bluuebunny/crossref_metadata_2025 huggingface dataset:
Alzheimer’s genetic risk factor FERMT2 (Kindlin-2) controls axonal growth and synaptic plasticity in an APP-dependent manner
Authors: Eysert Fanny , Coulon Audrey , Boscher Emmanuelle , Vreulx Anaїs-Camille , Flaig Amandine , Mendes Tiago , Hughes Sandrine , Grenier-Boley Benjamin , Hanoulle Xavier , Demiautte Florie , Bauer Charlotte , Marttinen Mikael , Takalo Mari , Amouyel Philippe , Desai Shruti , Pike Ian , Hiltunen Mikko , Chécler Frédéric , Farinelli Mélissa , Delay Charlotte , Malmanche Nicolas , Hébert Sébastien S. , Dumont Julie , Kilinc Devrim , Lambert Jean-Charles , Chapuis Julien
Published: November 2020

Although APP metabolism is being intensively investigated, a large fraction of its modulators is yet to be characterized. In this context, we combined two genome-wide high-content screenings to assess the functional impact of miRNAs and genes on APP metabolism and the signaling pathways involved. This approach highlighted the involvement ofFERMT2(or Kindlin-2), a genetic risk factor of Alzheimer’s disease (AD), as a potential key modulator of axon guidance, a neuronal process that depends on the regulation of APP metabolism. We found that FERMT2 directly interacts with APP to modulate its metabolism, and that FERMT2 underexpression impacts axonal growth, synaptic connectivity, and long-term potentiation in an APP-dependent manner. Last, the rs7143400-T allele, which is associated with an increased AD risk and localized within the 3′UTR of FERMT2, induced a downregulation of FERMT2 expression through binding of miR-4504 among others. This miRNA is mainly expressed in neurons and significantly overexpressed in AD brains compared to controls. Altogether, our data provide strong evidence for a detrimental effect of FERMT2 underexpression in neurons and insight into how this may influence AD pathogenesis.
Oligodendrocyte lineage cells and depression
Authors: Zhou Butian , Zhu Zhongqun , Ransom Bruce R. , Tong Xiaoping
Published: November 2020

Depression is a common mental illness, affecting more than 300 million people worldwide. Decades of investigation have yielded symptomatic therapies for this disabling condition but have not led to a consensus about its pathogenesis. There are data to support several different theories of causation, including the monoamine hypothesis, hypothalamic–pituitary–adrenal axis changes, inflammation and immune system alterations, abnormalities of neurogenesis and a conducive environmental milieu. Research in these areas and others has greatly advanced the current understanding of depression; however, there are other, less widely known theories of pathogenesis. Oligodendrocyte lineage cells, including oligodendrocyte progenitor cells and mature oligodendrocytes, have numerous important functions, which include forming myelin sheaths that enwrap central nervous system axons, supporting axons metabolically, and mediating certain forms of neuroplasticity. These specialized glial cells have been implicated in psychiatric disorders such as depression. In this review, we summarize recent findings that shed light on how oligodendrocyte lineage cells might participate in the pathogenesis of depression, and we discuss new approaches for targeting these cells as a novel strategy to treat depression.
Novel Aza-podophyllotoxin derivative induces oxidative phosphorylation and cell death via AMPK activation in triple-negative breast cancer
Authors: Tailor Dhanir , Going Catherine C. , Resendez Angel , Kumar Vineet , Nambiar Dhanya K. , Li Yang , Dheeraj Arpit , LaGory Edward Lewis , Ghoochani Ali , Birk Alisha M. , Stoyanova Tanya , Ye Jiangbin , Giaccia Amato J. , Le Quynh-Thu , Singh Rana P. , Sledge George W. , Pitteri Sharon J. , Malhotra Sanjay V.
Published: November 2020

Background

To circumvent Warburg effect, several clinical trials for different cancers are utilising a combinatorial approach using metabolic reprogramming and chemotherapeutic agents including metformin. The majority of these metabolic interventions work via indirectly activating AMP-activated protein kinase (AMPK) to alter cellular metabolism in favour of oxidative phosphorylation over aerobic glycolysis. The effect of these drugs is dependent on glycaemic and insulin conditions.  Therefore, development of small molecules, which can activate AMPK, irrespective of the energy state, may be a better approach for triple-negative breast cancer (TNBC) treatment.

Methods

Therapeutic effect of SU212 on TNBC cells was examined using in vitro and in vivo models.

Results

We developed and characterised the efficacy of novel AMPK activator (SU212) that selectively induces oxidative phosphorylation and decreases glycolysis in TNBC cells, while not affecting these pathways in normal cells.   SU212 accomplished this metabolic reprogramming by activating AMPK independent of energy stress and irrespective of the glycaemic/insulin state. This leads to mitotic phase arrest and apoptosis in TNBC cells. In vivo, SU212 inhibits tumour growth, cancer progression and metastasis.

Conclusions

SU212 directly activates AMPK in TNBC cells, but does not hamper glucose metabolism in normal cells. Our study provides compelling preclinical data for further development of SU212 for the treatment of TNBC.
Serum lipid profiles and risk of colorectal cancer: a prospective cohort study in the UK Biobank
Authors: Fang Zhe , He Mingming , Song Mingyang
Published: November 2020

Background

It remains unclear whether serum lipids influence colorectal cancer (CRC) risk.

Methods

We conducted a prospective cohort study of 380,087 adults aged 40–69 years in the UK Biobank. Serum high-density cholesterol, low-density cholesterol, total cholesterol, triglycerides, and apolipoprotein A and B were measured. We used Cox proportional hazard models to estimate the multivariable hazard ratios (HRs) of CRC according to one standard deviation (SD) increment in serum lipids. We conducted subgroup analysis by tumour anatomical subsites.

Results

During a median of 10.3 years of follow-up, we documented 2667 incident CRC cases. None of the lipid biomarkers was associated with the risk of CRC after adjusting for potential confounding factors, including body mass index and waist circumference. When assessed by cancer subsites, serum triglycerides was associated with an increased risk of cancer in the caecum and transverse colon, with the HR of 1.12 (95% CI, 1.00–1.25) and 1.29 (95% CI, 1.09–1.53), respectively; and apolipoprotein A was associated with a lower risk of hepatic flexure cancer (HR, 0.73, 95% CI, 0.56–0.96).

Conclusions

Serum lipid profiles were not associated with colorectal cancer risk after adjusting for obesity indicators. The potential subsite-specific effects of triglycerides and apolipoprotein A require further confirmation.
Analysis of a radiation-induced dwarf mutant of a warm-season turf grass reveals potential mechanisms involved in the dwarfing mutant
Authors: Lin Tianyi , Zhou Ren , Bi Bo , Song Liangyuan , Chai Mingliang , Wang Qiaomei , Song Guoqing
Published: November 2020

Zoysia matrella [L.] Merr. is a widely cultivated warm-season turf grass in subtropical and tropical areas. Dwarf varieties of Z. matrella are attractive to growers because they often reduce lawn mowing frequencies. In this study, we describe a dwarf mutant of Z. matrella induced from the 60Co-γ-irradiated calluses. We conducted morphological test and physiological, biochemical and transcriptional analyses to reveal the dwarfing mechanism in the mutant. Phenotypically, the dwarf mutant showed shorter stems, wider leaves, lower canopy height, and a darker green color than the wild type (WT) control under the greenhouse conditions. Physiologically, we found that the phenotypic changes of the dwarf mutant were associated with the physiological responses in catalase, guaiacol peroxidase, superoxide dismutase, soluble protein, lignin, chlorophyll, and electric conductivity. Of the four endogenous hormones measured in leaves, both indole-3-acetic acid and abscisic acid contents were decreased in the mutant, whereas the contents of gibberellin and brassinosteroid showed no difference between the mutant and the WT control. A transcriptomic comparison between the dwarf mutant and the WT leaves revealed 360 differentially-expressed genes (DEGs), including 62 up-regulated and 298 down-regulated unigenes. The major DEGs related to auxin transportation (e.g., PIN-FORMED1) and cell wall development (i.e., CELLULOSE SYNTHASE1) and expansin homologous genes were all down-regulated, indicating their potential contribution to the phenotypic changes observed in the dwarf mutant. Overall, the results provide information to facilitate a better understanding of the dwarfing mechanism in grasses at physiological and transcript levels. In addition, the results suggest that manipulation of auxin biosynthetic pathway genes can be an effective approach for dwarfing breeding of turf grasses.
Establishment and characterisation of testicular cancer patient-derived xenograft models for preclinical evaluation of novel therapeutic strategies
Authors: de Vries Gerda , Rosas-Plaza Ximena , Meersma Gert Jan , Leeuwenburgh Vincent C. , Kok Klaas , Suurmeijer Albert J. H. , van Vugt Marcel A. T. M. , Gietema Jourik A. , de Jong Steven
Published: November 2020

Testicular cancer (TC) is the most common solid tumour in young men. While cisplatin-based chemotherapy is highly effective in TC patients, chemoresistance still accounts for 10% of disease-related deaths. Pre-clinical models that faithfully reflect patient tumours are needed to assist in target discovery and drug development. Tumour pieces from eight TC patients were subcutaneously implanted in NOD scid gamma (NSG) mice. Three patient-derived xenograft (PDX) models of TC, including one chemoresistant model, were established containing yolk sac tumour and teratoma components. PDX models and corresponding patient tumours were characterised by H&E, Ki-67 and cyclophilin A immunohistochemistry, showing retention of histological subtypes over several passages. Whole-exome sequencing, copy number variation analysis and RNA-sequencing was performed on these TP53 wild type PDX tumours to assess the effects of passaging, showing high concordance of molecular features between passages. Cisplatin sensitivity of PDX models corresponded with patients’ response to cisplatin-based chemotherapy. MDM2 and mTORC1/2 targeted drugs showed efficacy in the cisplatin sensitive PDX models. In conclusion, we describe three PDX models faithfully reflecting chemosensitivity of TC patients. These models can be used for mechanistic studies and pre-clinical validation of novel therapeutic strategies in testicular cancer.
Long sequence single-exposure videography using spatially modulated illumination
Authors: Ek Simon , Kornienko Vassily , Kristensson Elias
Published: November 2020

Frequency recognition algorithm for multiple exposures (FRAME) is a single-exposure imaging technique that can be used for ultrafast videography, achieved through rapid illumination with spatially modulated laser pulses. To date, both the limit in sequence length as well as the relation between sequence length and image quality are unknown for FRAME imaging. Investigating these questions requires a flexible optical arrangement that has the capability of reaching significantly longer image sequences than currently available solutions. In this paper we present a new type of FRAME setup that fulfills this criteria. The setup relies only on (i) a diffractive optical element, (ii) an imaging lens and (iii) a digital micromirror device to generate a modulated pulse train with sequence lengths ranging from 2 to 1024 image frames. To the best of the authors’ knowledge, this is the highest number of temporally resolved frames imaged in a single-exposure.
Fish telocytes and their relation to rodlet cells in ruby-red-fin shark (rainbow shark) Epalzeorhynchos frenatum (Teleostei: Cyprinidae)
Authors: Abd-Elhafeez Hanan H. , Abdo Walied , Kamal Basma Mohamed , Soliman Soha A.
Published: November 2020

Telocytes comprise the major constituents of the supportive interstitial framework within the various organs. They form a 3D network between different types of stromal and non-stromal cells, which makes them distinctively vital. We have previously explored the origin of the peculiar rodlet cells, especially on their differential stages in aquatic species. The current study aimed at highlighting the relation of telocytes with different rodlet stages. Samples of fish, olfactory organs, and gills were processed for semi thin sections, transmission electron microscopy, and immunohistochemistry. It was evident in the study that telocytes formed a 3D interstitial network, entrapping stem cells and differentiating rodlet cells, to establish direct contact with stem cells. Differentiated stem cells and rodlet progenitor cells, practically in the granular and transitional stages, also formed ultrastructure junctional modifications, by which nanostructures are formed to establish cell contact with telocytes. Telocytes in turn also connected with macrophage progenitor cells. Telocytes (TCs) expressed CD34, CD117, VEGF, and MMP-9. In conclusion, telocytes established direct contact with the stem and rodlet cells in various differential stages. Telocytes may vitally influence stem/progenitor cell differentiation, regulate rodlet cell function, and express MPP-9 that may regulate immune cells functions especially, including movement and migration ability.
Knowledge on exotic mosquitoes in Germany, and public acceptance and effectiveness of Bti and two self-prepared insecticides against Aedes japonicus japonicus
Authors: Reuss Friederike , Kreß Aljoscha , Braun Markus , Magdeburg Axel , Pfenninger Markus , Müller Ruth , Mehring Marion
Published: November 2020

Mosquito-borne diseases are a continuous challenge to public health. To prevent transmission, Integrated Vector Management (IVM) applies preventive, control, and communicational strategies that should be feasible, environmentally benign, and sustainable. IVM shows higher efficiency when being supported by local communities. Accordingly, we applied a social-ecological approach to identify the public acceptance of control measures and effectiveness of Eurocent coins containing copper, clove essential oil (EO) and Bacillus thuringiensis israelensis (Bti). We performed field and laboratory experiments to demonstrate the toxicity of alternative substances against Aedes japonicus japonicus. In expert interviews, we asked for (1) knowledge on exotic mosquitoes in Germany, (2) potential chances of alternative substances in future mosquito control, and (3) their needs for further clarification before application. We assessed potential users’ (4) awareness of exotic mosquitoes and (5) willingness to apply the substances. Self-prepared copper coins and EO were clearly preferred by potential users over Bti. However, 100% mortality of the sensitive first stage could not be reached with the number of ten 5-Eurocent coins showing limited toxicity. Clove EO was shown to work as oviposition deterrent and larvicide with a LC50 of 17 mg l−1 (95% CI: 15–19 mg l−1). This study shows the importance of potential users’ perspectives in IVM and the need for authorised insecticides.
Mirror effect in atomic force microscopy profiles enables tip reconstruction
Authors: Marques-Moros Francisco , Forment-Aliaga Alicia , Pinilla-Cienfuegos Elena , Canet-Ferrer Josep
Published: November 2020

In this work, the tip convolution effect in atomic force microscopy is revisited to illustrate the capabilities of cubic objects for determination of the tip shape and size. Using molecular-based cubic nanoparticles as a reference, a two-step tip reconstruction process has been developed. First, the tip-to-face angle is estimated by means of an analysis of the convolution error while the tip radius is extracted from the experimental profiles. The results obtained are in good agreement with specification of the tip supplier even though the experiments have been conducted using real distribution of nanoparticles with dispersion in size and aspect ratio. This demonstrates the reliability of our method and opens the door for a more accurate tip reconstruction by using calibration standards.
Chiroptical property enhancement of chiral Eu(III) complex upon association with DNA-CTMA
Authors: Minami Haruki , Itamoto Natsumi , Watanabe Wataru , Li Ziying , Nakamura Kazuki , Kobayashi Norihisa
Published: November 2020

DNA-based materials have attracted much attention due to their unique photo-functional properties and potential applications in various fields such as luminescent and biological systems, nanodevices, etc. In this study, the photophysical properties of a chiral Eu(III) complex, namely (Eu(D-facam)3), within DNA films were extensively investigated. The enhancement of photoluminescence (more than 25-folds increase of luminescence quantum yield) and degree of circularly polarization in luminescence (glum = − 0.6) was observed upon interaction with DNA. Various photophysical analyses suggested that the emission enhancement was mainly due to an increase of the sensitization efficiency (high ηsens) from the ligands to Eu(III) and suppression of the vibrational deactivation upon immobilization onto the DNA molecule. From CD and VCD measurements, it was suggested that the coordination structure of Eu(D-facam)3 was affected by the interaction with DNA, suggesting that the structural change of Eu(D-facam)3 contributed to the improvement of its luminescent properties.
The transition from primary colorectal cancer to isolated peritoneal malignancy is associated with an increased tumour mutational burden
Authors: Hallam Sally , Stockton Joanne , Bryer Claire , Whalley Celina , Pestinger Valerie , Youssef Haney , Beggs Andrew D.
Published: November 2020

Colorectal Peritoneal metastases (CPM) develop in 15% of colorectal cancers. Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS & HIPEC) is the current standard of care in selected patients with limited resectable CPM. Despite selection using known prognostic factors survival is varied and morbidity and mortality are relatively high. There is a need to improve patient selection and a paucity of research concerning the biology of isolated CPM. We aimed to determine the biology associated with transition from primary CRC to CPM and of patients with CPM not responding to treatment with CRS & HIPEC, to identify those suitable for treatment with CRS & HIPEC and to identify targets for existing repurposed or novel treatment strategies. A cohort of patients with CPM treated with CRS & HIPEC was recruited and divided according to prognosis. Molecular profiling of the transcriptome (n = 25), epigenome (n = 24) and genome (n = 21) of CPM and matched primary CRC was performed. CPM were characterised by frequent Wnt/ β catenin negative regulator mutations, TET2 mutations, mismatch repair mutations and high tumour mutational burden. Here we show the molecular features associated with CPM development and associated with not responding to CRS & HIPEC. Potential applications include improving patient selection for treatment with CRS & HIPEC and in future research into novel and personalised treatments targeting the molecular features identified here.
Comparison of two tDCS protocols on pain and EEG alpha-2 oscillations in women with fibromyalgia
Authors: de Melo Géssika Araújo , de Oliveira Eliane Araújo , dos Santos Andrade Suellen Mary Marinho , Fernández-Calvo Bernardino , Torro Nelson
Published: November 2020

Transcranial Direct Current Stimulation (tDCS) has been used as an alternative treatment for pain reduction in fibromyalgia. In this study, in addition to behavioral measures, we analyzed oscillations in alpha 2 frequency band in the frontal, occipital, and parietal regions, in response to the application of two neuromodulation protocols in fibromyalgia. The study was a randomized, double-blind, placebo-controlled clinical trial with 31 women diagnosed with fibromyalgia. The participants were allocated to three groups with the anodic stimulation applied on the left motor cortex: Group 1, for five consecutive days; Group 2, for 10 consecutive days; and Group 3, sham stimulation for five consecutive days. Statistical analysis showed a reduction in pain intensity after treatment for groups in general [F (1.28) = 8.02; p = 0.008; η2 = 0.223], in addition to a reduction in alpha 2 in the frontal (p = 0.039; d = 0.384) and parietal (p = 0.021; d = 0.520) regions after the treatment on five consecutive days. We conclude that neuromodulation protocols produced similar effects on pain reduction, but differed with respect to the changes in the alpha 2 frequency band in the frontal and parietal regions.
miRNA profiles of canine cutaneous mast cell tumours with early nodal metastasis and evaluation as potential biomarkers
Authors: Zamarian Valentina , Ferrari Roberta , Stefanello Damiano , Ceciliani Fabrizio , Grieco Valeria , Minozzi Giulietta , Chiti Lavinia Elena , Arigoni Maddalena , Calogero Raffaele , Lecchi Cristina
Published: November 2020

Cutaneous mast cell tumours (MCTs) are common skin neoplasms in dogs. MicroRNAs (miRNAs) are post-transcriptional regulators involved in several cellular processes, and they can function as tumour promoters or suppressors. However, the role of miRNAs in canine MCTs has not yet been elucidated. Thus, the current study aimed to characterize miRNA profiles and to assess their value as biomarkers for MCTs. miRNA expression profiles were assessed in formalin-fixed, paraffin-embedded samples by next-generation sequencing. Ten samples were MCT tissues, and 7 were healthy adjacent tissues. Nine dysregulated miRNAs (DE-miRNAs) were then validated using RT-qPCR in a larger group of MCT samples, allowing the calculation of ROC curves and performance of multiple factor analysis (MFA). Pathway enrichment analysis was performed to investigate miRNA biological functions. The results showed that the expression of 63 miRNAs (18 up- and 45 downregulated) was significantly affected in MCTs. Five DE-miRNAs, namely, miR-21-5p, miR-92a-3p, miR-338, miR-379 and miR-885, were validated by RT-qPCR. The diagnostic accuracy of a panel of 3 DE-miRNAs—miR-21, miR-379 and miR-885—exhibited increased efficiency in discriminating animals with MCTs (AUC = 0.9854) and animals with lymph node metastasis (AUC = 0.8923). Multiple factor analysis revealed clusters based on nodal metastasis. Gene Ontology and KEGG analyses confirmed that the DE-miRNAs were involved in cell proliferation, survival and metastasis pathways. In conclusion, the present study demonstrated that the miRNA expression profile is changed in the MCT microenvironment, suggesting the involvement of the altered miRNAs in the epigenetic regulation of MCTs and identifying miR-21, miR-379 and miR-885 as promising biomarkers.
Mito Hacker: a set of tools to enable high-throughput analysis of mitochondrial network morphology
Authors: Rohani Ali , Kashatus Jennifer A. , Sessions Dane T. , Sharmin Salma , Kashatus David F.
Published: November 2020

Mitochondria are highly dynamic organelles that can exhibit a wide range of morphologies. Mitochondrial morphology can differ significantly across cell types, reflecting different physiological needs, but can also change rapidly in response to stress or the activation of signaling pathways. Understanding both the cause and consequences of these morphological changes is critical to fully understanding how mitochondrial function contributes to both normal and pathological physiology. However, while robust and quantitative analysis of mitochondrial morphology has become increasingly accessible, there is a need for new tools to generate and analyze large data sets of mitochondrial images in high throughput. The generation of such datasets is critical to fully benefit from rapidly evolving methods in data science, such as neural networks, that have shown tremendous value in extracting novel biological insights and generating new hypotheses. Here we describe a set of three computational tools,Cell Catcher,Mito CatcherandMiA, that we have developed to extract extensive mitochondrial network data on a single-cell level from multi-cell fluorescence images.Cell Catcherautomatically separates and isolates individual cells from multi-cell images;Mito Catcheruses the statistical distribution of pixel intensities across the mitochondrial network to detect and remove background noise from the cell and segment the mitochondrial network;MiAuses the binarized mitochondrial network to perform more than 100 mitochondria-level and cell-level morphometric measurements. To validate the utility of this set of tools, we generated a database of morphological features for 630 individual cells that encode 0, 1 or 2 alleles of the mitochondrial fission GTPase Drp1 and demonstrate that these mitochondrial data could be used to predict Drp1 genotype with 87% accuracy. Together, this suite of tools enables the high-throughput and automated collection of detailed and quantitative mitochondrial structural information at a single-cell level. Furthermore, the data generated with these tools, when combined with advanced data science approaches, can be used to generate novel biological insights.
Differences in serum protein electrophoretic pattern in dogs naturally infected with Babesia gibsoni and Babesia canis
Authors: Tóthová Csilla , Karasová Martina , Blaňarová Lucia , Fialkovičová Mária , Nagy Oskar
Published: November 2020

Canine babesiosis may cause several hematological and biochemical changes, but only limited studies are available regarding the possible differences of changes in animals infected by different Babesia parasites. The study focused on the evaluation of the differences in serum protein electrophoretic pattern between dogs naturally infected with B. gibsoni (17 dogs) and B. canis (40 dogs). The mean values of total proteins, β1-, β2- and γ-globulins were in dogs infected with B. gibsoni significantly higher (P < 0.05 and P < 0.001) than in dogs infected with B. canis. The relative concentrations of albumin, α1-, α2-globulins and the A/G ratios were in the B. gibsoni infected dogs significantly lower (P < 0.001), no significant differences were found in the relative concentrations of β1- and β2-globulins. Significant differences were found in most of the evaluated parameters when comparing the results in relation to the form of B. canis infection to B. gibsoni infection. Hematological indices showed significant differences between dogs infected with B. gibsoni and the complicated form of B. canis infection. In conclusion, the obtained results suggest differences in the changes of serum protein electrophoretic pattern between dogs infected with both Babesia species and thus, in the response to the infection caused by various Babesia parasites.
Dlec1 is required for spermatogenesis and male fertility in mice
Authors: Okitsu Yu , Nagano Mamoru , Yamagata Takahiro , Ito Chizuru , Toshimori Kiyotaka , Dohra Hideo , Fujii Wataru , Yogo Keiichiro
Published: November 2020

Deleted in lung and esophageal cancer 1 (DLEC1) is a tumour suppressor gene that is downregulated in various cancers in humans; however, the physiological and molecular functions ofDLEC1are still unclear. This study investigated the critical role ofDlec1in spermatogenesis and male fertility in mice.Dlec1was significantly expressed in testes, with dominant expression in germ cells. We disruptedDlec1in mice and analysed its function in spermatogenesis and male fertility.Dlec1deletion caused male infertility due to impaired spermatogenesis. Spermatogenesis progressed normally to step 8 spermatids inDlec1−/−mice, but in elongating spermatids, we observed head deformation, a shortened tail, and abnormal manchette organization. These phenotypes were similar to those of various intraflagellar transport (IFT)-associated gene-deficient sperm. In addition, DLEC1 interacted with tailless complex polypeptide 1 ring complex (TRiC) and Bardet–Biedl Syndrome (BBS) protein complex subunits, as well as α- and β-tubulin. DLEC1 expression also enhanced primary cilia formation and cilia length in A549 lung adenocarcinoma cells. These findings suggest that DLEC1 is a possible regulator of IFT and plays an essential role in sperm head and tail formation in mice.
Transcriptomic profiling of feline teeth highlights the role of matrix metalloproteinase 9 (MMP9) in tooth resorption
Authors: Lee S. , Bush S. J. , Thorne S. , Mawson N. , Farquharson C. , Bergkvist G. T.
Published: November 2020

Tooth resorption (TR) in domestic cats is a common and painful disease characterised by the loss of mineralised tissues from the tooth. Due to its progressive nature and unclear aetiology the only treatment currently available is to extract affected teeth. To gain insight into TR pathogenesis, we characterised the transcriptomic changes involved in feline TR by sequencing RNA extracted from 14 teeth (7 with and 7 without signs of resorption) collected from 11 cats. A paired comparison of teeth from the same cat with and without signs of resorption identified 1,732 differentially expressed genes, many of which were characteristic of osteoclast activity and differentiation, in particular matrix metalloproteinase 9 (MMP9). MMP9 expression was confirmed by qPCR and immunocytochemistry of odontoclasts located in TR lesions. A hydroxamate-based MMP9 inhibitor reduced both osteoclast formation and resorption activity while siRNA targeting MMP9 also inhibited osteoclast differentiation although had little effect on resorption activity. Overall, these results suggest that increased MMP9 expression is involved in the progress of TR pathogenesis and that MMP9 may be a potential therapeutic target in feline TR.
Overlap in processing advantages for minimal ingroups and the self
Authors: Enock Florence E. , Hewstone Miles R. C. , Lockwood Patricia L. , Sui Jie
Published: November 2020

Cognitive biases shape our perception of the world and our interactions with other people. Information related to the self and our social ingroups is prioritised for cognitive processing and can therefore form some of these key biases. However, ingroup biases may be elicited not only for established social groups, but also for minimal groups assigned by novel or random social categorisation. Moreover, whether these ‘ingroup biases’ are related to self-processing is unknown. Across three experiments, we utilised a social associative matching paradigm to examine whether the cognitive mechanisms underpinning the effects of minimal groups overlapped with those that prioritise the self, and whether minimal group allocation causes early processing advantages. We found significant advantages in response time and sensitivity (dprime) for stimuli associated with newly-assigned ingroups. Further, self-biases and ingroup-biases were positively correlated across individuals (Experiments 1 and 3). However, when the task was such that ingroup and self associations competed, only the self-advantage was detected (Experiment 2). These results demonstrate that even random group allocation quickly captures attention and enhances processing. Positive correlations between the self- and ingroup-biases suggest a common cognitive mechanism across individuals. These findings have implications for understanding how social biases filter our perception of the world.
Rampant loss of social traits during domestication of a Bacillus subtilis natural isolate
Authors: Barreto Hugo C. , Cordeiro Tiago N. , Henriques Adriano O. , Gordo Isabel
Published: November 2020

Most model bacteria have been domesticated in laboratory conditions. Yet, the tempo with which a natural isolate diverges from its ancestral phenotype under domestication to a novel laboratory environment is poorly understood. Such knowledge, however is essential to understanding the rate of evolution, the time scale over which a natural isolate can be propagated without loss of its natural adaptive traits, and the reliability of experimental results across labs. Using experimental evolution, phenotypic assays, and whole-genome sequencing, we show that within a week of propagation in a common laboratory environment, a natural isolate of Bacillus subtilis acquires mutations that cause changes in a multitude of traits. A single adaptive mutational step in the gene coding for the transcriptional regulator DegU impairs a DegU-dependent positive autoregulatory loop and leads to loss of robust biofilm architecture, impaired swarming motility, reduced secretion of exoproteases, and to changes in the dynamics of sporulation across environments. Importantly, domestication also resulted in improved survival when the bacteria face pressure from cells of the innate immune system. These results show that degU is a target for mutations during domestication and underscores the importance of performing careful and extremely short-term propagations of natural isolates to conserve the traits encoded in their original genomes.
Bioinspired material architectures from bighorn sheep horncore velar bone for impact loading applications
Authors: Aguirre Trevor G. , Fuller Luca , Ingrole Aniket , Seek Tim W. , Wheatley Benjamin B. , Steineman Brett D. , Donahue Tammy L. Haut , Donahue Seth W.
Published: November 2020

Rocky Mountain bighorn sheep rams (Ovis canadensis canadensis) routinely conduct intraspecific combat where high energy cranial impacts are experienced. Previous studies have estimated cranial impact forces to be up to 3400 N during ramming, and prior finite element modeling studies showed the bony horncore stores 3 × more strain energy than the horn during impact. In the current study, the architecture of the porous bone within the horncore was quantified, mimicked, analyzed by finite element modeling, fabricated via additive manufacturing, and mechanically tested to determine the suitability of the novel bioinspired material architecture for use in running shoe midsoles. The iterative biomimicking design approach was able to tailor the mechanical behavior of the porous bone mimics. The approach produced 3D printed mimics that performed similarly to ethylene–vinyl acetate shoe materials in quasi-static loading. Furthermore, a quadratic relationship was discovered between impact force and stiffness in the porous bone mimics, which indicates a range of stiffness values that prevents impact force from becoming excessively high. These findings have implications for the design of novel bioinspired material architectures for minimizing impact force.
Prediction of survival and recurrence in patients with pancreatic cancer by integrating multi-omics data
Authors: Baek Bin , Lee Hyunju
Published: November 2020

Predicting the prognosis of pancreatic cancer is important because of the very low survival rates of patients with this particular cancer. Although several studies have used microRNA and gene expression profiles and clinical data, as well as images of tissues and cells, to predict cancer survival and recurrence, the accuracies of these approaches in the prediction of high-risk pancreatic adenocarcinoma (PAAD) still need to be improved. Accordingly, in this study, we proposed two biological features based on multi-omics datasets to predict survival and recurrence among patients with PAAD. First, the clonal expansion of cancer cells with somatic mutations was used to predict prognosis. Using whole-exome sequencing data from 134 patients with PAAD from The Cancer Genome Atlas (TCGA), we found five candidate genes that were mutated in the early stages of tumorigenesis with high cellular prevalence (CP). CDKN2A, TP53, TTN, KCNJ18, and KRAS had the highest CP values among the patients with PAAD, and survival and recurrence rates were significantly different between the patients harboring mutations in these candidate genes and those harboring mutations in other genes (p = 2.39E−03, p = 8.47E−04, respectively). Second, we generated an autoencoder to integrate the RNA sequencing, microRNA sequencing, and DNA methylation data from 134 patients with PAAD from TCGA. The autoencoder robustly reduced the dimensions of these multi-omics data, and the K-means clustering method was then used to cluster the patients into two subgroups. The subgroups of patients had significant differences in survival and recurrence (p = 1.41E−03, p = 4.43E−04, respectively). Finally, we developed a prediction model for prognosis using these two biological features and clinical data. When support vector machines, random forest, logistic regression, and L2 regularized logistic regression were used as prediction models, logistic regression analysis generally revealed the best performance for both disease-free survival (DFS) and overall survival (OS) (accuracy [ACC] = 0.762 and area under the curve [AUC] = 0.795 for DFS; ACC = 0.776 and AUC = 0.769 for OS). Thus, we could classify patients with a high probability of recurrence and at a high risk of poor outcomes. Our study provides insights into new personalized therapies on the basis of mutation status and multi-omics data.
Concomitant genetic ablation of L-type Cav1.3 (α1D) and T-type Cav3.1 (α1G) Ca2+ channels disrupts heart automaticity
Authors: Baudot Matthias , Torre Eleonora , Bidaud Isabelle , Louradour Julien , Torrente Angelo G. , Fossier Lucile , Talssi Leïla , Nargeot Joël , Barrère-Lemaire Stéphanie , Mesirca Pietro , Mangoni Matteo E.
Published: November 2020

Cardiac automaticity is set by pacemaker activity of the sinus node (SAN). In addition to the ubiquitously expressed cardiac voltage-gated L-type Cav1.2 Ca2+ channel isoform, pacemaker cells within the SAN and the atrioventricular node co-express voltage-gated L-type Cav1.3 and T-type Cav3.1 Ca2+ channels (SAN-VGCCs). The role of SAN-VGCCs in automaticity is incompletely understood. We used knockout mice carrying individual genetic ablation of Cav1.3 (Cav1.3−/−) or Cav3.1 (Cav3.1−/−) channels and double mutant Cav1.3−/−/Cav3.1−/− mice expressing only Cav1.2 channels. We show that concomitant loss of SAN-VGCCs prevents physiological SAN automaticity, blocks impulse conduction and compromises ventricular rhythmicity. Coexpression of SAN-VGCCs is necessary for impulse formation in the central SAN. In mice lacking SAN-VGCCs, residual pacemaker activity is predominantly generated in peripheral nodal and extranodal sites by f-channels and TTX-sensitive Na+ channels. In beating SAN cells, ablation of SAN-VGCCs disrupted late diastolic local intracellular Ca2+ release, which demonstrates an important role for these channels in supporting the sarcoplasmic reticulum based “Ca2+clock” mechanism during normal pacemaking. These data implicate an underappreciated role for co-expression of SAN-VGCCs in heart automaticity and define an integral role for these channels in mechanisms that control the heartbeat.
Phenotype prediction and characterization of 25 pharmacogenes in Thais from whole genome sequencing for clinical implementation
Authors: Mauleekoonphairoj John , Chamnanphon Monpat , Khongphatthanayothin Apichai , Sutjaporn Boosamas , Wandee Pharawee , Poovorawan Yong , Nademanee Koonlawee , Pongpanich Monnat , Chariyavilaskul Pajaree
Published: November 2020

Publicly available pharmacogenomics (PGx) databases enable translation of genotype data into clinically actionable information. As variation within pharmacogenes is population-specific, this study investigated the spectrum of 25 clinically relevant pharmacogenes in the Thai population (n = 291) from whole genome sequencing. The bioinformatics tool Stargazer was used for phenotype prediction, through assignment of alleles and detection of structural variation. Known and unreported potentially deleterious PGx variants were identified. Over 25% of Thais carried a high-risk diplotype in CYP3A5, CYP2C19, CYP2D6, NAT2, SLCO1B1, and UGT1A1. CYP2D6 structural variants accounted for 83.8% of all high-risk diplotypes. Of 39 known PGx variants identified, six variants associated with adverse drug reactions were common. Allele frequencies of CYP3A5*3 (rs776746), CYP2B6*6 (rs2279343), and NAT2 (rs1041983) were significantly higher in Thais than East-Asian and global populations. 121 unreported variants had potential to exert clinical impact, majority were rare and population-specific, with 60.3% of variants absent from gnomAD database. This study demonstrates the population-specific variation in clinically relevant pharmacogenes, the importance of CYP2D6 structural variation detection in the Thai population, and potential of unreported variants in explaining drug response. These findings are essential in development of dosing guidelines, PGx testing, clinical trials, and drugs.
How to approach flow chemistry
Authors: Guidi Mara , Seeberger Peter H. , Gilmore Kerry
Published: November 2020

The intrinsic attributes of flow chemistry that facilitate and provide reproducible access to a range of processes are best exploited using modules targeting an overall effect: a selective transformation or the generation of a reactive intermediate.
A two-dimensional photonic crystal hydrogel biosensor for colorimetric detection of penicillin G and penicillinase inhibitors
Authors: Wang Changping , Xiao Fubing , Chen Qianshan , Wang Shihong , Zhou Jun , Wu Zhaoyang
Published: November 2020

A simple 2DPPCH biosensor was developed for colorimetric detection of penicillin G and penicillinase inhibitors based on the enzymatic hydrolysis reaction between penicillin G and penicillinase.
Energy transfer designing in lanthanide-doped upconversion nanoparticles
Authors: Cheng Xingwen , Tu Datao , Zheng Wei , Chen Xueyuan
Published: November 2020

The most recent development of optical property designing in lanthanide (Ln3+)-doped upconversion nanoparticles on the basis of energy transfer between Ln3+–Ln3+, Ln3+–dyes, and Ln3+–quantum dots has been reviewed.
A metal–organic framework supported iridium catalyst for the gas phase hydrogenation of ethylene
Authors: Perlata Ricardo A. , Huxley Michael T. , Shi Zhaolin , Zhang Yue-Biao , Sumby Christopher J. , Doonan Christian J.
Published: November 2020

Gas phase hydrogenation of ethylene by a MOF supported Iridium catalyst highlights the role of support and counteranion effects.
Enhanced solubility, permeability, and tabletability of nicorandil by salt and cocrystal formation
Authors: Mannava M. K. Chaitanya , Gunnam Anilkumar , Lodagekar Anurag , Shastri Nalini R. , Nangia Ashwini K. , Solomon K. Anand
Published: November 2020

Cocrystallization is a rational selection crystal engineering approach for the development of novel solid forms with enhanced physicochemical and mechanical properties.
Tailoring adsorption induced switchability of a pillared layer MOF by crystal size engineering
Authors: Abylgazina Leila , Senkovska Irena , Ehrling Sebastian , Bon Volodymyr , St. Petkov Petko , Evans Jack D. , Krylova Svetlana , Krylov Alexander , Kaskel Stefan
Published: November 2020

The main factors affecting switchability are identified for DUT-8(Zn): energetics of the host, particle size, and desolvation stress. They influence the flexible behaviour to the same order of magnitude and should be always considered collectively.
A surface sensitive hard X-ray spectroscopic method applied to observe the surface layer reduction reaction of Co oxide to Co metal
Authors: Abe Hitoshi , Niwa Yasuhiro , Kimura Masao
Published: November 2020

In situTREXS captures surface reactions.
Exploring the folding process of human βB2-crystallin using multiscale molecular dynamics and the Markov state model
Authors: Velasco-Bolom José-Luis , Domínguez Laura
Published: November 2020

Adequate knowledge of protein conformations is crucial for understanding their function and their association properties with other proteins.
Hindered rotor benchmarks for the transition states of free radical additions to unsaturated hydrocarbons
Authors: Sun Yanjin , Somers Kieran P. , Wang Quan-De , Farrell Caoimhe , Curran Henry J.
Published: November 2020

The partition function deviation ratios calculated using twelve DFT methods for rotors formed by ĊH3/Ċ2H3/Ċ2H5/CH3Ȯ + C2H2/C2H4 at 300 K.
Crystal facet-dependent activity of h-WO3 for selective conversion of furfuryl alcohol to ethyl levulinate
Authors: Gao Guoming , Lv Mingxuan , Shao Yuewen , Gao Guanggang , Zhao Hui , Zhang Shu , Wang Yi , Duan Ran , Chen Qifeng , Hu Xun
Published: November 2020

The (110) facet of h-WO3 boosted the selective conversion of furfuryl alcohol to ethyl levulinate.
Experimental and theoretical studies on thymine photodimerization mediated by oxidatively generated DNA lesions and epigenetic intermediates
Authors: Lineros-Rosa Mauricio , Francés-Monerris Antonio , Monari Antonio , Miranda Miguel Angel , Lhiaubet-Vallet Virginie
Published: November 2020

Combined spectroscopic and computational studies reveal that, in spite of their structural similarities, 5-formyluracil and 5-formylcytosine photosensitize cyclobutane thymine dimers through two different types of mechanisms.
Unraveling the antisolvent dripping delay effect on the Stranski–Krastanov growth of CH3NH3PbBr3thin films: a facile route for preparing a textured morphology with improved optoelectronic properties
Authors: Kumar Jitendra , Kumar Ramesh , Frohna Kyle , Moghe Dhanashree , Stranks Samuel D. , Bag Monojit
Published: November 2020

Controlled nucleation and growth by delaying the antisolvent dripping time leads to the formation of a textured perovskite thin film morphology with improved optoelectronic properties.
Non-precious-metal catalysts for alkaline water electrolysis: operando characterizations, theoretical calculations, and recent advances
Authors: Wang Jian , Gao Yang , Kong Hui , Kim Juwon , Choi Subin , Ciucci Francesco , Hao Yong , Yang Shihe , Shao Zongping , Lim Jongwoo
Published: November 2020

Advances of non-precious-metal catalysts for alkaline water electrolysis are reviewed, highlighting operando techniques and theoretical calculations in their development.
Interactive network of the dehydrogenation of alkanes, alkenes and alkynes – surface carbon hydrogenative coupling on Ru(111)
Authors: Jiao Yueyue , Ma Huan , Wang Hui , Li Yong-Wang , Wen Xiao-Dong , Jiao Haijun
Published: November 2020

The reaction mechanisms of the dehydrogenation and retrosynthesis of alkanes, the consecutive dissociation of methane, ethane, ethene and ethyne, as well as propane, propene and propyne, on the fcc Ru(111) surface has been computed.
Beyond organic solvents: synthesis of a 5-HT4 receptor agonist in water
Authors: Bailey J. Daniel , Helbling Edward , Mankar Amey , Stirling Matthew , Hicks Fred , Leahy David K.
Published: November 2020

A manufacturing process conducted almost entirely in water has been developed to produce TAK-954, an investigational 5-HT4 receptor agonist.
Nitromethane as a surrogate cyanating agent: 7-N,N-dimethylamino-4-hydroxycoumarin-catalyzed, metal-free synthesis of α-iminonitriles
Authors: Satyanarayana Iddum , Manjappa Kiran B. , Yang Ding-Yah
Published: November 2020

An alkali and cyanide free approach for the synthesis of α-iminonitrilesviaa base-mediated and 1,3-diketone-catalyzed reaction is reported. The preparation of target compounds was realized by use of nitromethane as solvent and cyanating agent, offering a greener process.
Selective hydrogenation of cinnamaldehyde over magnetic flower-like carbonaceous Pd catalysts
Authors: Zhang Dan , Wang Bowei , Yan Lijuan , Gao Ruixiao , Liu Lu , Xia Ziyi , Yan Xilong , Li Yang , Chen Ligong
Published: November 2020

Novel magnetic flower-like carbonaceous Pd catalysts are constructed for the selective hydrogenation of the CC bond.
Controllable stripping of radiolabeled group in vivo to optimize nuclear imaging via NO-responsive bioorthogonal cleavage reaction
Authors: Li Hua , Huang Lumei , Jiang Hailong , Fang Jianyang , Guo Zhide , Gao Fei , Chen Mei , Xu Duo , Li Zijing , Zhang Xianzhong
Published: November 2020

A novel “turn-off” strategy was developed for controllable radionuclide clearance in organisms.
The influence of additives on polymer matrix mobility and the glass transition
Authors: DeFelice Jeffrey , Lipson Jane E. G.
Published: November 2020

In this work, we probe how the interfacial effects of additive particles dispersed in a matrix can influence the local mobility of the material and its glass transition temperature,Tg.