bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-related increase in matrix stiffness downregulates α-Klotho in chondrocytes and induces cartilage degeneration
Authors: Iijima Hirotaka , Gilmer Gabrielle , Wang Kai , Bean Allison , He Yuchen , Lin Hang , Evans Christopher , Ambrosio Fabrisia
Published: March 2021

Enhanced mechanistic insight into age-related knee osteoarthritis (KOA) is an essential step to promote successful translation of animal research to bedside interventions. To this end, the goal of these studies was to interrogate molecular mechanisms driving age-related KOA in a mouse model and correspond findings to human knee cartilage. Unbiased mass spectrometry proteomics of cartilage tissue revealed PI3K/Akt signaling was the predominant pathway disrupted over time in male, but not female, mice. This finding was consistent with a significantly accelerated KOA progression in males when compared to female counterparts. In probing for upstream regulators of these age-dependent alterations, we found that α-Klotho, a suppressor of PI3K/Akt signaling and potent longevity protein, significantly decreased with aging in both mouse and human knee cartilage. Upstream of these alterations, we found that age-related increases in matrix stiffness initiated a cascade of altered nuclear morphology and downregulated α-Klotho expression, ultimately impairing chondrocyte health. Conversely, reducing matrix stiffness increased α-Klotho expression in chondrocytes, thus enhancing their chondrogencity and cartilage integrity. Collectively, our findings establish a novel mechanistic link between age-related alterations in ECM biophysical properties and regulation of cartilage health by α-Klotho.
Langerhans islets induce anti-tumor immunity at the expense of glycemic control and predict chemotherapy response in pancreatic cancer
Authors: Ahmed Azaz , Charoentong Pornpimol , Klotz Rosa , Köhler Sophia , Suarez-Carmona Meggy , Valous Nektarios A. , Ferber Dyke , Heikenwälder Mathias , Giese Nathalia , Hackert Thilo , Klupp Fee , Schneider Martin , Schmidt Thomas , Springfeld Christoph , Tanriver Yakup , Falk Christine S. , Zitvogel Laurence , Zörnig Inka , Jäger Dirk , Halama Niels
Published: March 2021

Induction of anti-tumor immunity in pancreatic ductal adenocarcinoma (PDA) is an unresolved challenge. Systematic investigation of the microenvironment of primary pancreatic tumors revealed a role of endocrine Langerhans islets in the coordination of immune activation. We found that intratumoral β-cells, regulated via STAT3, secrete C-C motif chemokine ligand 27 (CCL27) and thereby promote a TH1 phenotype in the microenvironment resulting in an enhanced T cell infiltration and prolonged patient survival. The local effect can be abrogated in a patient-based human explant model by inhibition of the CCL27 receptor CCR10. This defense mechanism is paralleled by an impaired metabolic function of Langerhans islets with reduced insulin levels resulting in a dysregulation of glycemic control in patients. Based on these findings, screening of PDA cases (n= 2264) led to the identification of type 2 diabetes mellitus (T2DM) and extractable glycated haemoglobin (HbA1c) levels as response markers for neoadjuvant chemotherapy with fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX). Collectively these data provide insights into the interconnection of T2DM and PDA, and link declining glycemic control to therapeutic efficacy, which can be utilized as a tool for clinical decision-making and improve patient management.
Individualized precision targeting of dorsal attention and default mode networks with rTMS in traumatic brain injury-associated depression
Authors: Siddiqi Shan H. , Kandala Sridhar , Hacker Carl D. , Trapp Nicholas T. , Leuthardt Eric C. , Carter Alexandre R. , Brody David L.
Published: March 2021

Background

At the group level, antidepressant efficacy of rTMS targets is inversely related to their normative connectivity with subgenual anterior cingulate cortex (sgACC). Individualized connectivity may yield better targets, particularly in patients with neuropsychiatric disorders who may have aberrant connectivity. However, sgACC connectivity shows poor test-retest reliability at the individual level. Individualized resting-state network mapping (RSNM) can reliably map inter-individual variability in brain network organization.

Objective

To identify individualized RSNM-based rTMS targets that reliably target the sgACC connectivity profile.

Methods

We used RSNM to identify network-based rTMS targets in 10 healthy controls and 13 individuals with traumatic brain injury-associated depression (TBI-D). These “RSNM targets” were compared with consensus structural targets and targets based on individualized anti-correlation with a group-mean-derived sgACC region (“anti-group-mean sgACC targets”). The TBI-D cohort was randomized to receive active (n=9) or sham (n=4) rTMS to RSNM targets.

Results

The group-mean sgACC connectivity profile was reliably estimated by individualized correlation with default mode network (DMN) and anti-correlation with dorsal attention network (DAN). Individualized RSNM targets were then identified based on DAN anti-correlation and DMN correlation. Counterintuitively, anti-correlation with the group-mean sgACC connectivity profile was stronger and more reliable for RSNM-derived targets than for “anti-group-mean sgACC targets”. Improvement in depression after RSNM-targeted rTMS was predicted by target anti-correlation with the portions of sgACC. Active treatment led to increased connectivity within and between several relevant regions.

Conclusions

RSNM may enable reliable individualized rTMS targeting, although further research is needed to determine whether this personalized approach can improve clinical outcomes.
The Neurodata Without Borders ecosystem for neurophysiological data science
Authors: Rübel Oliver , Tritt Andrew , Ly Ryan , Dichter Benjamin K. , Ghosh Satrajit , Niu Lawrence , Soltesz Ivan , Svoboda Karel , Frank Loren , Bouchard Kristofer E.
Published: March 2021

The neurophysiology of cells and tissues are monitored electrophysiologically and optically in diverse experiments and species, ranging from flies to humans. Understanding the brain requires integration of data across this diversity, and thus these data must be findable, accessible, interoperable, and reusable (FAIR). This requires a standard language for data and metadata that can coevolve with neuroscience. We describe design and implementation principles for a language for neurophysiology data. Our open-source software (Neurodata Without Borders, NWB) defines and modularizes the interdependent, yet separable, components of a data language. We demonstrate NWB’s impact through unified description of neurophysiology data across diverse modalities and species. NWB exists in an ecosystem, which includes data management, analysis, visualization, and archive tools. Thus, the NWB data language enables reproduction, interchange, and reuse of diverse neurophysiology data. More broadly, the design principles of NWB are generally applicable to enhance discovery across biology through data FAIRness.
Co-variation between glucocorticoids, behaviour and immunity supports the pace-of-life syndrome hypothesis: an experimental approach
Authors: Carbillet Jeffrey , Rey Benjamin , Palme Rupert , Monestier Chloé , Börger Luca , Lavabre Typhaine , Maublanc Marie-Line , Cebe Nicolas , Rames Jean-Luc , Loc’h Guillaume Le , Wasniewski Marine , Rannou Benoit , Gilot-Fromont Emmanuelle , Verheyden Hélène
Published: March 2021

The biomedical literature has consistently highlighted that long-term elevation of glucocorticoids might impair immune functions. In wild animals, patterns are less clear. Here, we re-explored the stress-immunity relationship considering the potential effects of behavioural profiles. Thirteen captive roe deer (Capreolus capreolus) were monitored over an eight-week period encompassing two capture events. We assessed how changes in baseline faecal cortisol metabolite (FCM) concentrations following a standardised capture protocol and vaccination affected changes in thirteen immune parameters of the innate and adaptive immunity, and whether behavioural profiles were linked to changes in baseline FCM levels and immune parameters. We found that individuals showing an increase in baseline FCM levels also exhibited an increase in immunity and were characterised by more reactive behavioural profiles (low activity levels, docility to manipulation and neophilia). Our results suggest that immunity of large mammals may be influenced by glucocorticoids, but also behavioural profiles, as it is predicted by the pace-of-life syndrome hypothesis. Our results highlight the need to consider co-variations between behaviour, immunity and glucocorticoids in order to improve our understanding of the among-individual variability in the stress-immunity relationships observed in wildlife, as they may be underpinned by different life-history strategies.
Crosstalk between enterocytes and innate lymphoid cell drives early IFN-γ-mediated control ofCryptosporidium
Authors: Gullicksrud Jodi , Sateriale Adam , Englies Julie , Gibson Alexis , Shaw Sebastian , Hutchins Zachary , Martin Lindsay , Christian David , Taylor Gregory A. , Yamamoto Masahiro , Beiting Daniel P. , Striepen Boris , Hunter Christopher A.
Published: March 2021

The intestinal parasite,Cryptosporidium, is a major contributor to global child mortality and causes opportunistic infection in immune deficient individuals. Innate resistance toCryptosporidium, which specifically invades enterocytes, is dependent on the production of IFN-γ, yet whether enterocytes contribute to parasite control is poorly understood. In this study, utilizing the natural mouse pathogen,Cryptosporidium tyzzeri, we show that epithelial-derived IL-18 synergized with IL-12 to stimulate innate lymphoid cell (ILC) production of IFN-γ. This innate IFN-γ was required for early parasite control. Loss of STAT1 in enterocytes, but not dendritic cells or macrophages, antagonized early parasite control. Transcriptional profiling of enterocytes from infected mice identified an IFN-γ signature and enrichment of anti-microbial effectors like IDO, GBP and IRG. Deletion experiments identified a role for Irgm1/m3 in parasite control. Thus, enterocytes promote ILC production of IFN-γ that acts on enterocytes to restrict the growth ofC. tyzzeri.
Spontaneous dimensional reduction and novel ground state degeneracy in a simple chain model
Authors: Škrbić Tatjana , Hoang Trinh Xuan , Giacometti Achille , Maritan Amos , Banavar Jayanth R.
Published: March 2021

Chain molecules play a key role in the polymer field and in living cells. Our focus is on a new homopolymer model of a linear chain molecule subject to an attractive self-interaction promoting compactness. We analyze the model using simple analytic arguments complemented by extensive computer simulations. We find several striking results: there is a first order transition from a high temperature random coil phase to a highly unusual low temperature phase; the modular ground states exhibit significant degeneracy; the ground state structures exhibit spontaneous dimensional reduction and have a two-layer structure; and the ground states are assembled from secondary motifs of helices and strands connected by tight loops. We discuss the similarities and notable differences between the ground state structures (we call these PoSSuM - Planar Structures with Secondary Motifs) in the novel phase and protein native state structures.
Discovery of indole-modified aptamers for highly specific recognition of protein glycoforms
Authors: Yoshikawa Alex M. , Rangel Alexandra , Feagin Trevor , Chun Elizabeth M. , Wan Leighton , Li Anping , Moekl Leonhard , Eisenstein Michael , Pitteri Sharon , Soh H. Tom
Published: March 2021

Glycosylation is one of the most abundant forms of post-translational modification, and can have a profound impact on a wide range of biological processes and diseases. Unfortunately, efforts to characterize such modifications in the context of basic and clinical research are severely hampered by the lack of affinity reagents that can differentiate protein glycoforms. This lack of reagents is largely due to the challenges associated with generating affinity reagents that can bind to particular glycan epitopes with robust affinity and specificity. In this work, we use a fluorescence-activated cell sorting (FACS)-based approach to generate and screen aptamers with indole-modified bases in an effort to isolate reagents that can differentiate between protein glycoforms. Using this approach, we were able to select multiple aptamers that exhibit strong selectivity for specific glycoforms of two different proteins, with the capacity to discriminate between molecules with identical tertiary structures that differ only in terms of their glycan modifications.
MCKAT, a multi-dimensional copy number variant kernel association test
Authors: Esfahani Nastaran Maus , Catchpoole Daniel , Khan Javed , Kennedy Paul J.
Published: March 2021

Background

Copy number variants (CNVs) are the gain or loss of DNA segments in the genome. Studies have shown that CNVs are linked to various disorders, including autism, intellectual disability, and schizophrenia.

Consequently, the interest in studying a possible association of CNVs to specific disease traits is growing. However, due to the specific multi-dimensional characteristics of the CNVs, methods for testing the association between CNVs and the disease-related traits are still underdeveloped. We propose a novel multi-dimensional CNV kernel association test (MCKAT) in this paper. We aim to find significant associations between CNVs and disease-related traits using kernel-based methods.

Results

We address the multi-dimensionality in CNV characteristics. We first design a single pair CNV kernel, which contains three sub-kernels to summarize the similarity between two CNVs considering all CNV characteristics. Then, aggregate single pair CNV kernel to the whole chromosome CNV kernel, which summarizes the similarity between CNVs in two or more chromosomes. Finally, the association between the CNVs and disease-related traits is evaluated by comparing the similarity in the trait with kernel-based similarity using a score test in a random effect model. We apply MCKAT on genome-wide CNV datasets to examine the association between CNVs and disease-related traits, which demonstrates the potential usefulness the proposed method has for the CNV association tests. We compare the performance of MCKAT with CKAT, a uni-dimensional kernel method. Based on the results, MCKAT indicates stronger evidence, smaller p-value, in detecting significant associations between CNVs and disease-related traits in both rare and common CNV datasets.

Conclusion

A multi-dimensional copy number variant kernel association test can detect significantly associated CNVs with any disease-related trait. MCKAT can help biologists detect significantly associated CNVs with any disease-related trait across a patient group instead of examining the CNVs case by case in each subject.
Gene duplications and phylogenomic conflict underlie major pulses of phenotypic evolution in gymnosperms
Authors: Stull Gregory W. , Qu Xiao-Jian , Parins-Fukuchi Caroline , Yang Ying-Ying , Yang Jun-Bo , Yang Zhi-Yun , Hu Yi , Ma Hong , Soltis Pamela S. , Soltis Douglas E. , Li De-Zhu , Smith Stephen A. , Yi Ting-Shuang
Published: March 2021

Inferring the intrinsic and extrinsic drivers of species diversification and phenotypic disparity across the Tree of Life is a major challenge in evolutionary biology. In green plants, polyploidy (or whole-genome duplication, WGD) is known to play a major role in microevolution and speciation1, but the extent to which WGD has shaped macroevolutionary patterns of diversification and phenotypic innovation across plant phylogeny remains an open question. Here we examine the relationship of various facets of genomic evolution—including gene and genome duplication, genome size, and chromosome number—with macroevolutionary patterns of phenotypic innovation, species diversification, and climatic occupancy in gymnosperms. We show that genomic changes, such as WGD and genome-size shifts, underlie the origins of most major extant gymnosperm clades, and notably our results support an ancestral WGD in the gymnosperm lineage. Spikes of gene duplication typically coincide with major spikes of phenotypic innovation, while increased rates of phenotypic evolution are typically found at nodes with high gene-tree conflict, representing historic population-level dynamics during speciation. Most shifts in gymnosperm diversification since the rise of angiosperms are decoupled from putative WGDs and instead are associated with increased rates of climatic occupancy evolution, particularly in cooler and/or more arid climatic conditions, suggesting that ecological opportunity, especially in the later Cenozoic, and environmental heterogeneity have driven a resurgence of gymnosperm diversification. Our study provides critical insight on the processes underlying diversification and phenotypic evolution in gymnosperms, with important broader implications for the major drivers of both micro- and macroevolution in plants.
A General LSTM-based Deep Learning Method for Estimating Neuronal Models and Inferring Neural Circuitry
Authors: Sheng Kaiwen , Qu Peng , Yang Le , Liu Xiaofei , He Liuyuan , Zhang Youhui , Ma Lei , Du Kai
Published: March 2021

Computational neural models are essential tools for neuroscientists to study the functional roles of single neurons or neural circuits. With the recent advances in experimental techniques, there is a growing demand to build up neural models at single neuron or large-scale circuit levels. A long-standing challenge to build up such models lies in tuning the free parameters of the models to closely reproduce experimental recordings. There are many advanced machine-learning-based methods developed recently for parameter tuning, but many of them are task-specific or requires onerous manual interference. There lacks a general and fully-automated method since now. Here, we present a Long Short-Term Memory (LSTM)-based deep learning method, General Neural Estimator (GNE), to fully automate the parameter tuning procedure, which can be directly applied to both single neuronal models and large-scale neural circuits. We made comprehensive comparisons with many advanced methods, and GNE showed outstanding performance on both synthesized data and experimental data. Finally, we proposed a roadmap centered on GNE to help guide neuroscientists to computationally reconstruct single neurons and neural circuits, which might inspire future brain reconstruction techniques and corresponding experimental design. The code of our work will be publicly available upon acceptance of this paper.
Discovery of viral myosin genes with complex evolutionary history within plankton
Authors: Kijima Soichiro , Delmont Tom O. , Miyazaki Urara , Gaia Morgan , Endo Hisashi , Ogata Hiroyuki
Published: March 2021

Nucleocytoplasmic large DNA viruses (NCLDVs) infect diverse eukaryotes and form a group of viruses with capsids encapsulating large genomes. Recent studies are increasingly revealing a spectacular array of functions encoded in their genomes, including genes for energy metabolisms, nutrient uptake, as well as cytoskeleton. Here, we report the discovery of genes homologous to myosins, the major eukaryotic motor proteins previously unrecognized in the virosphere, in environmental genomes of NCLDVs from the surface of the oceans. Interestingly, these genes were often accompanied by kinesin genes in the environmental genomes, suggesting a role of these viral proteins in the intracellular viral particle transport. Phylogenetic analyses indicate that most viral myosins (named “virmyosins”) belong to theImiterviralesorder, except for one belonging to thePhycodnaviridaefamily. On the one hand, the phylogenetic positions of virmyosin-encodingImiterviralesare scattered within theImitervirales. On the other hand,Imiterviralesvirmyosin genes form a monophyletic group in the phylogeny of diverse myosin sequences. Furthermore, phylogenetic trends for the virmyosin genes and viruses containing them were incongruent. Based on these results, we argue that multiple transfers of myosin homologs have occurred not only from eukaryotes to viruses but also between viruses, supposedly during co-infections of the same host.
A Synthesis of the Many Errors and Learning Processes of Visuomotor Adaptation
Authors: Morehead J. Ryan , Orban de Xivry Jean-Jacques
Published: March 2021

Visuomotor adaptation has one of the oldest experimental histories in psychology and neuroscience, yet its precise nature has always been a topic of debate. Here we offer a survey and synthesis of recent work on visuomotor adaptation that we hope will prove illuminating for this ongoing dialogue. We discuss three types of error signals that drive learning in adaptation tasks: task performance error, sensory prediction-error, and a binary target hitting error. Each of these errors has been shown to drive distinct learning processes. Namely, both target hitting errors and putative sensory prediction-errors drive an implicit change in visuomotor maps, while task performance error drives learning of explicit strategy use and non-motor decision-making. Each of these learning processes contributes to the overall learning that takes place in visuomotor adaptation tasks, and although the learning processes and error signals are independent, they interact in a complex manner. We outline many task contexts where the operation of these processes is counter-intuitive and offer general guidelines for their control, measurement and interpretation. We believe this new framework unifies several disparate threads of research in sensorimotor adaptation that often seem in conflict. We conclude by explaining how this more nuanced understanding of errors and learning processes could lend itself to the analysis of other types of sensorimotor adaptation, of motor skill learning, of the neural processing underlying sensorimotor adaptation in humans, of animal models and of brain computer interfaces.
PlotMI: interpretation of pairwise dependencies and positional preferences learned by deep learning models from sequence data
Authors: Hartonen Tuomo , Kivioja Teemu , Taipale Jussi
Published: March 2021

Deep learning models have recently gained success in various tasks related to understanding information coded in biological sequences. Although offering state-of-the art predictive performance, the predictions made by deep learning models can be difficult to understand. In virtually all biological research, the understanding of how a predictive model works is as, or even more important as the raw predictive performance. Thus interpretation of deep learning models is an emerging hot topic especially in context of biological research. Here we describe PlotMI, a mutual information based model interpretation tool that can intuitively visualize positional preferences and pairwise dependencies learned by any machine learning model trained on sequence data such as DNA, RNA or amino acid sequence. PlotMI can also be used to compare dependencies present in training data to the dependencies learned by the model and to compare dependencies learned by different types of models that are trained to perform the same task. PlotMI is freely available athttps://github.com/hartonen/plotMI.
Contrast adaptation improves spatial integration
Authors: Pinchuk-Yacobi Noga , Sagi Dov
Published: March 2021

The effects of contrast adaptation and contrast area summation were investigated using a contrast discrimination task. The task consisted of a target of variable size, and a pedestal with a fixed base contrast. Discrimination performance was examined for a condition in which the pedestal size was fixed, equal to the largest target size, and for a condition in which the pedestal size matched the target size and thus varied with it. Repeated performance of the task produced rapid within-session improvements for both conditions. For stimuli with a matching size of target and pedestal, the performance improved only for the larger targets, indicating the development of area summation, which was initially absent for these stimuli. However, the improvements were mostly temporary, and were not fully retained between subsequent sessions. The temporary nature of the sensitivity gains implies that they resulted, at least in part, from rapid adaptation to the stimulus contrast. We suggest that adaptation decorrelates and thus reduces the spatial noise generated by a high-contrast pedestal, leading to improved area summation and better contrast sensitivity. A decorrelation model successfully predicted our experimental results.
In-situ fiducial markers for 3D correlative cryo- fluorescence and FIB-SEM imaging
Authors: Scher Nadav , Rechav Katya , Paul-Gilloteaux Perrine , Avinoam Ori
Published: March 2021

1.

Imaging of cells and tissues has improved significantly over the last decade. Dual-beam instruments with a focused ion beam mounted on a scanning electron microscope (FIB-SEM), which offer high-resolution 3D imaging of large volumes and fields-of-view are becoming widely used in the life sciences. FIB-SEM has most recently been implemented on fully hydrated, cryo-immobilized, biological samples. However, correlative light and electron microscopy (CLEM) workflows combining cryo-fluorescence microscopy (cryo-FM) and FIB-SEM are not yet commonly available. Here, we demonstrate that fluorescently labeled lipid droplets can serve asin-situfiducial markers for correlating cryo-FM and FIB-SEM datasets, and that this approach can be used to target the acquisition of large FIB-SEM stacks spanning tens of microns under cryogenic conditions. We also show that cryo-FIB-SEM imaging is particularly informative for questions related to organelle structure and inter-organellar contacts, nuclear organization and mineral deposits in cells.
The hidden effects of agrochemicals on plant metabolism and root-associated microorganisms
Authors: Cesco S. , Lucini L. , Miras-Moreno B. , Borruso L. , Mimmo T. , Pii Y. , Puglisi E. , Spini G. , Taskin E. , Tiziani R. , Zangrillo M. S. , Trevisan M.
Published: March 2021

Agrochemicals are commonly used in agriculture to protect crops and ensure yields. Several of them are mobile within the plant and, being perceived as xenobiotics regardless of their protective/curative roles, they induce a reprogramming of secondary metabolism linked to the detoxification processes even in the absence of phenotype symptoms. Moreover, it is well documented that plants, thanks to the root exudation of different metabolites, are able to shape the microbial population at the rhizosphere and to significantly affect the processes occurring therein. Here we show that plant metabolic response to foliarly-applied pesticides is much broader than what previously thought and includes diverse and compound-specific hidden processes. Among others, stress-related metabolism and phytohormones profile underwent a considerable reorganization. Moreover, a distinctive microbial rearrangement of the rhizosphere was recorded following foliar application of pesticides. Such effects have unavoidably energetic and metabolic costs for the plant paving the way to both positive and negative aspects. The understanding of these effects is crucial for an increasingly sustainable use of pesticides in agriculture.

Highlight

The foliar application of pesticides induces a broad metabolic reprogramming in plant and shapes the microbial population of the rhizosphere.
In VitroAssessment of Efficacy and Cytotoxicity ofPrunus africanaExtracts on Prostate Cancer C4-2 Cells
Authors: Asuzu Peace C. , Aryee Alberta N.A. , Trompeter Nicholas , Mann Yasmin , Besong Samuel A. , Duncan Randall L. , Cooper Carlton R.
Published: March 2021

Phenolic compounds are products of secondary plant metabolism known for their biological activity including their antimicrobial, antioxidant, analgesic, stimulant, anti- carcinogenic, and aphrodisiac properties. The main objective of this study was to assess the potency/cytotoxic effects ofPrunus africanaextracts on prostate cancer cellsin vitro. Using different concentrations ofP. africanaextracts, prostate cancer C4-2 cells, a hormonally insensitive subline of LNCaP cells, were treated in a proliferation assay. A concentration dependent inhibition of cell growth in cells treated withP. africanabark and root extracts was present from days 1 through 3 of incubation, with the methanol extract of the bark showing the strongest effect. Compared to other plant parts, leaf extracts were significantly less cytotoxic at the same concentrations. As C4-2 cells are hormonally insensitive and designed to mimic advanced prostate cancer, crude extracts ofP. africanaare a possible treatment option, not only for hormone sensitive prostate cancer, but also advanced, hormonally insensitive prostate cancer.
Total number and ratio of GABAergic neuron types in the mouse lateral and basal amygdala
Authors: Vereczki Viktória K. , Müller Kinga , Krizsán Éva , Máté Zoltán , Fekete Zsuzsanna , Rovira-Esteban Laura , Veres Judit M. , Erdélyi Ferenc , Hájos Norbert
Published: March 2021

GABAergic neurons are key circuit elements in cortical networks. In spite of growing evidence showing that inhibitory cells play a critical role in the lateral (LA) and basal (BA) amygdala functions, neither the number of GABAergic neurons nor the ratio of their distinct types have been determined in these amygdalar nuclei. Using unbiased stereology, we found that the ratio of GABAergic neurons in the BA (22 %) is significantly higher than in the LA (16 %) in both male and female mice. No difference was observed between the right and left hemispheres in either sexes. In addition, we assessed the ratio of the major inhibitory cell types in both amygdalar nuclei. Using transgenic mice and a viral strategy for visualizing inhibitory cells combined with immunocytochemistry, we estimated that the following cell types together compose the vast majority of GABAergic cells in the LA and BA: axo-axonic cells (5.5-6 %), basket cells expressing parvalbumin (17-20 %) or cholecystokinin (7-9 %), dendrite-targeting inhibitory cells expressing somatostatin (10-16 %), NPY-containing neurogliaform cells (14-15 %), VIP and/or calretinin-expressing interneuron-selective interneurons (29-38 %) and GABAergic projection neurons expressing somatostatin and neuronal nitric oxide synthase (nNOS, 5.5-8 %). Our results show that these amygdalar nuclei contain all major GABAergic neuron types as found in other cortical regions. Furthermore, our data offer an essential reference for future studies aiming to reveal changes in GABAergic cell number and in inhibitory cell types typically observed under different pathological conditions, and to model functioning amygdalar networks in health and disease.

Significance statement

GABAergic cells in cortical structures, like in the lateral and basal nucleus of the amygdala, have a determinant role in controlling circuit operation. In this study, we provide the first estimate for the total number of inhibitory cells in these two amygdalar nuclei. In addition, our study is the first to define the ratio of the major GABAergic cell types present in these cortical networks. Taking into account that hyper-excitability in the amygdala, arising from the imbalance between excitation and inhibition typifies many altered brain functions including anxiety, posttraumatic stress disorder, schizophrenia and autism, uncovering the number and ratio of distinct amygdalar inhibitory cell types offers a solid base for comparing the changes in inhibition in pathological brain states.
The obstacles and potential clues of prime editing applications in tomato, a dicot plant
Authors: Van Vu Tien , Kim Jihae , Das Swati , Lee Jinsu , Kim Jae-Yean
Published: March 2021

Precision genome editing is highly desired for crop improvement. The recently emerged CRISPR/Cas technology offers great potential applications in precision plant genome engineering. A prime editing (PE) approach combining a reverse transcriptase (RT) with a Cas9 nickase and a “priming” extended guide RNA has shown a high frequency for precise genome modification in mammalian cells and several plant species. Nevertheless, the applications of the PE approach in dicot plants are still limited and inefficient. We designed and tested prime editors for precision editing of a synthetic sequence in a transient assay and for desirable alleles of 10 loci in tomato by stable transformation. Our data obtained by targeted deep sequencing also revealed only low PE efficiencies in both the tobacco and tomato systems. Further assessment of the activities of the PE components uncovered potential reasons for the inefficiency of the PE complexes. Modifying the pegRNA sequences by shortening or introducing mismatches to the primer binding sequences (PBS) in order to reduce their melting temperatures (Tm) did not enhance the PE efficiency at the SlBMP21, SlALC and SlALS1 loci. Our data show challenges of PE approach in tomato, indicating a further improvement of the PE system for the successful applications such as use of improved expression systems. Our work provides an important clue for the successful application of the PE approach in crop improvement.
In vitro and in vivo comparison of the MRI glucoCEST properties between native glucose and 3OMG in a murine tumor model
Authors: Anemone Annasofia , Capozza Martina , Arena Francesca , Zullino Sara , Bardini Paola , Terreno Enzo , Longo Dario Livio , Aime Silvio
Published: March 2021

Purpose

D-Glucose and 3-O-Methyl-D-glucose (3OMG) have been shown to provide contrast in MRI-CEST images. However, a systematic comparison between these two molecules has not yet been performed. This study dealt with the assessment of the effect of pH, saturation power level (B1) and magnetic field strength (B0) on the MRI-CEST contrast with the aim of comparing thein vivoCEST contrast detectability of these two agents in the glucoCEST procedure.

Methods

Phosphate buffered solutions of D-Glucose or 3OMG (20 mM) were prepared at different pH values and Z-spectra acquired at several B1levels and at 37°C.In vivoglucoCEST images were obtained at 3 T and 7 T over a period of 30 min after injection of D-Glucose or 3OMG (at the doses of 1.5 and 3 g/kg) in a murine melanoma tumour model.

Results

A markedly different pH dependence of CEST response was observed in vitro for D-Glucose and 3OMG. The glucoCEST contrast enhancement in the tumour region following the intravenous administration (at the dose 3 g/kg) resulted to be comparable for both the molecules: 1-2% at 3 T and 2-3% at 7 T. The ST% resulted almost constant for 3OMG over the 30 min period, whereas a significant increase in the case of D-Glucose was detected.

Conclusion

Our results show similar CEST contrast efficiency but different temporal kinetics for the metabolizable and the non-metabolizable glucose derivatives in tumour murine models when administered at the same doses.
A refraction correction for buried interfaces applied to in situ grazing-incidence X-ray diffraction studies on Pd electrodes
Authors: Landers Alan T. , Koshy David M. , Lee Soo Hong , Drisdell Walter S. , Davis Ryan C. , Hahn Christopher , Mehta Apurva , Jaramillo Thomas F.
Published: March 2021

In situ characterization of electrochemical systems can provide deep insights into the structure of electrodes under applied potential. Grazing-incidence X-ray diffraction (GIXRD) is a particularly valuable tool owing to its ability to characterize the near-surface structure of electrodes through a layer of electrolyte, which is of paramount importance in surface-mediated processes such as catalysis and adsorption. Corrections for the refraction that occurs as an X-ray passes through an interface have been derived for a vacuum–material interface. In this work, a more general form of the refraction correction was developed which can be applied to buried interfaces, including liquid–solid interfaces. The correction is largest at incidence angles near the critical angle for the interface and decreases at angles larger and smaller than the critical angle. Effective optical constants are also introduced which can be used to calculate the critical angle for total external reflection at the interface. This correction is applied to GIXRD measurements of an aqueous electrolyte–Pd interface, demonstrating that the correction allows for the comparison of GIXRD measurements at multiple incidence angles. This work improves quantitative analysis of d-spacing values from GIXRD measurements of liquid–solid systems, facilitating the connection between electrochemical behavior and structure under in situ conditions.
The presentation, recognition and diagnosis of autism in women and girls
Authors: Driver Bethany , Chester Verity
Published: March 2021

Purpose

Autistic women and girls have received comparatively less attention within clinical practice and research. Research suggests women tend to be diagnosed later than men, and are more likely to experience misdiagnosis.

Design/methodology/approach

This paper aims to report a narrative literature review that examines research on the presentation, recognition, and diagnosis of autistic women and girls.

Findings

Findings suggest that autistic females present differently to males and highlight low recognition of the female presentation of autism among the general public, in social spheres, educational, clinical and forensic settings. This lack of recognition appears to affect the likelihood of females being referred for diagnosis, the reliability of diagnostic assessments and subsequent access to support.

Originality/value

Recommendations for clinical practice focus on initiatives to increase awareness of the female presentation of autism, improving the diagnostic process for females, increasing female representation within autism training and for future research to support these goals.
Lifestyle segmentation of Czech food consumers: how sustainability and listening to music correspond to consumer lifestyles
Authors: Hrubá Renata , Sadílek Tomáš
Published: March 2021

Purpose

The purpose of this study is to segment Czech consumers based on their sustainable food consumption and their relationship with listening to music. Specifically, the authors attempt to answer the following question: is the relationship to music a segmentation difference for young consumers in the case of sustainability? The food-related lifestyle (FRL) concept is used as a framework; little attention has been paid to the FRL profile in the context of certain types of consumer orientations toward sustainability as a social value among consumers in Czechia.

Design/methodology/approach

In this research, the authors used 22 items related to sustainability (identify sustainability-oriented and health-oriented variables and socially and ethically oriented variables). The statistical data analysis techniques included factor analysis and cluster analysis. The results of the cluster analysis are the market segments. The total sample consists of 331 university students from Czechia. These data are from a continuous research project. A factor analysis identified six factors with satisfactory reliability coefficients. Using factor scores, a cluster analysis was run, resulting in four segments. These segments were further analyzed and described toward their sustainability orientation.

Findings

FRL concept was used to evaluate whether there are differences in the profiles of consumer orientations. Results emphasize the importance of personal characteristics and attitudes toward music, which in turn affect strategies to communicate with different segments to promote sustainable foods. Each segment has statistically significant differences in terms of its FRL.

Originality/value

This study explores the link between attitudes and behavior and suggests strategies to better understand the effect of information on consumer behavior. The results can help practitioners develop labeling strategies for fair-trade and sustainable foods to better focus on specific segments of consumers. This can be relevant when a sustainable food market is just starting, but hopes to reach more maturity in Czechia should be of the utmost importance for investors making long-term investments.
The potential of feminist technoscience for advancing research in information practice
Authors: Costello Kaitlin Light , Floegel Diana
Published: March 2021

Purpose

In this paper, we introduce feminist technoscience as an approach that will advance theory in information behavior and practice.

Design/methodology/approach

In this conceptual paper, we identify four common assumptions in information behavior and information practice research that limit theory development to date. Existing models and theories tend to rely on extractive logic, focus on a person-in-situation, depend on binary definitions and assume that information interaction changes people's lives for the better. This leads to extractive ways of discussing information interactions and limits our ability to fully theorize embodiment and affect in our discipline.

Findings

Feminist technoscience offers distinct ways of thinking about people, technology, bodies and power; in doing so, it responds to some perennial limitations in our research to date.

Originality/value

Feminist technoscience is a robust research paradigm that has not yet been fully applied in our discipline. Assumptions in information behavior and information practice research have led to models and theories that reflect a logic of extraction and are limited in their potential for characterizing both embodiment and affect. Feminist technoscience provides a way to conduct research that challenges these assumptions and addresses these limitations.
Sodium butyrate ameliorates non‐alcoholic fatty liver disease by upregulating miR‐150 to suppress CXCR4 expression
Authors: Zhang Ning , Qu Yunfei , Qin Bo
Published: March 2021

Sodium butyrate (NaB) in the gut of animals possesses the potential to modulate lipid metabolism, regulate innate immunity and protect intestinal health. Accumulating data have supported the important function of metabolites of intestinal microflora (MIM) in non‐alcoholic fatty liver disease (NAFLD). This study intended to investigate the role of NaB in NAFLD and its specific mechanism. Mice were fed a high‐fat diet (HFD) for 16 weeks to establish the NAFLD mouse model. The mice were intragastrically administrated MIM (200 µL/day) or NaB (200 mg/kg/day) by gavage for another 8 weeks. The morphology of liver tissues was observed by hematoxylin and eosin (H&E) staining, and the lipid deposition of liver tissues was examined by oil red O staining. The NAFLD cell model was constructed in alpha mouse liver 12 (AML12) cells by 24 hours of stimulation with 0.5 mM free fatty acids. After treatment with 10 mM NaB, AML12 cells were transfected with mimic‐miR‐150 or inhibitor‐miR‐150. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blotting were used to measure the contents of interleukin 1β (IL‐1β), IL‐6 and tumour necrosis factor α (TNF‐α) and the expression of microRNA (miR)‐150 and CXCR4 in liver tissues of mice and in AML12 cells. A luciferase reporter assay was applied to verify the binding relationship between miR‐150 and CXCR4. The H&E and oil red O staining results showed hepatic steatosis in the liver tissues of HFD‐fed mice. There were elevated contents of triacylglycerides (TG), total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), fasting blood glucose, enhanced activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST), increased homeostatic model assessment of insulin resistance scores and increased inflammatory responses in the serum of HFD‐fed mice. However, intervention with MIM or NaB reversed the above trends, indicating that MIM or NaB intervention relieved hepatic steatosis in mice. HFD‐fed mice had downregulated expression of miR‐150, whereas the expression level was upregulated after MIM or NaB treatment. Sodium butyrate attenuated NAFLD progression by regulating miR‐150. MiR‐150 can negatively target CXCR4. Sodium butyrate mitigates HFD‐induced NAFLD in mice by upregulating miR‐150 expression to downregulate CXCR4.
Specialty seeds: Nutrients, bioactives, bioavailability, and health benefits: A comprehensive review
Authors: Alasalvar Cesarettin , Chang Sui Kiat , Bolling Bradley , Oh Won Young , Shahidi Fereidoon
Published: March 2021

Seeds play important roles in human nutrition and health since ancient time. The term “specialty” has recently been applied to seeds to describe high‐value and/or uncommon food products. Since then, numerous studies have been conducted to identify various classes of bioactive compounds, including polyphenols in specialty seeds. This review discusses nutrients, fat‐soluble bioactives, polyphenols/bioactives, antioxidant activity, bioavailability, health benefits, and safety/toxicology of commonly consumed eight specialty seeds, namely, black cumin, chia, hemp, flax, perilla, pumpkin, quinoa, and sesame. Scientific results from the existing literature published over the last decade have been compiled and discussed. These specialty seeds, having numerous fat‐soluble bioactives and polyphenols, together with their corresponding antioxidant activities, have increasingly been consumed. Hence, these specialty seeds can be considered as a valuable source of dietary supplements and functional foods due to their health‐promoting bioactive components, polyphenols, and corresponding antioxidant activities. The phytochemicals from these specialty seeds demonstrate bioavailability in humans with promising health benefits. Additional long‐term and well‐design human intervention trials are required to ascertain the health‐promoting properties of these specialty seeds.
Long‐term stability of sex chromosome gene content allows accurate qPCR‐based molecular sexing across birds
Authors: Mazzoleni Sofia , Němec Pavel , Albrecht Tomáš , Lymberakis Petros , Kratochvíl Lukáš , Rovatsos Michail
Published: March 2021

Embryos, juveniles, and even adults of many bird species lack pronounced external sexually dimorphic characteristics. Accurate identification of sex is crucial for research (e.g., developmental, population, and evolutionary studies), management of wildlife species, and captive breeding programmes for both conservation and poultry. An accurate molecular sexing method applicable across the entire bird radiation is theoretically possible thanks to the long‐term stability of their ZZ/ZW sex chromosomes, but current methods are not applicable in a wide range of bird lineages. Here, we developed a novel molecular sexing method based on the comparison of gene copy number variation by quantitative real‐time PCR (qPCR) in conserved Z‐specific genes (CHRNA6,DDX4,LPAR1,TMEM161B,VPS13A), i.e. genes linked to Z but absent from W chromosomes. We tested the method across three paleognath and 70 neognath species covering the avian phylogeny. In addition, we designed primers for four Z‐specific genes (DOCK8,FUT10,PIGGandPSD3) for qPCR‐based molecular sexing in three paleognath species. We have demonstrated that the genesDOCK8,FUT10,PIGGandPSD3can identify sex in paleognath birds and the genesCHRNA6,DDX4,TMEM161B, andVPS13Acan reveal sex in neognath birds. The geneLPAR1can be used to accurately identify sex in both paleognath and neognath species. Along with outlining a novel method of practical importance for molecular sexing in birds, our study also documents in detail the conservation of sex chromosomes across the avian phylogeny.