bluuebunny/crossref_metadata_2025 huggingface dataset:
Decline and recovery in cell population densities of Heterosigma akashiwo (Raphidophyceae) as a novel bloom driver for the species
Authors: Kok Jerome Wai Kit , Leong Sandric Chee Yew
Published: July 2021

The frequency and intensity of harmful algal bloom (HAB) events have been increasing in many places around the world. Heterosigma akashiwo is a marine raphidophyte species known to cause HABs in many places across tropical and temperate climates. Studies of temperate strains have identified that H. akashiwo blooms are driven by mass activation of cysts which, for this species, can only form at <15°C temperatures. Although these temperatures do not occur in the tropics, there have been no comparative studies for tropical H. akashiwo. This study aimed to investigate whether tropical H. akashiwo can form cysts under warm temperatures, therefore having different responses from temperate strains. Results showed that tropical H. akashiwo were similar with temperate strains and could only form round cyst-like structures at 5°C but not 25°C. We also observed novel response of a decline and recovery in cell densities at 25°C. The decline was interrupted when the cultures were diluted, implying a tendency for H. akashiwo to rapidly spread and accumulate within surrounding waters, thereby facilitating blooms. This behaviour presents unique bloom concerns. Close monitoring of H. akashiwo distribution patterns is needed for better assessment of the bloom threat posed within tropical waters.
Development and preliminary evaluation of EMPOWER for surrogate decision-makers of critically ill patients
Authors: Lichtenthal Wendy G. , Viola Martin , Rogers Madeline , Roberts Kailey E. , Lief Lindsay , Cox Christopher E. , Brewin Chris R. , Xu Jiehui Cici , Maciejewski Paul K. , Pan Cynthia X. , Coats Taylor , Ouyang Daniel J. , Rabin Shayna , Vaughan Susan C. , Breitbart William , Marenberg Marjorie E. , Prigerson Holly G.
Published: July 2021

Objective

The objectives of this study were to develop and refine EMPOWER (Enhancing and Mobilizing the POtential for Wellness and Resilience), a brief manualized cognitive-behavioral, acceptance-based intervention for surrogate decision-makers of critically ill patients and to evaluate its preliminary feasibility, acceptability, and promise in improving surrogates’ mental health and patient outcomes.

Method

Part 1 involved obtaining qualitative stakeholder feedback from 5 bereaved surrogates and 10 critical care and mental health clinicians. Stakeholders were provided with the manual and prompted for feedback on its content, format, and language. Feedback was organized and incorporated into the manual, which was then re-circulated until consensus. In Part 2, surrogates of critically ill patients admitted to an intensive care unit (ICU) reporting moderate anxiety or close attachment were enrolled in an open trial of EMPOWER. Surrogates completed six, 15–20 min modules, totaling 1.5–2 h. Surrogates were administered measures of peritraumatic distress, experiential avoidance, prolonged grief, distress tolerance, anxiety, and depression at pre-intervention, post-intervention, and at 1-month and 3-month follow-up assessments.

Results

Part 1 resulted in changes to the EMPOWER manual, including reducing jargon, improving navigability, making EMPOWER applicable for a range of illness scenarios, rearranging the modules, and adding further instructions and psychoeducation. Part 2 findings suggested that EMPOWER is feasible, with 100% of participants completing all modules. The acceptability of EMPOWER appeared strong, with high ratings of effectiveness and helpfulness (M = 8/10). Results showed immediate post-intervention improvements in anxiety (d = −0.41), peritraumatic distress (d = −0.24), and experiential avoidance (d = −0.23). At the 3-month follow-up assessments, surrogates exhibited improvements in prolonged grief symptoms (d = −0.94), depression (d = −0.23), anxiety (d = −0.29), and experiential avoidance (d = −0.30).

Significance of results

Preliminary data suggest that EMPOWER is feasible, acceptable, and associated with notable improvements in psychological symptoms among surrogates. Future research should examine EMPOWER with a larger sample in a randomized controlled trial.
Capsaicin affects macrophage anti-inflammatory activity via the MAPK and NF-κB signaling pathways
Authors: Li Jingshuang , Wang Hui , Zhang Lili , An Ni , Ni Wan , Gao Quanqi , Yu Yang
Published: July 2021

Abstract: Capsaicin, the main constituent in chili, is an extremely spicy vanillin alkaloid and is found in several Capsicum species in China. Traditionally, it has been used to treat inflammatory diseases such as allergic rhinitis, neuralgia after shingles, refractory female urethral syndrome, spontaneous recalcitrant anal pruritus, and solid tumors. Constant stimulation of the body by inflammatory factors can lead to chronic inflammation. Capsaicin possesses anti-inflammatory activity; however, the underlying mechanism is unknown. We investigated the effect of capsaicin on the secretion of macrophage inflammatory factors in a lipopolysaccharide-induced inflammation model using 56 healthy, SPF grade, BALB/c mice. To this end, mice peritoneal macrophages were isolated and stimulated with lipopolysaccharide (1 μg/mL) and capsaicin (25, 50, 75, or 100 μg/mL) for 24 h. At all concentrations tested, capsaicin significantly promoted the phagocytosis of neutral red dye by macrophages. Furthermore, the gene expression and secretion of inflammatory cytokines significantly increased after induction with lipopolysaccharide (P<0.01); the interleukin (IL)-6 level was 204 μg/mL, tumor necrosis factor (TNF)-α level was 860 μg/mL, and nitric oxide (NO) level was 19.8 μg/mL. However, the treatment with capsaicin reduced their levels (P<0.01) and protein expression of lipopolysaccharide-induced extracellular signal-related kinase 1/2 and p65 (P<0.05). Overall, capsaicin reduced the secretion of inflammatory cytokines (P<0.01), interleukins, TNF-α (P<0.01), and NO by inhibiting the nuclear factor-kappa B and microtubule-associated protein kinase signaling pathways, and thereby reduced lipopolysaccharide-induced inflammatory response in macrophages.
The impact of percutaneous peripheral interventions on endothelial	function
Authors: Rammos Christos , Steinmetz Martin , Johnstone Mirjam , Manzke Anna , Lortz Julia , Petrikhovich Olga , Hendgen-Cotta Ulrike , Jánosi Rolf A. , Rassaf Tienush
Published: July 2021

Summary: Background: Treatment of symptomatic peripheral artery disease (PAD) through endovascular interventions is the primary revascularization strategy. Interventions restore perfusion but may cause severe injury to the vascular endothelium, which regulates vascular tone. Endothelial dysfunction is involved in the progression of cardiovascular disease, with higher incidences of vascular events. We aimed to determine the impact of percutaneous interventions on change in endothelial function. Patients and methods: Endothelial function was determined using flow-mediated dilation (FMD) before, the day after lower limb intervention with paclitaxel-coated balloons or stent guided interventions and after a six-month follow-up in the target limb, control limb and the systemic circulation in 42 PAD patients aged 70.2±9 years and 66% men. Additionally, macro- and microvascular function were assessed. Results: In PAD patients aged 70.2±9 years and 66% men, we observed an immediate enhancement of macro-, microvascular and endothelial function after endovascular treatment (FMD of superficial femoral artery (SFA) 3.7±0.2% to 4.1±0.1%, n=42, p=0.02), a sustained long-term improvement after 6-months (FMD SFA 3.7±0.2% to 4.2±0.1%, n=42, p=0.01), and moreover an improved systemic endothelial function (FMD brachial artery 4.3±0.1% to 4.7±0.2, n=42, p=0.01) following peripheral interventions. Subgroup analysis however revealed that following paclitaxel-based percutaneous intervention, the paclitaxel dosage applied was inversely related to the chronic improvement in local endothelial function (r=−0.6, n=22, p=0.005) without evidence for systemic effects (r=−0.25, p=0.27). Conclusions: We demonstrate an improved local and systemic endothelial function after treatment of atherosclerotic peripheral disease with a distinguished response after endovascular intervention with higher dosage of applied paclitaxel restraining the benefits. Further studies have to determine the optimal interventional strategy with respect to different treatment modalities to maintain vessel functions.
We Need Accomplices, Not Allies in the Fight for an Equitable Geoscience
Authors: Jones Jabari C.
Published: July 2021

The killing of George Floyd on May 25, 2020 sparked a global movement for black lives that extended into the geosciences. Nearly a year later, some momentum has been sustained, but the appetite for transformative change to generate a more equitable geoscience is lacking. In this article, I detail my struggles to balance science, activism, and anguish as a black geoscientist in Minneapolis over the last year. I suggest that a riskier and deeper involvement in the work of equity and inclusion is necessary to transform our discipline into a diverse, equitable, and inclusive space where all people can thrive.
High‐Resolution Ps Receiver Function Imaging of the Crust and Mantle Lithosphere Beneath Southern New England and Tectonic Implications
Authors: Luo Yantao , Long Maureen D. , Karabinos Paul , Kuiper Yvette D. , Rondenay Stéphane , Aragon John C. , Sawade Lucas , Makus Peter
Published: July 2021

Southern New England exhibits diverse geologic features resulting from past tectonic events. These include Proterozoic and early Paleozoic Laurentian units in the west, several Gondwana‐derived terranes that accreted during the Paleozoic in the east, and the Mesozoic Hartford Basin in the central part of the region. The Seismic Experiment for Imaging Structure beneath Connecticut (SEISConn) project involved the deployment of a dense array of 15 broadband seismometers across northern Connecticut to investigate the architecture of lithospheric structures beneath this region and interpret how they were created and modified by past tectonic events in the context of surface geology. We carried out P‐to‐S receiver function analysis on SEISConn data, including both single‐station analysis and common conversion point (CCP) stacking. Our images show that the westernmost part of Connecticut has a much deeper Moho than central and eastern Connecticut. The lateral transition is a well‐defined, ∼15 km step‐like offset of the Moho over a ∼20 km horizontal distance. The Moho step appears near the surface boundary between the Laurentian margin and the Gondwana‐derived Moretown terrane. Possible models for its formation include Ordovician underthrusting of Laurentia and/or modification by younger tectonic events. Other prominent features include a strong positive velocity gradient (PVG) beneath the Hartford basin corresponding to the bottom of the sedimentary units, several west‐dipping PVGs in the crust and mantle lithosphere that may correspond to relict slabs or shear zones from past subduction episodes, and a negative velocity gradient (NVG) that may correspond to the base of the lithosphere.
Gentle Topography Increases Vertical Transport of Coarse Dust by Orders of Magnitude
Authors: Heisel Michael , Chen Bicheng , Kok Jasper F. , Chamecki Marcelo
Published: July 2021

The presence of coarse mineral dust in the atmosphere has been substantiated in several recent measurement campaigns, which include observations of particles up to and above 100 μm in diameter. Yet, atmospheric dust models either do not include particles larger than 20 μm or severely underestimate their concentrations. One possibility for the underestimated concentrations is that models do not represent enhancements of particle transport due to subgrid‐scale topography. Here, large‐eddy simulations are used in combination with Lagrangian particle tracking to assess the impact of gentle two‐dimensional topography with 50 and 100 m elevation on the vertical transport of coarse dust in neutrally stratified conditions. The presence of topography significantly increases the likelihood that 5 and 20 μm particles reach several hundred meters in altitude. Further, topography increases this likelihood by orders of magnitude for larger 60 μm particles. Three mechanisms are observed to contribute to the increased vertical transport: a strong upward mean flow region on the uphill side of the topography, ejection of particles downwind of the topography crest, and enhanced vertical dispersion in the wake of the crest. The compounding effects of these mechanisms provide a pathway for coarse dust emitted from the surface to reach elevations where they can be further transported into the free atmosphere by large‐scale motions such as convective plumes. While these findings are motivated by mineral dust observations, they are generally applicable to other heavy aerosols such as pollen.
Hygroscopicity of Water‐Soluble PM2.5 in Rural Northwest China: Contrasting Contributors Between Summer and Winter
Authors: Chen Yukun , Wang Xin , Peng Huiying , Li Jianjun , Wang Yueshe , Wang Gehui , Li Jin , Wu Can , Liu Lang
Published: July 2021

In this study, we investigated the chemical composition and hygroscopicity of water‐soluble fraction in PM2.5 collected from a rural site of Guanzhong Basin, a highly polluted region in northwest China. We found that inorganic components are the main substances promoting the hygroscopic properties of particulate matter (PH) in summer, while in winter, an increasing contribution from water‐soluble organic matters (WSOM) was observed. The sulfate‐nitrate‐ammonium concentration is higher on heavily polluted days, and a high concentration of water‐soluble organic matter was observed in non‐polluting days. Hygroscopic growth factors, g(RH), with elevated relative humidity (RH) of water‐soluble matter (WSM) were measured for 50, 75, 100, 125, 150 nm by hygroscopic tandem differential mobility analyzer. An initial dry particle diameter of 100 nm was chosen as the research object because the particle size has little effect on the hygroscopic growth factor at RH = 90%. The g(90%)WSM and κWSM was in the range of 1.19–1.49 and 0.06–0.22 in summer, 1.24–1.49 and 0.08–0.22 in winter, respectively, which is similar to the hygroscopicity parameters of PH produced by biomass burning. The g(90%)WSOM and κWSOM, obtained using E‐AIM model and Zdanovskii‐Stokes‐Robinson approach, were in the range of 1.06–1.69 and 0.02–0.36 in summer, 1.06–1.58 and 0.02–0.28 in winter, respectively. The hygroscopicity parameters of water‐soluble organic matter is close to the value of levoglucosan, an indicator of biomass burning, implying this region is highly affected by biomass burning. Overall, our results revealed that PM2.5 in rural regions of Guanzhong Basin is mainly influenced by biomass burning.
PIAS2-mediated blockade of IFN-β signaling: a basis for sporadic Parkinson disease dementia
Authors: Magalhaes Joana , Tresse Emilie , Ejlerskov Patrick , Hu Erling , Liu Yawei , Marin Andrea , Montalant Alexia , Satriano Letizia , Rundsten Carsten Friis , Carlsen Eva Maria Meier , Rydbirk Rasmus , Sharifi-Zarchi Ali , Andersen Jesper Bøje , Aznar Susana , Brudek Tomasz , Khodosevich Konstantin , Prinz Marco , Perrier Jean-François Marie , Sharma Manu , Gasser Thomas , Issazadeh-Navikas Shohreh
Published: July 2021

Familial Parkinson disease (PD) is associated with rare genetic mutations, but the etiology in most patients with sporadic (s)PD is largely unknown, and the basis for its progression to dementia (sPDD) is poorly characterized. We have identified that loss of IFNβ or IFNAR1, the receptor for IFNα/β, causes pathological and behavioral changes resembling PDD, prompting us to hypothesize that dysregulated genes in IFNβ-IFNAR signaling pathway predispose one to sPD. By transcriptomic analysis, we found defective neuronal IFNβ-IFNAR signaling, including particularly elevated PIAS2 associated with sPDD. With meta-analysis of GWASs, we identified sequence variants in IFNβ-IFNAR-related genes in sPD patients. Furthermore, sPDD patients expressed higher levels of PIAS2 mRNA and protein in neurons. To determine its function in brain, we overexpressed PIAS2 under a neuronal promoter, alone or with human α-synuclein, in the brains of mice, which caused motor and cognitive impairments and correlated with intraneuronal phosphorylated (p)α-synuclein accumulation and dopaminergic neuron loss. Ectopic expression of neuronal PIAS2 blocked mitophagy, increased the accumulation of senescent mitochondrial and oxidative stress, as evidenced by excessive oxDJ1 and 8OHdG, by inactivating ERK1/2-P53 signaling. Conversely, PIAS2 knockdown rescued the clinicopathological manifestations of PDD in Ifnb–/– mice on restoring mitochondrial homeostasis, oxidative stress, and pERK1/2-pP53 signaling. The regulation of JAK-STAT2-PIAS2 signaling was crucial for neurite outgrowth and neuronal survival and excitability and thus might prevent cognitive impairments. Our findings provide insights into the progression of sPD and dementia and have implications for new therapeutic approaches.
Gut microbiota signature in treatment-naïve attention-deficit/hyperactivity disorder
Authors: Richarte Vanesa , Sánchez-Mora Cristina , Corrales Montserrat , Fadeuilhe Christian , Vilar-Ribó Laura , Arribas Lorena , Garcia Estela , Rosales-Ortiz Silvia Karina , Arias-Vasquez Alejandro , Soler-Artigas María , Ribasés Marta , Ramos-Quiroga Josep Antoni
Published: July 2021

Compelling evidence supports alterations in gut microbial diversity, bacterial composition, and/or relative abundance of several bacterial taxa in attention-deficit/hyperactivity disorder (ADHD). However, findings for ADHD are inconsistent among studies, and specific gut microbiome signatures for the disorder remain unknown. Given that previous studies have mainly focused on the pediatric form of the disorder and involved small sample sizes, we conducted the largest study to date to compare the gastrointestinal microbiome composition in 100 medication-naïve adults with ADHD and 100 sex-matched healthy controls. We found evidence that ADHD subjects have differences in the relative abundance of several microbial taxa. At the family level, our data support a lower relative abundance of Gracilibacteraceae and higher levels of Selenomonadaceae and Veillonellaceae in adults with ADHD. In addition, the ADHD group showed higher levels of Dialister and Megamonas and lower abundance of Anaerotaenia and Gracilibacter at the genus level. All four selected genera explained 15% of the variance of ADHD, and this microbial signature achieved an overall sensitivity of 74% and a specificity of 71% for distinguishing between ADHD patients and healthy controls. We also tested whether the selected genera correlate with age, body mass index (BMI), or scores of the ADHD rating scale but found no evidence of correlation between genera relative abundance and any of the selected traits. These results are in line with recent studies supporting gut microbiome alterations in neurodevelopment disorders, but further studies are needed to elucidate the role of the gut microbiota on the ADHD across the lifespan and its contribution to the persistence of the disorder from childhood to adulthood.
ZFP36 protects lungs from intestinal I/R-induced injury and fibrosis through the CREBBP/p53/p21/Bax pathway
Authors: Cao Yongmei , Huang Weifeng , Wu Fang , Shang Jiawei , Ping Feng , Wang Wei , Li Yingchuan , Zhao Xuan , Zhang Xiaoping
Published: July 2021

Acute lung injury induced by ischemia–reperfusion (I/R)-associated pulmonary inflammation is associated with high rates of morbidity. Despite advances in the clinical management of lung disease, molecular therapeutic options for I/R-associated lung injury are limited. Zinc finger protein 36 (ZFP36) is an AU-rich element-binding protein that is known to suppress the inflammatory response. A ZFP36 binding site occurs in the 3ʹ UTR of the cAMP‐response element-binding protein (CREB) binding protein (CREBBP) gene, which is known to interact with apoptotic proteins to promote apoptosis. In this study, we investigate the involvement of ZFP36 and CREBBP on I/R-induced lung injury in vivo and in vitro. Intestinal ischemia/reperfusion (I/R) activates inflammatory responses, resulting in injury to different organs including the lung. Lung tissues from ZFP36-knockdown mice and mouse lung epithelial (MLE)-2 cells were subjected to either Intestinal I/R or hypoxia/reperfusion, respectively, and then analyzed by Western blotting, immunohistochemistry, and real-time PCR. Silico analyses, pull down and RIP assays were used to analyze the relationship between ZFP36 and CREBBP. ZFP36 deficiency upregulated CREBBP, enhanced I/R-induced lung injury, apoptosis, and inflammation, and increased I/R-induced lung fibrosis. In silico analyses indicated that ZFP36 was a strong negative regulator of CREBBP mRNA stability. Results of pull down and RIP assays confirmed that ZFP36 direct interacted with CREBBP mRNA. Our results indicated that ZFP36 can mediate the level of inflammation-associated lung damage following I/R via interactions with the CREBBP/p53/p21/Bax pathway. The downregulation of ZFP36 increased the level of fibrosis.
c-FLIP regulates autophagy by interacting with Beclin-1 and influencing its stability
Authors: Tomaipitinca Luana , Petrungaro Simonetta , D’Acunzo Pasquale , Facchiano Angelo , Dubey Amit , Rizza Salvatore , Giulitti Federico , Gaudio Eugenio , Filippini Antonio , Ziparo Elio , Cecconi Francesco , Giampietri Claudia
Published: July 2021

c-FLIP (cellular FLICE-like inhibitory protein) protein is mostly known as an apoptosis modulator. However, increasing data underline that c-FLIP plays multiple roles in cellular homoeostasis, influencing differently the same pathways depending on its expression level and isoform predominance. Few and controversial data are available regarding c-FLIP function in autophagy. Here we show that autophagic flux is less effective inc-FLIP−/−than in WT MEFs (mouse embryonic fibroblasts). Indeed, we show that the absence of c-FLIP compromises the expression levels of pivotal factors in the generation of autophagosomes. In line with the role of c-FLIP as a scaffold protein, we found that c-FLIPLinteracts with Beclin-1 (BECN1: coiled-coil, moesin-like BCL2-interacting protein), which is required for autophagosome nucleation. By a combination of bioinformatics tools and biochemistry assays, we demonstrate that c-FLIPLinteraction with Beclin-1 is important to prevent Beclin-1 ubiquitination and degradation through the proteasomal pathway. Taken together, our data describe a novel molecular mechanism through which c-FLIPLpositively regulates autophagy, by enhancing Beclin-1 protein stability.
Carcinoma associated fibroblasts small extracellular vesicles with low miR-7641 promotes breast cancer stemness and glycolysis by HIF-1α
Authors: Liu Yonglei , Hua Fanli , Zhan Yanxia , Yang Yanfei , Xie Jianfang , Cheng Yunfeng , Li Feng
Published: July 2021

Fibroblasts play an important role in cancer development and progression. Small extracellular vesicles (sEVs) are one type of extracellular vesicles, which mediate the interaction between cancer-associated fibroblasts and cancer cells by transferring their contents. However, the roles of sEVs from cancer-associated fibroblasts on breast cancer stem cell properties are largely unraveled. The purpose of this study was to explore the roles of sEVs from cancer-associated fibroblasts on breast cancer progression. The miRNA array data showed a different miRNA profile between CAFs sEVs and normal fibroblasts sEVs. By verification using real-time RT-PCR, the data analysis indicated that miR-7641 levels were lower in sEVs from CAFs compared with NFs. The cellular functions were assayed and the results indicated that CAFs derived sEVs with low miR-7641 levels suppressed breast cancer cell survival, glycolysis, and stem cell properties via the HIF-1α pathway. Collectively, these findings indicated that sEVs from CAFs promoted breast cancer stem cell properties and glycolysis via miR-7641/HIF-1α, which was a possible new way for targeting breast cancer.
Combing machine learning and elemental profiling for geographical authentication of Chinese Geographical Indication (GI) rice
Authors: Xu Fei , Kong Fanzhou , Peng Hong , Dong Shuofei , Gao Weiyu , Zhang Guangtao
Published: July 2021

Identification of geographical origin is of great importance for protecting the authenticity of valuable agri-food products with designated origins. In this study, a robust and accurate analytical method that could authenticate the geographical origin of Geographical Indication (GI) products was developed. The method was based on elemental profiling using inductively coupled plasma mass spectrometry (ICP-MS) in combination with machine learning techniques for model building and feature selection. The method successfully predicted and classified six varieties of Chinese GI rice. The elemental profiles of 131 rice samples were determined, and two machine learning algorithms were implemented, support vector machines (SVM) and random forest (RF), together with the feature selection algorithm Relief. Prediction accuracy of 100% was achieved by both Relief-SVM and Relief-RF models, using only four elements (Al, B, Rb, and Na). The methodology and knowledge from this study could be used to develop reliable methods for tracing geographical origins and controlling fraudulent labeling of diverse high-value agri-food products.
Force generation by protein–DNA co-condensation
Authors: Quail Thomas , Golfier Stefan , Elsner Maria , Ishihara Keisuke , Murugesan Vasanthanarayan , Renger Roman , Jülicher Frank , Brugués Jan
Published: July 2021

Interactions between liquids and surfaces generate forces1,2 that are crucial for many processes in biology, physics and engineering, including the motion of insects on the surface of water3, modulation of the material properties of spider silk4 and self-assembly of microstructures5. Recent studies have shown that cells assemble biomolecular condensates via phase separation6. In the nucleus, these condensates are thought to drive transcription7, heterochromatin formation8, nucleolus assembly9 and DNA repair10. Here we show that the interaction between liquid-like condensates and DNA generates forces that might play a role in bringing distant regulatory elements of DNA together, a key step in transcriptional regulation. We combine quantitative microscopy, in vitro reconstitution, optical tweezers and theory to show that the transcription factor FoxA1 mediates the condensation of a protein–DNA phase via a mesoscopic first-order phase transition. After nucleation, co-condensation forces drive growth of this phase by pulling non-condensed DNA. Altering the tension on the DNA strand enlarges or dissolves the condensates, revealing their mechanosensitive nature. These findings show that DNA condensation mediated by transcription factors could bring distant regions of DNA into close proximity, suggesting that this physical mechanism is a possible general regulatory principle for chromatin organization that may be relevant in vivo.
MaxDIA enables library-based and library-free data-independent acquisition proteomics
Authors: Sinitcyn Pavel , Hamzeiy Hamid , Salinas Soto Favio , Itzhak Daniel , McCarthy Frank , Wichmann Christoph , Steger Martin , Ohmayer Uli , Distler Ute , Kaspar-Schoenefeld Stephanie , Prianichnikov Nikita , Yılmaz Şule , Rudolph Jan Daniel , Tenzer Stefan , Perez-Riverol Yasset , Nagaraj Nagarjuna , Humphrey Sean J. , Cox Jürgen
Published: July 2021

MaxDIA is a software platform for analyzing data-independent acquisition (DIA) proteomics data within the MaxQuant software environment. Using spectral libraries, MaxDIA achieves deep proteome coverage with substantially better coefficients of variation in protein quantification than other software. MaxDIA is equipped with accurate false discovery rate (FDR) estimates on both library-to-DIA match and protein levels, including when using whole-proteome predicted spectral libraries. This is the foundation of discovery DIA—hypothesis-free analysis of DIA samples without library and with reliable FDR control. MaxDIA performs three- or four-dimensional feature detection of fragment data, and scoring of matches is augmented by machine learning on the features of an identification. MaxDIA’s bootstrap DIA workflow performs multiple rounds of matching with increasing quality of recalibration and stringency of matching to the library. Combining MaxDIA with two new technologies—BoxCar acquisition and trapped ion mobility spectrometry—both lead to deep and accurate proteome quantification.
A study to quantify surgical plume and survey the efficiency of different local exhaust ventilations
Authors: Cheng Ping-Chia , Wen Ming-Hsun , Hsu Wan-Lun , Cheng Po-Wen , Liao Li-Jen
Published: July 2021

This study aimed to compare the concentration of surgical smoke produced by different tissues and electric diathermy modes and to measure the effectiveness of various local exhaust ventilations. We compared the surgical plume concentration from different tissues and settings with a porcine tissue model. We also compared the efficiency of three local exhaust ventilations: (1) a desktop unit (Medtronic Rapid Vac), (2) a central evacuation system with ENT suction, and (3) a central evacuation system with a urethral catheter (PAHSCO Urethral Catheter). In the cutting setting, the skin tissue had a higher concentration of total suspended particulates (TPS), which were 1990 ± 2000 (mean ± SD, μg/m3), 6440 ± 3000 and 9800 ± 2300 at 15, 30 and 45 s, respectively (p < 0.05). In the coagulation setting, the adipose tissue had a higher concentration of TPS, which were 3330 ± 2600, 11,200 ± 5500 and 15,800 ± 7300, respectively (p < 0.05). We found that all three smoke extractors had more than 96% efficiency in clearing surgical smoke. With electric diathermy, skin tissue in the cutting model and adipose tissue in the coagulation mode will produce higher concentration of particles within surgical plumes. An electric surgical scalpel adapted with a urethral catheter is a simple and effective way to exhaust smoke in surgical operations.
Laser induced crystallization of Co–Fe–B films
Authors: Almeida Maria , Sharma Apoorva , Matthes Patrick , Köhler Nicole , Busse Sandra , Müller Matthias , Hellwig Olav , Horn Alexander , Zahn Dietrich R. T. , Salvan Georgeta , Schulz Stefan E.
Published: July 2021

Local crystallization of ferromagnetic layers is crucial in the successful realization of miniaturized tunneling magnetoresistance (TMR) devices. In the case of Co–Fe–B TMR devices, used most successfully so far in applications and devices, Co–Fe–B layers are initially deposited in an amorphous state and annealed post-deposition to induce crystallization in Co–Fe, thereby increasing the device performance. In this work, first direct proof of locally triggered crystallization of 10 nm thick Co–Fe–B films by laser irradiation is provided by means of X-ray diffraction (XRD) using synchrotron radiation. A comparison with furnace annealing is performed for benchmarking purposes, covering different annealing parameters, including temperature and duration in the case of furnace annealing, as well as laser intensity and scanning speed for the laser annealing. Films of Co–Fe–B with different stoichiometry sandwiched between a Ru and a Ta or MgO layer were systematically assessed by XRD and SQUID magnetometry in order to elucidate the crystallization mechanisms. The transformation of Co–Fe–B films from amorphous to crystalline is revealed by the presence of pronounced CoFe(110) and/or CoFe(200) reflexes in the XRD θ-2θ scans, depending on the capping layer. For a certain window of parameters, comparable crystallization yields are obtained with furnace and laser annealing. Samples with an MgO capping layer required a slightly lower laser intensity to achieve equivalent Co–Fe crystallization yields, highlighting the potential of laser annealing to locally enhance the TMR ratio.
Handgrip strength as a moderator of the influence of age on olfactory impairment in US adult population ≥ 40 years of age
Authors: Ramírez-Vélez Robinson , López-Gil José Francisco , de Asteasu Mikel López Sáez , Izquierdo Mikel , García-Hermoso Antonio
Published: July 2021

The aim of this study was to determine whether handgrip strength attenuates the negative relationship between age and olfactory function in a representative US population sample 40 years old and over. A cross-sectional study was performed with 2861 adults from the US National Health and Nutrition Examination Survey NHANES (2013–2014). An 8-item odor identification test was applied to determine olfactory function. Muscle strength was determined through a handgrip dynamometer (defined as the sum of the largest handgrip strength reading from right and left hands). Moderation analysis was performed to test whether the association between age and olfactory impairment was moderated by handgrip strength. Moderation analysis highlighted two regions of significance: the first region was found at < 56.6 kg, indicating that the adverse influence of age on olfactory function may be greater for the participants in this area; the second region was found at ≥ 56.6 kg, indicating that the negative impact of age on olfactory function disappeared for adults who were above this estimate point. In conclusion, handgrip strength, a general indicator of muscle strength, moderates the relationship between age and olfactory ability in a US adult population aged 40 years and older. Our findings are clinically relevant, since they emphasize the importance of muscular fitness in adulthood and old age by diminishing the deleterious effect of aging on olfactory performance.
Unconventional Hall effect and its variation with Co-doping in van der Waals Fe3GeTe2
Authors: Chowdhury Rajeswari Roy , DuttaGupta Samik , Patra Chandan , Tretiakov Oleg A. , Sharma Sudarshan , Fukami Shunsuke , Ohno Hideo , Singh Ravi Prakash
Published: July 2021

Two-dimensional (2D) van der Waals (vdW) magnetic materials have attracted a lot of attention owing to the stabilization of long range magnetic order down to atomic dimensions, and the prospect of novel spintronic devices with unique functionalities. The clarification of the magnetoresistive properties and its correlation to the underlying magnetic configurations is essential for 2D vdW-based spintronic devices. Here, the effect of Co-doping on the magnetic and magnetotransport properties of Fe3GeTe2 have been investigated. Magnetotransport measurements reveal an unusual Hall effect behavior whose strength was considerably modified by Co-doping and attributed to arise from the underlying complicated spin textures. The present results provide a clue to tailoring of the underlying interactions necessary for the realization of a variety of unconventional spin textures for 2D vdW FM-based spintronics.
Identification of V6.51L as a selectivity hotspot in stereoselective A2B adenosine receptor antagonist recognition
Authors: Wang Xuesong , Jespers Willem , Prieto-Díaz Rubén , Majellaro Maria , IJzerman Adriaan P. , van Westen Gerard J. P. , Sotelo Eddy , Heitman Laura H. , Gutiérrez-de-Terán Hugo
Published: July 2021

The four adenosine receptors (ARs) A1AR, A2AAR, A2BAR, and A3AR are G protein-coupled receptors (GPCRs) for which an exceptional amount of experimental and structural data is available. Still, limited success has been achieved in getting new chemical modulators on the market. As such, there is a clear interest in the design of novel selective chemical entities for this family of receptors. In this work, we investigate the selective recognition of ISAM-140, a recently reported A2BAR reference antagonist. A combination of semipreparative chiral HPLC, circular dichroism and X-ray crystallography was used to separate and unequivocally assign the configuration of each enantiomer. Subsequently affinity evaluation for both A2A and A2B receptors demonstrate the stereospecific and selective recognition of (S)-ISAM140 to the A2BAR. The molecular modeling suggested that the structural determinants of this selectivity profile would be residue V2506.51 in A2BAR, which is a leucine in all other ARs including the closely related A2AAR. This was herein confirmed by radioligand binding assays and rigorous free energy perturbation (FEP) calculations performed on the L249V6.51 mutant A2AAR receptor. Taken together, this study provides further insights in the binding mode of these A2BAR antagonists, paving the way for future ligand optimization.
Regulation of Rac1 transcription by histone and DNA methylation in diabetic retinopathy
Authors: Kowluru Renu A. , Radhakrishnan Rakesh , Mohammad Ghulam
Published: July 2021

Cytosolic ROS, generated by NADPH oxidase 2 (Nox2) in diabetes, damage retinal mitochondria, which leads to the development of retinopathy. A small molecular weight G-protein essential for Nox2 activation, Rac1, is also transcriptionally activated via
active DNA methylation-hydroxymethylation. DNA methylation is a dynamic process, and can also be regulated by histone modifications; diabetes alters retinal histone methylation machinery. Our aim is to investigate the role of histone methylation (H3K9me3) of Rac1 promoter in dynamic DNA methylation- transcriptional activation. Using human retinal endothelial cells in 20 mM D-glucose, H3K9me3 at Rac1 promoter was quantified by chromatin-Immunoprecipitation technique. Crosstalk between H3K9me3 and DNA methylation was examined in cells transfected with siRNA of histone trimethyl-transferase, Suv39H1, or Dnmt1, exposed to high glucose. Key parameters were confirmed in retinal microvessels from streptozotocin-induced diabetic mice, with intravitreally administered Suv39H1-siRNA or Dnmt1-siRNA. Compared to cells in normal glucose, high glucose increased H3K9me3 and Suv39H1 binding at Rac1 promoter, and Suv39H1-siRNA prevented glucose-induced increase 5 hydroxy methyl cytosine (5hmC) and Rac1 mRNA. Similarly, in diabetic mice, Suv39H1-siRNA attenuated increase in 5hmC and Rac1 mRNA. Thus, H3K9me3 at Rac1 promoter assists in active DNA methylation-hydroxymethylation, activating Rac1 transcription. Regulation of Suv39H1-H3K9 trimethylation could prevent further epigenetic modifications, and prevent diabetic retinopathy.
DEEPMIR: a deep neural network for differential detection of cerebral microbleeds and iron deposits in MRI
Authors: Rashid Tanweer , Abdulkadir Ahmed , Nasrallah Ilya M. , Ware Jeffrey B. , Liu Hangfan , Spincemaille Pascal , Romero J. Rafael , Bryan R. Nick , Heckbert Susan R. , Habes Mohamad
Published: July 2021

Lobar cerebral microbleeds (CMBs) and localized non-hemorrhage iron deposits in the basal ganglia have been associated with brain aging, vascular disease and neurodegenerative disorders. Particularly, CMBs are small lesions and require multiple neuroimaging modalities for accurate detection. Quantitative susceptibility mapping (QSM) derived from in vivo magnetic resonance imaging (MRI) is necessary to differentiate between iron content and mineralization. We set out to develop a deep learning-based segmentation method suitable for segmenting both CMBs and iron deposits. We included a convenience sample of 24 participants from the MESA cohort and used T2-weighted images, susceptibility weighted imaging (SWI), and QSM to segment the two types of lesions. We developed a protocol for simultaneous manual annotation of CMBs and non-hemorrhage iron deposits in the basal ganglia. This manual annotation was then used to train a deep convolution neural network (CNN). Specifically, we adapted the U-Net model with a higher number of resolution layers to be able to detect small lesions such as CMBs from standard resolution MRI. We tested different combinations of the three modalities to determine the most informative data sources for the detection tasks. In the detection of CMBs using single class and multiclass models, we achieved an average sensitivity and precision of between 0.84–0.88 and 0.40–0.59, respectively. The same framework detected non-hemorrhage iron deposits with an average sensitivity and precision of about 0.75–0.81 and 0.62–0.75, respectively. Our results showed that deep learning could automate the detection of small vessel disease lesions and including multimodal MR data (particularly QSM) can improve the detection of CMB and non-hemorrhage iron deposits with sensitivity and precision that is compatible with use in large-scale research studies.
Retrospective review of 27 European cases of fatal elephant endotheliotropic herpesvirus-haemorrhagic disease reveals evidence of disseminated intravascular coagulation
Authors: Perrin K. L. , Kristensen A. T. , Bertelsen M. F. , Denk D.
Published: July 2021

Elephant endotheliotropic herpesvirus haemorrhagic disease (EEHV-HD) is widely acknowledged as the most common cause of mortality in young Asian elephants (Elephas maximus) in captivity. The objective of the current study was to perform a blinded, retrospective pathology review of European EEHV-HD fatalities, constituting the largest systematic assessment of EEHV-HD pathology to date. Findings between viral genotypes were compared with the aim to investigate if disseminated intravascular coagulation (DIC) could be substantiated as a significant complicating factor, thereby increasing the understanding of disease pathophysiology. Immunohistochemical staining confirmed endothelial cell (EC) damage and the presence of EC intranuclear inclusion bodies, demonstrating a direct viral cytopathic effect. Microthrombi were observed in 63% of cases in several organs, including lungs, which, together with widespread haemorrhage and thrombocytopenia reported in EEHV-HD case reports, supports the presence of overt DIC as a serious haemostatic complication of active EEHV infection. Death was attributed to widespread vascular damage with multi-organ dysfunction, including severe acute myocardial haemorrhage and subsequent cardiac failure. Systemic inflammation observed in the absence of bacterial infection may be caused by cytokine release syndrome. Findings reinforce the necessity to investigate cytokine responses and haemostatic status during symptomatic and asymptomatic EEHV viraemia, to potentially support the use of anti-inflammatory treatment in conjunction with anti-viral therapy and cardiovascular support.
Engineering tolerance to CLCuD in transgenic Gossypium hirsutum cv. HS6 expressing Cotton leaf curl Multan virus-C4 intron hairpin
Authors: Baig Mirza S. , Akhtar Sadia , Khan Jawaid A.
Published: July 2021

Cotton leaf curl disease (CLCuD), caused by begomoviruses in combination with betasatellite molecule, has adversely affected cotton industry of Indian subcontinent. To devise a CLCuD-control strategy, RNAi-mediated approach was followed in this study. Gossypium hirsutum cv. HS6 plants were transformed with intron-hairpin RNAi (ihpRNAi-C4) construct carrying silencing suppressor C4 gene of Cotton leaf curl Multan virus (CLCuMuV). Efficacy of the construct in imparting CLCuD resistance was evaluated in transgenic (T0, T1) cotton lines. Accumulation of CLCuMuV/betasatellite and attenuation of CLCuD symptoms in the transgenic lines were monitored at different times interval after virus inoculation. Northern hybridization revealed the expression of C4-gene derived siRNA. Expression of the ihpRNAi transcript was recorded higher in transgenic lines expressing siRNA which supposedly targeted the C4 gene. A significant delay in detection of virus as well as betasatellite was observed in the transgenic lines. At 30 days post inoculation (dpi), none of the lines tested positive. At 45 dpi, however, it could be detected in few lines having much lower titre as compared to non-transformed control plants. Notably, till 60 dpi, no significant progression of the virus/betasatellite DNA was observed and the plants did not exhibit any characteristic CLCuD symptoms. A tolerance phenomenon leading to escape of CLCuD symptoms in the transformed cotton was described.
Mapping the landscape of chromatin dynamics during naïve CD4+ T-cell activation
Authors: Iqbal Muhammad Munir , Serralha Michael , Kaur Parwinder , Martino David
Published: July 2021

T-cell activation induces context-specific gene expression programs that promote energy generation and biosynthesis, progression through the cell cycle and ultimately cell differentiation. The aim of this study was to apply the omni ATAC-seq method to characterize the landscape of chromatin changes induced by T-cell activation in mature naïve CD4+ T-cells. Using a well-established ex vivo protocol of canonical T-cell receptor signaling, we generated genome-wide chromatin maps of naïve T-cells from pediatric donors in quiescent or recently activated states. We identified thousands of individual chromatin accessibility peaks that are associated with T-cell activation, the majority of which were annotated intronic and intergenic enhancer regions. A core set of 3268 gene promoters underwent chromatin remodeling and concomitant changes in gene expression in response to activation, and were enriched in multiple pathways controlling cell cycle regulation, metabolism, inflammatory response genes and cell survival. Leukemia inhibitory factor (LIF) was among those factors that gained the highest accessibility and expression, in addition to IL2-STAT5 dependent chromatin remodeling in the T-cell activation response. Using publicly available data we found the chromatin response was far more dynamic at 24-h compared with 72-h post-activation. In total 546 associations were reproduced at both time-points with similar strength of evidence and directionality of effect. At the pathways level, the IL2-STAT5, KRAS signalling and UV response pathways were replicable at both time-points, although differentially modulated from 24 to 72 h post-activation.
Tunable multichannel Photonic spin Hall effect in metal-dielectric-metal waveguide
Authors: Zhao Li-Ming , Zhou Yun-Song
Published: July 2021

The discovery of Photonic spin Hall effect (PSHE) on surface plasmon polaritons (SPPs) is an important progress in photonics. In this paper, a method of realizing multi-channel PSHE in two-dimensional metal-air-metal waveguide is proposed. By modulating the phase difference $$\phi$$
ϕ
and polar angle $$\theta$$
θ
of the dipole source, the SPP can propagate along a specific channel. We further prove that PSHE results from the component wave interference theory. We believe that our findings will rich the application of SPPs in optical devices.
Hygienic quality of soil in the Gemer region (Slovakia) and the impact of risk elements contamination on cultivated agricultural products
Authors: Musilová Janette , Harangozo Ľuboš , Franková Hana , Lidiková Judita , Vollmannová Alena , Tóth Tomáš
Published: July 2021

The Gemer region (Slovakia) belongs to areas with a high concentration of risk elements. The contents of Cu, Ni, Pb, Cd, Hg and Mn were determined in soils and cultivated agricultural production from lands in three cadastres of the Gemer region (Henckovce (48.713845, 20.426189) and Nižná Slaná (48.717373, 20.4208423), cultivated crop—spring triticale; Gemerská Poloma (48.704523, 20.487645), cultivated crop—maize). Bioavailable forms of Pb (0.306–0.532 mg/kg) and Cd (0.104–0.154 mg/kg), pseudototal forms of Cd (3.07–3.98 mg/kg) and Hg (0.484–2.18 mg/kg) represented the highest risk in soils. The highest contents of Pb (Cd, Hg) were in maize from Gemerská Poloma: 0.898 (0.081, 0.399) mg/kg DM. Soils were classified based on several indicators of soil contamination. The highest values of indicators are: Contamination factor (Cf 29.1—Hg), Degree of contamination (Cdeg 51.5), Potential ecological risk factor (Er 1163—Hg), Potential ecological risk index (RI 1,520), Pollution load index (PLI 4.76), Geo-accumulation index (Igeo 5.60—Hg). All indicators concerned the lands of Henckovce and Gemerská Poloma, RI also concerned the land of Nižná Slaná. Bioaccumulation factor (BAF) was calculated to assess the plant's ability to absorb the risk element. For both crops and all risk elements, BAF values were < 1. Obtained results indicate heavy metal contamination of soils, therefore monitoring of soils in investigated area is necessary.