bluuebunny/crossref_metadata_2025 huggingface dataset:
Chlorine redox chemistry is widespread in microbiology
Authors: Barnum Tyler P , Coates John D
Published: October 2022

Chlorine is abundant in cells and biomolecules, yet the biology of chlorine oxidation and reduction is poorly understood. Some bacteria encode the enzyme chlorite dismutase (Cld), which detoxifies chlorite (ClO2−) by converting it to chloride (Cl−) and molecular oxygen (O2). Cld is highly specific for chlorite and aside from low hydrogen peroxide activity has no known alternative substrate. Here, we reasoned that because chlorite is an intermediate oxidation state of chlorine, Cld can be used as a biomarker for oxidized chlorine species. Cld was abundant in metagenomes from various terrestrial habitats. About 5% of bacterial and archaeal genera contain a microorganism encoding Cld in its genome, and within some genera Cld is highly conserved. Cld has been subjected to extensive horizontal gene transfer. Genes found to have a genetic association with Cld include known genes for responding to reactive chlorine species and uncharacterized genes for transporters, regulatory elements, and putative oxidoreductases that present targets for future research. Cld was repeatedly co-located in genomes with genes for enzymes that can inadvertently reduce perchlorate (ClO4−) or chlorate (ClO3−), indicating that in situ (per)chlorate reduction does not only occur through specialized anaerobic respiratory metabolisms. The presence of Cld in genomes of obligate aerobes without such enzymes suggested that chlorite, like hypochlorous acid (HOCl), might be formed by oxidative processes within natural habitats. In summary, the comparative genomics of Cld has provided an atlas for a deeper understanding of chlorine oxidation and reduction reactions that are an underrecognized feature of biology.
Altered language network lateralization in euthymic bipolar patients: a pilot study
Authors: Romeo Zaira , Marino Marco , Angrilli Alessandro , Semenzato Ilaria , Favaro Angela , Magnolfi Gianna , Padovan Giordano Bruno , Mantini Dante , Spironelli Chiara
Published: October 2022

Bipolar patients (BD) in the euthymic phase show almost no symptoms, nevertheless possibility of relapse is still present. We expected to find a psychobiological trace of their vulnerability by analyzing a specific network—the Language Network (LN)—connecting many high-level processes and brain regions measured at rest. According to Crow’s hypothesis on the key role of language in the origin of psychoses, we expected an altered asymmetry of the LN in euthymic BDs. Eighteen euthymic BD patients (10 females; age = 54.50 ± 11.38 years) and 16 healthy controls (HC) (8 females; age = 51.16 ± 11.44 years) underwent a functional magnetic resonance imaging scan at rest. The LN was extracted through independent component analysis. Then, LN time series was used to compute the fractional amplitude of the low-frequency fluctuation (fALFF) index, which was then correlated with clinical scales. Compared with HC, euthymic patients showed an altered LN with greater activation of Broca’s area right homologous and anterior insula together with reduced activation of left middle temporal gyrus. The normalized fALFF analysis on BD patients’ LN time series revealed that the Slow-5 fALFF band was positively correlated with residual mania symptoms but negatively associated with depression scores. In line with Crow’s hypothesis postulating an altered language hemispheric asymmetry in psychoses, we revealed, in euthymic BD patients, a right shift involving both the temporal and frontal linguistic hubs. The fALFF applied to LN allowed us to highlight a number of significant correlations of this measure with residual mania and depression psychiatric symptoms.
Inhibition of mTOR signaling protects human glioma cells from hypoxia-induced cell death in an autophagy-independent manner
Authors: Divé Iris , Klann Kevin , Michaelis Jonas B. , Heinzen Dennis , Steinbach Joachim P. , Münch Christian , Ronellenfitsch Michael W.
Published: October 2022

Although malignant gliomas frequently show aberrant activation of the mammalian target of rapamycin (mTOR), mTOR inhibitors have performed poorly in clinical trials. Besides regulating cell growth and translation, mTOR controls the initiation of autophagy. By recycling cellular components, autophagy can mobilize energy resources, and has thus been attributed cancer-promoting effects. Here, we asked whether the activation of autophagy represents an escape mechanism to pharmacological mTOR inhibition in glioma cells, and explored co-treatment with mTOR and autophagy inhibitors as a therapeutic strategy. Mimicking conditions of the glioma microenvironment, glioma cells were exposed to nutrient starvation and hypoxia. We analyzed autophagic activity, cell growth, viability and oxygen consumption following (co-)treatment with the mTOR inhibitors torin2 or rapamycin, and autophagy inhibitors bafilomycin A1 or MRT68921. Changes in global proteome were quantified by mass spectrometry. In the context of hypoxia and starvation, autophagy was strongly induced in glioma cells and further increased by mTOR inhibition. While torin2 enhanced glioma cell survival, co-treatment with torin2 and bafilomycin A1 failed to promote cell death. Importantly, treatment with bafilomycin A1 alone also protected glioma cells from cell death. Mechanistically, both compounds significantly reduced cell growth and oxygen consumption. Quantitative proteomics analysis showed that bafilomycin A1 induced broad changes in the cellular proteome. More specifically, proteins downregulated by bafilomycin A1 were associated with the mitochondrial respiratory chain and ATP synthesis. Taken together, our results show that activation of autophagy does not account for the cytoprotective effects of mTOR inhibition in our in vitro model of the glioma microenvironment. Our proteomic findings suggest that the pharmacological inhibition of autophagy induces extensive changes in the cellular proteome that can support glioma cell survival under nutrient-deplete and hypoxic conditions. These findings provide a novel perspective on the complex role of autophagy in gliomas.
A VEGFR targeting peptide-drug conjugate (PDC) suppresses tumor angiogenesis in a TACE model for hepatocellular carcinoma therapy
Authors: Wang Dongyuan , Liu Jiacheng , Li Tongqiang , Wang Yingliang , Liu Xiaoming , Bai Yaowei , Wang Chaoyang , Ju Shuguang , Huang Songjiang , Yang Chongtu , Zhou Chen , Zhang Yu , Xiong Bin
Published: October 2022

Transcatheter arterial chemoembolization (TACE) has become the preferred therapy for unresectable advanced hepatocellular carcinoma (HCC). However, the embolization of tumor-feeding arteries by TACE always leads to hypoxia-related tumor angiogenesis, which limited the therapeutic effect for HCC. In this paper, we used a VEGFR targeting peptide VEGF125 − 136 (QKRKRKKSRYKS) to conjugate with a lytic peptide (KLUKLUKKLUKLUK) to form a peptide-drug conjugate (PDC). We used cell affinity assay to detect the peptide binding ability to VEGFR highly expressed cell lines, and CCK8, cell apoptosis to confirm the cellular toxicity for different cell lines. Meanwhile, we created a VX2 tumor-bearing rabbit model to assess the in vivo anti-tumor effect of the peptide conjugate in combination with TAE. HE staining was used to verify the in vivo safety of the peptide conjugate. IHC was used to assess the anti-angiogenesis and cell toxicity of the peptide conjugate in tumor tissues. The peptide conjugate could not only target VEGFR in cell surface and inhibit VEGFR function, but also have potent anti-cancer effect. We luckily found the peptide conjugate showed potent cytotoxicity for liver cancer cell Huh7 (IC50 7.3 ± 0.74 μM) and endothelial cell HUVEC (IC50 10.7 ± 0.292 μM) and induced cell apoptosis of these two cell lines. We also found the peptide conjugate inhibited cell migration of HUVEC through wound healing assay. Besides, these peptides also showed better in vivo anti-tumor effect than traditional drug DOX through TACE in VX2 rabbit tumor model, and efficiently inhibit angiogenesis in tumor tissues with good safety. In conclusion, our work may provide an alternative option for clinical HCC therapy via TACE combination.
Role of K63-linked ubiquitination in cancer
Authors: Cao Liangzi , Liu Xiaofang , Zheng Bowen , Xing Chengzhong , Liu Jingwei
Published: October 2022

Ubiquitination is a critical type of post-translational modifications, of which K63-linked ubiquitination regulates interaction, translocation, and activation of proteins. In recent years, emerging evidence suggest involvement of K63-linked ubiquitination in multiple signaling pathways and various human diseases including cancer. Increasing number of studies indicated that K63-linked ubiquitination controls initiation, development, invasion, metastasis, and therapy of diverse cancers. Here, we summarized molecular mechanisms of K63-linked ubiquitination dictating different biological activities of tumor and highlighted novel opportunities for future therapy targeting certain regulation of K63-linked ubiquitination in tumor.
Lineage-coupled clonal capture identifies clonal evolution mechanisms and vulnerabilities of BRAFV600E inhibition resistance in melanoma
Authors: Zhang Ze-Yan , Ding Yingwen , Ezhilarasan Ravesanker , Lhakhang Tenzin , Wang Qianghu , Yang Jie , Modrek Aram S. , Zhang Hua , Tsirigos Aristotelis , Futreal Andrew , Draetta Giulio F. , Verhaak Roel G. W. , Sulman Erik P.
Published: October 2022

Targeted cancer therapies have revolutionized treatment but their efficacies are limited by the development of resistance driven by clonal evolution within tumors. We developed “CAPTURE”, a single-cell barcoding approach to comprehensively trace clonal dynamics and capture live lineage-coupled resistant cells for in-depth multi-omics analysis and functional exploration. We demonstrate that heterogeneous clones, either preexisting or emerging from drug-tolerant persister cells, dominated resistance to vemurafenib in BRAFV600E melanoma. Further integrative studies uncovered diverse resistance mechanisms. This includes a previously unrecognized and clinically relevant mechanism, chromosome 18q21 gain, which leads to vulnerability of the cells to BCL2 inhibitor. We also identified targetable common dependencies of captured resistant clones, such as oxidative phosphorylation and E2F pathways. Our study provides new therapeutic insights into overcoming therapy resistance in BRAFV600E melanoma and presents a platform for exploring clonal evolution dynamics and vulnerabilities that can be applied to study treatment resistance in other cancers.
High-quality microresonators in the longwave infrared based on native germanium
Authors: Ren Dingding , Dong Chao , Addamane Sadhvikas J. , Burghoff David
Published: October 2022

The longwave infrared (LWIR) region of the spectrum spans 8 to 14 μm and enables high-performance sensing and imaging for detection, ranging, and monitoring. Chip-scale LWIR photonics has enormous potential for real-time environmental monitoring, explosive detection, and biomedicine. However, realizing technologies such as precision sensors and broadband frequency combs requires ultra low-loss and low-dispersion components, which have so far remained elusive in this regime. Here, we use native germanium to demonstrate the first high-quality microresonators in the LWIR. These microresonators are coupled to partially-suspended Ge waveguides on a separate glass chip, allowing for the first unambiguous measurements of isolated linewidths. At 8 μm, we measured losses of 0.5 dB/cm and intrinsic quality (Q) factors of 2.5 × 105, nearly two orders of magnitude higher than prior LWIR resonators. Our work portends the development of novel sensing and nonlinear photonics in the LWIR regime.
Vitamin C epigenetically controls osteogenesis and bone mineralization
Authors: Thaler Roman , Khani Farzaneh , Sturmlechner Ines , Dehghani Sharareh S. , Denbeigh Janet M. , Zhou Xianhu , Pichurin Oksana , Dudakovic Amel , Jerez Sofia S. , Zhong Jian , Lee Jeong-Heon , Natarajan Ramesh , Kalajzic Ivo , Jiang Yong-hui , Deyle David R. , Paschalis Eleftherios P. , Misof Barbara M. , Ordog Tamas , van Wijnen Andre J.
Published: October 2022

Vitamin C deficiency disrupts the integrity of connective tissues including bone. For decades this function has been primarily attributed to Vitamin C as a cofactor for collagen maturation. Here, we demonstrate that Vitamin C epigenetically orchestrates osteogenic differentiation and function by modulating chromatin accessibility and priming transcriptional activity. Vitamin C regulates histone demethylation (H3K9me3 and H3K27me3) and promotes TET-mediated 5hmC DNA hydroxymethylation at promoters, enhancers and super-enhancers near bone-specific genes. This epigenetic circuit licenses osteoblastogenesis by permitting the expression of all major pro-osteogenic genes. Osteogenic cell differentiation is strictly and continuously dependent on Vitamin C, whereas Vitamin C is dispensable for adipogenesis. Importantly, deletion of 5hmC-writers, Tet1 and Tet2, in Vitamin C-sufficient murine bone causes severe skeletal defects which mimic bone phenotypes of Vitamin C-insufficient Gulo knockout mice, a model of Vitamin C deficiency and scurvy. Thus, Vitamin C’s epigenetic functions are central to osteoblastogenesis and bone formation and may be leveraged to prevent common bone-degenerating conditions.
DNA-delivered antibody cocktail exhibits improved pharmacokinetics and confers prophylactic protection against SARS-CoV-2
Authors: Parzych Elizabeth M. , Du Jianqiu , Ali Ali R. , Schultheis Katherine , Frase Drew , Smith Trevor R. F. , Cui Jiayan , Chokkalingam Neethu , Tursi Nicholas J. , Andrade Viviane M. , Warner Bryce M. , Gary Ebony N. , Li Yue , Choi Jihae , Eisenhauer Jillian , Maricic Igor , Kulkarni Abhijeet , Chu Jacqueline D. , Villafana Gabrielle , Rosenthal Kim , Ren Kuishu , Francica Joseph R. , Wootton Sarah K. , Tebas Pablo , Kobasa Darwyn , Broderick Kate E. , Boyer Jean D. , Esser Mark T. , Pallesen Jesper , Kulp Dan W. , Patel Ami , Weiner David B.
Published: October 2022

Monoclonal antibody therapy has played an important role against SARS-CoV-2. Strategies to deliver functional, antibody-based therapeutics with improved in vivo durability are needed to supplement current efforts and reach underserved populations. Here, we compare recombinant mAbs COV2-2196 and COV2-2130, which compromise clinical cocktail Tixagevimab/Cilgavimab, with optimized nucleic acid-launched forms. Functional profiling of in vivo-expressed, DNA-encoded monoclonal antibodies (DMAbs) demonstrated similar specificity, broad antiviral potency and equivalent protective efficacy in multiple animal challenge models of SARS-CoV-2 prophylaxis compared to protein delivery. In PK studies, DNA-delivery drove significant serum antibody titers that were better maintained compared to protein administration. Furthermore, cryo-EM studies performed on serum-derived DMAbs provide the first high-resolution visualization of in vivo-launched antibodies, revealing new interactions that may promote cooperative binding to trimeric antigen and broad activity against VoC including Omicron lineages. These data support the further study of DMAb technology in the development and delivery of valuable biologics.
Mode coupling bi-stability and spectral broadening in buckled carbon nanotube mechanical resonators
Authors: Rechnitz Sharon , Tabachnik Tal , Shlafman Michael , Shlafman Shlomo , Yaish Yuval E.
Published: October 2022

Bi-stable mechanical resonators play a significant role in various applications, such as sensors, memory elements, quantum computing and mechanical parametric amplification. While carbon nanotube based resonators have been widely investigated as promising NEMS devices, a bi-stable carbon nanotube resonator has never been demonstrated. Here, we report a class of carbon nanotube resonators in which the nanotube is buckled upward. We show that a small upward buckling yields record electrical frequency tunability, whereas larger buckling can achieve Euler-Bernoulli bi-stability, the smallest mechanical resonator with two stable configurations to date. We believe that these recently-discovered carbon nanotube devices will open new avenues for realizing nano-sensors, mechanical memory elements and mechanical parametric amplifiers. Furthermore, we present a three-dimensional theoretical analysis revealing significant nonlinear coupling between the in-plane and out-of-plane static and dynamic modes of motion, and a unique three-dimensional Euler-Bernoulli snap-through transition. We utilize this coupling to provide a conclusive explanation for the low quality factor in carbon nanotube resonators at room temperature, key in understanding dissipation mechanisms at the nano scale.
A method for multiplexed full-length single-molecule sequencing of the human mitochondrial genome
Authors: Keraite Ieva , Becker Philipp , Canevazzi Davide , Frias-López Cristina , Dabad Marc , Tonda-Hernandez Raúl , Paramonov Ida , Ingham Matthew John , Brun-Heath Isabelle , Leno Jordi , Abulí Anna , Garcia-Arumí Elena , Heath Simon Charles , Gut Marta , Gut Ivo Glynne
Published: October 2022

Methods to reconstruct the mitochondrial DNA (mtDNA) sequence using short-read sequencing come with an inherent bias due to amplification and mapping. They can fail to determine the phase of variants, to capture multiple deletions and to cover the mitochondrial genome evenly. Here we describe a method to target, multiplex and sequence at high coverage full-length human mitochondrial genomes as native single-molecules, utilizing the RNA-guided DNA endonuclease Cas9. Combining Cas9 induced breaks, that define the mtDNA beginning and end of the sequencing reads, as barcodes, we achieve high demultiplexing specificity and delineation of the full-length of the mtDNA, regardless of the structural variant pattern. The long-read sequencing data is analysed with a pipeline where our custom-developed software, baldur, efficiently detects single nucleotide heteroplasmy to below 1%, physically determines phase and can accurately disentangle complex deletions. Our workflow is a tool for studying mtDNA variation and will accelerate mitochondrial research.
The solution structure of Dead End bound to AU-rich RNA reveals an unusual mode of tandem RRM-RNA recognition required for mRNA regulation
Authors: Duszczyk Malgorzata M. , Wischnewski Harry , Kazeeva Tamara , Arora Rajika , Loughlin Fionna E. , von Schroetter Christine , Pradère Ugo , Hall Jonathan , Ciaudo Constance , Allain Frédéric H.-T.
Published: October 2022

Dead End (DND1) is an RNA-binding protein essential for germline development through its role in post-transcriptional gene regulation. The molecular mechanisms behind selection and regulation of its targets are unknown. Here, we present the solution structure of DND1’s tandem RNA Recognition Motifs (RRMs) bound to AU-rich RNA. The structure reveals how an NYAYUNN element is specifically recognized, reconciling seemingly contradictory sequence motifs discovered in recent genome-wide studies. RRM1 acts as a main binding platform, including atypical extensions to the canonical RRM fold. RRM2 acts cooperatively with RRM1, capping the RNA using an unusual binding pocket, leading to an unusual mode of tandem RRM-RNA recognition. We show that the consensus motif is sufficient to mediate upregulation of a reporter gene in human cells and that this process depends not only on RNA binding by the RRMs, but also on DND1’s double-stranded RNA binding domain (dsRBD), which is dispensable for binding of a subset of targets in cellulo. Our results point to a model where DND1 target selection is mediated by a non-canonical mode of AU-rich RNA recognition by the tandem RRMs and a role for the dsRBD in the recruitment of effector complexes responsible for target regulation.
Atomically dispersed chromium coordinated with hydroxyl clusters enabling efficient hydrogen oxidation on ruthenium
Authors: Zhang Bingxing , Zhang Baohua , Zhao Guoqiang , Wang Jianmei , Liu Danqing , Chen Yaping , Xia Lixue , Gao Mingxia , Liu Yongfeng , Sun Wenping , Pan Hongge
Published: October 2022

Overcoming the sluggish kinetics of alkaline hydrogen oxidation reaction (HOR) is challenging but is of critical importance for practical anion exchange membrane fuel cells. Herein, abundant and efficient interfacial active sites are created on ruthenium (Ru) nanoparticles by anchoring atomically isolated chromium coordinated with hydroxyl clusters (Cr1(OH)x) for accelerated alkaline HOR. This catalyst system delivers 50-fold enhanced HOR activity with excellent durability and CO anti-poisoning ability via switching the active sites from Ru surface to Cr1(OH)x-Ru interface. Fundamentally different from the conventional mechanism merely focusing on surface metal sites, the isolated Cr1(OH)x could provide unique oxygen species for accelerating hydrogen or CO spillover from Ru to Cr1(OH)x. Furthermore, the original oxygen species from Cr1(OH)x are confirmed to participate in hydrogen oxidation and H2O formation. The incorporation of such atomically isolated metal hydroxide clusters in heterostructured catalysts opens up new opportunities for rationally designing advanced electrocatalysts for HOR and other complex electrochemical reactions. This work also highlights the importance of size effect of co-catalysts, which should also be paid substantial attention to in the catalysis field.
Optic nerve sheath diameter and spaceflight: defining shortcomings and future directions
Authors: Fall Dylan A. , Lee Andrew G. , Bershad Eric M. , Kramer Larry A. , Mader Thomas H. , Clark Jonathan B. , Hirzallah Mohammad I.
Published: October 2022

Neuro-ocular changes during long-duration space flight are known as spaceflight-associated neuro-ocular syndrome (SANS). The ability to detect, monitor, and prevent SANS is a priority of current space medicine research efforts. Optic nerve sheath diameter (ONSD) measurement has been used both terrestrially and in microgravity as a proxy for measurements of elevated intracranial pressure. ONSD shows promise as a potential method of identifying and quantitating neuro-ocular changes during space flight. This review examines 13 studies measuring ONSD and its relationship to microgravity exposure or ground-based analogs, including head-down tilt, dry immersion, or animal models. The goal of this correspondence is to describe heterogeneity in the use of ONSD in the current SANS literature and make recommendations to reduce heterogeneity in future studies through standardization of imaging modalities, measurement techniques, and other aspects of study design.
Lysosomal lipid alterations caused by glucocerebrosidase deficiency promote lysosomal dysfunction, chaperone-mediated-autophagy deficiency, and alpha-synuclein pathology
Authors: Navarro-Romero Alba , Fernandez-Gonzalez Irene , Riera Jordi , Montpeyo Marta , Albert-Bayo Merce , Lopez-Royo Tresa , Castillo-Sanchez Pablo , Carnicer-Caceres Clara , Arranz-Amo Jose Antonio , Castillo-Ribelles Laura , Pradas Eddie , Casas Josefina , Vila Miquel , Martinez-Vicente Marta
Published: October 2022

Mutations in the GBA gene that encodes the lysosomal enzyme β-glucocerebrosidase (GCase) are a major genetic risk factor for Parkinson’s disease (PD). In this study, we generated a set of differentiated and stable human dopaminergic cell lines that express the two most prevalent GBA mutations as well as GBA knockout cell lines as a in vitro disease modeling system to study the relationship between mutant GBA and the abnormal accumulation of α-synuclein. We performed a deep analysis of the consequences triggered by the presence of mutant GBA protein and the loss of GCase activity in different cellular compartments, focusing primarily on the lysosomal compartment, and analyzed in detail the lysosomal activity, composition, and integrity. The loss of GCase activity generates extensive lysosomal dysfunction, promoting the loss of activity of other lysosomal enzymes, affecting lysosomal membrane stability, promoting intralysosomal pH changes, and favoring the intralysosomal accumulation of sphingolipids and cholesterol. These local events, occurring only at a subcellular level, lead to an impairment of autophagy pathways, particularly chaperone-mediated autophagy, the main α-synuclein degradative pathway. The findings of this study highlighted the role of lysosomal function and lipid metabolism in PD and allowed us to describe a molecular mechanism to understand how mutations in GBA can contribute to an abnormal accumulation of different α-synuclein neurotoxic species in PD pathology.
Dissipation of reactive inhibition is sufficient to explain post-rest improvements in motor sequence learning
Authors: Gupta Mohan W. , Rickard Timothy C.
Published: October 2022

The prevailing hypothesis for observed post-rest motor reaction time improvements is offline consolidation. In the present study, we present evidence for an alternate account involving the accrual and dissipation of reactive inhibition. Four groups of participants (N = 159) performed a finger-tapping task involving either massed (30 s per trial) or spaced (10 s per trial) training, and with one of two break intervals between each trial: 10 s or 30 s. After 360 s of training in each group, there was a 300 s rest period followed by a final test on the same task. The results show that the smaller the ratio of break time to on-task trial time during training, the larger the improvement in reaction time after the rest period. Those results are fully consistent with a model that assumes no facilitating offline consolidation, but rather learning that is concurrent with performance and reactive inhibition that builds during performance and dissipates during breaks.
Elucidation of the role of nucleolin as a cell surface receptor for nucleic acid-based adjuvants
Authors: Kitagawa Satoki , Matsuda Teppei , Washizaki Ayaka , Murakami Hirotomo , Yamamoto Takuya , Yoshioka Yasuo
Published: October 2022

Nucleic acid-based adjuvants such as CpG oligonucleotides (CpG ODNs) and poly(I:C) are potential vaccine adjuvants for infectious diseases and cancers. However, the mechanism by which their cell surface receptors promote their uptake into dendritic cells (DCs) and shuttle them to intracellular Toll-like receptors remains to be further investigated. Here, we demonstrated a role for nucleolin, a multifunctional DNA- and RNA-binding protein and a major constituent of the nucleolus, as one of the cell-surface receptors for nucleic acid-based adjuvants. Nucleolin on mouse DC surface bound directly to A-type CpG ODN, B-type CpG ODN, and poly(I:C) and promoted their internalization into cells following DC maturation in vitro. In human DCs, nucleolin also contributed to the binding and internalization of both types of CpG ODNs and subsequent cytokine production. Furthermore, nucleolin played a crucial role in cytokine production and activating antigen-specific antibodies and T cell responses induced by B-type CpG ODN in vivo in mice. Our findings provide valuable information that can help improve the efficacy and safety of these adjuvants.
Observation of the quantum Gouy phase
Authors: Hiekkamäki Markus , Barros Rafael F. , Ornigotti Marco , Fickler Robert
Published: October 2022

Controlling the evolution of photonic quantum states is crucial for most quantum information processing and metrology tasks. Due to its importance, many mechanisms of quantum state evolution have been tested in detail and are well understood; however, the fundamental phase anomaly of evolving waves, called the Gouy phase, has had a limited number of studies in the context of elementary quantum states of light, especially in the case of photon number states. Here we outline a simple method for calculating the quantum state evolution upon propagation and demonstrate experimentally how this quantum Gouy phase affects two-photon quantum states. Our results show that the increased phase sensitivity of multi-photon states also extends to this fundamental phase anomaly and has to be taken into account to fully understand the state evolution. We further demonstrate how the Gouy phase can be used as a tool for manipulating quantum states of any bosonic system in future quantum technologies, outline a possible application in quantum-enhanced sensing, and dispel a common misconception attributing the increased phase sensitivity of multi-photon quantum states solely to an effective de Broglie wavelength.
Electrons with Planckian scattering obey standard orbital motion in a magnetic field
Authors: Ataei Amirreza , Gourgout A. , Grissonnanche G. , Chen L. , Baglo J. , Boulanger M.-E. , Laliberté F. , Badoux S. , Doiron-Leyraud N. , Oliviero V. , Benhabib S. , Vignolles D. , Zhou J.-S. , Ono S. , Takagi H. , Proust C. , Taillefer Louis
Published: October 2022

In various so-called strange metals, electrons undergo Planckian dissipation1,2, a strong and anomalous scattering that grows linearly with temperature3, in contrast to the quadratic temperature dependence expected from the standard theory of metals. In some cuprates4,5 and pnictides6, a linear dependence of resistivity on a magnetic field has also been considered anomalous—possibly an additional facet of Planckian dissipation. Here we show that the resistivity of the cuprate strange metals Nd0.4La1.6−xSrxCuO4 (ref. 7) and La2−xSrxCuO4 (ref. 8) is quantitatively consistent with the standard Boltzmann theory of electron motion in a magnetic field, in all aspects—field strength, field direction, temperature and disorder level. The linear field dependence is found to be simply the consequence of scattering rate anisotropy. We conclude that Planckian dissipation is anomalous in its temperature dependence, but not in its field dependence. The scattering rate in these cuprates does not depend on field, which means that their Planckian dissipation is robust against fields up to at least 85 T.
neuromaps: structural and functional interpretation of brain maps
Authors: Markello Ross D. , Hansen Justine Y. , Liu Zhen-Qi , Bazinet Vincent , Shafiei Golia , Suárez Laura E. , Blostein Nadia , Seidlitz Jakob , Baillet Sylvain , Satterthwaite Theodore D. , Chakravarty M. Mallar , Raznahan Armin , Misic Bratislav
Published: October 2022

Imaging technologies are increasingly used to generate high-resolution reference maps of brain structure and function. Comparing experimentally generated maps to these reference maps facilitates cross-disciplinary scientific discovery. Although recent data sharing initiatives increase the accessibility of brain maps, data are often shared in disparate coordinate systems, precluding systematic and accurate comparisons. Here we introduce neuromaps, a toolbox for accessing, transforming and analyzing structural and functional brain annotations. We implement functionalities for generating high-quality transformations between four standard coordinate systems. The toolbox includes curated reference maps and biological ontologies of the human brain, such as molecular, microstructural, electrophysiological, developmental and functional ontologies. Robust quantitative assessment of map-to-map similarity is enabled via a suite of spatial autocorrelation-preserving null models. neuromaps combines open-access data with transparent functionality for standardizing and comparing brain maps, providing a systematic workflow for comprehensive structural and functional annotation enrichment analysis of the human brain.
Rhode Island gastroenterology video capsule endoscopy data set
Authors: Charoen Amber , Guo Averill , Fangsaard Panisara , Taweechainaruemitr Supakorn , Wiwatwattana Nuwee , Charoenpong Theekapun , Rich Harlan G.
Published: October 2022

Complete endoscopic evaluation of the small bowel is challenging due to its length and anatomy. Although several advances have been made to achieve diagnostic and therapeutic goals, including double-balloon enteroscopy, single-balloon enteroscopy, and spiral enteroscopy, video capsule endoscopy (VCE) remains the least invasive tool for complete visualization of the small bowel and is the preferred method for initial diagnostic evaluation. At present, interpretation of VCE data requires manual annotation of landmarks and abnormalities in recorded videos, which can be time consuming. Computer-assisted diagnostic systems using artificial intelligence may help to optimize VCE reading efficiency by reducing the need for manual annotation. Here we present a large VCE data set compiled from studies performed at two United States hospitals in Providence, Rhode Island, including 424 VCE studies and 5,247,588 total labeled images. In conjunction with existing published data sets, these files may aid in the development of algorithms to further improve VCE.
Dynamic gill and mucus microbiomes during a gill disease episode in farmed Atlantic salmon
Authors: Birlanga Victor B. , McCormack Grace , Ijaz Umer Z. , MacCarthy Eugene , Smith Cindy , Collins Gavin
Published: October 2022

Amoebic gill disease (AGD) and complex gill disease (CGD) are recurrent gill disorders in Atlantic salmon, resulting in significant aquaculture losses. The role of gill microbiomes in gill disease development is unclear. We undertook a longitudinal study to characterise the gill tissue and gill mucus microbiomes of farmed Atlantic salmon before, and during, a gill disease episode. Using a newly optimised DNA extraction protocol, we sequenced rRNA genes from microbiomes of gill samples taken from 105 individual salmon on a farm, over a summer season. The AGD aetiological agent, Neoparamoeba perurans, was PCR-quantified targeting 18S rRNA genes. Similar analyses were carried out on mucus samples. Mucus scrapings were suitable, non-lethal substitutes for characterisation of the gill prokaryotic community in this study. Gill tissue and gill mucus microbiomes changed during the campaign, correlating with N. perurans concentrations. Time explained 35% of the gill tissue and gill mucus microbiome variance, while N. perurans concentrations explained 5%. Genera including Dyadobacter, Shewanella and Pedobacter were maximally abundant in gill and mucus samples at the timepoint prior to the the detection of gill disorder signs, at T3. Shewanella was significantly more abundant before than during the gill disease episode, and we suggest this genus could be considered in future studies addressing relationships between gill disease and the gill microbiome.
Atmospheric muography for imaging and monitoring tropic cyclones
Authors: Tanaka Hiroyuki K. M. , Gluyas Jon , Holma Marko , Joutsenvaara Jari , Kuusiniemi Pasi , Leone Giovanni , Lo Presti Domenico , Matsushima Jun , Oláh László , Steigerwald Sara , Thompson Lee F. , Usoskin Ilya , Poluianov Stepan , Varga Dezső , Yokota Yusuke
Published: October 2022

Large-scale solid bodies on Earth such as volcanoes and man-made pyramids have been visualized with solid earth muography, and the recently invented technique, acqueous muography, has already demonstrated its capability to visualize ocean tides and tsunami. In this work, atmospheric muography, a technique to visualize and monitor the vertical profile of tropic cyclones (TCs) is presented for the first time. The density distribution and time-dependent behavior of several TCs which had approached Kagoshima, Japan, has been investigated with muography. The resultant time-sequential images captured their warm cores, and their movements were consistent with the TC trails and barometric pressure variations observed at meteorological stations. By combining multidirectional muographic images with barometric data, we anticipate that muography will become a useful tool to monitor the three-dimensional density distribution of a targeted mesoscale convective system.
Central autonomic network alterations in male endurance athletes
Authors: de la Cruz Feliberto , Geisler Maria , Schumann Andy , Herbsleb Marco , Kikinis Zora , Weiss Thomas , Bär Karl-Jürgen
Published: October 2022

Physical exercise causes marked adjustments in brain function and the cardiovascular system. Brain regions of the so-called central autonomic network (CAN) are likely to show exercise-related alterations due to their involvement in cardiac control, yet exercise-induced CAN changes remain unclear. Here we investigate the effects of intensive exercise on brain regions involved in cardiac autonomic regulation using resting-state functional connectivity (rsFC). We explored rsFC of six core regions within CAN, namely ventromedial prefrontal cortex, dorsolateral anterior cingulate cortex, left/right amygdala, and left/right anterior insula, in 20 endurance athletes and 21 non-athletes. We showed that athletes had enhanced rsFC within CAN and sensorimotor areas compared to non-athletes. Likewise, we identified two networks with increased rsFC encompassing autonomic and motor-related areas using network-based statistics analysis. In addition, rsFC displayed an inverse relationship with heart rate, where the stronger rsFC in athletes correlates with their slower heart rate. Despite this significant relationship, mediation analysis revealed that heart rate is a weak mediator of the effect of intensive physical training on rsFC. Our findings prove that physical exercise enhances brain connectivity in central autonomic and sensorimotor networks and highlight the close link between brain and heart.
The relationship between serum uric acid and colorectal cancer: a prospective cohort study
Authors: Li Wenqiang , Liu Tong , Siyin Sarah Tan , Zhang Qingsong , Wang Yiming , Cao Liying , Qu Jun
Published: October 2022

Serum uric acid (SUA) may play an important role in the occurrence of colorectal cancer (CRC). This study aims to explore the association of SUA with the risk of CRC incidence by drawing data from the Kailuan Study. We prospectively examined the association between SUA and risk of CRC incidence among 93,356 Chinese. Eligible participants were divided into three groups based on their tertiles of SUA. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CRC. During a median follow-up of 13.02 years, 583 new-onset CRC cases were identified. After adjustments were made for confounders, participants in the highest tertiles of SUA exhibited a 1.55-fold increased risk of CRC compared with patients with the lowest SUA levels (HRT3 vs. T1 = 1.55, 95% CI: 1.09–2.30). The associations of SUA with the risk of CRC were slightly reduced but remained substantial in the competing risk analyses when treating CRC unrelated death as the competing risk event. This study found a positive association of SUA with CRC incidence. Specific prevention efforts could be focused on the population with higher levels of SUA.
Prevalence of intestinal parasites and associated risk factors in HIV positive and negative patients in Northwest Region, Cameroon
Authors: Ntonifor Ngum Helen , Tamufor Abongwe Sidney Warra , Abongwa Lem Edith
Published: October 2022

Epidemiological understanding of intestinal parasitic infections is essential for the effective management of HIV infection. Therefore, this study was designed to assess the burden of intestinal parasites and associated risk factors. A cross-sectional study was conducted from May to December 2020 during which 200 HIV positive and 200 HIV negative participants were recruited. A total of 400 stool and venous blood samples were collected and used to identify the different intestinal parasites and for HIV diagnosis and viral load determination respectively. Results obtained revealed that the overall prevalence of intestinal parasites was 11% (44/400). Intestinal parasitosis was significantly (p = 0.025) higher in HIV-positive individuals 14.5% (29/200). Similarly, the prevalence of multiple parasitic infection 4.5% (18/400) and opportunistic helminths 3% (6/400) were insignificantly (p > 0.05) higher among HIV-positive individuals. Furthermore, prevalence of intestinal parasites was significantly (p = 0.004) greater in patients with viral load of > 1000 copies/mL 24.3% (13/46). Age group > 65 years, self-employment, living in Sub-urban areas, being HIV positive, primary level of education, use of potable tap water, and the use of water system toilets for faeces disposal were identified as associated risk factors to intestinal parasites. Intestinal parasites remain public health concern among patients with HIV. Prompt and effective antiretroviral treatment is required to reduce the intensity of the parasite.
The significance of elevated tumor markers among patients with interstitial lung diseases
Authors: Kwon Byoung Soo , Kim Eun Sun , Lim Sung Yoon , Song Myung Jin , Kim Yeon Wook , Kim Hyung-Jun , Lee Yeon Joo , Park Jong Sun , Cho Young-Jae , Yoon Ho Il , Lee Choon-Taek , Lee Jae Ho
Published: October 2022

The clinical implication of using serum tumor markers in patients with interstitial lung disease (ILD) is inconclusive. In this retrospective study, we analyzed the data of 1176 subjects (294 with ILDs and 882 healthy controls). Eligible patients were who had at least one or more available tumor marker results [carbohydrate antigen (CA) 19-9, CA 125, and carcinoembryonic antigen (CEA)] with no evidence of malignancies or other benign diseases that could be related to the increasing concentration of the values. The healthy controls selected from a health screening program were also screened for the presence of active cancer, and matched at a ratio of 1:3 with age and sex. The proportion of patients with abnormal values in the ILD group (121, idiopathic pulmonary fibrosis (IPF); 173, non-IPF-ILDs) was higher than in the matched control group (CEA, 21.5% vs. 5.5%; CA 19-9, 27.9% vs. 4.0%; CA 125, 36.4% vs. 2.0%). In the multivariable analysis, higher CEA levels were associated with shorter survival after adjusting for age, sex, lung function, and ILD subtypes (hazard ratio: 2.323, 95% confidence interval: 1.271–4.248, P = 0.006). In subgroup analysis, CEA remained a prognostic factor in patients with non-IPF-ILDs, but not in those with IPF.
The current status of chronic kidney disease-mineral and bone disorder management in China
Authors: Zhan Ya , He Xin , Hong Daqing , Wang Li , Li Guisen
Published: October 2022

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is one of the most common complications of patients with chronic kidney disease (CKD). After considering updated international and domestic CKD-MBD management guidelines, the current management status of CKD-MBD in China remains unclear. We aimed to investigate the management status of CKD-MBD in China. A nationwide survey was combined with a real-world study from Sichuan. Targets recommended in KDIGO 2017 and Chinese 2019 guidelines were used as targets. We compared the data between Sichuan from western China and the eastern developed areas of China, and also compared the results of the real-world data from Sichuan with those of DOPPS5. In the questionnaire, a total of 51,039 maintenance hemodialysis (MHD) patients from 272 centers were involved. Estimated achievement rates for Ca (2.1–2.5 mmol/L), P (1.13–1.78 mmol/L), and iPTH (150–600 pg/mL) levels were 57.1%, 41.1% and 52.0%, respectively. Differences in MBD management between Sichuan from questionnaire and central region. In the real-world survey, a total of 7,053 patients were enrolled. Among them, 57.6%, 24.3%, and 55.0% of patients met corrected Ca, serum P, and iPTH targets specified in Chinese 2019 guidelines, respectively. The comprehensive achievement rate was 7.5%. There are differences in MBD management between Sichuan and DOPPS5 regions, with Sichuan being relatively poorer. The level of the above parameters varies among different genders, age groups, and hospital grades. The achievement rate of serum P was higher in tertiary hospitals and elderly patients (P < 0.05). Current MBD management is poor. Phosphate levels in patients treated in secondary and lower hospitals and young dialysis patients should be strengthened.
Behavioral correlates of temporal attention biases during emotional prosody perception
Authors: Guex Raphaël , Grandjean Didier , Frühholz Sascha
Published: October 2022

Emotional prosody perception (EPP) unfolds in time given the intrinsic temporal nature of auditory stimuli, and has been shown to be modulated by spatial attention. Yet, the influence of temporal attention (TA) on EPP remains largely unexplored. TA studies manipulate subject’s motor preparedness according to an upcoming event, with targets to discriminate during short attended trials arriving quickly, and, targets to discriminate during long unattended trials arriving at a later time point. We used here a classic paradigm manipulating TA to investigate its influence on behavioral responses to EPP (n = 100) and we found that TA bias was associated with slower reaction times (RT) for angry but not neutral prosodies and only during short trials. Importantly, TA biases were observed for accuracy measures only for angry voices and especially during short trials, suggesting that neutral stimuli are less subject to TA biases. Importantly, emotional facilitation, with faster RTs for angry voices in comparison to neutral voices, was observed when the stimuli were temporally attended and during short trials, suggesting an influential role of TA during EPP. Together, these results demonstrate for the first time the major influence of TA in RTs and behavioral performance while discriminating emotional prosody.
Statistical modeling approach for PM10 prediction before and during confinement by COVID-19 in South Lima, Perú
Authors: Cabello-Torres Rita Jaqueline , Estela Manuel Angel Ponce , Sánchez-Ccoyllo Odón , Romero-Cabello Edison Alessandro , Ávila Fausto Fernando García , Castañeda-Olivera Carlos Alberto , Valdiviezo-Gonzales Lorgio , Eulogio Carlos Enrique Quispe , De La Cruz Alex Rubén Huamán , López-Gonzales Javier Linkolk
Published: October 2022

A total of 188,859 meteorological-PM$$_{10}$$

10

data validated before (2019) and during the COVID-19 pandemic (2020) were used. In order to predict PM$$_{10}$$

10

in two districts of South Lima in Peru, hourly, daily, monthly and seasonal variations of the data were analyzed. Principal Component Analysis (PCA) and linear/nonlinear modeling were applied. The results showed the highest annual average PM$$_{10}$$

10

for San Juan de Miraflores (SJM) (PM$$_{10}$$

10

-SJM: 78.7 $$\upmu$$
μ
g/m$$^{3}$$

3

) and the lowest in Santiago de Surco (SS) (PM$$_{10}$$

10

-SS: 40.2 $$\upmu$$
μ
g/m$$^{3}$$

3

). The PCA showed the influence of relative humidity (RH)-atmospheric pressure (AP)-temperature (T)/dew point (DP)-wind speed (WS)-wind direction (WD) combinations. Cool months with higher humidity and atmospheric instability decreased PM$$_{10}$$

10

values in SJM and warm months increased it, favored by thermal inversion (TI). Dust resuspension, vehicular transport and stationary sources contributed more PM$$_{10}$$

10

at peak times in the morning and evening. The Multiple linear regression (MLR) showed the best correlation (r = 0.6166), followed by the three-dimensional model LogAP-LogWD-LogPM$$_{10}$$

10

(r = 0.5753); the RMSE-MLR (12.92) exceeded that found in the 3D models (RMSE $$<0.3$$

<
0.3

) and the NSE-MLR criterion (0.3804) was acceptable. PM$$_{10}$$

10

prediction was modeled using the algorithmic approach in any scenario to optimize urban management decisions in times of pandemic.