bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteins associated with future suicide attempts in bipolar disorder: A large-scale biomarker discovery study
Authors: Sandberg Johan V. , Hansson Caroline , Göteson Andreas , Joas Erik , Jakobsson Joel , Pålsson Erik , Landén Mikael 
Published: June 2022

AbstractSuicide is a major cause of death worldwide. Several biological systems have been implicated in suicidal behavior but studies of candidate biomarkers have failed to produce clinically relevant biomarkers for suicide prediction. The objective of the present study was to identify novel candidate biomarkers for suicidal behavior. We used a nested case-control study design where a large cohort of patients with bipolar disorder (N = 5 110) were followed up to 8 years after blood sampling. We included patients that attempted suicide during follow-up (N = 348) and matched bipolar disorder patients from the same cohort who did not attempt suicide during the study period (N = 348) and analyzed a total of 92 proteins with a neuro exploratory multiplex panel. Using a multivariate classification algorithm devised to minimize bias in variable selection, we identified a parsimonious set of proteins that best discriminated bipolar disorder patients with and without prospective suicide attempts. The algorithm selected 16 proteins for the minimal-optimal classification model, which outperformed 500 models with permuted outcome (p = 0.0004) but had low sensitivity (53%) and specificity (64%). The candidate proteins were then entered in separate logistic regression models to calculate protein-specific associations with prospective suicide attempts. In individual analyses, three of these proteins were significantly associated with prospective suicide attempt (SCGB1A1, ANXA10, and CETN2). Most of the candidate proteins are novel to suicide research.
RING finger 138 deregulation distorts NF-кB signaling and facilities colitis switch to aggressive malignancy
Authors: Lu Yalan , Huang Rong , Ying Jianming , Li Xingchen , Jiao Tao , Guo Lei , Zhou Haitao , Wang Han , Tuersuntuoheti Amannisa , Liu Jianmei , Chen Qichen , Wang Yanhong , Su Luying , Guo Changyuan , Xu Fu , Wang Ziyi , Lu Yan , Li Kai , Liang Junbo , Huang Zhen , Chen Xiao , Yao Jinjie , Hu Hanjie , Cheng Xiaowen , Wan Yufeng , Chen Xinyan , Zhang Ning , Miao Shiying , Cai Jianqiang , Wang Linfang , Liu Changzheng , Song Wei , Zhao Hong 
Published: June 2022

AbstractProlonged activation of nuclear factor (NF)-кB signaling significantly contributes to the development of colorectal cancer (CRC). New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction. Here, we discovered the critical role of RING finger 138 (RNF138) in CRC tumorigenesis through regulating the NF-кB signaling, which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response. RNF138−/− mice were hyper-susceptible to the switch from colitis to aggressive malignancy, which coincided with sustained aberrant NF-кB signaling in the colonic cells. Furthermore, RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein (NIBP) to the cytoplasm, which requires the ubiquitin interaction motif (UIM) domain. More importantly, we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings, raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling. Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients, we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth. Overall, our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression, and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation.
MNK2 deficiency potentiates β-cell regeneration via translational regulation
Authors: Karampelias Christos , Watt Kathleen , Mattsson Charlotte L. , Ruiz Ángel Fernández , Rezanejad Habib , Mi Jiarui , Liu Xiaojing , Chu Lianhe , Locasale Jason W. , Korbutt Gregory S. , Rovira Meritxell , Larsson Ola , Andersson Olov 
Published: June 2022

AbstractRegenerating pancreatic β-cells is a potential curative approach for diabetes. We previously identified the small molecule CID661578 as a potent inducer of β-cell regeneration, but its target and mechanism of action have remained unknown. We now screened 257 million yeast clones and determined that CID661578 targets MAP kinase-interacting serine/threonine kinase 2 (MNK2), an interaction we genetically validated in vivo. CID661578 increased β-cell neogenesis from ductal cells in zebrafish, neonatal pig islet aggregates and human pancreatic ductal organoids. Mechanistically, we found that CID661578 boosts protein synthesis and regeneration by blocking MNK2 from binding eIF4G in the translation initiation complex at the mRNA cap. Unexpectedly, this blocking activity augmented eIF4E phosphorylation depending on MNK1 and bolstered the interaction between eIF4E and eIF4G, which is necessary for both hypertranslation and β-cell regeneration. Taken together, our findings demonstrate a targetable role of MNK2-controlled translation in β-cell regeneration, a role that warrants further investigation in diabetes.
Differential regulation of degradation and immune pathways underlies adaptation of the ectosymbiotic nematode Laxus oneistus to oxic-anoxic interfaces
Authors: Paredes Gabriela F. , Viehboeck Tobias , Markert Stephanie , Mausz Michaela A. , Sato Yui , Liebeke Manuel , König Lena , Bulgheresi Silvia 
Published: June 2022

AbstractEukaryotes may experience oxygen deprivation under both physiological and pathological conditions. Because oxygen shortage leads to a reduction in cellular energy production, all eukaryotes studied so far conserve energy by suppressing their metabolism. However, the molecular physiology of animals that naturally and repeatedly experience anoxia is underexplored. One such animal is the marine nematode Laxus oneistus. It thrives, invariably coated by its sulfur-oxidizing symbiont Candidatus Thiosymbion oneisti, in anoxic sulfidic or hypoxic sand. Here, transcriptomics and proteomics showed that, whether in anoxia or not, L. oneistus mostly expressed genes involved in ubiquitination, energy generation, oxidative stress response, immune response, development, and translation. Importantly, ubiquitination genes were also highly expressed when the nematode was subjected to anoxic sulfidic conditions, together with genes involved in autophagy, detoxification and ribosome biogenesis. We hypothesize that these degradation pathways were induced to recycle damaged cellular components (mitochondria) and misfolded proteins into nutrients. Remarkably, when L. oneistus was subjected to anoxic sulfidic conditions, lectin and mucin genes were also upregulated, potentially to promote the attachment of its thiotrophic symbiont. Furthermore, the nematode appeared to survive oxygen deprivation by using an alternative electron carrier (rhodoquinone) and acceptor (fumarate), to rewire the electron transfer chain. On the other hand, under hypoxia, genes involved in costly processes (e.g., amino acid biosynthesis, development, feeding, mating) were upregulated, together with the worm’s Toll-like innate immunity pathway and several immune effectors (e.g., bactericidal/permeability-increasing proteins, fungicides). In conclusion, we hypothesize that, in anoxic sulfidic sand, L. oneistus upregulates degradation processes, rewires the oxidative phosphorylation and reinforces its coat of bacterial sulfur-oxidizers. In upper sand layers, instead, it appears to produce broad-range antimicrobials and to exploit oxygen for biosynthesis and development.
Insights for crystal mush storage utilizing mafic enclaves from the 2011–12 Cordón Caulle eruption
Authors: Winslow Heather , Ruprecht Philipp , Gonnermann Helge M. , Phelps Patrick R. , Muñoz-Saez Carolina , Delgado Francisco , Pritchard Matthew , Amigo Alvaro 
Published: June 2022

AbstractTwo distinct types of rare crystal-rich mafic enclaves have been identified in the rhyolite lava flow from the 2011–12 Cordón Caulle eruption (Southern Andean Volcanic Zone, SVZ). The majority of mafic enclaves are coarsely crystalline with interlocking olivine-clinopyroxene-plagioclase textures and irregular shaped vesicles filling the crystal framework. These enclaves are interpreted as pieces of crystal-rich magma mush underlying a crystal-poor rhyolitic magma body that has fed recent silicic eruptions at Cordón Caulle. A second type of porphyritic enclaves, with restricted mineral chemistry and spherical vesicles, represents small-volume injections into the rhyolite magma. Both types of enclaves are basaltic end-members (up to 9.3 wt% MgO and 50–53 wt% SiO2) in comparison to enclaves erupted globally. The Cordón Caulle enclaves also have one of the largest compositional gaps on record between the basaltic enclaves and the rhyolite host at 17 wt% SiO2. Interstitial melt in the coarsely-crystalline enclaves is compositionally identical to their rhyolitic host, suggesting that the crystal-poor rhyolite magma was derived directly from the underlying basaltic magma mush through efficient melt extraction. We suggest the 2011–12 rhyolitic eruption was generated from a primitive basaltic crystal-rich mush that short-circuited the typical full range of magmatic differentiation in a single step.
Conditioned taste aversion in the cricket Gryllus bimaculatus
Authors: Lyu Hui , Mizunami Makoto 
Published: June 2022

AbstractConditioned taste aversion (CTA) is a form of classical conditioning in which animals associate the taste of a food with illness caused by toxin contained in the food. CTA in mammals is achieved with a long interval of up to several hours between food ingestion and illness induced by LiCl injection. Insects also exhibit CTA, but not much is known about its features. We investigated whether the cricket Gryllus bimaculatus exhibits CTA when ingestion of a sugar solution is followed by LiCl injection. Crickets that ingested sucrose solution 5–10 min before LiCl injection exhibited reduction of sucrose consumption tested 24 or 48 h after injection compared to that tested 24 h before injection. In contrast, crickets that ingested sucrose solution 5–10 min after LiCl injection or 1 h or 8 h before or after injection did not exhibit reduction of sucrose consumption, indicating that reduction of sucrose consumption by CTA training is pairing-specific. We conclude that CTA in crickets is similar to that in mammals in that one-trial pairing is sufficient to achieve memory retention for days, but it differs in that it is achieved with a relatively short interval (< 1 h) between food ingestion and toxin injection.
Examination of diverse iron-chelating agents for the protection of differentiated PC12 cells against oxidative injury induced by 6-hydroxydopamine and dopamine
Authors: Hašková Pavlína , Applová Lenka , Jansová Hana , Homola Pavel , Franz Katherine J. , Vávrová Kateřina , Roh Jaroslav , Šimůnek Tomáš 
Published: June 2022

AbstractLabile redox-active iron ions have been implicated in various neurodegenerative disorders, including the Parkinson's disease (PD). Iron chelation has been successfully used in clinical practice to manage iron overload in diseases such as thalassemia major; however, the use of conventional iron chelators in pathological states without systemic iron overload remains at the preclinical investigative level and is complicated by the risk of adverse outcomes due to systemic iron depletion. In this study, we examined three clinically-used chelators, namely, desferrioxamine, deferiprone and deferasirox and compared them with experimental agent salicylaldehyde isonicotinoyl hydrazone (SIH) and its boronate-masked prochelator BSIH for protection of differentiated PC12 cells against the toxicity of catecholamines 6-hydroxydopamine and dopamine and their oxidation products. All the assayed chelating agents were able to significantly reduce the catecholamine toxicity in a dose-dependent manner. Whereas hydrophilic chelator desferrioxamine exerted protection only at high and clinically unachievable concentrations, deferiprone and deferasirox significantly reduced the catecholamine neurotoxicity at concentrations that are within their plasma levels following standard dosage. SIH was the most effective iron chelator to protect the cells with the lowest own toxicity of all the assayed conventional chelators. This favorable feature was even more pronounced in prochelator BSIH that does not chelate iron unless its protective group is cleaved in disease-specific oxidative stress conditions. Hence, this study demonstrated that while iron chelation may have general neuroprotective potential against catecholamine auto-oxidation and toxicity, SIH and BSIH represent promising lead molecules and warrant further studies in more complex animal models.
Magnetic order and disorder environments in superantiferromagnetic $$\hbox {NdCu}_{\mathbf{2}}$$ nanoparticles
Authors: Jefremovas E. M. , Svedlindh P. , Damay F. , Alba Venero D. , Michels A. , Blanco J. A. , Fernández Barquín L. 
Published: June 2022

AbstractMagnetic nanoparticles exhibit two different local symmetry environments, one ascribed to the core and one corresponding to the nanoparticle surface. This implies the existence of a dual spin dynamics, leading to the presence of two different magnetic arrangements governed by different correlation lengths. In this work, two ensembles of $$\hbox {NdCu}_{2}$$

NdCu
2

nanoparticles with mean sizes of 18 nm and 13 nm have been produced to unravel the magnetic couplings established among the magnetic moments located within the core and at the nanoparticle surface. To this end, we have combined neutron diffraction measurements, appropriate to investigate magnetically-ordered spin arrangements, with time-dependent macroscopic AC susceptibility measurements to reveal memory and aging effects. The observation of the latter phenomena are indicative of magnetically-frustrated states. The obtained results indicate that, while the $$\hbox {Nd}^{3{+}}$$

Nd

3
+

magnetic moments located within the nanoparticle core keep the bulk antiferromagnetic commensurate structure in the whole magnetic state, the correlations among the surface spins give rise to a collective frustrated spin-glass phase. The interpretation of the magnetic structure of the nanoparticles is complemented by specific-heat measurements, which further support the lack of incommensurability in the nanoparticle state.
Global assessment of spatiotemporal variability of wet, normal and dry conditions using multiscale entropy-based approach
Authors: Sreeparvathy Vijay , Srinivas V. V. 
Published: June 2022

AbstractIn recent decades, human-induced climate change has caused a worldwide increase in the frequency/intensity/duration of extreme events, resulting in enormous disruptions to life and property. Hence, a comprehensive understanding of global-scale spatiotemporal trends and variability of extreme events at different intensity levels (e.g., moderate/severe/extreme) and durations (e.g., short-term/long-term) of normal, dry and wet conditions is essential in predicting/forecasting/mitigating future extreme events. This article analyses these aspects using estimates of a non-stationary standardized precipitation evapotranspiration index corresponding to different accumulation periods for 0.5° resolution CRU grids at globe-scale. Results are analyzed with respect to changes in land-use/landcover and geographic/location indicators (latitude, longitude, elevation) at different time scales (decadal/annual/seasonal/monthly) for each continent. The analysis showed an (i) increasing trend in the frequency/count of both dry and wet conditions and variability of dry conditions, and (ii) contrasting (decreasing) trend in the variability of wet conditions, possibly due to climate change-induced variations in atmospheric circulations. Globally, the highest variability in the wet and dry conditions is found during the Northern hemisphere's winter season. The decadal-scale analysis showed that change in variability in dry and wet conditions has been predominant since the 1930s and 1950s, respectively and is found to be increasing in recent decades.
Waveform changes of laser speckle flowgraphy in the temporal optic nerve head and peripapillary atrophy after trabeculectomy in open-angle glaucoma
Authors: Sasaki Makoto , Higashide Tomomi , Takeshima Satoshi , Takamatsu Yuki , Manbo Yoshimi , Udagawa Sachiko , Sugiyama Kazuhisa 
Published: June 2022

AbstractA prospective study was conducted on 33 eyes of 33 patients with open-angle glaucoma who underwent trabeculectomy to investigate hemodynamic changes in the temporal optic nerve head (ONH) and peripapillary atrophy (PPA) after trabeculectomy. Laser speckle flowgraphy of ONH and PPA was performed at baseline and at 1, 3, and 6 months postoperatively. The waveforms of the mean blur rate in the tissue area (MT) in the temporal ONH, βPPA (with Bruch’s membrane), and γPPA (without Bruch’s membrane) were evaluated. Mean intra-ocular pressure (IOP) decreased from 19.1 ± 0.8 to 8.5–9.6 ± 0.7 mmHg at postoperative visits. The average MT in the βPPA region increased significantly at all postoperative time points, whereas those in the ONH and γPPA regions remained unchanged. The blowout score (BOS) increased significantly, and the resistivity index decreased significantly at all time points in all regions, which was associated with decreased IOP. The current study showed two novel findings: MT increased after trabeculectomy only in βPPA, where the choroid was present. IOP decrease-associated BOS increase occurred postoperatively in all regions, which indicates that IOP reduction may decrease vascular transmural pressure and contribute to stable blood flow uniformly, despite structural differences between the regions.
New site at Olduvai Gorge (AGS, Bed I, 1.84 Mya) widens the range of locations where hominins engaged in butchery
Authors: Stancampiano Lavinia M. , Sistiaga Ainara , del Val David Uribelarrea , Aramendi Julia , Baquedano Enrique , Mabulla Audax , Domínguez-Rodrigo Manuel , Magill Clayton R. 
Published: June 2022

AbstractOutstanding questions about human evolution include systematic connections between critical landscape resources—such as water and food—and how these shaped the competitive and biodiverse environment(s) that our ancestors inhabited. Here, we report fossil n-alkyl lipid biomarkers and their associated δ13C values across a newly discovered Olduvai Gorge site (AGS) dated to 1.84 million years ago, enabling a multiproxy analysis of the distributions of critical local landscape resources across an explicit locus of hominin activity. Our results reveal that AGS was a seasonally waterlogged, largely unvegetated lakeside site situated near an ephemeral freshwater river surrounded by arid-adapted C4 grasses. The sparse vegetation at AGS contrasts with reconstructed (micro)habitats at the other anthropogenic sites at Olduvai Gorge, suggesting that central-provisioning places depended more heavily on water access than vegetation viz. woody plants as is often observed for modern hunter-gatherers. As hominins at AGS performed similar butchering activities as at other Bed I sites, our results suggest they did not need the shelter of trees and thus occupied a competitive position within the predatory guild.
Watching Parkinson’s disease with wrist-based sensors
Authors: Diao James A. , Raza Marium M. , Venkatesh Kaushik P. , Kvedar Joseph C. 
Published: June 2022

AbstractParkinson’s disease (PD) lacks sensitive, objective, and reliable measures for disease progression and response. This presents a challenge for clinical trials given the multifaceted and fluctuating nature of PD symptoms. Innovations in digital health and wearable sensors promise to more precisely measure aspects of patient function and well-being. Beyond research trials, digital biomarkers and clinical outcome assessments may someday support clinician-initiated or closed-loop treatment adjustments. A recent study from Verily Life Sciences presents results for a smartwatch-based motor exam intended to accelerate the development and evaluation of therapies for PD.
Lead removal at trace concentrations from water by inactive yeast cells
Authors: Stathatou Patritsia M. , Athanasiou Christos E. , Tsezos Marios , Goss John W. , Blackburn L. Camron , Tourlomousis Filippos , Mershin Andreas , Sheldon Brian W. , Padture Nitin P. , Darling Eric M. , Gao Huajian , Gershenfeld Neil 
Published: June 2022

AbstractTraces of heavy metals found in water resources, due to mining activities and e-waste discharge, pose a global threat. Conventional treatment processes fail to remove toxic heavy metals, such as lead, from drinking water in a resource-efficient manner when their initial concentrations are low. Here, we show that by using the yeast Saccharomyces cerevisiae we can effectively remove trace lead from water via a rapid mass transfer process, called biosorption, achieving an uptake of up to 12 mg lead per gram of biomass in solutions with initial lead concentrations below 1 part per million. Through spectroscopic analyses, we found that the yeast cell wall plays a crucial role in this process, with its mannoproteins and β-glucans being the key potential lead adsorbents. Furthermore, by employing nanomechanical characterization in the yeast biomass, we discovered that biosorption is linked to an increase in cell wall stiffness. These findings open new opportunities for using environmentally friendly and abundant biomaterials for advanced water treatment targeting emerging contaminants.
G-protein-coupled receptor kinase 4 causes renal angiotensin II type 2 receptor dysfunction by increasing its phosphorylation
Authors: Zhang Fuwei , Lei Lifu , Huang Juan , Wang Weiwei , Su Qian , Yan Hongjia , Chen Caiyu , Zheng Shuo , Ren Hongmei , Li Zhuxin , Jose Pedro A. , Hu Yijie , Si Liangyi , Zeng Chunyu , Yang Jian 
Published: June 2022

Abstract
Activation of the angiotensin II type 2 receptor (AT2R) induces diuresis and natriuresis. Increased expression or/and activity of G-protein-coupled receptor kinase 4 (GRK4) or genetic variants (e.g., GRK4γ142V) cause sodium retention and hypertension. Whether GRK4 plays a role in the regulation of AT2R in the kidney remains unknown. In the present study, we found that spontaneously hypertensive rats (SHRs) had increased AT2R phosphorylation and impaired AT2R-mediated diuretic and natriuretic effects, as compared with normotensive Wistar-Kyoto (WKY) rats. The regulation by GRK4 of renal AT2R phosphorylation and function was studied in human (h) GRK4γ transgenic mice. hGRK4γ142V transgenic mice had increased renal AT2R phosphorylation and impaired AT2R-mediated natriuresis, relative to hGRK4γ wild-type (WT) littermates. These were confirmed in vitro; AT2R phosphorylation was increased and AT2R-mediated inhibition of Na+-K+-ATPase activity was decreased in hGRK4γ142V, relative to hGRK4γ WT-transfected renal proximal tubule (RPT) cells. There was a direct physical interaction between renal GRK4 and AT2R that was increased in SHRs, relative to WKY rats. Ultrasound-targeted microbubble destruction of renal GRK4 decreased the renal AT2R phosphorylation and restored the impaired AT2R-mediated diuresis and natriuresis in SHRs. In vitro studies showed that GRK4 siRNA reduced AT2R phosphorylation and reversed the impaired AT2R-mediated inhibition of Na+-K+-ATPase activity in SHR RPT cells. Our present study shows that GRK4, at least in part, impairs renal AT2R-mediated diuresis and natriuresis by increasing its phosphorylation; inhibition of GRK4 expression and/or activity may be a potential strategy to improve the renal function of AT2R.