bluuebunny/crossref_metadata_2025 huggingface dataset:
Replication collisions induced by de-repressed S-phase transcription are connected with malignant transformation of adult stem cells
Authors: Zhang Ting , Künne Carsten , Ding Dong , Günther Stefan , Guo Xinyue , Zhou Yonggang , Yuan Xuejun , Braun Thomas
Published: November 2022

Transcription replication collisions (TRCs) constitute a major intrinsic source of genome instability but conclusive evidence for a causal role of TRCs in tumor initiation is missing. We discover that lack of the H4K20-dimethyltransferase KMT5B (also known as SUV4-20H1) in muscle stem cells de-represses S-phase transcription by increasing H4K20me1 levels, which induces TRCs and aberrant R-loops in oncogenic genes. The resulting replication stress and aberrant mitosis activate ATR-RPA32-P53 signaling, promoting cellular senescence, which turns into rapid rhabdomyosarcoma formation when p53 is absent. Inhibition of S-phase transcription ameliorates TRCs and formation of R-loops in Kmt5b-deficient MuSCs, validating the crucial role of H4K20me1-dependent, tightly controlled S-phase transcription for preventing collision errors. Low KMT5B expression is prevalent in human sarcomas and associated with tumor recurrence, suggesting a common function of KMT5B in sarcoma formation. The study uncovers decisive functions of KMT5B for maintaining genome stability by repressing S-phase transcription via control of H4K20me1 levels.
Third primary SARS-CoV-2 mRNA vaccines enhance antibody responses in most patients with haematological malignancies
Authors: Cook Lucy B. , O’Dell Gillian , Vourvou Eleni , Palanicawandar Renuka , Marks Sasha , Milojkovic Dragana , Apperley Jane F. , Loaiza Sandra , Claudiani Simone , Bua Marco , Hockings Catherine , Macdonald Donald , Chaidos Aris , Pavlu Jiri , Cooper Nichola , Fidler Sarah , Randell Paul , Innes Andrew J.
Published: November 2022

SARS-CoV-2 infection, and resulting disease, COVID-19, has a high mortality amongst patients with haematological malignancies. Global vaccine rollouts have reduced hospitalisations and deaths, but vaccine efficacy in patients with haematological malignancies is known to be reduced. The UK-strategy offered a third, mRNA-based, vaccine as an extension to the primary course in these patients. The MARCH database is a retrospective observational study of serological responses in patients with blood disorders. Here we present data on 381 patients with haematological malignancies. By comparison with healthy controls, we report suboptimal responses following two primary vaccines, with significantly enhanced responses following the third primary dose. These responses however are heterogeneous and determined by haematological malignancy sub-type and therapy. We identify a group of patients with continued suboptimal vaccine responses who may benefit from additional doses, prophylactic extended half-life neutralising monoclonal therapies (nMAB) or prompt nMAB treatment in the event of SARS-CoV-2 infection.
Accurate graphene quantum Hall arrays for the new International System of Units
Authors: He Hans , Cedergren Karin , Shetty Naveen , Lara-Avila Samuel , Kubatkin Sergey , Bergsten Tobias , Eklund Gunnar
Published: November 2022

Graphene quantum Hall effect (QHE) resistance standards have the potential to provide superior realizations of three key units in the new International System of Units (SI): the ohm, the ampere, and the kilogram (Kibble Balance). However, these prospects require different resistance values than practically achievable in single graphene devices (~12.9 kΩ), and they need bias currents two orders of magnitude higher than typical breakdown currents IC ~ 100 μA. Here we present experiments on quantization accuracy of a 236-element quantum Hall array (QHA), demonstrating RK/236 ≈ 109 Ω with 0.2 part-per-billion (nΩ/Ω) accuracy with IC ≥ 5 mA (~1 nΩ/Ω accuracy for IC = 8.5 mA), using epitaxial graphene on silicon carbide (epigraphene). The array accuracy, comparable to the most precise universality tests of QHE, together with the scalability and reliability of this approach, pave the road for wider use of graphene in the new SI and beyond.
Critical role of hydrogen sorption kinetics in electrocatalytic CO2 reduction revealed by on-chip in situ transport investigations
Authors: Mu Zhangyan , Han Na , Xu Dan , Tian Bailin , Wang Fangyuan , Wang Yiqi , Sun Yamei , Liu Cheng , Zhang Panke , Wu Xuejun , Li Yanguang , Ding Mengning
Published: November 2022

Precise understanding of interfacial metal−hydrogen interactions, especially under in operando conditions, is crucial to advancing the application of metal catalysts in clean energy technologies. To this end, while Pd-based catalysts are widely utilized for electrochemical hydrogen production and hydrogenation, the interaction of Pd with hydrogen during active electrochemical processes is complex, distinct from most other metals, and yet to be clarified. In this report, the hydrogen surface adsorption and sub-surface absorption (phase transition) features of Pd and its alloy nanocatalysts are identified and quantified under operando electrocatalytic conditions via on-chip electrical transport measurements, and the competitive relationship between electrochemical carbon dioxide reduction (CO2RR) and hydrogen sorption kinetics is investigated. Systematic dynamic and steady-state evaluations reveal the key impacts of local electrolyte environment (such as proton donors with different pKa) on the hydrogen sorption kinetics during CO2RR, which offer additional insights into the electrochemical interfaces and optimization of the catalytic systems.
Improved pharmacodynamics of epidermal growth factor via microneedles-based self-powered transcutaneous electrical stimulation
Authors: Yang Yuan , Luo Ruizeng , Chao Shengyu , Xue Jiangtao , Jiang Dongjie , Feng Yun Hao , Guo Xin Dong , Luo Dan , Zhang Jiaping , Li Zhou , Wang Zhong Lin
Published: November 2022

Epidermal growth factor is an excellent drug for promoting wound healing; however, its conventional administration strategies are associated with pharmacodynamic challenges, such as low transdermal permeability, reduction, and receptor desensitization. Here, we develop a microneedle-based self-powered transcutaneous electrical stimulation system (mn-STESS) by integrating a sliding free-standing triboelectric nanogenerator with a microneedle patch to achieve improved epidermal growth factor pharmacodynamics. We show that the mn-STESS facilitates drug penetration and utilization by using microneedles to pierce the stratum corneum. More importantly, we find that it converts the mechanical energy of finger sliding into electricity and mediates transcutaneous electrical stimulation through microneedles. We demonstrate that the electrical stimulation applied by mn-STESS acts as an “adjuvant” that suppresses the reduction of epidermal growth factor by glutathione and upregulates its receptor expression in keratinocyte cells, successfully compensating for receptor desensitization. Collectively, this work highlights the promise of self-powered electrical adjuvants in improving drug pharmacodynamics, creating combinatorial therapeutic strategies for traditional drugs.
Flash drug release from nanoparticles accumulated in the targeted blood vessels facilitates the tumour treatment
Authors: Zelepukin Ivan V. , Griaznova Olga Yu. , Shevchenko Konstantin G. , Ivanov Andrey V. , Baidyuk Ekaterina V. , Serejnikova Natalia B. , Volovetskiy Artur B. , Deyev Sergey M. , Zvyagin Andrei V.
Published: November 2022

Tumour microenvironment hinders nanoparticle transport deep into the tissue precluding thorough treatment of solid tumours and metastatic nodes. We introduce an anticancer drug delivery concept termed FlaRE (Flash Release in Endothelium), which represents alternative to the existing approaches based on enhanced permeability and retention effect. This approach relies on enhanced drug-loaded nanocarrier accumulation in vessels of the target tumour or metastasised organ, followed by a rapid release of encapsulated drug within tens of minutes. It leads to a gradient-driven permeation of the drug to the target tissue. This pharmaceutical delivery approach is predicted by theoretical modelling and validated experimentally using rationally designed MIL-101(Fe) metal-organic frameworks. Doxorubicin-loaded MIL-101 nanoparticles get swiftly trapped in the vasculature of the metastasised lungs, disassemble in the blood vessels within 15 minutes and release drug, which rapidly impregnates the organ. A significant improvement of the therapeutic outcome is demonstrated in animal models of early and late-stage B16-F1 melanoma metastases with 11-fold and 4.3-fold decrease of pulmonary melanoma nodes, respectively.
Valence-skipping and quasi-two-dimensionality of superconductivity in a van der Waals insulator
Authors: Zhang Caorong , Huang Junwei , Zhai Kun , Akhtari Keivan , Shen Zhiwei , Ao Lingyi , Li Zeya , Qin Feng , Chang Yukai , Zhou Ling , Tang Ming , Dai Xueting , Qiu Caiyu , Zhang Yi , Wang Lin , Liu Zhongyuan , Tian Yongjun , Bahramy Mohammad Saeed , Yuan Hongtao
Published: November 2022

Valence fluctuation of interacting electrons plays a crucial role in emergent quantum phenomena in correlated electron systems. The theoretical rationale is that this effect can drive a band insulator into a superconductor through charge redistribution around the Fermi level. However, the root cause of such a fluctuating leap in the ionic valency remains elusive. Here, we demonstrate a valence-skipping-driven insulator-to-superconductor transition and realize quasi-two-dimensional superconductivity in a van der Waals insulator GeP under pressure. This is shown to result from valence skipping of the Ge cation, altering its average valency from 3+ to 4+, turning GeP from a layered compound to a three-dimensional covalent system with superconducting critical temperature reaching its maximum of 10 K. Such a valence-skipping-induced superconductivity with a quasi-two-dimensional nature in thin samples, showing a Berezinskii-Kosterlitz-Thouless-like character, is further confirmed by angle-dependent upper-critical-field measurements. These findings provide a model system to examine competing order parameters in valence-skipping systems.
Engineering high quality graphene superlattices via ion milled ultra-thin etching masks
Authors: Barcons Ruiz David , Herzig Sheinfux Hanan , Hoffmann Rebecca , Torre Iacopo , Agarwal Hitesh , Kumar Roshan Krishna , Vistoli Lorenzo , Taniguchi Takashi , Watanabe Kenji , Bachtold Adrian , Koppens Frank H. L.
Published: November 2022

Nanofabrication research pursues the miniaturization of patterned feature size. In the current state of the art, micron scale areas can be patterned with features down to ~30 nm pitch using electron beam lithography. Here, we demonstrate a nanofabrication technique which allows patterning periodic structures with a pitch down to 16 nm. It is based on focused ion beam milling of suspended membranes, with minimal proximity effects typical to standard electron beam lithography. The membranes are then transferred and used as hard etching masks. We benchmark our technique by electrostatically inducing a superlattice potential in graphene and observe bandstructure modification in electronic transport. Our technique opens the path towards the realization of very short period superlattices in 2D materials, but with the ability to control lattice symmetries and strength. This can pave the way for a versatile solid-state quantum simulator platform and the study of correlated electron phases.
Theoretical insights into the Peierls plasticity in SrTiO3 ceramics via dislocation remodelling
Authors: Li Yi , Liu Xiangyang , Zhang Peng , Han Yi , Huang Muzhang , Wan Chunlei
Published: November 2022

An in-depth understanding of the dislocations motion process in non-metallic materials becomes increasingly important, stimulated by the recent emergence of ceramics and semiconductors with unexpected room temperature dislocation-mediated plasticity. In this work, local misfit energy is put forward to accurately derive the Peierls stress and model the dislocation process in SrTiO3 ceramics instead of the generalized stacking fault (GSF) approach, which considers the in-plane freedom degrees of the atoms near the shear plane and describes the breaking and re-bonding processes of the complex chemical bonds. Particularly, we discover an abnormal shear-dependence of local misfit energy, which originates from the re-bonding process of the Ti-O bonds and the reversal of lattice dipoles. In addition, this approach predicts that oxygen vacancies in the SrTiO3 can facilitate the nucleation and activation of dislocations with improvement of fracture toughness, owing to the reduction of average misfit energy and Peierls stress due to the disappearance of lattice dipole reversal. This work provides undiscovered insights into the dislocation process in non-metallic materials, which may bring implications to tune the plasticity and explore unknown ductile compositions.
Symbiotic bacteria-dependent expansion of MR1-reactive T cells causes autoimmunity in the absence of Bcl11b
Authors: Shibata Kensuke , Motozono Chihiro , Nagae Masamichi , Shimizu Takashi , Ishikawa Eri , Motooka Daisuke , Okuzaki Daisuke , Izumi Yoshihiro , Takahashi Masatomo , Fujimori Nao , Wing James B. , Hayano Takahide , Asai Yoshiyuki , Bamba Takeshi , Ogawa Yoshihiro , Furutani-Seiki Makoto , Shirai Mutsunori , Yamasaki Sho
Published: November 2022

MHC class I-related protein 1 (MR1) is a metabolite-presenting molecule that restricts MR1-reactive T cells including mucosal-associated invariant T (MAIT) cells. In contrast to MAIT cells, the function of other MR1-restricted T cell subsets is largely unknown. Here, we report that mice in which a T cell-specific transcription factor, B-cell lymphoma/leukemia 11B (Bcl11b), was ablated in immature thymocytes (Bcl11b∆iThy mice) develop chronic inflammation. Bcl11b∆iThy mice lack conventional T cells and MAIT cells, whereas CD4+IL-18R+ αβ T cells expressing skewed Traj33 (Jα33)+ T cell receptors (TCR) accumulate in the periphery, which are necessary and sufficient for the pathogenesis. The disorders observed in Bcl11b∆iThy mice are ameliorated by MR1-deficiency, transfer of conventional T cells, or germ-free conditions. We further show the crystal structure of the TCR expressed by Traj33+ T cells expanded in Bcl11b∆iThy mice. Overall, we establish that MR1-reactive T cells have pathogenic potential.
Zinc- and magnesium-doped hydroxyapatite-urea nanohybrids enhance wheat growth and nitrogen uptake
Authors: Sharma Bhaskar , Afonso Luis O. B. , Singh Manoj Pratap , Soni Udit , Cahill David M.
Published: November 2022

The ongoing and unrestrained application of nitrogen fertilizer to agricultural lands has been directly linked to climate change and reductions in biodiversity. The agricultural sector needs a technological upgrade to adopt sustainable methods for maintaining high yield. We report synthesis of zinc and magnesium doped and undoped hydroxyapatite nanoparticles, and their urea nanohybrids, to sustainably deliver nitrogen to wheat. The urea nanohybrids loaded with up to 42% nitrogen were used as a new source of nitrogen and compared with a conventional urea-based fertilizer for efficient and sufficient nitrogen delivery to pot-grown wheat. Doping with zinc and magnesium manipulated the hydroxyapatite crystallinity for smaller size and higher nitrogen loading capacity. Interestingly, 50% and 25% doses of urea nanohybrids significantly boosted the wheat growth and yield compared with 100% doses of urea fertilizer. In addition, the nutritional elements uptake and grain protein and phospholipid levels were significantly enhanced in wheat treated with nanohybrids. These results demonstrate the potential of the multi-nutrient complexes, the zinc and magnesium doped and undoped hydroxyapatite-urea nanoparticles, as nitrogen delivery agents that reduce nitrogen inputs by at least 50% while maintaining wheat plant growth and nitrogen uptake to the same level as full-dose urea treatments.
Chromosome painting and phylogenetic analysis suggest that the genus Lophostoma (Chiroptera, Phyllostomidae) is paraphyletic
Authors: da Silva Natalia Karina Nascimento , Nagamachi Cleusa Yoshiko , Rodrigues Luis Reginaldo Ribeiro , O’Brien Patricia Caroline Mary , Yang Fengtang , Ferguson-Smith Malcolm Andrew , Pieczarka Julio Cesar
Published: November 2022

The subfamily Phyllostominae (Chiroptera, Phyllostomidae) comprises 10 genera of Microchiroptera bats from the Neotropics. The taxonomy of this group is controversial due to incongruities in the phylogenetic relationships evident from different datasets. The genus Lophostoma currently includes eight species whose phylogenetic relationships have not been resolved. Integrative analyzes including morphological, molecular and chromosomal data are powerful tools to investigate the phylogenetics of organisms, particularly if obtained by chromosomal painting. In the present work we performed comparative genomic mapping of three species of Lophostoma (L. brasiliense 2n = 30, L. carrikeri 2n = 26 and L. schulzi 2n = 26), by chromosome painting using whole chromosome probes from Phyllostomus hastatus and Carollia brevicauda; this included mapping interstitial telomeric sites. The karyotype of L. schulzi (LSC) is a new cytotype. The species L. brasiliense and L. carrikeri showed interstitial telomeric sequences that probably resulted from expansions of repetitive sequences near pericentromeric regions. The addition of chromosomal painting data from other species of Phyllostominae allowed phylogeny construction by maximum parsimony, and the determination that the genera of this subfamily are monophyletic, and that the genus Lophostoma is paraphyletic. Additionally, a review of the taxonomic status of LSC is suggested to determine if this species should be reclassified as part of the genus Tonatia.
Naturally-aged microglia exhibit phagocytic dysfunction accompanied by gene expression changes reflective of underlying neurologic disease
Authors: Thomas Alyssa L. , Lehn Maria A. , Janssen Edith M. , Hildeman David A. , Chougnet Claire A.
Published: November 2022

Age-associated microglial dysfunction contributes to the accumulation of amyloid-β (Aβ) plaques in Alzheimer’s disease. Although several studies have shown age-related declines in the phagocytic capacity of myeloid cells, relatively few have examined phagocytosis of normally aged microglia. Furthermore, much of the existing data on aging microglial function have been generated in accelerated genetic models of Alzheimer’s disease. Here we found that naturally aged microglia phagocytosed less Aβ over time. To gain a better understanding of such dysfunction, we assessed differences in gene expression between young and old microglia that either did or did not phagocytose Aβ. Young microglia had both phagocytic and neuronal maintenance signatures indicative of normal microglial responses, whereas, old microglia, regardless of phagocytic status, exhibit signs of broad dysfunction reflective of underlying neurologic disease states. We also found downregulation of many phagocytic receptors on old microglia, including TREM2, an Aβ phagocytic receptor. TREM2 protein expression was diminished in old microglia and loss of TREM2+ microglia was correlated with impaired Aβ uptake, suggesting a mechanism for phagocytic dysfunction in old microglia. Combined, our work reveals that normally aged microglia have broad changes in gene expression, including defects in Aβ phagocytosis that likely underlies the progression to neurologic disease.
Peripheral arterial elasticity changes derived by volume-oscillometry in reaction to hyperemia as a possible assessment of flow-mediated vasodilatation
Authors: Yamakoshi Takehiro , Rolfe Peter , Yamakoshi Ken-ichi
Published: November 2022

The flow-mediated dilation (FMD) test is commonly utilized and is the only technique for the assessment of vascular endothelial cell function. With this test, the augmentation of a brachial artery diameter following reactive hyperemia is measured precisely using ultrasonography by a skilled operator. This is a hospital-only test, and would be more useful if conveniently performed at home. This paper describes a first approach for studying the impact of changes in peripheral arterial elasticity, with prospects towards possible assessment of functional reactivity. A recently developed smartphone-based instrument was used to measure elastic properties of finger and radial arteries, related to stiffness and vasodilatation, as a function of distending pressure derived by photo-plethysmographic volume-oscillometry. Elasticity changes in both arteries before and after a 5-min supra-systolic upper-arm cuff occlusion were successfully obtained in 15 normal volunteers. The index-values of stiffness and vasodilatation showed, respectively, a significant decrease and increase (p < 0.01), demonstrating clearly the expected elasticity changes with hyperemia, which could be consistent with the clinically-stated reaction in an FMD test. The results suggest that this method could easily provide important information of both elasticity and vasodilatation. It appears promising as a convenient assessment method to contribute to arteriosclerotic cardiovascular screening.
Tumor suppressor DEAR1 regulates mammary epithelial cell fate and predicts early onset and metastasis in triple negative breast cancer
Authors: Le Uyen Q. , Chen Nanyue , Balasenthil Seetharaman , Lurie Eugene , Yang Fei , Liu Suyu , Rubin Laura , Solis Soto Luisa Maren , Raso Maria Gabriela , Batra Harsh , Sahin Aysegul A. , Wistuba Ignacio I. , Killary Ann McNeill
Published: November 2022

Triple negative breast cancer (TNBC) is a disease of poor prognosis, with the majority classified as the basal-like subtype associated with epithelial-mesenchymal transition and metastasis. Because basal breast cancers originate from proliferative luminal progenitor-like cells upon dysregulation of proper luminal differentiation, genes regulating luminal-basal transition are critical to elucidate novel therapeutic targets to improve TNBC outcomes. Herein we demonstrate that the tumor suppressor DEAR1/TRIM62 is a critical regulator of luminal cell fate. DEAR1 loss in human mammary epithelial cells results in significantly enhanced mammosphere formation that is accelerated in the presence of TGF-β/SMAD3 signaling. Mammospheres formed following DEAR1 loss are enriched for ALDH1A1 and CK5 expression, EpCAM−/CD49f+ and CD44high/24low basal-like epithelial cells, indicating that DEAR1 regulates stem/progenitor cell properties and luminal-basal progenitor transition. We show that DEAR1 maintains luminal differentiation as a novel ubiquitin ligase for SNAI2/SLUG, a master regulator driving stemness and generation of basal-like progenitor populations. We also identify a significant inverse correlation between DEAR1 and SNAI2 expression in a 103 TNBC case cohort and show that low DEAR1 expression significantly correlates with young age of onset and shorter time to metastasis, suggesting DEAR1 could serve as a biomarker to stratify early onset TNBCs for targeted stem cell therapies.
Pulmonary non-tuberculous mycobacteria in colonisation and disease in The Gambia
Authors: Okoi Catherine , Anderson Suzanne T. , Mulwa Sarah , Worwui Archibald , Antonio Martin , Gehre Florian , Adetifa Ifedayo
Published: November 2022

The clinical relevance of pulmonary non-tuberculous mycobacteria (PNTM) in The Gambia is unknown. The aim of this study was to estimate the prevalence of non-tuberculous mycobacteria (NTM) in colonisation, and the burden of clinically relevant pulmonary NTM (PNTM) disease in The Gambia. This was a cross-sectional study of the prevalence of NTM in participants aged ≥ 15 years, in a nationwide tuberculosis (TB) prevalence survey between December 2011 and January 2013. We enrolled 903 participants with suspected NTM and NTM cultures were confirmed by 16S rRNA gene sequencing analyses. We applied the American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) diagnostic criteria to determine clinical relevance of NTM. A total of 575 participants had acid-fast bacilli (AFB) positive Mycobacterial Growth Indicator Tube (MGIT) cultures and 229 (39.8%) were NTM. M. avium complex was by far the most isolated NTM (71.0%), followed by M. fortuitum (9.5%) and M. nonchromogenicum (2.9%). Older participants (> 24 years old) were four times more likely to have NTM in their sputa. Only 20.5% (9/44) NTM cases met the ATS/IDSA criteria for NTM disease. This study provides important data on the prevalence of NTM in pulmonary samples of suspected TB cases with AFB positive cultures from a nationally representative population in The Gambia. Enhanced PNTM surveillance is recommended to better understand the contribution of NTM to pulmonary disease.
Extraction and mapping of downpour impact and their Cumulonimbus origin, 20 May 2020, Vâlcea (Romania) via Sentinnel-1 SAR dual polarization
Authors: Hachemi Kamel , Grecu Florina , Constantin Dana Maria , Ioana-Toroimac Gabriela
Published: November 2022

The aim of this work is to study the impact and characteristics of the meteorological phenomenon that occurred on May 20, 2020 in Vâlcea County, Romania. For this purpose, we used SAR radar images from the Sentinel-1 series at different dates, before, during and after the event. The methodology consists in exploiting and combining the two polarisations, VV and VH, of the recorded radar wave. The results obtained can be summarised as the extraction of areas completely covered by water and areas characterised by high roughness and very high humidity. The latter (roughness/humidity) can have two different origins. The first one corresponds to an area affected by downpours, giving a high roughness due to the interaction of water drops with the ground and also to the presence of hail, amplified by the wind factor. On the other hand, the second one coincides, quite simply, with the presence of a thundercloud, precisely a Cumulonimbus, which formed in that particular place as a result of the favourable geomorphological characteristics and meteorological conditions, giving a high humidity due to the high water content. We also determined the total impacted area of about 96.71 km2, whose 60.17 km2 of water covered area, which is 2.45% of the study area. The remaining 36.54 km2 (1.49%) represents the affected rough surface, located in the plain, or the humid surface corresponding to the area of the Cumulonimbus head covering the plain.
Gut bacteriome and metabolome of Ascaris lumbricoides in patients
Authors: Klomkliew Pavit , Sawaswong Vorthon , Chanchaem Prangwalai , Nimsamer Pattaraporn , Adisakwattana Poom , Phuphisut Orawan , Tipthara Phornpimon , Tarning Joel , Payungporn Sunchai , Reamtong Onrapak
Published: November 2022

The most frequent intestinal helminth infections in humans are attributed to Ascaris lumbricoides, and there are concerns over the anthelminthic resistance of this species. The gut microbiota has essential roles in host physiology. Therefore, discovering host-parasite–microbiota interactions could help develop alternative helminthiasis treatments. Additionally, these interactions are modulated by functional metabolites that can reveal the mechanisms of infection and disease progression. Thus, we aimed to investigate bacteriomes in the gut of helminths and fecal samples of patients via next-generation sequencing. Our results showed that infection intensity was associated with the bacterial composition of helminth guts but not with the intestinal bacteriome of human hosts. Moreover, the metabolomes of A. lumbricoides in the heavy and light ascariasis cases were characterized using ultra-high performance liquid chromatography/time-of-flight mass spectrometry. Increased levels of essential biomolecules, such as amino acids, lipids, and nucleotide precursors, were found in the guts of helminths isolated from heavily infected patients, implying that these metabolites are related to egg production and ascariasis pathogenicity. These findings are the first step towards a more complete understanding of the mechanisms by which the bacteriome of helminth guts affect their colonization and may reveal novel and more effective approaches to parasitic disease therapy.
A robust bacterial high-throughput screening system to evaluate single nucleotide polymorphisms of human homogentisate 1,2-dioxygenase in the context of alkaptonuria
Authors: Lequeue Sien , Neuckermans Jessie , Nulmans Ine , Schwaneberg Ulrich , Vanhaecke Tamara , De Kock Joery
Published: November 2022

Alkaptonuria (AKU) is a rare inborn error of metabolism caused by a defective homogentisate 1,2-dioxygenase (HGD), an enzyme involved in the tyrosine degradation pathway. Loss of HGD function leads to the accumulation of homogentisic acid (HGA) in connective body tissues in a process called ochronosis, which results on the long term in an early-onset and severe osteoarthropathy. HGD’s quaternary structure is known to be easily disrupted by missense mutations, which makes them an interesting target for novel treatment strategies that aim to rescue enzyme activity. However, only prediction models are available providing information on a structural basis. Therefore, anE. colibased whole-cell screening was developed to evaluate HGD missense variants in 96-well microtiter plates. The screening principle is based on HGD’s ability to convert the oxidation sensitive HGA into maleylacetoacetate. More precisely, catalytic activity could be deduced from pyomelanin absorbance measurements, derived from the auto-oxidation of remaining HGA. Optimized screening conditions comprised severalE. coliexpression strains, varied expression temperatures and varied substrate concentrations. In addition, plate uniformity, signal variability and spatial uniformity were investigated and optimized. Finally, eight HGD missense variants were generated via site-directed mutagenesis and evaluated with the developed high-throughput screening (HTS) assay. For the HTS assay, quality parameters passed the minimum acceptance criterion for Z’ values > 0.4 and single window values > 2. We found that activity percentagesversuswildtype HGD were 70.37 ± 3.08% (for M368V), 68.78 ± 6.40% (for E42A), 58.15 ± 1.16% (for A122V), 69.07 ± 2.26% (for Y62C), 35.26 ± 1.90% (for G161R), 35.86 ± 1.14% (for P230S), 23.43 ± 4.63% (for G115R) and 19.57 ± 11.00% (for G361R). To conclude, a robust, simple, and cost-effective HTS system was developed to reliably evaluate and distinguish human HGD missense variants by their HGA consumption ability. This HGA quantification assay may lay the foundation for the development of novel treatment strategies for missense variants in AKU.
Knockdown of the long noncoding RNA PURPL induces apoptosis and sensitizes liver cancer cells to doxorubicin
Authors: Berhane Tsinat , Holm Anja , Karstensen Kasper Thystrup , Petri Andreas , Ilieva Mirolyuba Simeonova , Krarup Henrik , Vyberg Mogens , Løvendorf Marianne Bengtson , Kauppinen Sakari
Published: November 2022

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with increasing incidence in western countries. Most HCC patients have advanced cancer at the time of diagnosis due to the asymptomatic nature of early-stage HCC and do not qualify for potentially curative surgical treatment, thus, highlighting the need for new therapeutic strategies. Long noncoding RNAs (lncRNAs) comprise a large and heterogeneous group of non-protein coding transcripts that play important regulatory roles in numerous biological processes in cancer. In this study, we performed RNA sequencing of liver biopsies from ten HCC, ten hepatitis C virus-associated HCC, and four normal livers to identify dysregulated lncRNAs in HCC. We show that the lncRNA p53-upregulated-regulator-of-p53-levels (PURPL) is upregulated in HCC biopsies and that its expression is p53-dependent in liver cancer cell lines. In addition, antisense oligonucleotide-mediated knockdown of PURPL inhibited cell proliferation, induced apoptosis, and sensitized HepG2 human HCC cells to treatment with the chemotherapeutic agent doxorubicin. In summary, our findings suggest that PURPL could serve as a new therapeutic target for reversing doxorubicin resistance in HCC.
Durability and strength degradation of xanthan gum based biopolymer treated soil subjected to severe weathering cycles
Authors: Lee Minhyeong , Kwon Yeong-Man , Park Dong-Yeup , Chang Ilhan , Cho Gye-Chun
Published: November 2022

Biopolymer-based soil treatments have shown effectiveness in soil improvement, with successful field-scale implementation. In this study, we explored the effect of cyclic wetting–drying (W–D) and freezing–thawing (F–T) on the strength durability of biopolymer-treated soils. The results indicate that cyclic W–D and F–T gradually degrade soil strength owing to water adsorption and local biopolymer dilution. Poorly graded sand was highly vulnerable to these weathering effects; however, this problem was mitigated when the soil contained a fines content of 15–25%. These biopolymer-treated soils effectively resisted numerous cycles of both W–D and F–T, indicating that biopolymer-treated soils are suitable for earthen slope reinforcement.
Impacts of the US southeast wood pellet industry on local forest carbon stocks
Authors: Aguilar Francisco X. , Sudekum Houston , McGarvey Ronald , Knapp Benjamin , Domke Grant , Brandeis Consuelo
Published: November 2022

We assessed the net impacts of a wood-dependent pellet industry of global importance on contemporaneous local forest carbon component pools (live trees, standing-dead trees, soils) and total stocks. We conducted post-matched difference-in-differences analyses of forest inventory data between 2000 and 2019 to infer industrial concurrent and lagged effects in the US coastal southeast. Results point to contemporaneous carbon neutrality. We found net incremental effects on carbon pools within live trees, and no net effects on standing-dead tree nor soil pools. However, we found concurrent lower carbon levels in soils, mixed effects associated with increased procurement pressures and large mill pelletization capacity, and possible spillover effects on standing-dead tree carbon pools beyond commercial procurement distances. There is robust evidence that although some trade-offs between carbon pools exist, the wood pellet industry in this particular context and period has met the overall condition of forest carbon neutrality.
Random lasing and replica symmetry breaking in GeO2-PbO-MgO glass–ceramics doped with neodymium
Authors: Câmara Josivanir G. , da Silva Davinson M. , Kassab Luciana R. P. , Silva-Neto Manoel L. , Palacios Guillermo , de Araújo Cid B.
Published: November 2022

We investigated the random lasing process and Replica Symmetry Breaking (RSB) phenomenon in neodymium ions (Nd3+) doped lead-germanate glass–ceramics (GCs) containing MgO. Glass samples were fabricated by conventional melt-quenching technique and the GCs were obtained by carefully devitrifying the parent glasses at 830 °C for different time intervals. The partial crystallization of the parent glasses was verified by X-ray diffraction. Photoluminescence (PL) enhancement of $$\approx$$
≈
500% relative to the parent glasses was observed for samples with a higher crystallinity degree (annealed during 5 h). Powders with grains having average size of 2 µm were prepared by griding the GCs samples. The Random Laser (RL) was excited at 808 nm, in resonance with the Nd3+ transition 4I9/2 → {4F5/2, 2H9/2}, and emitted at 1068 nm (transition 4F3/2 → 4I11/2). The RL performance was clearly enhanced for the sample with the highest crystallinity degree whose energy fluence excitation threshold (EFEth) was 0.25 mJ/mm2. The enhanced performance is attributed to the residence-time growth of photons inside the sample and the higher quantum efficiency of Nd3+ incorporated within the microcrystals, where radiative losses are reduced. Moreover, the phenomenon of Replica Symmetry Breaking (RSB), characteristic of a photonic-phase-transition, was detected by measuring the intensity fluctuations of the RL emission. The Parisi overlap parameter was determined for all samples, for excitation below and above the EFEth. This is the first time, for the best of the authors knowledge, that RL emission and RSB are reported for a glass–ceramic system.
A new negative feedback mechanism for MAPK pathway inactivation through Srk1 MAPKAP kinase
Authors: Marquina Maribel , Lambea Eva , Carmona Mercé , Sánchez-Marinas Marta , López-Aviles Sandra , Ayte José , Hidalgo Elena , Aligue Rosa
Published: November 2022

The fission yeast mitogen-activated kinase (MAPK) Sty1 is essential for cell survival in response to different environmental insults. In unstimulated cells, Sty1 forms an inactive ternary cytoplasmatic complex with the MAPKK Wis1 and the MAPKAP kinase Srk1. Wis1 phosphorylates and activates Sty1, inducing the nuclear translocation of the complex. Once in the nucleus, Sty1 phosphorylates and activates Srk1, which in turns inhibits Cdc25 and cell cycle progression, before being degraded in a proteasome-dependent manner. In parallel, active nuclear Sty1 activates the transcription factor Atf1, which results in the expression of stress response genes including pyp2 (a MAPK phosphatase) and srk1. Despite its essentiality in response to stress, persistent activation of the MAPK pathway can be deleterious and induces cell death. Thus, timely pathway inactivation is essential to ensure an appropriate response and cell viability. Here, uncover a role for the MAPKAP kinase Srk1 as an essential component of a negative feedback loop regulating the Sty1 pathway through phosphorylation and inhibition of the Wis1 MAPKK. This feedback regulation by a downstream kinase in the pathway highlights an additional mechanism for fine-tuning of MAPK signaling. Thus, our results indicate that Srk1 not only facilitates the adaptation to stress conditions by preventing cell cycle progression, but also plays an instrumental role regulating the upstream kinases in the stress MAPK pathway.
Defect-free and crystallinity-preserving ductile deformation in semiconducting Ag2S
Authors: Misawa Masaaki , Hokyo Hinata , Fukushima Shogo , Shimamura Kohei , Koura Akihide , Shimojo Fuyuki , Kalia Rajiv K. , Nakano Aiichiro , Vashishta Priya
Published: November 2022

Typical ductile materials are metals, which deform by the motion of defects like dislocations in association with non-directional metallic bonds. Unfortunately, this textbook mechanism does not operate in most inorganic semiconductors at ambient temperature, thus severely limiting the development of much-needed flexible electronic devices. We found a shear-deformation mechanism in a recently discovered ductile semiconductor, monoclinic-silver sulfide (Ag2S), which is defect-free, omni-directional, and preserving perfect crystallinity. Our first-principles molecular dynamics simulations elucidate the ductile deformation mechanism in monoclinic-Ag2S under six types of shear systems. Planer mass movement of sulfur atoms plays an important role for the remarkable structural recovery of sulfur-sublattice. This in turn arises from a distinctively high symmetry of the anion-sublattice in Ag2S, which is not seen in other brittle silver chalcogenides. Such mechanistic and lattice-symmetric understanding provides a guideline for designing even higher-performance ductile inorganic semiconductors.
Evaluation of three biometric devices: ocular parameters and calculated intraocular lens power
Authors: Lender Rivkah , Mirsky Devora , Greenberger Riki , Boim Zipora , Ben-Yaakov Lee , Kashtan Chaya , Naffar Ibrahim , Shine Shira , Chowers Itay , Ben-Eli Hadas
Published: November 2022

Cataract surgery is among the most common medical procedures, and accurate ocular biometry measurements are key for successful visual outcome. The current study evaluated data obtained by the Eyestar 900, Anterion, IOLMaster700 biometers and the Pentacam corneal topographer. Compared values were axial length (AL), anterior chamber depth (ACD), steep- and flat-K, cylinder and axis. Clinical impact was assessed by calculating intraocular lens (IOL) power using the mean values of every parameter and the Barrett and Kane formulas, stratified by device and amount of cylinder. IOL was re-calculated for each device substituting Pentacam K-values. This study included 196 eyes (98 participants) of cataract surgery candidates. When comparing the IOLMaster to the Eyestar (157 eyes), no difference was found in mean AL or ACD measurements (P > 0.05). Steep-K measurements differed between these devices and the Pentacam (P = 0.01). AL and ACD measurements differed between the IOLMaster and Anterion (38 eyes; P < 0.05). Strong correlations (range 0.72–0.99) were found between all four devices. Bland–Altman analysis demonstrated excellent agreement between biometry devices other than ACD between the IOLMaster and Eyestar. Calculated IOL power was 0.50–1.00 diopter (D) lower with the IOLMaster. Cylinder power was 0.75D higher in all biometers when Pentacam K-values were substituted.
Risk factors of developmental dysplasia of the hip in a single clinical center
Authors: Xiao Huan , Tang Yi , Su Yuxi
Published: November 2022

Developmental dysplasia of the hip (DDH) is the main cause of early-onset hip osteoarthritis in adulthood. Early screening of DDH is the key to avoiding these severe complications. This study aimed to assure the risk factors are suitable for screening patients with DDH in our region. We retrospectively analyzed 10,668 patients (21,336 hips) at our hospital. Overall, 204 patients with pathological DDH and 408 patients with normal hips were included in this study. All patients were diagnosed by performing ultrasound examinations according to the Graf technique. The risk factors were assessed based on patients’ clinical data. Pearson’s chi-square or Fisher’s exact tests and multivariate logistic regression analysis were performed for statistical analysis. A total of 204 patients were diagnosed with pathologic DDH and were treated with the Pavlik harness. Among these, 184 patients were female. There were 73 cases of first birth, 13 had oligohydramnios, 13 had foot deformity, 31 had breech delivery, 6 had congenital muscular torticollis. Female sex, vaginal delivery, breech presentation, oligohydramnios and foot deformity were identified as the risk factors for DDH. The risk factors of DDH in our clinical center were confirmed in our clinical center, this can supply the screening advice for the doctors.
Scenarios for Ecodesign in loudspeaker’s motor
Authors: de Almeida Allan Di Cunto D’Avila , Garde Ivan Aritz Aldaya , dos Santos Mirian Paula , Penchel Rafael Abrantes , Filho Lúcio Cardozo , de Oliveira José Augusto
Published: November 2022

The worldwide loudspeaker market follows the growing tendency of electronic entertainment technologies both in quantity and variety. Consequently, the environmental impacts caused during the life cycle of loudspeakers increase in the same proportion, going in the opposite direction to what is determined by world environmental laws and regulations and global market tendencies. Even so, the environmental performance of this type of product is not considered in the decision-making process for technological updates in loudspeaker design. In this sense, Ecodesign is the most adequate Life Cycle Engineering tool applied in the design of a product since the environmental performance is considered throughout the different design stages. However, the feasibility of Ecodesign in products requiring complex production chains relies on splitting the product into subsystems and components. Thus, the present work focuses on evaluating the environmental performance of a classic loudspeaker motor, which is composed of a magnet, coil, and coil former. Eight raw material substitution scenarios are proposed and analyzed, which allowed the proposal identification with the best environmental performance within the current technologies. This represents an initial step toward the complete Ecodesign of a loudspeaker and sets the procedure to be followed with the other constitutive parts.
Behavior of echocardiographic parameters of right ventricular function after tricuspid surgery
Authors: Rodríguez Torres Diego José , Quintero Lucía Torres , Segura-Rodriguez Diego , Jimenez Jose Manuel Garrido , Molina Maria Esteban , Martínez Francisco Gomera , Escobar Eduardo Moreno , Orta Rocío García
Published: November 2022

Evaluation of right ventricular (RV) function after tricuspid valve surgery is complex. The objective was to identify the most appropriate RV function parameters for this purpose. This prospective study included 70 patients undergoing cardiac and tricuspid valve (TV) surgery. RV size and function parameters were determined at 3 months and 1-year post-surgery. Categorical variables were analyzed with the McNemar test and numerical variables with the Student’s t-test for related samples or, when non-normally distributed, the Wilcoxon test. Spearman's rho was used to determine correlations between variables at 3 months and 1 year. RV diameters were reduced at 3 months post-surgery and were then unchanged at 1 year. Tricuspid annular plane systolic excursion (TAPSE) and S′ wave values were worse at 3 months and then improved at 1 year (t-score-2.35, p 0.023; t-score-2.68; p 0.010). There was no significant reduction in free wall longitudinal strain (LS) or shortening fraction (SF) at 3 months (t-score 1.421 and − 1.251; p 0.218 and 0.172), and they were only slightly below pre-surgical values at 1 year. No relationship was found between RV function parameters and mortality or major complications. During the first few months after TV surgery, LS may be a more appropriate parameter to evaluate global ventricular function in comparison to TAPSE. At 1 year, good correlations are observed between TAPSE, S′ wave, and LS values.
Amazonian Anopheles with low numbers of oocysts transmit Plasmodium vivax sporozoites during a blood meal
Authors: Pereira-Silva Jordam William , Martins-Campos Keillen Monick , Ferreira-Neto José Vicente , Lacerda Marcus Vinicius Guimarães , Pessoa Felipe Arley Costa , Ríos-Velásquez Claudia María
Published: November 2022

Anopheles darlingi is the main malarial vector in the Brazilian Amazon region. An. nuneztovari s.l., An. triannulatus s.l., An. evansae, and An. benarrochi s.l. do not have a defined role as malarial vectors, although they have been found to be naturally infected with Plasmodium vivax, and some develop oocysts. In this study, we evaluated the importance of low numbers of oocysts in sporozoite salivary gland invasion and transmission. Field-collected mosquitoes were experimentally infected with P. vivax. The infection rates and oocyst and sporozoite infection intensities were evaluated and compared with those of An. aquasalis. We found the highest number of oocysts in An. darlingi (mean = 39.47) and the lowest in An. nuneztovari s.l. (mean = 2). The highest number of sporozoites was observed in An. darlingi (mean = 610) and lowest in An. benarrochi s.l. (mean = 30). Plasmodium vivax DNA was detected in the saliva of all mosquito species after a blood meal. Regardless of the number of oocysts, all species transmitted sporozoites during blood meals. Considering the abundance of these mosquitoes and transmission of sporozoites, it is logical to assume that An. nuneztovari s.l. and An. triannulatus s.l. are involved in the transmission of P. vivax.