bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial extracellular vesicles in the microbiome of first-pass meconium in newborn infants
Authors: Turunen Jenni , Tejesvi Mysore V. , Suokas Marko , Virtanen Nikke , Paalanne Niko , Kaisanlahti Anna , Reunanen Justus , Tapiainen Terhi 
Published: August 2022

Abstract
Background
Bacterial extracellular vesicles (EVs) are more likely to cross biological barriers than whole-cell bacteria. We previously observed EV-sized particles by electron microscopy in the first-pass meconium of newborn infants. We hypothesized that EVs may be of bacterial origin and represent a novel entity in the human microbiome during fetal and perinatal periods.

Methods
We extracted EVs from first-pass meconium samples of 17 newborn infants and performed bacterial 16S rRNA gene sequencing of the vesicles. We compared the EV content from the meconium samples of infants based on the delivery mode, and in vaginal delivery samples, based on the usage of intrapartum antibiotics.

Results
We found bacterial EVs in all first-pass meconium samples. All EV samples had bacterial RNA. Most of the phyla present in the samples were Firmicutes (62%), Actinobacteriota (18%), Proteobacteria (10%), and Bacteroidota (7.3%). The most abundant genera were Streptococcus (21%) and Staphylococcus (17%). The differences between the delivery mode and exposure to antibiotics were not statistically significant.

Conclusions
Bacterial EVs were present in the first-pass meconium of newborn infants. Bacterial EVs may represent an important novel feature of the gut microbiome during fetal and perinatal periods.

Impact

We show that bacterial extracellular vesicles are present in the microbiome of first-pass meconium in newborn infants.

This is a novel finding. To our knowledge, this is the first study to report the presence of bacterial extracellular vesicles in the gut microbiome during fetal and perinatal periods.

This finding is important because bacterial extracellular vesicles are more likely to cross biological barriers than whole-cell bacteria. Thus, the early gut microbiome may potentially interact with the host through bacterial EVs.
shRNA‑mediated knockdown of KNTC1 inhibits non-small-cell lung cancer through regulating PSMB8
Authors: Liu Ruijun , Liu Ruili , Guo Zhiyi , Ren Jianghao , Huang Jia , Luo Qingquan , Tan Qiang 
Published: August 2022

AbstractIn view of the important roles played by Kinetochore proteins in mitosis, we believed that they may contribute to the development and progression of human cancers, which has been reported recently elsewhere. Kinetochore-associated 1 (KNTC1) participates in the segregation of sister chromatids during mitosis, the effects of which on non-small-cell lung cancer (NSCLC) remain unclear. Here, we sought to identify the biological significance of KNTC1 in NSCLC. KNTC1 protein expression in NSCLC tissues was investigated by immunohistochemistry. Lentivirus delivered short hairpin RNA (shRNA) was utilized to establish KNTC1 silence NSCLC cell lines. The effects of KNTC1 depletion on NSCLC cell proliferation, migration, apoptosis, and tumor formation were analyzed by MTT assay, wound-healing assay, transwell assay, flow cytometry assay, and in nude mouse models in vivo. After KNTC1 reduction, NSCLC cell viability, proliferation, migration, and invasion were restrained. A xenograft tumor model was also provided to demonstrate the inhibited tumorigenesis in NSCLC. In addition, the downstream mechanism analysis indicated that KNTC1 depletion was positively associated with PSMB8. The findings of the present study suggested that KNTC1 may have a pivotal role in mediating NSCLC progression and may act as a novel therapeutic target for NSCLC.
An open-label pilot study of recombinant granulocyte-colony stimulating factor in Friedreich’s ataxia
Authors: Kemp Kevin C. , Georgievskaya Anastasia , Hares Kelly , Redondo Juliana , Bailey Steven , Rice Claire M. , Scolding Neil J. , Metcalfe Chris , Wilkins Alastair 
Published: August 2022

AbstractFriedreich’s ataxia (FA) is an inherited progressive neurodegenerative disease for which there is no proven disease-modifying treatment. Here we perform an open‐label, pilot study of recombinant human granulocyte-colony stimulating factor (G-CSF) administration in seven people with FA (EudraCT: 2017-003084-34); each participant receiving a single course of G-CSF (Lenograstim; 1.28 million units per kg per day for 5 days). The primary outcome is peripheral blood mononuclear cell frataxin levels over a 19-day period. The secondary outcomes include safety, haematopoietic stem cell (HSC) mobilisation, antioxidant levels and mitochondrial enzyme activity. The trial meets pre-specified endpoints. We show that administration of G-CSF to people with FA is safe. Mobilisation of HSCs in response to G-CSF is comparable to that of healthy individuals. Notably, sustained increases in cellular frataxin concentrations and raised PGC-1α and Nrf2 expression are detected. Our findings show potential for G-CSF therapy to have a clinical impact in people with FA.
Erasure conversion for fault-tolerant quantum computing in alkaline earth Rydberg atom arrays
Authors: Wu Yue , Kolkowitz Shimon , Puri Shruti , Thompson Jeff D. 
Published: August 2022

AbstractExecuting quantum algorithms on error-corrected logical qubits is a critical step for scalable quantum computing, but the requisite numbers of qubits and physical error rates are demanding for current experimental hardware. Recently, the development of error correcting codes tailored to particular physical noise models has helped relax these requirements. In this work, we propose a qubit encoding and gate protocol for171Yb neutral atom qubits that converts the dominant physical errors into erasures, that is, errors in known locations. The key idea is to encode qubits in a metastable electronic level, such that gate errors predominantly result in transitions to disjoint subspaces whose populations can be continuously monitored via fluorescence. We estimate that 98% of errors can be converted into erasures. We quantify the benefit of this approach via circuit-level simulations of the surface code, finding a threshold increase from 0.937% to 4.15%. We also observe a larger code distance near the threshold, leading to a faster decrease in the logical error rate for the same number of physical qubits, which is important for near-term implementations. Erasure conversion should benefit any error correcting code, and may also be applied to design new gates and encodings in other qubit platforms.
Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses
Authors: Pardi Norbert , Carreño Juan Manuel , O’Dell George , Tan Jessica , Bajusz Csaba , Muramatsu Hiromi , Rijnink Willemijn , Strohmeier Shirin , Loganathan Madhumathi , Bielak Dominika , Sung Molly M. H. , Tam Ying K. , Krammer Florian , McMahon Meagan 
Published: August 2022

AbstractMessenger RNA (mRNA) vaccines represent a new, effective vaccine platform with high capacity for rapid development. Generation of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is a necessity for reducing influenza-associated morbidity and mortality. Here we focus on the development of a universal influenza B virus vaccine based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform. We evaluate vaccine candidates based on different target antigens that afford protection against challenge with ancestral and recent influenza B viruses from both antigenic lineages. A pentavalent vaccine combining all tested antigens protects mice from morbidity at a very low dose of 50 ng per antigen after a single vaccination. These findings support the further advancement of nucleoside-modified mRNA-LNPs expressing multiple conserved antigens as universal influenza virus vaccine candidates.
Identification of a non-axisymmetric mode in laboratory experiments searching for standard magnetorotational instability
Authors: Wang Yin , Gilson Erik P. , Ebrahimi Fatima , Goodman Jeremy , Caspary Kyle J. , Winarto Himawan W. , Ji Hantao 
Published: August 2022

AbstractThe standard magnetorotational instability (SMRI) is a promising mechanism for turbulence and rapid accretion in astrophysical disks. It is a magnetohydrodynamic (MHD) instability that destabilizes otherwise hydrodynamically stable disk flow. Due to its microscopic nature at astronomical distances and stringent requirements in laboratory experiments, SMRI has remained unconfirmed since its proposal, despite its astrophysical importance. Here we report a nonaxisymmetric MHD instability in a modified Taylor-Couette experiment. To search for SMRI, a uniform magnetic field is imposed along the rotation axis of a swirling liquid-metal flow. The instability initially grows exponentially, becoming prominent only for sufficient flow shear and moderate magnetic field. These conditions for instability are qualitatively consistent with SMRI, but at magnetic Reynolds numbers below the predictions of linear analyses with periodic axial boundaries. Three-dimensional numerical simulations, however, reproduce the observed instability, indicating that it grows linearly from the primary axisymmetric flow modified by the applied magnetic field.
Repeated genetic adaptation to altitude in two tropical butterflies
Authors: Montejo-Kovacevich Gabriela , Meier Joana I. , Bacquet Caroline N. , Warren Ian A. , Chan Yingguang Frank , Kucka Marek , Salazar Camilo , Rueda-M Nicol , Montgomery Stephen H. , McMillan W. Owen , Kozak Krzysztof M. , Nadeau Nicola J. , Martin Simon H. , Jiggins Chris D. 
Published: August 2022

AbstractRepeated evolution can provide insight into the mechanisms that facilitate adaptation to novel or changing environments. Here we study adaptation to altitude in two tropical butterflies, Heliconius erato and H. melpomene, which have repeatedly and independently adapted to montane habitats on either side of the Andes. We sequenced 518 whole genomes from altitudinal transects and found many regions differentiated between highland (~ 1200 m) and lowland (~ 200 m) populations. We show repeated genetic differentiation across replicate populations within species, including allopatric comparisons. In contrast, there is little molecular parallelism between the two species. By sampling five close relatives, we find that a large proportion of divergent regions identified within species have arisen from standing variation and putative adaptive introgression from high-altitude specialist species. Taken together our study supports a role for both standing genetic variation and gene flow from independently adapted species in promoting parallel local adaptation to the environment.
Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health
Authors: Gadd Danni A. , Hillary Robert F. , McCartney Daniel L. , Shi Liu , Stolicyn Aleks , Robertson Neil A. , Walker Rosie M. , McGeachan Robert I. , Campbell Archie , Xueyi Shen , Barbu Miruna C. , Green Claire , Morris Stewart W. , Harris Mathew A. , Backhouse Ellen V. , Wardlaw Joanna M. , Steele J. Douglas , Oyarzún Diego A. , Muniz-Terrera Graciela , Ritchie Craig , Nevado-Holgado Alejo , Chandra Tamir , Hayward Caroline , Evans Kathryn L. , Porteous David J. , Cox Simon R. , Whalley Heather C. , McIntosh Andrew M. , Marioni Riccardo E. 
Published: August 2022

AbstractCharacterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4058 plasma proteins are performed (N = 774), identifying 2928 CpG-protein associations after adjustment for multiple testing. These are independent of known genetic protein quantitative trait loci (pQTLs) and common lifestyle effects. Phenome-wide association studies of each protein are then performed in relation to 15 neurological traits (N = 1,065), identifying 405 associations between the levels of 191 proteins and cognitive scores, brain imaging measures or APOE e4 status. We uncover 35 previously unreported DNA methylation signatures for 17 protein markers of brain health. The epigenetic and proteomic markers we identify are pertinent to understanding and stratifying brain health.
Microbe capture by splenic macrophages triggers sepsis via T cell-death-dependent neutrophil lifespan shortening
Authors: Ioannou Marianna , Hoving Dennis , Aramburu Iker Valle , Temkin Mia I. , De Vasconcelos Nathalia M. , Tsourouktsoglou Theodora-Dorita , Wang Qian , Boeing Stefan , Goldstone Robert , Vernardis Spyros , Demichev Vadim , Ralser Markus , David Sascha , Stahl Klaus , Bode Christian , Papayannopoulos Venizelos 
Published: August 2022

AbstractThe mechanisms linking systemic infection to hyperinflammation and immune dysfunction in sepsis are poorly understood. Extracellular histones promote sepsis pathology, but their source and mechanism of action remain unclear. Here, we show that by controlling fungi and bacteria captured by splenic macrophages, neutrophil-derived myeloperoxidase attenuates sepsis by suppressing histone release. In systemic candidiasis, microbial capture via the phagocytic receptor SIGNR1 neutralizes myeloperoxidase by facilitating marginal zone infiltration and T cell death-dependent histone release. Histones and hyphae induce cytokines in adjacent CD169 macrophages including G-CSF that selectively depletes mature Ly6Ghigh neutrophils by shortening their lifespan in favour of immature Ly6Glow neutrophils with a defective oxidative burst. In sepsis patient plasma, these mediators shorten mature neutrophil lifespan and correlate with neutrophil mortality markers. Consequently, high G-CSF levels and neutrophil lifespan shortening activity are associated with sepsis patient mortality. Hence, by exploiting phagocytic receptors, pathogens degrade innate and adaptive immunity through the detrimental impact of downstream effectors on neutrophil lifespan.
Ultra-flat and long-lived plasmons in a strongly correlated oxide
Authors: Gao Han , Ding Chao , Son Jaeseok , Zhu Yangyu , Wang Mingzheng , Yu Zhi Gen , Chen Jianing , Wang Le , Chambers Scott A. , Noh Tae Won , Zhao Mingwen , Li Yangyang 
Published: August 2022

AbstractPlasmons in strongly correlated systems are attracting considerable attention due to their unconventional behavior caused by electronic correlation effects. Recently, flat plasmons with nearly dispersionless frequency-wave vector relations have drawn significant interest because of their intriguing physical origin and promising applications. However, these flat plasmons exist primarily in low-dimensional materials with limited wave vector magnitudes (q < ~0.7 Å−1). Here, we show that long-lived flat plasmons can propagate up to ~1.2 Å−1 in α-Ti2O3, a strongly correlated three-dimensional Mott-insulator, with an ultra-small energy fluctuation (<40 meV). The strong correlation effect renormalizes the electronic bands near Fermi level with a small bandwidth, which is responsible for the flat plasmons in α-Ti2O3. Moreover, these flat plasmons are not affected by Landau damping over a wide range of wave vectors (q < ~1.2 Å−1) due to symmetry constrains on the electron wavefunctions. Our work provides a strategy for exploring flat plasmons in strongly correlated systems, which in turn may give rise to novel plasmonic devices in which flat and long-lived plasmons are desirable.
MYC sensitises cells to apoptosis by driving energetic demand
Authors: Edwards-Hicks Joy , Su Huizhong , Mangolini Maurizio , Yoneten Kubra K. , Wills Jimi , Rodriguez-Blanco Giovanny , Young Christine , Cho Kevin , Barker Heather , Muir Morwenna , Guerrieri Ania Naila , Li Xue-Feng , White Rachel , Manasterski Piotr , Mandrou Elena , Wills Karen , Chen Jingyu , Abraham Emily , Sateri Kianoosh , Qian Bin-Zhi , Bankhead Peter , Arends Mark , Gammoh Noor , von Kriegsheim Alex , Patti Gary J. , Sims Andrew H. , Acosta Juan Carlos , Brunton Valerie , Kranc Kamil R. , Christophorou Maria , Pearce Erika L. , Ringshausen Ingo , Finch Andrew J. 
Published: August 2022

AbstractThe MYC oncogene is a potent driver of growth and proliferation but also sensitises cells to apoptosis, which limits its oncogenic potential. MYC induces several biosynthetic programmes and primary cells overexpressing MYC are highly sensitive to glutamine withdrawal suggesting that MYC-induced sensitisation to apoptosis may be due to imbalance of metabolic/energetic supply and demand. Here we show that MYC elevates global transcription and translation, even in the absence of glutamine, revealing metabolic demand without corresponding supply. Glutamine withdrawal from MRC-5 fibroblasts depletes key tricarboxylic acid (TCA) cycle metabolites and, in combination with MYC activation, leads to AMP accumulation and nucleotide catabolism indicative of energetic stress. Further analyses reveal that glutamine supports viability through TCA cycle energetics rather than asparagine biosynthesis and that TCA cycle inhibition confers tumour suppression on MYC-driven lymphoma in vivo. In summary, glutamine supports the viability of MYC-overexpressing cells through an energetic rather than a biosynthetic mechanism.
Shielded soft force sensors
Authors: Aksoy Bekir , Hao Yufei , Grasso Giulio , Digumarti Krishna Manaswi , Cacucciolo Vito , Shea Herbert 
Published: August 2022

AbstractForce and strain sensors made of soft materials enable robots to interact intelligently with their surroundings. Capacitive sensing is widely adopted thanks to its low power consumption, fast response, and facile fabrication. Capacitive sensors are, however, susceptible to electromagnetic interference and proximity effects and thus require electrical shielding. Shielding has not been previously implemented in soft capacitive sensors due to the parasitic capacitance between the shield and sensing electrodes, which changes when the sensor is deformed. We address this crucial challenge by patterning the central sensing elastomer layer to control its compressibility. One design uses an ultrasoft silicone foam, and the other includes microchannels filled with liquid metal and air. The force resolution is sub-mN both in normal and shear directions, yet the sensor withstands large forces (>20 N), demonstrating a wide dynamic range. Performance is unaffected by nearby high DC and AC electric fields and even electric sparks.
Designing against phase and property heterogeneities in additively manufactured titanium alloys
Authors: Zhang Jingqi , Liu Yingang , Sha Gang , Jin Shenbao , Hou Ziyong , Bayat Mohamad , Yang Nan , Tan Qiyang , Yin Yu , Liu Shiyang , Hattel Jesper Henri , Dargusch Matthew , Huang Xiaoxu , Zhang Ming-Xing 
Published: August 2022

AbstractAdditive manufacturing (AM) creates digitally designed parts by successive addition of material. However, owing to intrinsic thermal cycling, metallic parts produced by AM almost inevitably suffer from spatially dependent heterogeneities in phases and mechanical properties, which may cause unpredictable service failures. Here, we demonstrate a synergistic alloy design approach to overcome this issue in titanium alloys manufactured by laser powder bed fusion. The key to our approach is in-situ alloying of Ti−6Al−4V (in weight per cent) with combined additions of pure titanium powders and iron oxide (Fe2O3) nanoparticles. This not only enables in-situ elimination of phase heterogeneity through diluting V concentration whilst introducing small amounts of Fe, but also compensates for the strength loss via oxygen solute strengthening. Our alloys achieve spatially uniform microstructures and mechanical properties which are superior to those of Ti−6Al−4V. This study may help to guide the design of other alloys, which not only overcomes the challenge inherent to the AM processes, but also takes advantage of the alloy design opportunities offered by AM.
Human brain structural connectivity matrices–ready for modelling
Authors: Škoch Antonín , Rehák Bučková Barbora , Mareš Jan , Tintěra Jaroslav , Sanda Pavel , Jajcay Lucia , Horáček Jiří , Španiel Filip , Hlinka Jaroslav 
Published: August 2022

AbstractThe human brain represents a complex computational system, the function and structure of which may be measured using various neuroimaging techniques focusing on separate properties of the brain tissue and activity. We capture the organization of white matter fibers acquired by diffusion-weighted imaging using probabilistic diffusion tractography. By segmenting the results of tractography into larger anatomical units, it is possible to draw inferences about the structural relationships between these parts of the system. This pipeline results in a structural connectivity matrix, which contains an estimate of connection strength among all regions. However, raw data processing is complex, computationally intensive, and requires expert quality control, which may be discouraging for researchers with less experience in the field. We thus provide brain structural connectivity matrices in a form ready for modelling and analysis and thus usable by a wide community of scientists. The presented dataset contains brain structural connectivity matrices together with the underlying raw diffusion and structural data, as well as basic demographic data of 88 healthy subjects.
New diterpenes from the marine sponge Spongionella sp. overcome drug resistance in prostate cancer by inhibition of P-glycoprotein
Authors: Dyshlovoy Sergey A. , Shubina Larisa K. , Makarieva Tatyana N. , Hauschild Jessica , Strewinsky Nadja , Guzii Alla G. , Menshov Alexander S. , Popov Roman S. , Grebnev Boris B. , Busenbender Tobias , Oh-Hohenhorst Su Jung , Maurer Tobias , Tilki Derya , Graefen Markus , Bokemeyer Carsten , Stonik Valentin A. , von Amsberg Gunhild 
Published: August 2022

AbstractSpongian diterpenes are a group of marine natural compounds possessing various biological activities. However, their anticancer activity is still poorly studied and understood. We isolated six spongian diterpenes from the marine sponge Spongionella sp., including one new spongionellol A and five previously known molecules. The structures were elucidated using a detailed analysis MS and NMR spectra as well as by comparison with previously reported data. Two of them, namely, spongionellol A and 15,16-dideoxy-15α,17β-dihydroxy-15,17-oxidospongian-16-carboxylate-15,17-diacetate exhibited high activity and selectivity in human prostate cancer cells, including cells resistant to hormonal therapy and docetaxel. The mechanism of action has been identified as caspase-dependent apoptosis. Remarkably, both compounds were able to suppress expression of androgen receptor (AR) and AR-splice variant 7, as well as AR-dependent signaling. The isolated diterpenes effectively inhibited drug efflux mediated by multidrug-resistance protein 1 (MDR1; p-glycoprotein). Of note, a synergistic effect of the compounds with docetaxel, a substrate of p-glycoprotein, suggests resensitization of p-glycoprotein overexpressing cells to standard chemotherapy. In conclusion, the isolated spongian diterpenes possess high activity and selectivity towards prostate cancer cells combined with the ability to inhibit one of the main drug-resistance mechanism. This makes them promising candidates for combinational anticancer therapy.