bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent measures of impulsive action and choice are partially related and differentially modulated by dopamine D1- and D2-like receptors in a rat model of impulsivity
Authors: Bellés Lidia , Arrondeau Chloé , Urueña-Méndez Ginna , Ginovart Nathalie 
Published: August 2022

AbstractImpulsivity is a multidimensional construct, but the relationships between its constructs and their respective underlying dopaminergic underpinnings in the normal population remain unclear. A large cohort of Roman high-(RHA) and low- (RLA) avoidance rats were tested for impulsive action and risky decision-making in the rat gambling task, and then for delay discounting in the delay discounting task to concurrently measure the relationships among the three constructs of impulsivity using a within-subject design. Then, we evaluated the effects of dopaminergic drugs on the three constructs of impulsivity, considering innate differences in impulsive behaviors at baseline. Risky decision-making and delay discounting were positively correlated, indicating that both constructs of impulsive choice are related. Impulsive action positively correlated with risky decision-making but not with delay discounting, suggesting partial overlap between impulsive action and impulsive choice. RHAs showed a more impulsive phenotype in the three constructs of impulsivity compared to RLAs, demonstrating the comorbid nature of impulsivity in a normal population. While amphetamine increased impulsive action and had no effects on risky decision-making regardless of baseline levels of impulsivity, it decreased delay discounting but only in high impulsive RHAs. Conversely, the D1R agonist SKF81297, D3R agonist PD128907 and D2/3R partial agonist aripiprazole decreased impulsive action irrespective of baseline levels of impulsivity, whereas D2/3R agonism with quinpirole decreased it exclusively in high impulsive RHAs. Risky decision-making was increased by SKF81297 and quinpirole but not PD128907 and aripiprazole, with quinpirole producing baseline-dependent effects, increasing risky decision-making only in low impulsive RLAs. Finally, while SKF81297, PD128907 and aripiprazole increased delay discounting irrespective of baseline levels of impulsivity, quinpirole decreased it in low impulsive RLAs only. These findings indicate that the acute effects of dopamine drugs were partially overlapping across dimensions of impulsivity, and that only D2/3R agonism showed baseline-dependent effects on the three constructs of impulsivity.
Social media at metabolic meetings: who is tweeting what and for whom?
Authors: Nurse James 
Published: August 2022

BACKGROUNDThe social media site Twitter has been widely embraced in medical circles for its ability to connect individuals and support rapid information sharing. Critics say that the messages shared may not accurately reflect what was said and that sharing meeting content could devalue conferences themselves. It is unclear how it is used at SSIEM and what value it may bring.METHODSTwitter’s tweetdeck software was used to find all tweets containing the conference ‘hashtag’ #SSIEM2018. All tweets were reviewed to identify the author, see what had been shared and count replies, likes and retweets. Authors were grouped by professional background and tweet content was broken down by type of material shared and theme.RESULTS122 relevant tweets were sent during the fortnight at the beginning of September 2018, creating over 400,000 impressions. There were a further 73 replies with approximately 13 engagements (likes, replies or retweets) per tweet. 36 people wrote tweets (rate: 3.4 per person [1-33]). One quarter of the tweets shared poster content and over one third of tweets related to Phenylketonuria materials. 50 of the tweets were produced by just two accounts, both intended to provide information to patients and their families.DISCUSSIONTweets where no hashtag was used cannot be identified and restrictions within Twitter prevent certain analyses on tweet data greater than 30 days old. However, Twitter uptake within metabolic medicine is significantly behind other specialities where conference tweets can exceed 20,000. Information shared is typically intended for patients rather than other health professionals; this suggests a different uptake to more mainstream specialities. Presenting teams should be aware that their work may be received directly by patients and families and consider how best to present their messages for all who may receive them.
Bioassay-guided isolation and characterization of anti-bacterial compound fromSonneratia apetalaBuch. Ham leaf, from Maharashtra coast of India
Authors: Dhane-Sarkar Jaimini , Sarkar Chiradeep , Jadhav B.L. 
Published: August 2022

AbstractMangroves, collection of plants growing in coastal intertidal zones, are rich source of unique bioactive phytochemicals present in their bark, roots, leaves and fruits. They show anti-diabetic, anti-cancer, anti-hypertensive, anti-malarial, anti-bacterial, anti-inflammatory and anti-oxidant properties. In this study, a bioassay-guided isolation and characterization approach was taken to study the anti-bacterial compound fromSonnerartia apetalaBuch. Ham leaf. Petroleum ether, acetone and water extracts were prepared and tested against eight human pathogenic bacteria. Water and acetone extracts have shown the inhibition of bacteria but the acetone extract was carried forward for further study. The compound was isolated using preparative column chromatography method. The isolated compound was studied for anti-bacterial activity using TLC-bioautography . The bioactive compound was isolated and tested against standard antibiotics and showed positive results againstE. coliandB.subtilis. The isolated pure compound was studied for detection of elements and melting point. Further chacterization was done using UV-Vis spectroscopy and FT-IR spectroscopy indicating absorption in the UV spectrum and presence of aromatic and aliphatic groups. This study validates the importance ofSonneratia apetalaleaves as an important resource in traditional medicine for anti-bacterial remedies aimed at human pathogenic diseases.
A novel batokine Breg controls adipose thermogenesis and glucose homeostasis
Authors: Chen Qingbo , Huang Lei , Pan Dongning , Hu Kai , Li Rui , Zhu Lihua J. , Guertin David A. , Wang Yong-Xu 
Published: August 2022

AbstractBatokines selectively expressed in brown and beige adipocytes remain to be identified and their potential signaling role in adipose thermogenesis are largely unknown. Here we identified a batokine we named as Breg acting as a key regulator for adipose thermogenesis and glucose homeostasis. Breg expression is adipose-specific and highly brown fat-enriched, and its secretion is stimulated by β3-adrenergic activation. Gain-of-functional studies collectively showed that secreted Breg promotes adipose thermogenesis, lowers glucose level, and protects against obesity. Adipose-specific Breg knockout mice are defective in white fat browning, and are susceptible to high fat diet-induced obesity and hyperglycemia, demonstrating the physiological importance of this batokine in energy metabolism. Mechanistically, Breg binds to a putative receptor on adipocyte surface and activates protein kinase A independently of β-adrenergic signaling. These results establish Breg as a major upstream signaling component in thermogenesis and offer a potential avenue for the treatment of obesity and diabetes.
Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds
Authors: Wamhoff Eike-Christian , Ronsard Larance , Feldman Jared , Knappe Grant A. , Hauser Blake M. , Romanov Anna , Lam Evan , Denis Kerri St. , Boucau Julie , Barczak Amy K , Balazs Alejandro B. , Schmidt Aaron , Lingwood Daniel , Bathe Mark 
Published: August 2022

AbstractMultivalent antigen display is a well-established principle to enhance humoral immunity. Protein-based virus-like particles (VLPs) are commonly used to spatially organize antigens. However, protein-based VLPs are limited in their ability to control valency on fixed scaffold geometries and are thymus-dependent antigens that elicit neutralizing B cell memory themselves, which can distract immune responses. Here, we investigated DNA origami as an alternative material for multivalent antigen display in vivo, applied to the receptor binding domain (RBD) of SARS-CoV-2 that is the primary antigenic target of neutralizing antibody responses. Icosahedral DNA-VLPs elicited neutralizing antibodies to SARS-CoV-2 in a valency-dependent manner following sequential immunization in mice, quantified by pseudo-and live-virus neutralization assays. Further, induction of B cell memory against the RBD required T cell help, but the immune sera did not contain boosted, class-switched antibodies against the DNA scaffold. This contrasted with protein-based VLP display of the RBD that elicited B cell memory against both the target antigen and the scaffold. Thus, DNA-based VLPs enhance target antigen immunogenicity without generating off-target, scaffold-directed immune memory, thereby offering a potentially important alternative material for particulate vaccine design.
Conformational Heterogeneity of RNA Stem-Loop Hairpins Bound to FUS RNA Recognition Motif with Disordered RGG Tail Revealed by Unbiased Molecular Dynamics Simulations
Authors: Pokorná Pavlína , Krepl Miroslav , Campagne Sébastien , Šponer Jiří 
Published: August 2022

AbstractRNA-protein complexes use diverse binding strategies, ranging from structurally well-defined interfaces to completely disordered regions. Experimental characterization of flexible segments is challenging and can be aided by atomistic molecular dynamics (MD) simulations. Here we used extended set of microsecond-scale MD trajectories (400 μs in total) to study two FUS-RNA constructs previously characterized by NMR spectroscopy. The FUS protein contains well-structured RNA Recognition Motif domain followed by presumably disordered RGG tail and bind RNA stem-loop hairpins. Our simulations provide several suggestions complementing the experiments but also reveal major methodological difficulties in studies of such complex RNA-protein interfaces. Despite efforts to stabilize the binding via system-specific force-field adjustments, we have observed progressive distortions of the RNA-protein interface inconsistent with experimental data, as in detail documented. We further propose that the dynamics is so rich that its converged description would not be achievable even upon stabilizing the system. Still, after careful analysis of the trajectories, we have made several suggestions regarding the binding. We identify substates in the RNA loops which can explain the NOE data. The RGG tail localized in the minor groove remains disordered, sampling countless transient interactions with the RNA. There are long-range couplings among the different elements contributing to the recognition, which can lead to allosteric communication throughout the system. Overall, the RNA-FUS systems form dynamical ensembles that cannot be fully represented by single static structures. Thus, albeit imperfect, MD simulations represent a viable tool to investigate them.
Estimating sequence diversity of prion protein gene (PRNP) in Portuguese populations of two cervid species: red deer and fallow deer
Authors: Pereira Jorge C. , Gonçalves-Anjo Nuno , Orge Leonor , Pires Maria A. , Rocha Sara , Figueira Luís , Matos Ana C. , Silva João , Mendonça Paula , Carvalho Paulo , Tavares Paula , Lima Carla , Alves Anabela , Esteves Alexandra , Pinto Maria L. , Pires Isabel , Gama Adelina , Sargo Roberto , Silva Filipe , Seixas Fernanda , Vieira-Pinto Madalena , Bastos Estela 
Published: August 2022

AbstractAmong the transmissible spongiform encephalopathies (TSEs), chronic wasting disease (CWD) in cervids is now a rising concern in wildlife within Europe, after the detection of the first case in Norway in 2016, in a wild reindeer and until June 2022 a total of 34 cases were described in Norway, Sweden and Finland. The definite diagnosis is postmortem, performed in target areas of the brain and lymph nodes. Samples are first screened using a rapid test and, if positive, confirmed by immunohistochemistry and Western immunoblotting. The study of the genetics of the prion protein gene, PRNP, has been proved to be a valuable tool for determining the relative susceptibility to TSEs. In the present study, the exon 3 of PRNP gene of 143 samples from red deer (Cervus elaphus) and fallow deer (Dama dama) of Portugal was analyzed. Three single nucleotide polymorphisms (SNPs) were found in red deer – codon A136A, codon T98A, codon Q226E – and no sequence variation was detected in fallow deer. The low genetic diversity found in our samples is compatible with previous studies in Europe. The comparison with results from North America, suggests that the free-ranging deer from our study may present susceptibility to CWD, although lack of experimental data and the necessity of extensive survey are necessary to evaluate these populations.
Multimodal Assessment of Non-Alcoholic Fatty Liver Disease with Transmission-Reflection Optoacoustic Ultrasound
Authors: Lafci Berkan , Hadjihambi Anna , Konstantinou Christos , Herraiz Joaquin L. , Pellerin Luc , Burton Neal C. , Deán-Ben Xosé Luís , Razansky Daniel 
Published: August 2022

AbstractNon-alcoholic fatty liver disease (NAFLD) is an umbrella term referring to a group of conditions associated to fat deposition and damage of liver tissue. Early detection of fat accumulation is essential to avoid progression of NAFLD to serious pathological stages such as liver cirrhosis and hepatocellular carcinoma. We exploited the unique capabilities of transmission-reflection optoacoustic ultrasound (TROPUS), which combines the advantages of optical and acoustic contrasts, for an early-stage multi-parametric assessment of NAFLD in mice. The multispectral optoacoustic imaging allowed for spectroscopic differentiation of lipid content, as well as the bio-distributions of oxygenated and deoxygenated hemoglobin in liver tissues in vivo. The pulse-echo (reflection) ultrasound (US) imaging further provided a valuable anatomical reference whilst transmission US facilitated the mapping of speed of sound changes in lipid-rich regions, which was consistent with the presence of macrovesicular hepatic steatosis in the NAFLD livers examined with ex vivo histological staining. The proposed multimodal approach facilitates quantification of liver abnormalities at early stages using a variety of optical and acoustic contrasts, laying the ground for translating the TROPUS approach toward diagnosis and monitoring NAFLD in patients.
Regulation of Macrophage IFNγ-Stimulated Gene Expression by the Transcriptional Coregulator CITED1
Authors: Subramani Aarthi , Hite Maria E. L. , Kondee Hursha , Millican Grace E. , McClelland Erin E. , Seipelt-Thiemann Rebecca L. , Nelson David E. 
Published: August 2022

AbstractMacrophages are highly dynamic innate immune cells that adopt temporary phenotypes, known as polarization states, in response to changing environmental signals to combat microbial infection and contribute to the maintenance of tissue homeostasis. During the early stages of an infection, exposure to interferon-gamma (IFNγ) and microbial ligands induce M1 polarization, a heightened proinflammatory anti-microbial state, by regulating the expression of interferon stimulated genes (ISGs). While this response must be sufficiently vigorous to ensure the successful clearance of invading pathogens, it must also be spatially and temporally restricted to prevent uncontrolled inflammation that could result in tissue damage and disease. This is controlled by a variety of cell-extrinsic and -intrinsic mechanisms, including the expression of CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2), a transcriptional coregulator that limits IFNγ-stimulated proinflammatory gene expression by inhibiting STAT1- and IRF1-regulated ISGs. In this study, we show that CITED1, another member of the CITED family of proteins, is itself an ISG and is expressed in a STAT1-dependent manner, and that IFNγ stimulates the nuclear accumulation of fluorescently tagged CITED1 proteins. In contrast to CITED2, ectopic expression of CITED1 enhanced the expression of a subset of ISGs, includingCcl2, Ifit3b, Isg15, andOas2. This effect was reversed in aCited1null cell line produced by CRISPR-based genomic editing. Collectively, these data show that CITED1 helps to maintain proinflammatory gene expression during periods of prolonged IFNγ exposure and suggests a distinct and antagonistic relationship between CITED proteins in the regulation of macrophage inflammatory function.
Systematic transcriptomic analysis and temporal modelling of the senescent human fibroblast
Authors: Scanlan R-L. , Pease L. , O’Keefe H. , Martinez-Guimerá A. , Shanley D , Wordsworth J 
Published: August 2022

AbstractCellular senescence is a diverse phenotype characterised by permanent cell cycle arrest and an inflammatory senescence associated secretory phenotype (SASP). Typically, senescent cells are removed by the immune system. This process becomes dysregulated with age and senescent cells accumulate leading to chronic inflammatory signalling. Identifying senescent cells is challenging due to the heterogeneity of senescence, and senotherapy often requires a combinatorial approach. Here we have taken an integrative approach to investigate senescence development at the transcriptomic and protein level. We systematically collected 119 transcriptomic datasets related to human fibroblasts, forming an online database describing the relevant study variables which users can filter to select variables and genes of interest. Our own analysis of the database identified 28 genes significantly up- or downregulated across four senescence types (DNA-damage induced senescence (DDIS), oncogene-induced senescence (OIS), replicative senescence, and bystander induced senescence); 14 genes consistently downregulated, 10 genes consistently upregulated and 4 genes regulation dependent on senescence type. We also found gene expression patterns of conventional senescence markers were highly specific and reliable for different senescence inducers, cell lines, and timepoints. Conclusions of existing studies based on single datasets were supported such as differences in p53 and inflammatory signals between DDIS and OIS. However, contrary to some early observations, both p16 and p21 mRNA levels appeared to rise quickly, depending on senescence type, and persist for at least 8-11 days. Additionally, little evidence was found to support an initial TGF-β-centric SASP. To support our transcriptomic analysis, we computationally modelled temporal protein changes of core senescence proteins in DDIS and OIS, as well as performed knockdown interventions. We conclude that while universal biomarkers of senescence are difficult to identify, conventional senescence markers follow predictable profiles and construction of a workflow for studying senescence could lead to more reproducible data and understanding of senescence heterogeneity.
Alleviating cell lysate-induced inhibition to enable RT-PCR from single cells in picoliter-volume double emulsion droplets
Authors: Khariton Margarita , McClune Conor J. , Brower Kara K. , Klemm Sandy , Sattely Elizabeth S. , Fordyce Polly M. , Wang Bo 
Published: August 2022

AbstractMicrofluidic droplet assays enable single-cell PCR and sequencing assays at unprecedented scale, with most methods encapsulating cells within nanoliter sized single emulsion droplets (water-in-oil). Encapsulating cells within picoliter double emulsion (DE) (water-in-oil-in-water) droplets allows sorting on commercially available FACS machines, making it possible to isolate single cells based on phenotypes of interest for downstream sequencing and PCR analyses. However, DE droplets must be within the range of large cells (<20 pl) for sorting on standard cytometers, posing challenges for molecular biology as prior reports suggest that reverse transcription (RT) and PCR amplification cannot proceed efficiently at volumes below 1 nL due to cell lysate-induced inhibition. To overcome this limitation, we used a plate-based RT-PCR assay designed to mimic reactions in picoliter droplets to systematically quantify and ameliorate the inhibition. We find that RT-PCR is blocked by lysate-induced cleavage of nucleic acid probes and primers, but that this cleavage can be efficiently alleviated through heat lysis that simultaneously inactivates inhibitory lysate components. We further show that the magnitude of RT-PCR inhibition depends strongly on cell type, but that RT-PCR can proceed in low-picoscale reaction volumes for most cell lines tested. Finally, we demonstrate one-step RT-PCR from single cells in 20 pL double emulsion droplets with fluorescence detectable via FACS. These results open up exciting new avenues for improving picoscale droplet RT-PCR reactions and expanding microfluidic droplet based single-cell analysis technologies.
Patterns of NFkB activation resulting from damage, reactive microglia, cytokines, and growth factors in the mouse retina
Authors: Palazzo Isabella , Kelly Lisa , Koenig Lindsay , Fischer Andy J. 
Published: August 2022

AbstractMüller glia are a cellular source for neuronal regeneration in vertebrate retinas. However, the capacity for retinal regeneration varies widely across species. Understanding the mechanisms that regulate the reprogramming of Müller glia into progenitor cells is key to reversing the loss of vision that occurs with retinal diseases. In the mammalian retina, NFκB signaling promotes glial reactivity and represses the reprogramming of Müller glia into progenitor cells. Here we investigate different cytokines, growth factors, cell signaling pathways, and damage paradigms that influence NFκB-signaling in the mouse retina. We find that exogenous TNF and IL1β potently activate NFκB-signaling in Müller glia in undamaged retinas, and this activation is independent of microglia. By comparison, TLR1/2 agonist indirectly activates NFκB-signaling in Müller glia, and this activation depends on the presence of microglia as Tlr2 is predominantly expressed by microglia, but not other types of retinal cells. Exogenous FGF2 did not activate NFκB-signaling, whereas CNTF, Osteopontin, WNT4, or inhibition of GSK3β activated NFκB in Müller glia in the absence of neuronal damage. By comparison, dexamethasone, a glucocorticoid agonist, suppressed NFκB-signaling in Müller glia in damaged retinas, in addition to reducing numbers of dying cells and the accumulation of reactive microglia. Although NMDA-induced retinal damage activated NFκB in Müller glia, optic nerve crush had no effect on NFκB activation within the retina, whereas glial cells within the optic nerve were responsive. We conclude that the NFκB pathway is activated in retinal Müller glia in response to many different cell signaling pathways, and activation often depends on signals produced by reactive microglia.