bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of ferroptosis in kidney tubular cell death under diabetic conditions
Authors: Kim Seonghun , Kang Shin-Wook , Joo Jeongho , Han Seung Hyeok , Shin Huiyoon , Nam Bo Young , Park Jimin , Yoo Tae-Hyun , Kim Gyuri , Lee Pureunchowon , Park Jung Tak
Published: February 2021

Kidney tubular cell death induced by transforming growth factor-β1 (TGF-β1) is known to contribute to diabetic nephropathy, a major complication of diabetes. Caspase-3-dependent apoptosis and caspase-1-dependent pyroptosis are also involved in tubular cell death under diabetic conditions. Recently, ferroptosis, an atypical form of iron-dependent cell death, was reported to cause kidney disease, including acute kidney injury. Ferroptosis is primed by lipid peroxide accumulation through the cystine/glutamate antiporter system Xc− (xCT) and glutathione peroxidase 4 (GPX4)-dependent mechanisms. The aim of this study was to evaluate the role of ferroptosis in diabetes-induced tubular injury. TGF-β1-stimulated proximal tubular epithelial cells and diabetic mice models were used for in vitro and in vivo experiments, respectively. xCT and GPX4 expression, cell viability, glutathione concentration, and lipid peroxidation were quantified to indicate ferroptosis. The effect of ferroptosis inhibition was also assessed. In kidney biopsy samples from diabetic patients, xCT and GPX4 mRNA expression was decreased compared to nondiabetic samples. In TGF-β1-stimulated tubular cells, intracellular glutathione concentration was reduced and lipid peroxidation was enhanced, both of which are related to ferroptosis-related cell death. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, alleviated TGF-β1-induced ferroptosis. In diabetic mice, kidney mRNA and protein expressions of xCT and GPX4 were reduced compared to control. Kidney glutathione concentration was decreased, while lipid peroxidation was increased in these mice, and these changes were alleviated by Fer-1 treatment. Ferroptosis is involved in kidney tubular cell death under diabetic conditions. Ferroptosis inhibition could be a therapeutic option for diabetic nephropathy.
HMGB1 orchestrates STING-mediated senescence via TRIM30α modulation in cancer cells
Authors: Lee Je-Jung , Park In Ho , Kwak Man Sup , Rhee Woo Joong , Kim Songhee H. , Shin Jeon-Soo
Published: February 2021

Although cellular senescence has emerged as a novel therapeutic concept in cancer, its underlying mechanisms remain unclear. High mobility group box 1 (HMGB1) and stimulator of interferon genes (STING) are involved in senescence. However, their interactions in senescence have not been reported. Therefore, in this study, we investigated the relationships between HMGB1 and STING in senescence in cancer and other cells. In mouse melanoma cells and several other cell lines, doxorubicin treatment induced senescence in an HMGB1-dependent manner. These responses were mediated by STING, and this function of STING was negatively regulated by the E3 ligase tripartite motif protein 30α (TRIM30α). We also found that HMGB1 bound to the TRIM30α promoter and then suppressed its expression by inhibiting its transcription, which enhanced STING-induced senescence. This mechanism was further mediated by signal transducer and activator of transcription 6 (STAT6) and p21. Overall, our findings demonstrated that HMGB1 orchestrated STING-STAT6-p21-mediated senescence by regulating TRIM30α as an alternative anticancer mechanism.
Assessing the influence of climate on wintertime SARS-CoV-2 outbreaks
Authors: Baker Rachel E. , Yang Wenchang , Vecchi Gabriel A. , Metcalf C. Jessica E. , Grenfell Bryan T.
Published: February 2021

High susceptibility has limited the role of climate in the SARS-CoV-2 pandemic to date. However, understanding a possible future effect of climate, as susceptibility declines and the northern-hemisphere winter approaches, is an important open question. Here we use an epidemiological model, constrained by observations, to assess the sensitivity of future SARS-CoV-2 disease trajectories to local climate conditions. We find this sensitivity depends on both the susceptibility of the population and the efficacy of non-pharmaceutical interventions (NPIs) in reducing transmission. Assuming high susceptibility, more stringent NPIs may be required to minimize outbreak risk in the winter months. Our results suggest that the strength of NPIs remain the greatest determinant of future pre-vaccination outbreak size. While we find a small role for meteorological forecasts in projecting outbreak severity, reducing uncertainty in epidemiological parameters will likely have a more substantial impact on generating accurate predictions.
Genome-wide fine-mapping identifies pleiotropic and functional variants that predict many traits across global cattle populations
Authors: Xiang Ruidong , MacLeod Iona M. , Daetwyler Hans D. , de Jong Gerben , O’Connor Erin , Schrooten Chris , Chamberlain Amanda J. , Goddard Michael E.
Published: February 2021

The difficulty in finding causative mutations has hampered their use in genomic prediction. Here, we present a methodology to fine-map potentially causal variants genome-wide by integrating the functional, evolutionary and pleiotropic information of variants using GWAS, variant clustering and Bayesian mixture models. Our analysis of 17 million sequence variants in 44,000+ Australian dairy cattle for 34 traits suggests, on average, one pleiotropic QTL existing in each 50 kb chromosome-segment. We selected a set of 80k variants representing potentially causal variants within each chromosome segment to develop a bovine XT-50K genotyping array. The custom array contains many pleiotropic variants with biological functions, including splicing QTLs and variants at conserved sites across 100 vertebrate species. This biology-informed custom array outperformed the standard array in predicting genetic value of multiple traits across populations in independent datasets of 90,000+ dairy cattle from the USA, Australia and New Zealand.
Host interneurons mediate plasticity reactivated by embryonic inhibitory cell transplantation in mouse visual cortex
Authors: Zheng XiaoTing , Salinas Kirstie J. , Velez Dario X. Figueroa , Nakayama Taylor , Lin Xiaoxiao , Banerjee Dhruba , Xu Xiangmin , Gandhi Sunil P.
Published: February 2021

The adult brain lacks sensitivity to changes in the sensory environment found in the juvenile brain. The transplantation of embryonic interneurons has been shown to restore juvenile plasticity to the adult host visual cortex. It is unclear whether transplanted interneurons directly mediate the renewed cortical plasticity or whether these cells act indirectly by modifying the host interneuron circuitry. Here we find that the transplant-induced reorganization of mouse host circuits is specifically mediated by Neuregulin (NRG1)/ErbB4 signaling in host parvalbumin (PV) interneurons. Brief visual deprivation reduces the visual activity of host PV interneurons but has negligible effects on the responses of transplanted PV interneurons. Exogenous NRG1 both prevents the deprivation-induced reduction in the visual responses of host PV interneurons and blocks the transplant-induced reorganization of the host circuit. While deletion of ErbB4 receptors from host PV interneurons blocks cortical plasticity in the transplant recipients, deletion of the receptors from the donor PV interneurons does not. Altogether, our results indicate that transplanted embryonic interneurons reactivate cortical plasticity by rejuvenating the function of host PV interneurons.
SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanced ACE2-binding affinity
Authors: Ozono Seiya , Zhang Yanzhao , Ode Hirotaka , Sano Kaori , Tan Toong Seng , Imai Kazuo , Miyoshi Kazuyasu , Kishigami Satoshi , Ueno Takamasa , Iwatani Yasumasa , Suzuki Tadaki , Tokunaga Kenzo
Published: February 2021

The causative agent of the COVID-19 pandemic, SARS-CoV-2, is steadily mutating during continuous transmission among humans. Such mutations can occur in the spike (S) protein that binds to the ACE2 receptor and is cleaved by TMPRSS2. However, whether S mutations affect SARS-CoV-2 cell entry remains unknown. Here, we show that naturally occurring S mutations can reduce or enhance cell entry via ACE2 and TMPRSS2. A SARS-CoV-2 S-pseudotyped lentivirus exhibits substantially lower entry than that of SARS-CoV S. Among S variants, the D614G mutant shows the highest cell entry, as supported by structural and binding analyses. Nevertheless, the D614G mutation does not affect neutralization by antisera against prototypic viruses. Taken together, we conclude that the D614G mutation increases cell entry by acquiring higher affinity to ACE2 while maintaining neutralization susceptibility. Based on these findings, further worldwide surveillance is required to understand SARS-CoV-2 transmissibility among humans.
Experimental demonstration of quantum advantage for NP verification with limited information
Authors: Centrone Federico , Kumar Niraj , Diamanti Eleni , Kerenidis Iordanis
Published: February 2021

In recent years, many computational tasks have been proposed as candidates for showing a quantum computational advantage, that is an advantage in the time needed to perform the task using a quantum instead of a classical machine. Nevertheless, practical demonstrations of such an advantage remain particularly challenging because of the difficulty in bringing together all necessary theoretical and experimental ingredients. Here, we show an experimental demonstration of a quantum computational advantage in a prover-verifier interactive setting, where the computational task consists in the verification of an NP-complete problem by a verifier who only gets limited information about the proof sent by an untrusted prover in the form of a series of unentangled quantum states. We provide a simple linear optical implementation that can perform this verification task efficiently (within a few seconds), while we also provide strong evidence that, fixing the size of the proof, a classical computer would take much longer time (assuming only that it takes exponential time to solve an NP-complete problem). While our computational advantage concerns a specific task in a scenario of mostly theoretical interest, it brings us a step closer to potential useful applications, such as server-client quantum computing.
Giant optical anisotropy in transition metal dichalcogenides for next-generation photonics
Authors: Ermolaev G. A. , Grudinin D. V. , Stebunov Y. V. , Voronin K. V. , Kravets V. G. , Duan J. , Mazitov A. B. , Tselikov G. I. , Bylinkin A. , Yakubovsky D. I. , Novikov S. M. , Baranov D. G. , Nikitin A. Y. , Kruglov I. A. , Shegai T. , Alonso-González P. , Grigorenko A. N. , Arsenin A. V. , Novoselov K. S. , Volkov V. S.
Published: February 2021

Large optical anisotropy observed in a broad spectral range is of paramount importance for efficient light manipulation in countless devices. Although a giant anisotropy has been recently observed in the mid-infrared wavelength range, for visible and near-infrared spectral intervals, the problem remains acute with the highest reported birefringence values of 0.8 in BaTiS3 and h-BN crystals. This issue inspired an intensive search for giant optical anisotropy among natural and artificial materials. Here, we demonstrate that layered transition metal dichalcogenides (TMDCs) provide an answer to this quest owing to their fundamental differences between intralayer strong covalent bonding and weak interlayer van der Waals interaction. To do this, we made correlative far- and near-field characterizations validated by first-principle calculations that reveal a huge birefringence of 1.5 in the infrared and 3 in the visible light for MoS2. Our findings demonstrate that this remarkable anisotropy allows for tackling the diffraction limit enabling an avenue for on-chip next-generation photonics.
Intrinsic donor-bound excitons in ultraclean monolayer semiconductors
Authors: Rivera Pasqual , He Minhao , Kim Bumho , Liu Song , Rubio-Verdú Carmen , Moon Hyowon , Mennel Lukas , Rhodes Daniel A. , Yu Hongyi , Taniguchi Takashi , Watanabe Kenji , Yan Jiaqiang , Mandrus David G. , Dery Hanan , Pasupathy Abhay , Englund Dirk , Hone James , Yao Wang , Xu Xiaodong
Published: February 2021

The monolayer transition metal dichalcogenides are an emergent semiconductor platform exhibiting rich excitonic physics with coupled spin-valley degree of freedom and optical addressability. Here, we report a new series of low energy excitonic emission lines in the photoluminescence spectrum of ultraclean monolayer WSe2. These excitonic satellites are composed of three major peaks with energy separations matching known phonons, and appear only with electron doping. They possess homogenous spatial and spectral distribution, strong power saturation, and anomalously long population (>6 µs) and polarization lifetimes (>100 ns). Resonant excitation of the free inter- and intravalley bright trions leads to opposite optical orientation of the satellites, while excitation of the free dark trion resonance suppresses the satellitesʼ photoluminescence. Defect-controlled crystal synthesis and scanning tunneling microscopy measurements provide corroboration that these features are dark excitons bound to dilute donors, along with associated phonon replicas. Our work opens opportunities to engineer homogenous single emitters and explore collective quantum optical phenomena using intrinsic donor-bound excitons in ultraclean 2D semiconductors.
Malignant subclone drives metastasis of genetically and phenotypically heterogenous cell clusters through fibrotic niche generation
Authors: Kok Sau Yee , Oshima Hiroko , Takahashi Kei , Nakayama Mizuho , Murakami Kazuhiro , Ueda Hiroki R. , Miyazono Kohei , Oshima Masanobu
Published: February 2021

A concept of polyclonal metastasis has recently been proposed, wherein tumor cell clusters break off from the primary site and are disseminated. However, the involvement of driver mutations in such polyclonal mechanism is not fully understood. Here, we show that non-metastatic AP cells metastasize to the liver with metastatic AKTP cells after co-transplantation to the spleen. Furthermore, AKTP cell depletion after the development of metastases results in the continuous proliferation of the remaining AP cells, indicating a role of AKTP cells in the early step of polyclonal metastasis. Importantly, AKTP cells, but not AP cells, induce fibrotic niche generation when arrested in the sinusoid, and such fibrotic microenvironment promotes the colonization of AP cells. These results indicate that non-metastatic cells can metastasize via the polyclonal metastasis mechanism using the fibrotic niche induced by malignant cells. Thus, targeting the fibrotic niche is an effective strategy for halting polyclonal metastasis.
Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry
Authors: Roelands Jessica , Mall Raghvendra , Almeer Hossam , Thomas Remy , Mohamed Mahmoud G. , Bedri Shahinaz , Al-Bader Salha Bujassoum , Junejo Kulsoom , Ziv Elad , Sayaman Rosalyn W. , Kuppen Peter J. K. , Bedognetti Davide , Hendrickx Wouter , Decock Julie
Published: February 2021

Breast cancer largely dominates the global cancer burden statistics; however, there are striking disparities in mortality rates across countries. While socioeconomic factors contribute to population-based differences in mortality, they do not fully explain disparity among women of African ancestry (AA) and Arab ancestry (ArA) compared to women of European ancestry (EA). In this study, we sought to identify molecular differences that could provide insight into the biology of ancestry-associated disparities in clinical outcomes. We applied a unique approach that combines the use of curated survival data from The Cancer Genome Atlas (TCGA) Pan-Cancer clinical data resource, improved single-nucleotide polymorphism-based inferred ancestry assignment, and a novel breast cancer subtype classification to interrogate the TCGA and a local Arab breast cancer dataset. We observed an enrichment of BasalMyo tumors in AA patients (38 vs 16.5% in EA, p = 1.30E − 10), associated with a significant worse overall (hazard ratio (HR) = 2.39, p = 0.02) and disease-specific survival (HR = 2.57, p = 0.03). Gene set enrichment analysis of BasalMyo AA and EA samples revealed differences in the abundance of T-regulatory and T-helper type 2 cells, and enrichment of cancer-related pathways with prognostic implications (AA: PI3K-Akt-mTOR and ErbB signaling; EA: EGF, estrogen-dependent and DNA repair signaling). Strikingly, AMPK signaling was associated with opposing prognostic connotation (AA: 10-year HR = 2.79, EA: 10-year HR = 0.34). Analysis of ArA patients suggests enrichment of BasalMyo tumors with a trend for differential enrichment of T-regulatory cells and AMPK signaling. Together, our findings suggest that the disparity in the clinical outcome of AA breast cancer patients is likely related to differences in cancer-related and microenvironmental features.
Label-free characterization of single extracellular vesicles using two-photon fluorescence lifetime imaging microscopy of NAD(P)H
Authors: Sorrells Janet E. , Martin Elisabeth M. , Aksamitiene Edita , Mukherjee Prabuddha , Alex Aneesh , Chaney Eric J. , Marjanovic Marina , Boppart Stephen A.
Published: February 2021

The heterogeneous nature of extracellular vesicles (EVs) creates the need for single EV characterization techniques. However, many common biochemical and functional EV analysis techniques lack single EV resolution. Two-photon fluorescence lifetime imaging microscopy (FLIM) is widely used to functionally characterize the reduced form of nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate (NAD(P)H) in cells and tissues. Here, we demonstrate that FLIM can also be used to image and characterize NAD(P)H in single isolated EVs. EVs were isolated using standard differential ultracentrifugation techniques from multiple cell lines and imaged using a custom two-photon FLIM system. The presented data show that the NAD(P)H fluorescence lifetimes in isolated cell-derived EVs follow a wide Gaussian distribution, indicating the presence of a range of different protein-bound and free NAD(P)H species. EV NAD(P)H fluorescence lifetime distribution has a larger standard deviation than that of cells and a significantly different fluorescence lifetime distribution than the nuclei, mitochondria, and cytosol of cells. Additionally, changes in the metabolic conditions of cells were reflected in changes in the mean fluorescence lifetime of NAD(P)H in the produced EVs. These data suggest that FLIM of NAD(P)H could be a valuable tool for EV research.
Systemic nicotine enhances opioid self-administration and modulates the formation of opioid-associated memories partly through actions within the insular cortex
Authors: Loney Gregory C. , King Christopher P. , Meyer Paul J.
Published: February 2021

Habitual use of nicotine containing products increases propensity to misuse prescription opioids and its prevalence is substantially increased in individuals currently involved in opioid-treatment programs. Nicotine enhances self-administration of many classes of drugs in rodents, though evidence for direct effects on opioids is lacking. We sought to measure the effects of nicotine pretreatment on the reinforcing efficacy of opioids in both self-administration and contextual conditioning paradigms. First, we measured the effect of systemic nicotine pretreatment on self-administration of two opioids. Additionally, we measured the degree to which systemic nicotine pretreatment impacts the formation of morphine-associated contextual memories in conditioned taste avoidance and place preference paradigms. Given the involvement of the insula in the maintenance of substance abuse, its importance in nicotine addiction, and findings that insular inactivation impairs contextual drug conditioning, we examined whether nicotine administered directly to the insula could recapitulate the effects of systemic nicotine. We demonstrate that systemic nicotine pretreatment significantly enhances opioid self-administration and alters contextual conditioning. Furthermore, intra-insula nicotine similarly altered morphine contextual conditioning by blocking the formation of taste avoidance at all three morphine doses tested (5.0, 10, and 20 mg/kg), while shifting the dose–response curve of morphine in the place preference paradigm rightward. In conclusion, these data demonstrate that nicotine facilitates opioid intake and is partly acting within the insular cortex to obfuscate aversive opiate memories while potentiating approach to morphine-associated stimuli at higher doses.
Meta-analysis of the effect of the pringle maneuver on long-term oncological outcomes following liver resection
Authors: Khajeh Elias , Shafiei Saeed , Al-Saegh Sadeq Ali-Hasan , Ramouz Ali , Hammad Ahmed , Ghamarnejad Omid , Al-Saeedi Mohammed , Rahbari Nuh , Reissfelder Christoph , Mehrabi Arianeb , Probst Pascal , Oweira Hani
Published: February 2021

Hepatic pedicle clamping reduces intraoperative blood loss and the need for transfusion, but its long-term effect on survival and recurrence remains controversial. The aim of this meta-analysis was to evaluate the effect of the Pringle maneuver (PM) on long-term oncological outcomes in patients with primary or metastatic liver malignancies who underwent liver resection. Literature was searched in the Cochrane Central Register of Controlled Trials (CENTRAL), Medline (via PubMed), and Web of Science databases. Survival was measured as the survival rate or as a continuous endpoint. Pooled estimates were represented as odds ratios (ORs) using the Mantel–Haenszel test with a random-effects model. The literature search retrieved 435 studies. One RCT and 18 NRS, including 7480 patients who underwent liver resection with the PM (4309 cases) or without the PM (3171 cases) were included. The PM did not decrease the 1-year overall survival rate (OR 0.86; 95% CI 0.67–1.09; P = 0.22) or the 3- and 5-year overall survival rates. The PM did not decrease the 1-year recurrence-free survival rate (OR 1.06; 95% CI 0.75–1.50; P = 0.75) or the 3- and 5-year recurrence-free survival rates. There is no evidence that the Pringle maneuver has a negative effect on recurrence-free or overall survival rates.
Deep action learning enables robust 3D segmentation of body organs in various CT and MRI images
Authors: Zhong Xia , Amrehn Mario , Ravikumar Nishant , Chen Shuqing , Strobel Norbert , Birkhold Annette , Kowarschik Markus , Fahrig Rebecca , Maier Andreas
Published: February 2021

In this study, we propose a novel point cloud based 3D registration and segmentation framework using reinforcement learning. An artificial agent, implemented as a distinct actor based on value networks, is trained to predict the optimal piece-wise linear transformation of a point cloud for the joint tasks of registration and segmentation. The actor network estimates a set of plausible actions and the value network aims to select the optimal action for the current observation. Point-wise features that comprise spatial positions (and surface normal vectors in the case of structured meshes), and their corresponding image features, are used to encode the observation and represent the underlying 3D volume. The actor and value networks are applied iteratively to estimate a sequence of transformations that enable accurate delineation of object boundaries. The proposed approach was extensively evaluated in both segmentation and registration tasks using a variety of challenging clinical datasets. Our method has fewer trainable parameters and lower computational complexity compared to the 3D U-Net, and it is independent of the volume resolution. We show that the proposed method is applicable to mono- and multi-modal segmentation tasks, achieving significant improvements over the state-of-the-art for the latter. The flexibility of the proposed framework is further demonstrated for a multi-modal registration application. As we learn to predict actions rather than a target, the proposed method is more robust compared to the 3D U-Net when dealing with previously unseen datasets, acquired using different protocols or modalities. As a result, the proposed method provides a promising multi-purpose segmentation and registration framework, particular in the context of image-guided interventions.
Species traits affect phenological responses to climate change in a butterfly community
Authors: Zografou Konstantina , Swartz Mark T. , Adamidis George C. , Tilden Virginia P. , McKinney Erika N. , Sewall Brent J.
Published: February 2021

Diverse taxa have undergone phenological shifts in response to anthropogenic climate change. While such shifts generally follow predicted patterns, they are not uniform, and interspecific variation may have important ecological consequences. We evaluated relationships among species’ phenological shifts (mean flight date, duration of flight period), ecological traits (larval trophic specialization, larval diet composition, voltinism), and population trends in a butterfly community in Pennsylvania, USA, where the summer growing season has become warmer, wetter, and longer. Data were collected over 7–19 years from 18 species or species groups, including the extremely rare eastern regal fritillary Speyeria idalia idalia. Both the direction and magnitude of phenological change over time was linked to species traits. Polyphagous species advanced and prolonged the duration of their flight period while oligophagous species delayed and shortened theirs. Herb feeders advanced their flight periods while woody feeders delayed theirs. Multivoltine species consistently prolonged flight periods in response to warmer temperatures, while univoltine species were less consistent. Butterflies that shifted to longer flight durations, and those that had polyphagous diets and multivoltine reproductive strategies tended to decline in population. Our results suggest species’ traits shape butterfly phenological responses to climate change, and are linked to important community impacts.
Addressing unpredictability may be the key to improving performance with current clinically prescribed myoelectric prostheses
Authors: Chadwell A. , Kenney L. , Thies S. , Head J. , Galpin A. , Baker R.
Published: February 2021

The efferent control chain for an upper-limb myoelectric prosthesis can be separated into 3 key areas: signal generation, signal acquisition, and device response. Data were collected from twenty trans-radial myoelectric prosthesis users using their own clinically prescribed devices, to establish the relative impact of these potential control factors on user performance (user functionality and everyday prosthesis usage). By identifying the key factor(s), we can guide future developments to ensure clinical impact. Skill in generating muscle signals was assessed via reaction times and signal tracking. To assess the predictability of signal acquisition, we inspected reaction time spread and undesired hand activations. As a measure of device response, we recorded the electromechanical delay between electrode stimulation and the onset of hand movement. Results suggest abstract measures of skill in controlling muscle signals are poorly correlated with performance. Undesired activations of the hand or incorrect responses were correlated with almost all kinematics and gaze measures suggesting unpredictability is a key factor. Significant correlations were also found between several measures of performance and the electromechanical delay; however, unexpectedly, longer electromechanical delays correlated with better performance. Future research should focus on exploring causes of unpredictability, their relative impacts on performance and interventions to address this.
Evaluating very high energy electron RBE from nanodosimetric pBR322 plasmid DNA damage
Authors: Small K. L. , Henthorn N. T. , Angal-Kalinin D. , Chadwick A. L. , Santina E. , Aitkenhead A. , Kirkby K. J. , Smith R. J. , Surman M. , Jones J. , Farabolini W. , Corsini R. , Gamba D. , Gilardi A. , Merchant M. J. , Jones R. M.
Published: February 2021

This paper presents the first plasmid DNA irradiations carried out with Very High Energy Electrons (VHEE) over 100–200 MeV at the CLEAR user facility at CERN to determine the Relative Biological Effectiveness (RBE) of VHEE. DNA damage yields were measured in dry and aqueous environments to determine that ~ 99% of total DNA breaks were caused by indirect effects, consistent with other published measurements for protons and photons. Double-Strand Break (DSB) yield was used as the biological endpoint for RBE calculation, with values found to be consistent with established radiotherapy modalities. Similarities in physical damage between VHEE and conventional modalities gives confidence that biological effects of VHEE will also be similar—key for clinical implementation. Damage yields were used as a baseline for track structure simulations of VHEE plasmid irradiation using GEANT4-DNA. Current models for DSB yield have shown reasonable agreement with experimental values. The growing interest in FLASH radiotherapy motivated a study into DSB yield variation with dose rate following VHEE irradiation. No significant variations were observed between conventional and FLASH dose rate irradiations, indicating that no FLASH effect is seen under these conditions.
Involvement of MCH-oxytocin neural relay within the hypothalamus in murine nursing behavior
Authors: Kato Yoko , Katsumata Harumi , Inutsuka Ayumu , Yamanaka Akihiro , Onaka Tatsushi , Minami Shiro , Orikasa Chitose
Published: February 2021

Multiple sequential actions, performed during parental behaviors, are essential elements of reproduction in mammalian species. We showed that neurons expressing melanin concentrating hormone (MCH) in the lateral hypothalamic area (LHA) are more active in rodents of both sexes when exhibiting parental nursing behavior. Genetic ablation of the LHA-MCH neurons impaired maternal nursing. The post-birth survival rate was lower in pups born to female mice with congenitally ablated MCH neurons under control of tet-off system, exhibiting reduced crouching behavior. Virgin female and male mice with ablated MCH neurons were less interested in pups and maternal care. Chemogenetic and optogenetic stimulation of LHA-MCH neurons induced parental nursing in virgin female and male mice. LHA-MCH GABAergic neurons project fibres to the paraventricular hypothalamic nucleus (PVN) neurons. Optogenetic stimulation of PVN induces nursing crouching behavior along with increasing plasma oxytocin levels. The hypothalamic MCH neural relays play important functional roles in parental nursing behavior in female and male mice.
Rotational hyperspectral scanner and related image reconstruction algorithm
Authors: Luo Longqiang , Li Shuo , Yao Xinli , He Sailing
Published: February 2021

We design and implement a compact and lightweight hyperspectral scanner. Based on this, a novel rotational hyperspectral scanner was demonstrated. Different from translational scanning, rotational scanning is a moveless and stable scanning method. We also designed a relevant image algorithm to reconstruct the image from an angular recorded hyperspectral data cube. The algorithm works well even with uncertain radial and tangential offset, which is caused by mechanical misalignment. The system shown a spectral resolution of 5 nm after calibration. Finally, spatial accuracy and spectral precision were discussed, based on some additional experiments.
Antibiotic-resistant bacteria and gut microbiome communities associated with wild-caught shrimp from the United States versus imported farm-raised retail shrimp
Authors: Sharma Laxmi , Nagpal Ravinder , Jackson Charlene R. , Patel Dhruv , Singh Prashant
Published: February 2021

In the United States, farm-raised shrimp accounts for ~ 80% of the market share. Farmed shrimp are cultivated as monoculture and are susceptible to infections. The aquaculture industry is dependent on the application of antibiotics for disease prevention, resulting in the selection of antibiotic-resistant bacteria. We aimed to characterize the prevalence of antibiotic-resistant bacteria and gut microbiome communities in commercially available shrimp. Thirty-one raw and cooked shrimp samples were purchased from supermarkets in Florida and Georgia (U.S.) between March–September 2019. The samples were processed for the isolation of antibiotic-resistant bacteria, and isolates were characterized using an array of molecular and antibiotic susceptibility tests. Aerobic plate counts of the cooked samples (n = 13) varied from < 25 to 6.2 log CFU/g. Isolates obtained (n = 110) were spread across 18 genera, comprised of coliforms and opportunistic pathogens. Interestingly, isolates from cooked shrimp showed higher resistance towards chloramphenicol (18.6%) and tetracycline (20%), while those from raw shrimp exhibited low levels of resistance towards nalidixic acid (10%) and tetracycline (8.2%). Compared to wild-caught shrimp, the imported farm-raised shrimp harbored distinct gut microbiota communities and a higher prevalence of antibiotic-resistance genes in their gut. The presence of antibiotic-resistant strains in cooked shrimps calls for change in processing for their mitigation.
Author Correction: Artificial intelligence provides greater accuracy in the classification of modern and ancient bone surface modifications
Authors: Domínguez‑Rodrigo Manuel , Cifuentes‑Alcobendas Gabriel , Jiménez‑García Blanca , Abellán Natalia , Pizarro‑Monzo Marcos , Organista Elia , Baquedano Enrique
Published: February 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Dogs display owner-specific expectations based on olfaction
Authors: Bräuer Juliane , Blasi Damian
Published: February 2021

Most current knowledge about dogs’ understanding of, and reacting to, their environment is limited to the visual or auditory modality, but it remains unclear how olfaction and cognition are linked together. Here we investigate how domestic dogs search for their owners using their excellent olfactory sense. We raise the question whether dogs have a representation of someone when they smell their track. The question is what they expect when they follow a trail or whether they perceive an odour as a relevant or non-relevant stimulus. We adopted a classical violation-of-expectation paradigm—and as targets we used two persons that were both important to the dog, usually the owners. In the critical condition subjects could track the odour trail of one target, but at the end of the trail they find another target. Dogs showed an increased activity when the person did not correspond with the trail compared to a control condition. Moreover, we found huge individual differences in searching behaviour supporting the assumption that dogs are only able to smell when they really sniff, and that the temperature has an influence on dogs performance. Results are discussed in the light of how cognitive abilities, motivation and odour perception influence each other.
Dynamic variations in salinity and potassium grade of a potassium-rich brine deposit in Lop Nor basin, China
Authors: Ma Lichun , Wang Kai , Zhang Yu , Tang Qingfeng , Yan Hui
Published: February 2021

The Quaternary Lop Nor playa is the largest production base of potassium sulfate in the world. It has a mining history of more than 10 years, and its share in the Chinese potassium sulfate market is about 50% to-date. In this basin, the high-salinity potassium-rich brines are mainly contained in Middle Pleistocene–Holocene glauberite strata. Based on the monitoring of the underground brine table and geochemical analysis, this study reveals variations in the underground brine table and potassium-bearing grade before and after large-scale mining in the Lop Nor potash deposit. The results showed that the underground brine table and potassium sulfate grade decreased by varying degrees over sub-mineral areas after large-scale mining. The underground brine table declined by 8.5 m, on average, in the Luobei depression, by 6.4 m in the Tenglong platform and by 1.9 m in the Xinqing platform. However, the potassium-bearing grade showed the different trend. The Tenglong platform had the largest decline with average decreases in layers W1, W2 and W3 of 18.2%, 13.0% and 24.8%, respectively. In the Xinqing platform, the average decrease in layersW2 and W3 were 17.4% and 16.0% respectively. The Luobei depression decreases were relatively small (W1, W2 and W3 decreased 4.3%, 4.2% and 3.1%, respectively). This research provides a theoretical basis for the rational development and sustainable use of the potassium-rich brines in the Lop Nor basin.
Novel TLR 7/8 agonists for improving NK cell mediated antibody-dependent cellular cytotoxicity (ADCC)
Authors: Khanna Vidhi , Kim Hyunjoon , Zhang Wenqiu , Larson Peter , Shah Manan , Griffith Thomas S. , Ferguson David , Panyam Jayanth
Published: February 2021

There is a significant interest in designing therapeutic agents that can enhance ADCC and thereby improve clinical responses with approved antibodies. We recently reported the combination of an imidazoquinoline-based TLR7/8 agonist (522) with a monoclonal antibody improved ADCC in vitro and in vivo. In the present study, we tested several new small molecule TLR7/8 agonists that induce significantly higher cytokines compared to both the FDA-approved TLR7 agonist, imiquimod, and 522. We evaluated these agonists in combination with monoclonal antibody therapy, with the main goal of enhancing ADCC. Our studies show these TLR7/8 agonists induce robust pro-inflammatory cytokine secretion and activate NK cells. Specifically, we found the agonists 574 and 558 significantly enhanced NK cell-mediated ADCC in vitro as well as enhanced the anti-cancer efficacy of monoclonal antibodies in two different in vivo mouse models. Additionally, we found the agonists were able to stimulate CD8 T cells, likely indicative of an early adaptive immune response.
Degradation of atrazine and bromacil in two forestry waste products
Authors: James Trevor K. , Ghanizadeh Hossein , Harrington Kerry C. , Bolan Nanthi S.
Published: February 2021

The persistence and degradation of two common herbicides, atrazine and bromacil in two organic media, wood pulp and sawdust were compared with two soils. The hypothesis tested was that herbicide degradation will be faster in high organic matter media compared to soil. Degradation of two herbicides was carried out in four different temperature regimes and in sterilised media. The degradation half-life (t½) was determined under above-mentioned conditions then compared to degradation in soil. The degradation as quantified by t½ of the herbicides was generally longer in both organic media. Although microbial degradation was an important factor in the mineralisation of these herbicides, overall, the pH of the media had a more profound effect on the desorption and subsequent degradation rate than the organic carbon content. The results of this study revealed that the hypothesis was only partially correct as organic matter content per se did not strongly relate to degradation rates which were mainly governed by pH and microbial activity.
Surface Chemistry of Colloidal Nanocrystals
Authors: Daniel-da-Silva Ana Luísa , Trindade Tito
Published: February 2021

The chemistry of nanomaterials has developed considerably in the past two decades, and concepts that have emerged from these developments are now well established. The surface modification of nanoparticles is a subject of intense research interest given its importance for many applications across a number of disciplines. This comprehensive guide is the first to be devoted to the surface chemistry of inorganic nanocrystals. Following an introduction to the physical chemistry of surfaces, chapters cover topics such as the surface modification of nanoparticles, water compatible, polymer-based, and inorganic nanocomposites, as well as relevant applications in catalysis, biotechnology and nanomedicine. Highlighting recent advances, Surface Chemistry of Colloidal Nanocrystals provides an integrated approach to chemical aspects related to the surface of nanocrystals. Written by prestigious scientists, this will be a useful resource for students and researchers working in surface science, nanoscience and materials science as well as those interested in the applications of the nanomaterials in areas such as health science, biology, and environmental engineering.
Interfacial biocatalysis in bacteria-stabilized Pickering emulsions for microbial transformation of hydrophobic chemicals
Authors: Xie Haisheng , Zhao Wenyu , Ali Daniel Chikere , Zhang Xuehong , Wang Zhilong
Published: February 2021

The Pickering emulsion interface is an exceptional habitat for bacteria to grow by simultaneously utilizing hydrophobic and hydrophilic chemicals.
Effects of different treatment atmospheres on CeO2/g-C3N4 photocatalytic CO2 reduction: good or bad?
Authors: Pu Yu , Li Wanqin , Cai Yandi , Wei Xiaoqian , Wang Xin , Chen Chong , Zou Weixin , Dong Lin
Published: February 2021

CeO2/g-C3N4 with heat treatment under different atmospheres were synthesized. The built-in electric field led to a Z-scheme photocatalytic system on CeCN-N2.
LC-DAD-ESI-MS/MS analysis and cytotoxic and antiproliferative effects of chlorogenic acid derivative rich extract from Nerium oleander L. pink flowers
Authors: Ayouaz Siham , Oliveira-Alves Sheila Cristina , Serra Ana Teresa , Lefsih Khalef , Samah Madani , Bento da Silva Andreia , Madani Khodir , Bronze Maria Rosário
Published: February 2021

Nerium oleander L. is a widely used medicinal plant for pharmaceutical purposes.
Bi19S27I3 nanorods: a new candidate for photothermal therapy in the first and second biological near-infrared windows
Authors: Xiong Jinsong , Bian Qinghuan , Lei Shuijin , Deng Yatian , Zhao Kehan , Sun Shunqiang , Fu Qi , Xiao Yanhe , Cheng Baochang
Published: February 2021

For the first time, Bi19S27I3 nanorods are utilized as a promising nanoplatform for photothermal therapy in NIR-I and NIR-II windows.
Lithiated three-membered heterocycles as chiral nucleophiles in the enantioselective synthesis of 1-oxaspiro[2,3]hexanes
Authors: Cocco Andrea , Rubanu Maria Grazia , Sechi Maria Laura , Frongia Angelo , Mastrorilli Pietro , Degennaro Leonardo , Colella Marco , Luisi Renzo , Secci Francesco
Published: February 2021

Enantiomerically enriched oxaspiro- and azaspirohexanes were synthesized through a two-step addition of configurably stable Li-styrene oxide (or aziridine) to 3-substituted cyclobutanones and base-mediated Payne rearrangement sequence with high yields and selectivity.
Recent approaches to the synthesis of tetrahydrocarbazoles
Authors: Chaudhari Tohasib Yusub , Tandon Vibha
Published: February 2021

The tetrahydrocarbazole (THC) motif is ubiquitous in natural products and biologically active compounds.
Genome mining of cryptic tetronate natural products from a PKS-NRPS encoding gene cluster in Trichoderma harzianum t-22
Authors: Zhu Yiguang , Wang Junfeng , Mou Pengyun , Yan Yan , Chen Mengbin , Tang Yi
Published: February 2021

The gene cluster of trihazones was identified from Trichoderma harzianum t-22 and heterologously activated in Aspergillus nidualns. The α-KG dependent dioxygenase ThnC was confirmed to catalyze exocyclic double bond formation.
N-Heterocyclic carbene catalyzed asymmetric [3 + 3] cycloaddtion of β,β-disubstituted, α,β-unsaturated carboxylic esters with 3-aminobenzofurans
Authors: He Chonglong , Zhou Yipeng , Li Zhanhuan , Xu Jianfeng , Chen Xingkuan
Published: February 2021

An NHC-catalyzed β-carbon functionalization reaction to afford enantioenriched benzofuran fused δ-lactams bearing an all-carbon quaternary stereocenter is documented.
Ni-Catalyzed asymmetric hetero-Diels–Alder reactions of conjugated vinyl azides: synthesis of chiral azido polycycles
Authors: Li Shunian , Lu Haifeng , Xu Zhenghu , Wei Fang
Published: February 2021

We report herein an efficient Ni(ii)/Feng ligand-catalyzed asymmetric hetero-Diels–Alder reaction between conjugated vinyl azides with carbonyl groups, providing a synthesis of complicated chiral azido polycycles in high yields and excellent enantioselectivities.
Nonpeptide small molecules with a ten-membered macrolactam or a morpholine motif from the insect American cockroach and their antiangiogenic activity
Authors: Yan Yong-Ming , Meng Xiao-Hui , Bai Hong-Fu , Cheng Yong-Xian
Published: February 2021

(±)-Periplactam A (1), a rare ten-membered macrolactam composed of lignan and putrescine, (±)-periplanol E (2), a dimeric phenethyl alcohol derivative formed via morpholine, and periplactams B (3) and C (4) were isolated from American cockroach.
Stability andin vivosafety of gold, titanium nitride and parylene C coatings on NdFeB magnets implanted in muscles towards a new generation of myokinetic prosthetic limbs
Authors: Iacovacci Veronica , Naselli Irene , Salgarella Alice Rita , Clemente Francesco , Ricotti Leonardo , Cipriani Christian
Published: February 2021

NdFeB magnets implantation in muscles could enable limb prostheses control by means of a myokinetic interface. Parylene C proved as optimal coating for corrosion resistance,in vitrobiocompatibility and safe implantability in rabbit muscle.
A comprehensive review on antimicrobial face masks: an emerging weapon in fighting pandemics
Authors: Pullangott Gayathri , Kannan Uthradevi , S. Gayathri , Kiran Degala Venkata , Maliyekkal Shihabudheen M.
Published: February 2021

Schematic representation of antimicrobial face masks with details of various antimicrobial agents and its preparation route.
A tailored phosphoaspartate probe unravels CprR as a response regulator in Pseudomonas aeruginosa interkingdom signaling
Authors: Allihn Patrick W. A. , Hackl Mathias W. , Ludwig Christina , Hacker Stephan M. , Sieber Stephan A.
Published: February 2021

Phosphoaspartate (pAsp) is a labile posttranslational modification involved in bacterial signaling. To monitor pAsp we designed a chemical proteomics method and revealed insights into the antimicrobial response triggered by a human peptide hormone.
New insights into the disulfide bond formation enzymes in epidithiodiketopiperazine alkaloids
Authors: Liu Huan , Fan Jie , Zhang Peng , Hu Youcai , Liu Xingzhong , Li Shu-Ming , Yin Wen-Bing
Published: February 2021

A FAD-dependent oxidoreductase TdaR was responsible for α, β-disulfide formation in the biosynthesis of pretrichodermamide A. TdaR, together with its homologs AclT and GliT, catalysed not only α, α- but also α, β-disulfide formation in fungi.
Multiplexed and amplified chemiluminescence resonance energy transfer (CRET) detection of genes and microRNAs using dye-loaded hemin/G-quadruplex-modified UiO-66 metal–organic framework nanoparticles
Authors: Zhang Pu , Ouyang Yu , Willner Itamar
Published: February 2021

Hemin/G-quadruplex DNAzyme-modified metal–organic framework nanoparticles act as functional hybrids for the catalyzed oxidation of luminol by H2O2, causing chemiluminescence and activation of chemiluminescence resonance energy transfer to the dye loads.
The effects of nanobubbles on the assembly of glucagon amyloid fibrils
Authors: Wang Yujiao , Guo Zhen , Tan Tingyuan , Ji Yuwen , Hu Jun , Zhang Yi
Published: February 2021

Nanobubble-treated glucagon formed fibrils with an apparent height of 4 nm, in contrast to those of 2 nm in the control.
A nitrogenous pre-intercalation strategy for the synthesis of nitrogen-doped Ti3C2Tx MXene with enhanced electrochemical capacitance
Authors: Yang Fangli , Hegh Dylan , Song Dongxing , Zhang Jizhen , Usman Ken Aldren S. , Wang Zhiyu , Zhang Peng , Ma Weigang , Yang Wenrong , Qin Si , Razal Joselito M.
Published: February 2021

A two-step pre-intercalation strategy is developed, using ammonium citrate as an all-in-one intercalant, antioxidant and nitrogen source, for producing nitrogen-doped Ti3C2Tx MXene with improved electrochemical capacitance and high-rate performance.