Miracle-dz/UniFAR-FTUs huggingface dataset:
Silencing of PARP2 Blocks Autophagic Degradation

Poly(ADP-Ribose) polymerases (PARPs) are enzymes that metabolize NAD+. PARP1 and PARP10 were previously implicated in the regulation of autophagy. Here we showed that cytosolic electron-dense particles appear in the cytoplasm of C2C12 myoblasts in which PARP2 is silenced by shRNA. The cytosolic electron-dense bodies resemble autophagic vesicles and, in line with that, we observed an increased number of LC3-positive and Lysotracker-stained vesicles. Silencing of PARP2 did not influence the maximal number of LC3-positive vesicles seen upon chloroquine treatment or serum starvation, suggesting that the absence of PARP2 inhibits autophagic breakdown. Silencing of PARP2 inhibited the activity of AMP-activated kinase (AMPK) and the mammalian target of rapamycin complex 2 (mTORC2). Treatment of PARP2-silenced C2C12 cells with AICAR, an AMPK activator, nicotinamide-riboside (an NAD+ precursor), or EX-527 (a SIRT1 inhibitor) decreased the number of LC3-positive vesicles cells to similar levels as in control (scPARP2) cells, suggesting that these pathways inhibit autophagic flux upon PARP2 silencing. We observed a similar increase in the number of LC3 vesicles in primary PARP2 knockout murine embryonic fibroblasts. We provided evidence that the enzymatic activity of PARP2 is important in regulating autophagy. Finally, we showed that the silencing of PARP2 induces myoblast differentiation. Taken together, PARP2 is a positive regulator of autophagic breakdown in mammalian transformed cells and its absence blocks the progression of autophagy.
Opposing Changes in the Functional Architecture of Large-Scale Networks in Bipolar Mania and Depression.

OBJECTIVE Manic and depressive phases of bipolar disorder (BD) show opposite symptoms in psychomotor, thought, and affective dimensions. Neuronally, these may depend on distinct patterns of alterations in the functional architecture of brain intrinsic activity. Therefore, the study aimed to characterize the spatial and temporal changes of resting-state activity in mania and depression, by investigating the regional homogeneity (ReHo) and degree of centrality (DC), in different frequency bands. METHODS Using resting-state functional magnetic resonance imaging (fMRI), voxel-wise ReHo and DC were calculated-in the standard frequency band (SFB: 0.01-0.10 Hz), as well as in Slow5 (0.01-0.027 Hz) and Slow4 (0.027-0.073 Hz)-and compared between manic (n = 36), depressed (n = 43), euthymic (n = 29) patients, and healthy controls (n = 112). Finally, clinical correlations were investigated. RESULTS Mania was mainly characterized by decreased ReHo and DC in Slow4 in the medial prefrontal cortex (as part of the default-mode network [DMN]), which in turn correlated with manic symptomatology. Conversely, depression was mainly characterized by decreased ReHo in SFB in the primary sensory-motor cortex (as part of the sensorimotor network [SMN]), which in turn correlated with depressive symptomatology. CONCLUSIONS Our data show a functional reconfiguration of the spatiotemporal structure of intrinsic brain activity to occur in BD. Mania might be characterized by a predominance of sensorimotor over associative networks, possibly driven by a deficit of the DMN (reflecting in internal thought deficit). Conversely, depression might be characterized by a predominance of associative over sensorimotor networks, possibly driven by a deficit of the SMN (reflecting in psychomotor inhibition).
How nasopharyngeal pneumococcal carriage evolved during and after a PCV13-to-PCV10 vaccination programme switch in Belgium, 2016 to 2018

Background The current carriage study was set up to reinforce surveillance during/after the PCV13-to-PCVC10 switch in Belgium. Aim This observational study monitored carriage of Streptococcus pneumoniae (Sp) serotypes, particularly those no longer covered (3, 6A, 19A), as well as Haemophilus influenzae (Hi), because PCV10 contains the non-typeable Hi protein D. Methods A total of 2,615 nasopharyngeal swabs from children (6–30 months old) attending day care were collected in three periods over 2016–2018. Children’s demographic and clinical characteristics and vaccination status were obtained through a questionnaire. Sp and Hi were identified by culture and PCR. Pneumococcal strains were tested for antimicrobial (non-)susceptibility by disc diffusion and serotyped by Quellung-reaction (Quellung-reaction and PCR for serotypes 3, 6A, 19A). Results The carriage prevalence of Sp (> 75%) remained stable over the successive periods but that of Hi increased (87.4%, 664 Hi-carriers/760 in 2016 vs 93.9%, 895/953 in 2017–2018). The proportion of non-PCV13 vaccine serotypes decreased (94.6%, 438 isolates/463 in 2016 vs 89.7%, 599/668 in 2017–2018) while that of PCV13-non-PCV10 vaccine serotypes (3 + 6A + 19A) increased (0.9%, 4 isolates/463 in 2016 vs 7.8%, 52/668 in 2017–2018), with serotype 19A most frequently identified (87.9%, 58/66 isolates). Non-susceptibility of pneumococci against any of the tested antibiotics was stable over the study period (> 44%). Conclusions During and after the PCV13-to-PCV10 vaccine switch, the proportion of non-PCV13 serotypes decreased, mainly due to a serotype 19A carriage prevalence increase. These results complement invasive pneumococcal disease surveillance data, providing further basis for pneumococcal vaccination programme policy making.
#Climatechange vs. #Globalwarming: Characterizing Two Competing Climate Discourses on Twitter with Semantic Network and Temporal Analyses

Distinct perceptions of the global climate is one of the factors preventing society from achieving consensus or taking collaborative actions on this issue. The public has not even reached an agreement on the naming of the global concern, showing preference for either “climate change” or “global warming”, and few previous studies have addressed these two competing discourses resulting from distinct climate concerns by differently linking numerous climate concepts. Based on the 6,662,478 tweets containing #climatechange or #globalwarming generated between 1 January 2009 and 31 December 2018, we constructed the semantic networks of the two discourses and examined their evolution over the decade. The findings indicate that climate change demonstrated a more scientific perspective and showed an attempt to condense climate discussions rather than diffuse the topic by frequently addressing sub-topics simultaneously. Global warming triggered more political responses and showed a greater connection with phenomena. Temporal analysis suggests that traditional political discussions were gradually fading in both discourses but more recently started to revive in the form of discourse alliance in the climate change discourse. The associations between global warming and weather abnormalitiessuddenly strengthened around 2012. Climate change is becoming more dominant than global warming in public discussions. Although two discourses have shown more similarities in the rank order of important climate concepts, apparent disagreements continue about how these concepts are associated. These findings lay the groundwork for researchers and communicators to narrow the discrepancy between diverse climate perceptions.
Social Support and Women’s Reproductive Decision Making: Testing Emergent Fit of “Optimizing Support for the Preservation of Self”

Despite the strong association between social support and positive health outcomes, little is understood about its role in women’s reproductive decision making. Developing insight into how women perceive, mobilize, and experience social support is critical to understanding their lived experiences of reproductive decision making and to implementing appropriate supporting structures to help women realize their reproductive choices. In this study, emergent fit with existing inductive research on the phenomenon of reproductive support is discussed. The existing theory of “optimizing social support for the preservation of self” and its underpinning categorical framework is maintained, but the extant categorical themes were all nuanced, refined, replaced, or removed to better reflect the support phenomenon among a wider cohort of women. This article builds on the existing knowledge base by producing a substantive theory of “optimizing social support for the preservation of self” with wider applicability.
Role of Polymer Micelles in the Delivery of Photodynamic Therapy Agent to Liposomes and Cells

The use of nanocarriers for hydrophobic photosensitizers, in the context of photodynamic therapy (PDT) to improve pharmacokinetics and bio-distribution, is well-established. However, the mechanisms at play in the internalization of nanocarriers are not well-elucidated, despite its importance in nanocarrier design. In this study, we focus on the mechanisms involved in copolymer poly(ethylene oxide)-block-poly(ε-caprolactone) PEO-PCL and poly(ethylene oxide)-block-poly styrene PEO-PS micelles - membrane interactions through complementary physico-chemical studies on biomimetic membranes, and biological experiments on two-dimensional (2D) and three-dimensional (3D) cell cultures. Förster Resonance Energy Transfer measurements on fluorescently-labelled lipid vesicles, and flow cytometry on two cancerous cell lines enabled the evaluation in the uptake of a photosensitizer, Pheophorbide a (Pheo), and copolymer chains towards model membranes, and cells, respectively. The effects of calibrated light illumination for PDT treatment on lipid vesicle membranes, i.e., leakage and formation of oxidized lipids, and cell viability, were assessed. No significant differences were observed between the ability of PEO-PCL and PEO-PS micelles in delivering Pheo to model membranes, but Pheo was found in higher concentrations in cells in the case of PEO-PCL. These higher Pheo concentrations did not correspond to better performances in PDT treatment. We demonstrated that there are subtle differences in PEO-PCL and PEO-PS micelles for the delivery of Pheo.
The Effects of Caffeine Ingestion on Measures of Rowing Performance: A Systematic Review and Meta-Analysis

The purpose of this paper was to conduct a systematic review and a meta-analysis of studies examining the acute effects of caffeine ingestion on measures of rowing performance. Crossover and placebo-controlled experiments that investigated the effects of caffeine ingestion on measures of rowing performance were included. The PEDro checklist was used to assess the methodological quality of the included studies. Seven studies of good and excellent methodological quality were included. None of the included studies examined on-water rowing. The majority of studies that were included in the meta-analysis used a 2000m rowing distance with only one using 1000m distance. Results of the main meta-analysis indicated that caffeine enhances performance on a rowing ergometer compared to placebo with a mean difference of −4.1 s (95% confidence interval (CI): −6.4, −1.8 s). These values remained consistent in the analysis in which the study that used a 1000m distance was excluded (mean difference: −4.3 s; 95% CI: −6.9, −1.8 s). We also found a significant increase in mean power (mean difference: 5.7 W; 95% CI: 2.1, 9.3 W) and minute ventilation (mean difference: 3.4 L/min; 95% CI: 1.7, 5.1 L/min) following caffeine ingestion. No significant differences between caffeine and placebo were found for the rating of perceived exertion, oxygen consumption, respiratory exchange ratio, and heart rate. This meta-analysis found that acute caffeine ingestion improves 2000m rowing ergometer performance by ~4 s. Our results support the use of caffeine pre-exercise as an ergogenic aid for rowing performance.
Role for ribosome-associated quality control in sampling proteins for MHC class I-mediated antigen presentation

Significance Pathogens and tumors are detected by the immune system through the display of intracellular peptides on MHC-I complexes. These peptides are generated by the ubiquitin−proteasome system preferentially from newly synthesized polypeptides. Here we show that the ribosome-associated quality control (RQC) pathway, responsible for proteasomal degradation of polypeptide chains that stall during translation, mediates efficient antigen presentation of model proteins independent of their intrinsic folding properties. Immunopeptidome characterization of RQC-deficient cells shows that RQC contributes to the presentation of a wide variety of proteins, including proteins that may otherwise evade presentation due to efficient folding. By identifying endogenous substrates of the RQC pathway in human cells, our results also enable the analysis of common principles causing ribosome stalling under physiological conditions. Mammalian cells present a fingerprint of their proteome to the adaptive immune system through the display of endogenous peptides on MHC-I complexes. MHC-I−bound peptides originate from protein degradation by the proteasome, suggesting that stably folded, long-lived proteins could evade monitoring. Here, we investigate the role in antigen presentation of the ribosome-associated quality control (RQC) pathway for the degradation of nascent polypeptides that are encoded by defective messenger RNAs and undergo stalling at the ribosome during translation. We find that degradation of model proteins by RQC results in efficient MHC-I presentation, independent of their intrinsic folding properties. Quantitative profiling of MHC-I peptides in wild-type and RQC-deficient cells by mass spectrometry showed that RQC substantially contributes to the composition of the immunopeptidome. Our results also identify endogenous substrates of the RQC pathway in human cells and provide insight into common principles causing ribosome stalling under physiological conditions.
Diet quality over time is associated with better development in rural Nepali children

Abstract Developmental delays affect between 150 and 200 million children <5 years of age worldwide. Outside of diet supplement studies, relatively little is known about the relationships between diet quality and developmental status in resource‐poor settings. We examined associations between different aspects of dietary quality (dietary diversity score [DDS] and animal‐source food [ASF] consumption) and child development (assessed using the Ages and Stages Questionnaire‐3 [ASQ‐3]) among children whose families were enrolled in a community development intervention trial (implemented by Heifer Nepal) in western Nepal. Two sets of analyses were performed: (a) cross‐sectional Sample (N = 629) seen at the endline survey and (b) longitudinal sample (N = 269) with complete dietary records (six surveys over 48 months). In both samples, child development was significantly related to household wealth, maternal education, and especially home environmental quality. In the cross‐sectional sample, greater consumption of eggs (adjusted odds ratio [aOR] 0.80, p = .04) or dairy products (aOR 0.95, p = .05) over the previous 7 days significantly reduced odds of low total ASQ score, by logistic regression analysis. In the longitudinal sample, only egg consumption and cumulative DDS and ASF scores were associated with significantly reduced odds of low total ASQ score (aORs 0.59–0.89). In adjusted linear regression analysis, both cumulative DDS (β [CI]: 1.92 [0.4, 3.5]) and ASF scores (2.46 [0.3, 4.7]) were significantly associated with greater continuous total child development. Programmes targeting child development must address home environmental quality as well as long‐term diet quality.
Superficial ingroup love? Collective narcissism predicts ingroup image defense, outgroup prejudice, and lower ingroup loyalty.

We examined the associations between the need for personal control, different types of ingroup commitment, and group-related outcomes: (1) defensive responses to ingroup criticism, (2) ingroup disloyalty, and (3) outgroup attitudes. We assumed that collective narcissism (i.e., a belief in ingroup's greatness which is contingent on external validation and stems from frustrated individual needs) should be concerned with defending the ingroup image and derogating outgroups, but not necessarily with being loyal to the ingroup. Secure ingroup identification (i.e., a confidently held ingroup evaluation, which stems from satisfied needs), in contrast, should predict greater ingroup loyalty and positive outgroup attitudes. We expected these effects to be especially strong once we account for the overlap between collective narcissism and group-level self-investment - a key component of ingroup identification. In a nationally representative sample of Polish adults (n = 1,007), collective narcissism (net of group-level self-investment) mediated between low personal control and ingroup image defense, lower group loyalty, and less positive outgroup attitudes. Secure ingroup identification (group-level self-investment net of collective narcissism) mediated between high personal control and ingroup loyalty and positive outgroup attitudes. It was not associated with ingroup image defense. Implications for understanding the role of identification in inter- and intra-group relations are discussed.
Innate Immunity: A Common Denominator between Neurodegenerative and Neuropsychiatric Diseases

The intricate relationships between innate immunity and brain diseases raise increased interest across the wide spectrum of neurodegenerative and neuropsychiatric disorders. Barriers, such as the blood–brain barrier, and innate immunity cells such as microglia, astrocytes, macrophages, and mast cells are involved in triggering disease events in these groups, through the action of many different cytokines. Chronic inflammation can lead to dysfunctions in large-scale brain networks. Neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and frontotemporal dementia, are associated with a substrate of dysregulated immune responses that impair the central nervous system balance. Recent evidence suggests that similar phenomena are involved in psychiatric diseases, such as depression, schizophrenia, autism spectrum disorders, and post-traumatic stress disorder. The present review summarizes and discusses the main evidence linking the innate immunological response in neurodegenerative and psychiatric diseases, thus providing insights into how the responses of innate immunity represent a common denominator between diseases belonging to the neurological and psychiatric sphere. Improved knowledge of such immunological aspects could provide the framework for the future development of new diagnostic and therapeutic approaches.
Early Last Interglacial ocean warming drove substantial ice mass loss from Antarctica

Significance Fifty years ago, it was speculated that the marine-based West Antarctic Ice Sheet is vulnerable to warming and may have melted in the past. Testing this hypothesis has proved challenging due to the difficulty of developing in situ records of ice sheet and environmental change spanning warm periods. We present a multiproxy record that implies loss of the West Antarctic Ice Sheet during the Last Interglacial (129,000 to 116,000 y ago), associated with ocean warming and the release of greenhouse gas methane from marine sediments. Our ice sheet modeling predicts that Antarctica may have contributed several meters to global sea level at this time, suggesting that this ice sheet lies close to a “tipping point” under projected warming. The future response of the Antarctic ice sheet to rising temperatures remains highly uncertain. A useful period for assessing the sensitivity of Antarctica to warming is the Last Interglacial (LIG) (129 to 116 ky), which experienced warmer polar temperatures and higher global mean sea level (GMSL) (+6 to 9 m) relative to present day. LIG sea level cannot be fully explained by Greenland Ice Sheet melt (∼2 m), ocean thermal expansion, and melting mountain glaciers (∼1 m), suggesting substantial Antarctic mass loss was initiated by warming of Southern Ocean waters, resulting from a weakening Atlantic meridional overturning circulation in response to North Atlantic surface freshening. Here, we report a blue-ice record of ice sheet and environmental change from the Weddell Sea Embayment at the periphery of the marine-based West Antarctic Ice Sheet (WAIS), which is underlain by major methane hydrate reserves. Constrained by a widespread volcanic horizon and supported by ancient microbial DNA analyses, we provide evidence for substantial mass loss across the Weddell Sea Embayment during the LIG, most likely driven by ocean warming and associated with destabilization of subglacial hydrates. Ice sheet modeling supports this interpretation and suggests that millennial-scale warming of the Southern Ocean could have triggered a multimeter rise in global sea levels. Our data indicate that Antarctica is highly vulnerable to projected increases in ocean temperatures and may drive ice–climate feedbacks that further amplify warming.
Shifts in coralline algae, macroalgae, and coral juveniles in the Great Barrier Reef associated with present‐day ocean acidification

Seawater acidification from increasing CO2 is often enhanced in coastal waters due to elevated nutrients and sedimentation. Our understanding of the effects of ocean and coastal acidification on present‐day ecosystems is limited. Here we use data from three independent large‐scale reef monitoring programs to assess coral reef responses associated with changes in mean aragonite saturation state (Ωar) in the Great Barrier Reef World Heritage Area (GBR). Spatial declines in mean Ωar are associated with monotonic declines in crustose coralline algae (up to 3.1‐fold) and coral juvenile densities (1.3‐fold), while non‐calcifying macroalgae greatly increase (up to 3.2‐fold), additionally to their natural changes across and along the GBR. These three key groups of organisms are important proxies for coral reef health. Our data suggest a tipping point at Ωar 3.5–3.6 for these coral reef health indicators. Suspended sediments acted as an additive stressor. The latter suggests that effective water quality management to reduce suspended sediments might locally and temporarily reduce the pressure from ocean acidification on these organisms.
Virulence properties and antimicrobial resistance of Pseudomonas aeruginosa isolated from cave waters at Roraima Tepui, Guayana Highlands

Pseudomonas aeruginosa is a prominent member of emerging waterborne pathogens. The environmental reservoirs of multi‐resistant phenotypes and other virulence factors in this bacterium are poorly understood. Our study aimed to determine the virulence properties of P. aeruginosa isolated from Roraima Sur Cave (RSC) waters at Guayana Highlands. Based on the best identification at species level by biochemical tests, 16S rRNA sequencing and phylogenetic inferences, one RSC isolate named LG11 was characterized for virulence properties in comparison with P. aeruginosa reference strains. PCR amplification of alginate, elastase, exoenzyme S, exotoxin A, neuraminidase and Quorum‐Sensing genes showed a high virulence potential in LG11. This isolate demonstrated multi‐resistance to ceftriaxone, tigecycline and imipenem. Pyocyanin production was greater in LG11 (0·478 µg ml−1) than the strain ATCC 10145 (0·316 µg ml−1), but the highest pigment concentration (2·140 µg ml−1) was displayed by the clinical strain CVCM 937 (P = 0·000175). Pronounced biomass production on granite and glass (P < 0·05) and well‐developed biofilms indicated the ability of P. aeruginosa from RSC to colonize surfaces found in human and healthcare environments. These data suggest that waters from pristine ecosystems such as RSC could be reservoirs of this opportunistic bacterium carrying important virulence properties with potential epidemiological implications.