) is an inherited disease caused by deficiency of the enzyme alpha‐l‐iduronidase (IDUA). MPS I affects several tissues, including the brain, leading to cognitive impairment in the severe form of the disease. Currently available treatments do not reach the brain. Therefore, in this study, we performed nasal administration (NA) of liposomal complexes carrying two plasmids encoding for the CRISPR/Cas9 system and for the IDUA gene targeting the ROSA26 locus, aiming at brain delivery in MPS I mice.

Methods

Liposomes were prepared by microfluidization, and the plasmids were complexed to the formulations by adsorption. Physicochemical characterization of the formulations and complexes, in vitro permeation, and mucoadhesion in porcine nasal mucosa (PNM) were assessed. We performed NA repeatedly for 30 days in young MPS I mice, which were euthanized at 6 months of age after performing behavioral tasks, and biochemical and molecular aspects were evaluated.

Results

Monodisperse mucoadhesive complexes around 110 nm, which are able to efficiently permeate the PNM. In animals, the treatment led to a modest increase in IDUA activity in the lung, heart, and brain areas, with reduction of glycosaminoglycan (GAG) levels in serum, urine, tissues, and brain cortex. Furthermore, treated mice showed improvement in behavioral tests, suggesting prevention of the cognitive damage.

Conclusion

Nonviral gene editing performed through nasal route represents a potential therapeutic alternative for the somatic and neurologic symptoms of MPS I and possibly for other neurological disorders.
Assessment of CD39 expression in regulatory T‐cell subsets by disease severity in adult and juvenile COVID‐19 cases
Authors: Simsek Abdurrahman , Kizmaz Muhammed A. , Cagan Eren , Dombaz Fatma , Tezcan Gulcin , Asan Ali , Demir H. Ibrahim , Bal S. Haldun , Ermis Digdem Y. , Dilektaslı Aslı G. , Kazak Esra , Akalin E. Halis , Oral H. Barbaros , Budak Ferah
Published: January 2022

COVID‐19 is a disease characterized by acute respiratory failure and is a major health problem worldwide. Here, we aimed to investigate the role of CD39 expression in Treg cell subsets in COVID‐19 immunopathogenesis and its relationship to disease severity. One hundred and ninety COVID‐19 patients (juveniles, adults) and 43 volunteers as healthy controls were enrolled in our study. Flow cytometric analysis was performed using a 10‐color monoclonal antibody panel from peripheral blood samples. In adult patients, CD39+ Tregs increased with disease severity. In contrast, CD39+ Tregs were decreased in juvenile patients in an age‐dependent manner. Overall, our study reveals an interesting profile of CD39‐expressing Tregs in adult and juvenile cases of COVID‐19. Our results provide a better understanding of the possible role of Tregs in the mechanism of immune response in COVID‐19 cases.
Case fatality and mortality rates, socio‐demographic profile, and clinical features of COVID‐19 in the elderly population: A population‐based registry study in Iran
Authors: Esmaeili Elham D. , Fakhari Ali , Naghili Behrouz , Khodamoradi Farzad , Azizi Hosein
Published: January 2022

We aimed to investigate COVID‐19 case fatality rate (CFR), mortality, and screening in the older population of East Azerbaijan Province. We conducted a population‐based registry study from Death Registration System in the elderly population (N = 433 445) from the outbreak that emerged up to May 30, 2021 (before vaccination). We analyzed CFR and mortality rates due to COVID‐19 as well as the case findings and characteristics in the elderly population. Logistic regression analysis was carried out for the association between COVID‐19 mortality and effective factors. During the study, the province had 18 079 confirmed cases and 4390 deaths. The male to female CFR risk ratio was 3.2. The overall CFR and mortality rates were 24% and 1%, respectively. CFR and mortality ranged from 9.56% to 0.37% in the 60–64 age group to 70% and 2.6% in the age group ≥85 years, respectively. We found a significant trend in CFR and mortality of COVID‐19 with advanced age. Male sex, advanced age, marital status, and living alone were associated with an increased risk of COVID‐19 fatality. COVID‐19 mortality measures were higher in the older population of this province. Advanced treatment supports and interventions are needed to reduce mortality rates of COVID‐19 in the elderly population.