bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct photo-oxidation-induced cell death pathways lead to selective killing of human breast cancer cells
Authors: Dos Santos Ancély F. , Inague Alex , Arini Gabriel S. , Terra Letícia F. , Wailemann Rosangela A. M. , Pimentel André C. , Yoshinaga Marcos Y. , Silva Ricardo R. , Severino Divinomar , de Almeida Daria Raquel Q. , Gomes Vinícius M. , Bruni-Cardoso Alexandre , Terra Walter R. , Miyamoto Sayuri , Baptista Maurício S. , Labriola Leticia
Published: December 2020

Lack of effective treatments for aggressive breast cancer is still a major global health problem. We have previously reported that photodynamic therapy using methylene blue as photosensitizer (MB-PDT) massively kills metastatic human breast cancer, marginally affecting healthy cells. In this study, we aimed to unveil the molecular mechanisms behind MB-PDT effectiveness and specificity towards tumor cells. Through lipidomics and biochemical approaches, we demonstrated that MB-PDT efficiency and specificity rely on polyunsaturated fatty acid-enriched membranes and on the better capacity to deal with photo-oxidative damage displayed by non-tumorigenic cells. We found out that, in tumorigenic cells, lysosome membrane permeabilization is accompanied by ferroptosis and/or necroptosis. Our results also pointed at a cross-talk between lysosome-dependent cell death (LDCD) and necroptosis induction after photo-oxidation, and contributed to broaden the understanding of MB-PDT-induced mechanisms and specificity in breast cancer cells. Therefore, we demonstrated that efficient approaches could be designed on the basis of lipid composition and metabolic features for hard-to-treat cancers. The results further reinforce MB-PDT as a therapeutic strategy for highly aggressive human breast cancer cells.
CircRNA hsa_circRNA_104348 promotes hepatocellular carcinoma progression through modulating miR-187-3p/RTKN2 axis and activating Wnt/β-catenin pathway
Authors: Huang Guanqun , Liang Min , Liu Haiyan , Huang Jianhong , Li Peiqing , Wang Chong , Zhang Yidan , Lin Ye , Jiang Xianhan
Published: December 2020

Circular RNAs (circRNAs) have confirmed to participate in diverse biological functions in cancer. However, the expression patterns of circRNAs on hepatocellular carcinoma (HCC) remains unclear. In the present study, we clarified that hsa_circRNA_104348 was dramatically upregulated in HCC tissues and cells. Patients with HCC displaying high hsa_circRNA_104348 level possessed poor prognosis. Has_circ_104348 facilitated proliferation, migration, and invasion, meanwhile suppressed apoptosis of HCC cell. Furthermore, hsa_circRNA_104348 directly targeted miR-187–3p, could regulate miR-187-3p to affect proliferation, migration, invasion, and apoptosis of HCC cells, and may have effect on Wnt/β-catenin signaling pathway. Moreover, RTKN2 could be a direct target of miR-187-3p. In addition, knockdown of hsa_circRNA_104348 attenuated HCC tumorigenesis and lung metastasis in vivo. Taken together, these findings indicated that circular RNA hsa_circRNA_104348 might function as a competing endogenous RNA (ceRNA) to promotes HCC progression by targeting miR-187–3p/RTKN2 axis and activating Wnt/β-catenin pathway.
Detection of eye contact with deep neural networks is as accurate as human experts
Authors: Chong Eunji , Clark-Whitney Elysha , Southerland Audrey , Stubbs Elizabeth , Miller Chanel , Ajodan Eliana L. , Silverman Melanie R. , Lord Catherine , Rozga Agata , Jones Rebecca M. , Rehg James M.
Published: December 2020

Eye contact is among the most primary means of social communication used by humans. Quantification of eye contact is valuable as a part of the analysis of social roles and communication skills, and for clinical screening. Estimating a subject’s looking direction is a challenging task, but eye contact can be effectively captured by a wearable point-of-view camera which provides a unique viewpoint. While moments of eye contact from this viewpoint can be hand-coded, such a process tends to be laborious and subjective. In this work, we develop a deep neural network model to automatically detect eye contact in egocentric video. It is the first to achieve accuracy equivalent to that of human experts. We train a deep convolutional network using a dataset of 4,339,879 annotated images, consisting of 103 subjects with diverse demographic backgrounds. 57 subjects have a diagnosis of Autism Spectrum Disorder. The network achieves overall precision of 0.936 and recall of 0.943 on 18 validation subjects, and its performance is on par with 10 trained human coders with a mean precision 0.918 and recall 0.946. Our method will be instrumental in gaze behavior analysis by serving as a scalable, objective, and accessible tool for clinicians and researchers.
Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report
Authors: Buckland Matthew S. , Galloway James B. , Fhogartaigh Caoimhe Nic , Meredith Luke , Provine Nicholas M. , Bloor Stuart , Ogbe Ane , Zelek Wioleta M. , Smielewska Anna , Yakovleva Anna , Mann Tiffeney , Bergamaschi Laura , Turner Lorinda , Mescia Frederica , Toonen Erik J. M. , Hackstein Carl-Philipp , Akther Hossain Delowar , Vieira Vinicius Adriano , Ceron-Gutierrez Lourdes , Periselneris Jimstan , Kiani-Alikhan Sorena , Grigoriadou Sofia , Vaghela Devan , Lear Sara E. , Török M. Estée , Hamilton William L. , Stockton Joanne , Quick Josh , Nelson Peter , Hunter Michael , Coulter Tanya I. , Devlin Lisa ,   CITIID-NIHR COVID-19 BioResource Collaboration,   MRC-Toxicology Unit COVID-19 Consortium, Bradley John R. , Smith Kenneth G. C. , Ouwehand Willem H. , Estcourt Lise , Harvala Heli , Roberts David J. , Wilkinson Ian B. , Screaton Nick , Loman Nicholas , Doffinger Rainer , Lyons Paul A. , Morgan B. Paul , Goodfellow Ian G. , Klenerman Paul , Lehner Paul J. , Matheson Nicholas J. , Thaventhiran James E. D.
Published: December 2020

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.
Spectral extension and synchronization of microcombs in a single microresonator
Authors: Zhang Shuangyou , Silver Jonathan M. , Bi Toby , Del’Haye Pascal
Published: December 2020

Broadband optical frequency combs are extremely versatile tools for precision spectroscopy, ultrafast ranging, as channel generators for telecom networks, and for many other metrology applications. Here, we demonstrate that the optical spectrum of a soliton microcomb generated in a microresonator can be extended by bichromatic pumping: one laser with a wavelength in the anomalous dispersion regime of the microresonator generates a bright soliton microcomb while another laser in the normal dispersion regime both compensates the thermal effect of the microresonator and generates a repetition-rate-synchronized second frequency comb. Numerical simulations agree well with experimental results and reveal that a bright optical pulse from the second pump is passively formed in the normal dispersion regime and trapped by the primary soliton. In addition, we demonstrate that a dispersive wave can be generated and influenced by cross-phase-modulation-mediated repetition-rate synchronization of the two combs. The demonstrated technique provides an alternative way to generate broadband microcombs and enables the selective enhancement of optical power in specific parts of a comb spectrum.
Activation of the IRE1 RNase through remodeling of the kinase front pocket by ATP-competitive ligands
Authors: Ferri Elena , Le Thomas Adrien , Wallweber Heidi Ackerly , Day Eric S. , Walters Benjamin T. , Kaufman Susan E. , Braun Marie-Gabrielle , Clark Kevin R. , Beresini Maureen H. , Mortara Kyle , Chen Yung-Chia A. , Canter Breanna , Phung Wilson , Liu Peter S. , Lammens Alfred , Ashkenazi Avi , Rudolph Joachim , Wang Weiru
Published: December 2020

Inositol-Requiring Enzyme 1 (IRE1) is an essential component of the Unfolded Protein Response. IRE1 spans the endoplasmic reticulum membrane, comprising a sensory lumenal domain, and tandem kinase and endoribonuclease (RNase) cytoplasmic domains. Excess unfolded proteins in the ER lumen induce dimerization and oligomerization of IRE1, triggering kinase trans-autophosphorylation and RNase activation. Known ATP-competitive small-molecule IRE1 kinase inhibitors either allosterically disrupt or stabilize the active dimeric unit, accordingly inhibiting or stimulating RNase activity. Previous allosteric RNase activators display poor selectivity and/or weak cellular activity. In this study, we describe a class of ATP-competitive RNase activators possessing high selectivity and strong cellular activity. This class of activators binds IRE1 in the kinase front pocket, leading to a distinct conformation of the activation loop. Our findings reveal exquisitely precise interdomain regulation within IRE1, advancing the mechanistic understanding of this important enzyme and its investigation as a potential small-molecule therapeutic target.
Revealing 3D magnetization of thin films with soft X-ray tomography: magnetic singularities and topological charges
Authors: Hierro-Rodriguez A. , Quirós C. , Sorrentino A. , Alvarez-Prado L. M. , Martín J. I. , Alameda J. M. , McVitie S. , Pereiro E. , Vélez M. , Ferrer S.
Published: December 2020

The knowledge of how magnetization looks inside a ferromagnet is often hindered by the limitations of the available experimental methods which are sensitive only to the surface regions or limited in spatial resolution. Here we report a vector tomographic reconstruction based on soft X-ray transmission microscopy and magnetic dichroism data, which has allowed visualizing the three-dimensional magnetization in a ferromagnetic thin film heterostructure. Different non-trivial topological textures have been resolved and the determination of their topological charge has allowed us to identify a Bloch point and a meron-like texture. Our method relies only on experimental data and might be of wide application and interest in 3D nanomagnetism.
Isolation of a member of the candidate phylum ‘Atribacteria’ reveals a unique cell membrane structure
Authors: Katayama Taiki , Nobu Masaru K. , Kusada Hiroyuki , Meng Xian-Ying , Hosogi Naoki , Uematsu Katsuyuki , Yoshioka Hideyoshi , Kamagata Yoichi , Tamaki Hideyuki
Published: December 2020

A key feature that differentiates prokaryotic cells from eukaryotes is the absence of an intracellular membrane surrounding the chromosomal DNA. Here, we isolate a member of the ubiquitous, yet-to-be-cultivated phylum ‘Candidatus Atribacteria’ (also known as OP9) that has an intracytoplasmic membrane apparently surrounding the nucleoid. The isolate, RT761, is a subsurface-derived anaerobic bacterium that appears to have three lipid membrane-like layers, as shown by cryo-electron tomography. Our observations are consistent with a classical gram-negative structure with an additional intracytoplasmic membrane. However, further studies are needed to provide conclusive evidence for this unique intracellular structure. The RT761 genome encodes proteins with features that might be related to the complex cellular structure, including: N-terminal extensions in proteins involved in important processes (such as cell-division protein FtsZ); one of the highest percentages of transmembrane proteins among gram-negative bacteria; and predicted Sec-secreted proteins with unique signal peptides. Physiologically, RT761 primarily produces hydrogen for electron disposal during sugar degradation, and co-cultivation with a hydrogen-scavenging methanogen improves growth. We propose RT761 as a new species, Atribacter laminatus gen. nov. sp. nov. and a new phylum, Atribacterota phy. nov.
Disulfide stabilization of human norovirus GI.1 virus-like particles focuses immune response toward blockade epitopes
Authors: Verardi Raffaello , Lindesmith Lisa C. , Tsybovsky Yaroslav , Gorman Jason , Chuang Gwo-Yu , Edwards Caitlin E. , Brewer-Jensen Paul D. , Mallory Michael L. , Ou Li , Schön Arne , Shi Wei , Tully Ena S. , Georgiou George , Baric Ralph S. , Kwong Peter D.
Published: December 2020

Human noroviruses are non-enveloped, single-strand RNA viruses that cause pandemic outbreaks of acute gastroenteritis. A bivalent vaccine containing GI.1 and GII.4 virus-like particles (VLPs) has been shown to be safe and highly immunogenic, but its efficacy and durability have been limited. Here, we show that norovirus GI.1 VLPs are unstable and contain a substantial fraction of dissociated VLP components. Broadly reactive, non-neutralizing antibodies isolated from vaccinated donors bound to the dissociated components, but not to the intact VLPs. Engineering of interprotomer disulfide bonds within the shell domain prevented disassembly of the VLPs, while preserving antibody accessibility to blockade epitopes. Without adjuvant, mice immunized with stabilized GI.1 VLPs developed faster blockade antibody titers compared to immunization with wild-type GI.1 VLPs. In addition, immunization with stabilized particles focused immune responses toward surface-exposed epitopes and away from occluded epitopes. Overall, disulfide-stabilized norovirus GI.1 VLPs elicited improved responses over the non-disulfide-stabilized version, suggesting their promise as candidate vaccines.
Dynamics of social network emergence explain network evolution
Authors: Pomeroy Caleb , Bond Robert M. , Mucha Peter J. , Cranmer Skyler J.
Published: December 2020

Networked systems emerge and subsequently evolve. Although several models describe the process of network evolution, researchers know far less about the initial process of network emergence. Here, we report temporal survey results of a real-world social network starting from its point of inception. We find that individuals’ ties undergo an initial cycle of rapid expansion and contraction. This process helps to explain the eventual interactions and working structure in the network (in this case, scientific collaboration). We propose a stylized concept and model of “churn” to describe the process of network emergence and stabilization. Our empirical and simulation results suggest that these network emergence dynamics may be instrumental for explaining network details, as well as behavioral outcomes at later time periods.
Development of whole-genome multiplex assays and construction of an integrated genetic map using SSR markers in Senegalese sole
Authors: Guerrero-Cózar Israel , Perez-Garcia Cathaysa , Benzekri Hicham , Sánchez J. J. , Seoane Pedro , Cruz Fernando , Gut Marta , Zamorano Maria Jesus , Claros M. Gonzalo , Manchado Manuel
Published: December 2020

The Senegalese sole (Solea senegalensis) is an economically important flatfish species. In this study, a genome draft was analyzed to identify microsatellite (SSR) markers for whole-genome genotyping. A subset of 224 contigs containing SSRs were preselected and validated by using a de novo female hybrid assembly. Overall, the SSR density in the genome was 886.7 markers per megabase of genomic sequences and the dinucleotide motif was the most abundant (52.4%). In silico comparison identified a set of 108 SSRs (with di-, tetra- or pentanucleotide motifs) widely distributed in the genome and suitable for primer design. A total of 106 markers were structured in thirteen multiplex PCR assays (with up to 10-plex) and the amplification conditions were optimized with a high-quality score. Main genetic diversity statistics and genotyping reliability were assessed. A subset of 40 high polymorphic markers were selected to optimize four supermultiplex PCRs (with up to 11-plex) for pedigree analysis. Theoretical exclusion probabilities and real parentage allocation tests using parent–offspring information confirmed their robustness and effectiveness for parental assignment. These new SSR markers were combined with previously published SSRs (in total 229 makers) to construct a new and improved integrated genetic map containing 21 linkage groups that matched with the expected number of chromosomes. Synteny analysis with respect to C. semilaevis provided new clues on chromosome evolution in flatfish and the formation of metacentric and submetacentric chromosomes in Senegalese sole.
CoMix: comparing mixing patterns in the Belgian population during and after lockdown
Authors: Coletti Pietro , Wambua James , Gimma Amy , Willem Lander , Vercruysse Sarah , Vanhoutte Bieke , Jarvis Christopher I. , Van Zandvoort Kevin , Edmunds John , Beutels Philippe , Hens Niel
Published: December 2020

The COVID-19 pandemic has shown how a newly emergent communicable disease can lay considerable burden on public health. To avoid system collapse, governments have resorted to several social distancing measures. In Belgium, this included a lockdown and a following period of phased re-opening. A representative sample of Belgian adults was asked about their contact behaviour from mid-April to the beginning of August, during different stages of the intervention measures in Belgium. Use of personal protection equipment (face masks) and compliance to hygienic measures was also reported. We estimated the expected reproduction number computing the ratio of $$\hbox {R}_{0}$$

R
0

with respect to pre-pandemic data. During the first two waves (the first month) of the survey, the reduction in the average number of contacts was around 80% and was quite consistent across all age-classes. The average number of contacts increased over time, particularly for the younger age classes, still remaining significantly lower than pre-pandemic values. From the end of May to the end of July , the estimated reproduction number has a median value larger than one, although with a wide dispersion. Estimated $$\hbox {R}_{0}$$

R
0

fell below one again at the beginning of August. We have shown how a rapidly deployed survey can measure compliance to social distancing and assess its impact on COVID-19 spread. Monitoring the effectiveness of social distancing recommendations is of paramount importance to avoid further waves of COVID-19.
Impact of needle positioning on ablation success of irreversible electroporation: a unicentric retrospective analysis
Authors: Mathy René Michael , Tinoush Parham , da Florencia Ricardo Daniel , Braun Alexander , Ghamarnejad Omid , Radeleff Boris , Kauczor Hans-Ulrich , Chang De-Hua
Published: December 2020

Irreversible electroporation (IRE) is an ablation procedure in which cell death is induced by ultrashort electrical pulses. In this unicentric retrospective study we investigated the influence of needle positioning on ablation success. 15 IREs with residual tumor after ablation, detected in the first follow-up MRI, were included, and compared with 30 successful ablations. Evaluation of needle geometry revealed significantly higher values for needle divergence (NDiv, 7.0° vs. 3.7°, p = 0.02), tumor-center-to-ablation-center distance (TACD, 11.6 vs. 3.2 mm, p < 0.001), tumor-to-needle distance (4.7 vs. 1.9 mm, p = 0.04), and tumor diameter per needle (7.5 vs. 5.9 mm/needle, p = 0.01) in patients with residual tumor. The average number of needles used was higher in the group without residual tumor after ablation (3.1 vs. 2.4, p = 0.04). In many cases with residual tumor, needle depth was too short (2.1 vs. 6.8 mm tumor overlap beyond the most proximal needle tip, p < 0.01). The use of a stereotactic navigation system in 10 cases resulted in a lower NDiv value (2.1° vs. 5.6°, p < 0.01). Thus, correct needle placement seems to be a crucial factor for success and the assistance of a stereotactic navigation system might be helpful. As most important geometrical parameter TACD could be identified. Main reasons for high TACD were insufficient needle depth and a lesion location out of the needle plane.
Endoscopic vs. microscopic transsphenoidal pituitary surgery: a single centre study
Authors: Møller Morten Winkler , Andersen Marianne Skovsager , Glintborg Dorte , Pedersen Christian Bonde , Halle Bo , Kristensen Bjarne Winther , Poulsen Frantz Rom
Published: December 2020

Endoscopic pituitary surgery has shown promising results. This study reports the experiences of experienced microscopic pituitary surgeons changing to the endoscopic technique, and the beneficial effects on the postoperative outcomes. 45 transsphenoidal endoscopic-assisted surgeries performed in 2016–2017 were compared with 195 microscope-assisted surgeries performed in 2007–2017 for pituitary adenoma. Tumour size, hormonal status and vision were assessed preoperatively and 3–5 months postoperatively. Cases were identified through electronic patient records. GTR was achieved in 39% of the endoscopic operations vs. 22% of microscopic operations, p = 0.018. Mean duration of surgery was 86 min (77–95) with the endoscopic technique vs. 106 min (101–111) with the microscopic technique, p < 0.001. New hypothalamus–pituitary–adrenal axis deficiencies were observed after 3% of endoscopic vs. 34% microscopic operations, p = 0.001, and overall fewer postoperative pituitary deficiencies were observed in the endoscope-assisted group. Complications within 30 days of surgery occurred in 17% of endoscopic operations vs. 27% of microscopic operations (p > 0.05). Normalization of visual impairment occurred in 37% of the cases with preoperative visual impairment in the endoscopic group vs. 35% of those in the microscopic group (p > 0.05). The endoscopic technique performed better as a surgical procedure for pituitary adenomas. We found no statistically significant differences in complication rate or visual improvement between the two techniques.
DUSP5 expression in left ventricular cardiomyocytes of young hearts regulates thyroid hormone (T3)-induced proliferative ERK1/2 signaling
Authors: Bogush Nikolay , Tan Lin , Naib Hussain , Faizullabhoy Ebrahim , Calvert John W. , Iismaa Siiri E. , Gupta Ankan , Ramchandran Ramani , Martin David I. K. , Graham Robert M. , Husain Ahsan , Naqvi Nawazish
Published: December 2020

Cardiomyocytes of newborn mice proliferate after injury or exposure to growth factors. However, these responses are diminished after postnatal day-6 (P6), representing a barrier to building new cardiac muscle in adults. We have previously shown that exogenous thyroid hormone (T3) stimulates cardiomyocyte proliferation in P2 cardiomyocytes, by activating insulin-like growth factor-1 receptor (IGF-1R)-mediated ERK1/2 signaling. But whether exogenous T3 functions as a mitogen in post-P6 murine hearts is not known. Here, we show that exogenous T3 increases the cardiomyocyte endowment of P8 hearts, but the proliferative response is confined to cardiomyocytes of the left ventricular (LV) apex. Exogenous T3 stimulates proliferative ERK1/2 signaling in apical cardiomyocytes, but not in those of the LV base, which is inhibited by expression of the nuclear phospho-ERK1/2-specific dual-specificity phosphatase, DUSP5. Developmentally, between P7 and P14, DUSP5 expression increases in the myocardium from the LV base to its apex; after this period, it is uniformly expressed throughout the LV. In young adult hearts, exogenous T3 increases cardiomyocyte numbers after DUSP5 depletion, which might be useful for eliciting cardiac regeneration.
Upregulation of PI3K/AKT/PTEN pathway is correlated with glucose and glutamine metabolic dysfunction during tamoxifen resistance development in MCF-7 cells
Authors: Hamadneh Lama , Abuarqoub Rama , Alhusban Ala , Bahader Mohamad
Published: December 2020

Tamoxifen resistance is emerging as a big challenge in endocrine therapy of luminal A breast cancer patients. In this study, we aimed to determine the molecular changes of PI3K/AKT/PTEN signaling pathway during tamoxifen-resistance development using gradually increased doses of tamoxifen in one model, while fixing tamoxifen treatment dose at 35 μM for several times in the second model. An upregulation of AKT/PI3K genes was noticed at 30 μM tamoxifen concentration in cells treated with a gradual increase of tamoxifen doses. In the second model, significant upregulation of AKT1 was seen in cells treated with 35 μM tamoxifen for three times. All genes studied showed a significant increase in expression in resistant cells treated with 50 µM and 35 µM six times tamoxifen. These genes’ upregulation was accompanied by PTEN and GSK3 ß genes’ down-regulation, and it was in correlation to the changes in the metabolic rate of glucose in tamoxifen-resistant models. A significant increase in glucose consumption rate from culture media was observed in tamoxifen resistant cells with the highest consumption rate reported in the first day of culturing. Increased glucose consumption rates were also correlated with GLUL significant gene expression and non-significant change in c-MYC gene expression that may lead to increased endogenous glutamine synthesis. As a result, several molecular and metabolic changes precede acquired tamoxifen resistance could be used as resistance biomarkers or targets to reverse tamoxifen resistance.
A comparative UHPLC-Q/TOF–MS-based eco-metabolomics approach reveals temperature adaptation of four Nepenthes species
Authors: Wong Changi , Ling Yee Soon , Wee Julia Lih Suan , Mujahid Aazani , Müller Moritz
Published: December 2020

Nepenthes, as the largest family of carnivorous plants, is found with an extensive geographical distribution throughout the Malay Archipelago, specifically in Borneo, Philippines, and Sumatra. Highland species are able to tolerate cold stress and lowland species heat stress. Our current understanding on the adaptation or survival mechanisms acquired by the different Nepenthes species to their climatic conditions at the phytochemical level is, however, limited. In this study, we applied an eco-metabolomics approach to identify temperature stressed individual metabolic fingerprints of four Nepenthes species: the lowlanders N. ampullaria, N. rafflesiana and N. northiana, and the highlander N. minima. We hypothesized that distinct metabolite regulation patterns exist between the Nepenthes species due to their adaptation towards different geographical and altitudinal distribution. Our results revealed not only distinct temperature stress induced metabolite fingerprints for each Nepenthes species, but also shared metabolic response and adaptation strategies. The interspecific responses and adaptation of N. rafflesiana and N. northiana likely reflected their natural habitat niches. Moreover, our study also indicates the potential of lowlanders, especially N. ampullaria and N. rafflesiana, to produce metabolites needed to deal with increased temperatures, offering hope for the plant genus and future adaption in times of changing climate.
Relationship between fatty pancreas and hypertriglyceridemic waist phenotype: a cross-sectional study
Authors: Yu Xiaoping , Wang Dan , Xiao Weiming , Shi Xinlin , She Qiang , Sun Hongguang , Qi Tingyue , Xu Renyan , Li Guiqing , Liu Xinnong , Gong Weijuan , Yan Zhigang , Ding Yanbing , Lu Guotao
Published: December 2020

Hypertriglyceridemic waist phenotype (HTWP) and its quantitative indicator, waist circumference-triglyceride index (WTI), are common quantitative indices of visceral obesity and are closely related to metabolic diseases. The purpose of this study was to investigate the relationship between fatty pancreas (FP) and HTWP in China. FP was diagnosed using trans-abdominal ultrasonography in all participants. According to the waist circumference and serum triglyceride levels, the participants were divided into four phenotype groups: normal waist circumference-normal triglyceride, normal waist circumference-elevated triglyceride, elevated waist circumference-normal triglyceride, and elevated waist circumference-elevated triglyceride (indicating HTWP). Clinical characteristics and biochemical indices were compared among the groups. Receiver operating characteristic (ROC) curves were used to evaluate the utility of WTI as a reference factor for FP screening. The HTWP group had a higher prevalence of metabolic syndrome (84.2%), FP (10.4%), fatty liver (64.5%), and hypertension (15.8%) than the other three phenotype groups. The occurrence rate of HTWP and the median WTI were significantly higher in participants with FP than in those without FP (54.7% vs 21.0%, 222 ± 135 vs 142 ± 141, p < 0.001). In the ROC curve analysis, when the maximum area under the curve was 0.746, the WTI was 107.09 and the corresponding sensitivity and specificity were 90.6% and 51.9%, respectively. HTWP is closely associated with FP and can be used as a reference factor for FP screening.
Low-motion fMRI data can be obtained in pediatric participants undergoing a 60-minute scan protocol
Authors: Horien Corey , Fontenelle Scuddy , Joseph Kohrissa , Powell Nicole , Nutor Chaela , Fortes Diogo , Butler Maureen , Powell Kelly , Macris Deanna , Lee Kangjoo , Greene Abigail S. , McPartland James C. , Volkmar Fred R. , Scheinost Dustin , Chawarska Katarzyna , Constable R. Todd
Published: December 2020

Performing functional magnetic resonance imaging (fMRI) scans of children can be a difficult task, as participants tend to move while being scanned. Head motion represents a significant confound in fMRI connectivity analyses. One approach to limit motion has been to use shorter MRI protocols, though this reduces the reliability of results. Hence, there is a need to implement methods to achieve high-quality, low-motion data while not sacrificing data quantity. Here we show that by using a mock scan protocol prior to a scan, in conjunction with other in-scan steps (weighted blanket and incentive system), it is possible to achieve low-motion fMRI data in pediatric participants (age range: 7–17 years old) undergoing a 60 min MRI session. We also observe that motion is low during the MRI protocol in a separate replication group of participants, including some with autism spectrum disorder. Collectively, the results indicate it is possible to conduct long scan protocols in difficult-to-scan populations and still achieve high-quality data, thus potentially allowing more reliable fMRI findings.
Predictors for clinical effectiveness of baricitinib in rheumatoid arthritis patients in routine clinical practice: data from a Japanese multicenter registry
Authors: Takahashi Nobunori , Asai Shuji , Kobayakawa Tomonori , Kaneko Atsushi , Watanabe Tatsuo , Kato Takefumi , Nishiume Tsuyoshi , Ishikawa Hisato , Yoshioka Yutaka , Kanayama Yasuhide , Watanabe Tsuyoshi , Hirano Yuji , Hanabayashi Masahiro , Yabe Yuichiro , Yokota Yutaka , Suzuki Mochihito , Sobue Yasumori , Terabe Kenya , Ishiguro Naoki , Kojima Toshihisa
Published: December 2020

This study aimed to evaluate the short-term effectiveness and safety profiles of baricitinib and explore factors associated with improved short-term effectiveness in patients with rheumatoid arthritis (RA) in clinical settings. A total of 113 consecutive RA patients who had been treated with baricitinib were registered in a Japanese multicenter registry and followed for at least 24 weeks. Mean age was 66.1 years, mean RA disease duration was 14.0 years, 71.1% had a history of use of biologics or JAK inhibitors (targeted DMARDs), and 48.3% and 40.0% were receiving concomitant methotrexate and oral prednisone, respectively. Mean DAS28-CRP significantly decreased from 3.55 at baseline to 2.32 at 24 weeks. At 24 weeks, 68.2% and 64.1% of patients achieved low disease activity (LDA) and moderate or good response, respectively. Multivariate logistic regression analysis revealed that no previous targeted DMARD use and lower DAS28-CRP score at baseline were independently associated with achievement of LDA at 24 weeks. While the effectiveness of baricitinib was similar regardless of whether patients had a history of only one or multiple targeted DMARDs use, patients with previous use of non-TNF inhibitors or JAK inhibitors showed lower rates of improvement in DAS28-CRP. The overall retention rate for baricitinib was 86.5% at 24 weeks, as estimated by Kaplan–Meier analysis. The discontinuation rate due to adverse events was 6.5% at 24 weeks. Baricitinib significantly improved RA disease activity in clinical practice. Baricitinib was significantly more effective when used as a first-line targeted DMARDs.
Metabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brains
Authors: Tanaka Emi , Ogawa Yuko , Fujii Ritsuko , Shimonaka Tomomi , Sato Yoshiaki , Hamazaki Takashi , Nagamura-Inoue Tokiko , Shintaku Haruo , Tsuji Masahiro
Published: December 2020

Ischemic brain injury provokes complex, time-dependent downstream pathways that ultimately lead to cell death. We aimed to demonstrate the levels of a wide range of metabolites in brain lysates and their on-tissue distribution following neonatal stroke and cell therapies. Postnatal day 12 mice underwent middle cerebral artery occlusion (MCAO) and were administered 1 × 105 cells after 48 h. Metabolomic analysis of the injured hemisphere demonstrated that a variety of amino acids were significantly increased and that tricarboxylic acid cycle intermediates and some related amino acids, such as glutamate, were decreased. With the exception of the changes in citric acid, neither mesenchymal stem/stromal cells nor CD34+ cells ameliorated these changes. On-tissue visualization with matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) imaging revealed that the signal intensity of glutamate was significantly decreased in the infarct area, consistent with the metabolomic analysis, while its intensity was significantly increased in the peri-infarct area after MCAO. Although cell therapies did not ameliorate the changes in metabolites in the infarct area, mesenchymal stem cells ameliorated the increased levels of glutamate and carnitine in the peri-infarct area. MALDI-MS imaging showed the location-specific effect of cell therapies even in this subacute setting after MCAO. These methodologies may be useful for further investigation of possible treatments for ischemic brain injury.
Development of immunohistochemistry and in situ hybridisation for the detection of SARS-CoV and SARS-CoV-2 in formalin-fixed paraffin-embedded specimens
Authors: Lean Fabian Z. X. , Lamers Mart M. , Smith Samuel P. , Shipley Rebecca , Schipper Debby , Temperton Nigel , Haagmans Bart L. , Banyard Ashley C. , Bewley Kevin R. , Carroll Miles W. , Brookes Sharon M. , Brown Ian , Nuñez Alejandro
Published: December 2020

The rapid emergence of SARS-CoV-2, the causative agent of COVID-19, and its dissemination globally has caused an unprecedented strain on public health. Animal models are urgently being developed for SARS-CoV-2 to aid rational design of vaccines and therapeutics. Immunohistochemistry and in situ hybridisation techniques that facilitate reliable and reproducible detection of SARS-CoV and SARS-CoV-2 viral products in formalin-fixed paraffin-embedded (FFPE) specimens would be of great utility. A selection of commercial antibodies generated against SARS-CoV spike protein and nucleoprotein, double stranded RNA, and RNA probe for spike genes were evaluated for the ability to detect FFPE infected cells. We also tested both heat- and enzymatic-mediated virus antigen retrieval methods to determine the optimal virus antigen recovery as well as identifying alternative retrieval methods to enable flexibility of IHC methods. In addition to using native virus infected cells as positive control material, the evaluation of non-infected cells expressing coronavirus (SARS, MERS) spike as a biosecure alternative to assays involving live virus was undertaken. Optimized protocols were successfully applied to experimental animal-derived tissues. The diverse techniques for virus detection and control material generation demonstrated in this study can be applied to investigations of coronavirus pathogenesis and therapeutic research in animal models.
Hemipteran defensive odors trigger predictable color biases in jumping spider predators
Authors: Vickers Michael E. , Taylor Lisa A.
Published: December 2020

Multimodal warning displays often pair one signal modality (odor) with a second modality (color) to avoid predation. Experiments with bird predators suggest these signal components interact synergistically, with aversive odors triggering otherwise hidden aversions to particular prey colors. In a recent study, this phenomenon was found in a jumping spider (Habronattus trimaculatus), with the defensive odor from a coreid bug (Acanthocephala femorata) triggering an aversion to red. Here, we explore how generalizable this phenomenon is by giving H. trimaculatus the choice between red or black prey in the presence or absence of defensive odors secreted from (1) eastern leaf-footed bugs (Leptoglossus phyllopus, Hemiptera), (2) grass stinkbugs (Mormidea pama, Hemiptera), (3) Asian ladybird beetles (Harmonia axyridis, Coleoptera), and (4) eastern lubber grasshoppers (Romalea microptera, Orthoptera). As expected, in the presence of the hemipteran odors, spiders were less likely to attack red prey (compared to no odor). Unexpectedly, the beetle and grasshopper odors did not bias spiders away from red. Our results with the hemipteran odors were unique to red; follow-up experiments indicated that these odors did not affect biases for/against green prey. We discuss our findings in the context of generalized predator foraging behavior and the functions of multimodal warning displays.
First assessment of POPs and cytochrome P450 expression in Cuvier’s beaked whales (Ziphius cavirostris) skin biopsies from the Mediterranean Sea
Authors: Baini Matteo , Panti Cristina , Fossi Maria Cristina , Tepsich Paola , Jiménez Begoña , Coomber Frazer , Bartalini Alice , Muñoz-Arnanz Juan , Moulins Aurelie , Rosso Massimiliano
Published: December 2020

The Cuvier's beaked whale (Ziphius cavirostris) is one of the least known cetacean species worldwide. The decreasing population trend and associated threats has led to the IUCN categorising the Mediterranean subpopulation as Vulnerable on the Red List of Threatened Species. This study aimed to investigate for the first time the ecotoxicological status of Cuvier's beaked whale in the NW Mediterranean Sea. The study sampled around the 20% of the individuals belonging to the Ligurian subpopulation, collecting skin biopsies from free-ranging specimens. The levels of polychlorinated biphenyl (PCBs), polybrominated diphenyl ethers (PBDEs) and induction of cytochrome's P450 (CYP1A1 and CYP2B isoforms) were evaluated. Results highlighted that the pattern of concentration for the target contaminants was PCBs > PBDEs and the accumulation values were linked to age and sex, with adult males showing significantly higher levels than juvenile. Concerns raised by the fact that 80% of the individuals had PCB levels above the toxicity threshold for negative physiological effects in marine mammals. Therefore, these findings shed light on this silent and serious threat never assessed in the Mediterranean Cuvier’s beaked whale population, indicating that anthropogenic pressures, including chemical pollution, may represent menaces for the conservation of this species in the Mediterranean Sea.
Growth, ionic homeostasis, and physiological responses of cotton under different salt and alkali stresses
Authors: Guo Huijuan , Huang Zhijie , Li Meiqi , Hou Zhenan
Published: December 2020

To better understand the mechanism of salt tolerance, we analyzed cotton growth and the ionomes in different tissues under different types of salt–alkali stress. Cotton was exposed to the soil salt and alkali stresses, NaCl, Na2SO4, and Na2CO3 + NaHCO3, in a pot study. Salt and alkali stress significantly inhibited cotton growth, significantly reduced root length, surface area, and volume, and significantly increased relative electrical conductivity (REC) and malondialdehyde (MDA) content but also significantly increased antioxidant enzyme activities, and proline (Pro) content. The REC in leaves was higher under salt stress than under alkali stress, but the effects on Pro were in the order Na2CO3 + NaHCO3 > NaCl > Na2SO4. Principal component analysis showed a significant difference in ion composition under the different types of salt–alkali stress. Under the three types of salt–alkali stress, concentrations of Na and Mo increased significantly in different organs of cotton plants. Under NaCl stress, the absorption of Ca was inhibited, the transport capacity of P, Mg, and Cu was reduced, and the ion balance was maintained by promoting the uptake and transport of Zn, Mn, Al, and Mo. Under Na2SO4 stress, the absorption of P and Ca was inhibited, the transport capacity of Mg, B, and Cu was reduced, and the ion balance was maintained by promoting the uptake and transport of S, Zn, Fe, Mo, Al, and Co. Under Na2CO3 + NaHCO3 stress, the absorption of P and S was inhibited, the transport capacity of Mg and B was reduced, but that of Al and Fe increased, and the ion balance was maintained by promoting the uptake and transport of Mn, Mo, Ni, and Co. The relative expression of GhSOS1 and GhNHX1 in leaves increased significantly under salt stress but decreased under alkali stress. These results suggest that cotton is well-adapted to salt–alkali stress via the antioxidant enzyme system, adjustment of osmotic substances, and reconstruction of ionic equilibrium; neutral salt stress primarily disrupts the ion balance, whereas alkali stress decreases the ability to regulate Na and inhibits the absorption of mineral elements, as well as disrupts the ion balance; and the changes in the expression of salt tolerance-related genes may partially explain the accumulation of Na ions in cotton under salt–alkali stress.
Comparative transcriptomics indicates endogenous differences in detoxification capacity after formic acid treatment between honey bees and varroa mites
Authors: Genath Antonia , Sharbati Soroush , Buer Benjamin , Nauen Ralf , Einspanier Ralf
Published: December 2020

Formic acid (FA) has been used for decades to control Varroa destructor, one of the most important parasites of the western honey bee, Apis mellifera. The rather unselective molecular mode of action of FA and its possible effects on honeybees have long been a concern of beekeepers, as it has undesirable side effects that affect the health of bee colonies. This study focuses on short-term transcriptomic changes as analysed by RNAseq in both larval and adult honey bees and in mites after FA treatment under applied conditions. Our study aims to identify those genes in honey bees and varroa mites differentially expressed upon a typical FA hive exposure scenario. Five detoxification-related genes were identified with significantly enhanced and one gene with significantly decreased expression under FA exposure. Regulated genes in our test setting included members of various cytochrome P450 subfamilies, a flavin-dependent monooxygenase and a cytosolic 10-formyltetrahydrofolate dehydrogenase (FDH), known to be involved in formate metabolism in mammals. We were able to detect differences in the regulation of detoxification-associated genes between mites and honey bees as well as between the two different developmental stages of the honey bee. Additionally, we detected repressed regulation of Varroa genes involved in cellular respiration, suggesting mitochondrial dysfunction and supporting the current view on the mode of action of FA—inhibition of oxidative phosphorylation. This study shows distinct cellular effects induced by FA on the global transcriptome of both host and parasite in comparison. Our expression data might help to identify possible differences in the affected metabolic pathways and thus make a first contribution to elucidate the mode of detoxification of FA.
Neutrophil-to-lymphocyte ratio is an independent predictor for survival outcomes in cervical cancer: a systematic review and meta-analysis
Authors: Zou Peijun , Yang E. , Li Zhengyu
Published: December 2020

This updated meta-analysis sought to explore whether pretreatment neutrophil-to-lymphocyte ratio (NLR) could serve as an independent predictor for survival outcomes in patients with cervical cancer. We searched PubMed, Embase, Web of science and Scopus for studies on the association of pretreatment serum NLR with overall survival (OS) and progression-free survival (PFS) among patients with cervical cancer. Included studies with a hazard ratio (HR) and 95% confidence interval (CI) or a p-value were weighted by generic inverse-variance and pooled in a random effects meta-analysis. Subgroup analyses were conducted according to regions, NLR cut-off values and treatments. Publication bias was analyzed by Egger’s and Begg’s tests. A total of 14 studies comprising 6041 patients were included. The median cut-off value for NLR was 2.46 (range from 1.60 to 3.80). The higher NLR was associated to worse OS (HR 1.86, 95% CI 1.44–2.40) and PFS (HR 1.67, 95% CI 1.25–2.23), compared with lower NLR. This association still exited when analyzed according to regions, NLR cut-off values. Moreover, Significant association between NLR and OS was observed in studies which included patients with early stage disease and receiving radical surgeries. High NLR is independently associated with decreased OS and PFS in patients with cervical cancer. Pretreatment NLR is of independent value to predict the survival outcomes in patients with cervical cancer, regardless of regions and primary treatments.
Natural history of social and sexual behavior in fruit flies
Authors: Dukas Reuven
Published: December 2020

The past 2 decades have seen fruit flies being widely adopted for research on social behavior and aggression. This fruitful research, however, has not been well tied to fruit flies’ natural history. To address this knowledge gap, I conducted a field study. My goal was to inform future research conducted in artificial surroundings, and to inspire new investigations that can rely more heavily on fruit flies’ actual natural behavior. My two main novel findings were first, that flies in the field showed significant sociability, as they formed social groups rather than dispersed randomly among fruits of similar quality. Second, males showed fair levels of aggression towards each other as indicated by a lunging rate of 17 per hour, and lower rates of wing threat and boxing. Courtship was the most prominent activity on fruits, with females rejecting almost all males’ advances. This resulted in an estimated mating rate of 0.6 per female per day. Flies showed a striking peak of activity early in the mornings, even at cold temperatures, followed by inactivity for much of the day and night. Flies, however, handled well high temperatures approaching 40 °C by hiding away from fruit and concentrating activity in the cooler, early mornings. My field work highlights a few promising lines of future research informed by fruit flies’ natural history. Most importantly, we do not understand the intriguing dynamics that generate significant sociability despite frequent aggressive interactions on fruits. Males’ responses to female rejection signals varied widely, perhaps because the signals differed in information content perceived by flies but not humans. Finally, flies tolerated cold early mornings perhaps owing to fitness benefits associated with increased mating and feeding opportunities at this time. Flies were adept at handling very high temperatures under the natural daily temperature fluctuations and availability of shelters, and this can inform more realistic research on the effects of global warming on animals in their natural settings.