bluuebunny/crossref_metadata_2025 huggingface dataset:
The virtual element method
Authors: Beirão Da Veiga Lourenço , Brezzi Franco , Marini L. Donatella , Russo Alessandro
Published: May 2023

The present review paper has several objectives. Its primary aim is to give an idea of the general features of virtual element methods (VEMs), which were introduced about a decade ago in the field of numerical methods for partial differential equations, in order to allow decompositions of the computational domain into polygons or polyhedra of a very general shape.

Nonetheless, the paper is also addressed to readers who have already heard (and possibly read) about VEMs and are interested in gaining more precise information, in particular concerning their application in specific subfields such as
${C}^1$
-approximations of plate bending problems or approximations to problems in solid and fluid mechanics.
ON THREE-VALUED PRESENTATIONS OF CLASSICAL LOGIC
Authors: DA RÉ BRUNO , SZMUC DAMIAN , CHEMLA EMMANUEL , ÉGRÉ PAUL
Published: May 2023

Given a three-valued definition of validity, which choice of three-valued truth tables for the connectives can ensure that the resulting logic coincides exactly with classical logic? We give an answer to this question for the five monotonic consequence relations
$st$
,
$ss$
,
$tt$
,
$ss\cap tt$
, and
$ts$
, when the connectives are negation, conjunction, and disjunction. For
$ts$
and
$ss\cap tt$
the answer is trivial (no scheme works), and for
$ss$
and
$tt$
it is straightforward (they are the collapsible schemes, in which the middle value acts like one of the classical values). For
$st$
, the schemes in question are the Boolean normal schemes that are either monotonic or collapsible.
Transition to retirement impact on risk of depression and suicidality: results from a longitudinal analysis of the Survey of Health, Ageing and Retirement in Europe (SHARE)
Authors: Mosconi G. , Vigezzi G. P. , Bertuccio P. , Amerio A. , Odone A.
Published: May 2023

Aims

Depression is among the main contributors to older adults’ mental health burden. Retirement, one of the major life transitions, has been claimed to influence mental health substantially. Following up on a previous meta-analysis, the study aims to assess from a longitudinal perspective short- and long-term impacts of transitioning to retirement on depression risk and suicidality in older adults across Europe.

Methods

We conducted a longitudinal study using data from the Survey of Health, Ageing and Retirement in Europe (SHARE), collected between 2004 and 2020 in 27 European countries plus Israel. To estimate relative risks (RR) and 95% confidence intervals (95% CIs) for depression and suicidality at seven time intervals before and after retirement, we fitted adjusted generalized estimating equation models for repeated measures.

Results

We included 8,998 individuals employed at baseline and retired at follow-up (median follow-up time: 9 years; maximum: 16 years). Compared to the year of retirement, the risk of depression was 11% lower in the following year (RR 0.89; 95% CI 0.81–0.99), 9% lower after 2 years (RR 0.91; 95% CI 0.82–1.00) and after 3 years (RR 0.91; 95% CI 0.81–1.01). Significant estimates remained among females, married individuals, those with an intermediate or higher level of education, former manual workers and those who retired at or before their country’s median retirement age. A significant increase in depressive symptoms emerged from the tenth year after retirement among former non-manual workers (RR 1.21; 95% CI 1.05–1.40) and late retirees (RR 1.37; 95% CI 1.16–1.63). No heterogeneity emerged among strata. As for suicidality, we reported an increase in risk only 5 years or more after retirement, namely +30% 5–9 years after retirement (RR 1.30; 95% CI 1.04–1.64) and +47% 10 or more years after retirement (RR 1.47; 95% CI 1.09–1.98). Sensitivity analyses excluding subjects who reported a diagnosis of depression over the study period and those retirees who declared to receive a disability pension confirmed the results obtained in the overall analysis.

Conclusions

Longitudinal adjusted data suggest an independent effect of retiring associated with a reduction in depression and suicidality risk in the short run, with its effect decreasing in the long run. Such trends are particularly evident among selected subgroups of elderly populations. If greater flexibility in pensionable age may help prevent depression late in life, the transition to retirement is to be accompanied by targeted health promotion interventions. In an ageing society, welfare policies should be evaluated, considering their long-term impact on mental health.
Microscale Magnetic Inversion of Remanent Magnetization Mineral Sources From the Black Hill Norite, South Australia
Authors: Lee M. D. , McEnroe S. , Pastore Z. , Church N. , Schmidt P.
Published: May 2023

Inverse modeling of regional‐scale aeromagnetic data is complicated due to the non‐uniqueness principle and interference of anomalies, especially with increased source‐sensor separation. This is why in situ data and constraints are required to create a reliable inversion model. However, these complications even exist when analysis is conducted at a microscale level with the magnetic mapping of a thin section. Here, we assess the impact of magnetic minerals on adjacent non‐magnetic minerals, specifically magnetite and ilmenite, respectively. The sample is from the Black Hill Norite, South Australia, which has been the focus of both paleomagnetic and geophysical modeling. Here, we conduct inverse modeling of all opaque minerals in the thin section. During post‐modeling, the opaque minerals are identified as magnetite or ilmenite using backscatter electron imaging for quantifiable classification. The results show that ilmenite will exhibit a magnetic intensity and direction when magnetite lamellae are present or when it is adjacent to a magnetite grain from which the ilmenite grain was oxy‐exsolved. We also assess the scale of interpretation by modeling the grains both as a singular volume (frustum) and as a series of smaller volumes (tabular arrays). It is shown that although the magnetic field generated by the frustums and the tabular arrays are quantitatively similar to the original measured magnetic field from the scanning magnetic microscope, the tabular array produces a closer fit to the modeled anomaly.
Direct H2S, HS− and pH Measurements of High‐Temperature Hydrothermal Vent Fluids With In Situ Raman Spectroscopy
Authors: Li Lianfu , Li Zimeng , Zhong Richen , Du Zengfeng , Luan Zhendong , Xi Shichuan , Zhang Xin
Published: May 2023

Hydrothermal H2S is an important energy source for hydrothermal ecosystems. However, it is difficult to obtain accurate hydrogen sulfide concentrations in high‐temperature hydrothermal fluids because they are highly susceptible to oxidation and compositional variability with mixing. In this study, a new in situ approach for measuring H2S, HS− and pH in hydrothermal fluids was developed and applied to the detections of Okinawa Trough hydrothermal activities. The in situ total H2S concentrations in the Jade and Biwako fluids were determined to be 31.4 and 76.7 mmol/kg, respectively. The in situ measured pH of the Jade fluids was determined to be 6.3, which has exceeded that of a neutral fluid at a specific temperature and pressure, indicating that the pH of Jade fluids is weakly alkaline. The pH transition of hydrothermal fluids from alkaline to acidic may be attributed to the thermal decomposition of organic matter and sulfide precipitation.
Long‐Term Support Is Needed for Crucial Ground‐Based Sensor Networks
Authors: Gannon J. L. , Morley S. , Lugaz N. , Liu H. , Carter B. , Zou S.
Published: May 2023

Recently, many in the space weather community have taken up the cause to advocate for an orphan among our own. It’s an important fight—for ground‐based sensor networks. Although ground‐based sensors are used across all disciplines of space weather, in terms of long‐term support, they have no single clear home in any United States agency or department. This has resulted in an ongoing struggle throughout the community to maintain important space weather sensors and networks.
Metabolic influence of core ciliates within the rumen microbiome
Authors: Andersen Thea O , Altshuler Ianina , Vera-Ponce de León Arturo , Walter Juline M , McGovern Emily , Keogh Kate , Martin Cécile , Bernard Laurence , Morgavi Diego P , Park Tansol , Li Zongjun , Jiang Yu , Firkins Jeffrey L , Yu Zhongtang , Hvidsten Torgeir R , Waters Sinead M , Popova Milka , Arntzen Magnus Ø , Hagen Live H , Pope Phillip B
Published: May 2023

Protozoa comprise a major fraction of the microbial biomass in the rumen microbiome, of which the entodiniomorphs (order: Entodiniomorphida) and holotrichs (order: Vestibuliferida) are consistently observed to be dominant across a diverse genetic and geographical range of ruminant hosts. Despite the apparent core role that protozoal species exert, their major biological and metabolic contributions to rumen function remain largely undescribed in vivo. Here, we have leveraged (meta)genome-centric metaproteomes from rumen fluid samples originating from both cattle and goats fed diets with varying inclusion levels of lipids and starch, to detail the specific metabolic niches that protozoa occupy in the context of their microbial co-habitants. Initial proteome estimations via total protein counts and label-free quantification highlight that entodiniomorph species Entodinium and Epidinium as well as the holotrichs Dasytricha and Isotricha comprise an extensive fraction of the total rumen metaproteome. Proteomic detection of protozoal metabolism such as hydrogenases (Dasytricha, Isotricha, Epidinium, Enoploplastron), carbohydrate-active enzymes (Epidinium, Diplodinium, Enoploplastron, Polyplastron), microbial predation (Entodinium) and volatile fatty acid production (Entodinium and Epidinium) was observed at increased levels in high methane-emitting animals. Despite certain protozoal species having well-established reputations for digesting starch, they were unexpectedly less detectable in low methane emitting-animals fed high starch diets, which were instead dominated by propionate/succinate-producing bacterial populations suspected of being resistant to predation irrespective of host. Finally, we reaffirmed our abovementioned observations in geographically independent datasets, thus illuminating the substantial metabolic influence that under-explored eukaryotic populations have in the rumen, with greater implications for both digestion and methane metabolism.
UDP-glucuronate metabolism controls RIPK1-driven liver damage in nonalcoholic steatohepatitis
Authors: Zhang Tao , Zhang Na , Xing Jing , Zhang Shuhua , Chen Yulu , Xu Daichao , Gu Jinyang
Published: May 2023

Hepatocyte apoptosis plays an essential role in the progression of nonalcoholic steatohepatitis (NASH). However, the molecular mechanisms underlying hepatocyte apoptosis remain unclear. Here, we identify UDP-glucose 6-dehydrogenase (UGDH) as a suppressor of NASH-associated liver damage by inhibiting RIPK1 kinase-dependent hepatocyte apoptosis. UGDH is progressively reduced in proportion to NASH severity. UGDH absence from hepatocytes hastens the development of liver damage in male mice with NASH, which is suppressed by RIPK1 kinase-dead knockin mutation. Mechanistically, UGDH suppresses RIPK1 by converting UDP-glucose to UDP-glucuronate, the latter directly binds to the kinase domain of RIPK1 and inhibits its activation. Recovering UDP-glucuronate levels, even after the onset of NASH, improved liver damage. Our findings reveal a role for UGDH and UDP-glucuronate in NASH pathogenesis and uncover a mechanism by which UDP-glucuronate controls hepatocyte apoptosis by targeting RIPK1 kinase, and suggest UDP-glucuronate metabolism as a feasible target for more specific treatment of NASH-associated liver damage.
Recovery of homogeneous photocatalysts by covalent organic framework membranes
Authors: Yang Hao , Xu Jinhui , Cao Hui , Wu Jie , Zhao Dan
Published: May 2023

Transition metal-based homogeneous photocatalysts offer a wealth of opportunities for organic synthesis. The most versatile ruthenium(II) and iridium(III) polypyridyl complexes, however, are among the rarest metal complexes. Moreover, immobilizing these precious catalysts for recycling is challenging as their opacity may obstruct light transmission. Recovery of homogeneous catalysts by conventional polymeric membranes is promising but limited, as the modulation of their pore structure and tolerance of polar organic solvents are challenging. Here, we report the effective recovery of homogeneous photocatalysts using covalent organic framework (COF) membranes. An array of COF membranes with tunable pore sizes and superior organic solvent resistance were prepared. Ruthenium and iridium photoredox catalysts were recycled for 10 cycles in various types of photochemical reactions, constantly achieving high catalytical performance, high recovery rates, and high permeance. We successfully recovered the photocatalysts at gram-scale. Furthermore, we demonstrated a cascade isolation of an iridium photocatalyst and purification of a small organic molecule product with COF membranes possessing different pore sizes. Our results indicate an intriguing potential to shift the paradigm of the pharmaceutical and fine chemical synthesis campaign.
Monoterpenoid aryl hydrocarbon receptor allosteric antagonists protect against ultraviolet skin damage in female mice
Authors: Ondrová Karolína , Zůvalová Iveta , Vyhlídalová Barbora , Krasulová Kristýna , Miková Eva , Vrzal Radim , Nádvorník Petr , Nepal Binod , Kortagere Sandhya , Kopečná Martina , Kopečný David , Šebela Marek , Rastinejad Fraydoon , Pu Hua , Soural Miroslav , Rolfes Katharina Maria , Haarmann-Stemmann Thomas , Li Hao , Mani Sridhar , Dvořák Zdeněk
Published: May 2023

The human aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is a pivotal regulator of human physiology and pathophysiology. Allosteric inhibition of AhR was previously thought to be untenable. Here, we identify carvones as noncompetitive, insurmountable antagonists of AhR and characterize the structural and functional consequences of their binding. Carvones do not displace radiolabeled ligands from binding to AhR but instead bind allosterically within the bHLH/PAS-A region of AhR. Carvones do not influence the translocation of ligand-activated AhR into the nucleus but inhibit the heterodimerization of AhR with its canonical partner ARNT and subsequent binding of AhR to the promoter of CYP1A1. As a proof of concept, we demonstrate physiologically relevant Ahr-antagonism by carvones in vivo in female mice. These substances establish the molecular basis for selective targeting of AhR regardless of the type of ligand(s) present and provide opportunities for the treatment of disease processes modified by AhR.
Comprehensive insights from composition to functional microbe-based biodiversity of the infant human gut microbiota
Authors: Lugli Gabriele Andrea , Mancabelli Leonardo , Milani Christian , Fontana Federico , Tarracchini Chiara , Alessandri Giulia , van Sinderen Douwe , Turroni Francesca , Ventura Marco
Published: May 2023

During infancy, gut microbiota development is a crucial process involved in the establishment of microbe–host interactions which may persist throughout adulthood, and which are believed to influence host health. To fully understand the complexities of such interactions, it is essential to assess gut microbiota diversity of newborns and its associated microbial dynamics and relationships pertaining to health and disease. To explore microbial biodiversity during the first 3 years of human life, 10,935 shotgun metagenomic datasets were taxonomically and functionally classified. Microbial species distribution between infants revealed the presence of eight major Infant Community State Types (ICSTs), being dominated by 17 bacterial taxa, whose distribution was shown to correspond to the geographical origin and infant health status. In total, 2390 chromosomal sequences of the predominant taxa were reconstructed from metagenomic data and used in combination with 44,987 publicly available genomes to trace the distribution of microbial Population Subspecies (PS) within the different infant groups, revealing patterns of multistrain coexistence among ICSTs. Finally, implementation of a metagenomic- and metatranscriptomic-based metabolic profiling highlighted different enzymatic expression patterns of the gut microbiota that allowed us to acquire insights into mechanistic aspects of health-gut microbiota interplay in newborns. Comparison between metagenomic and metatranscriptomic data highlights how a complex environment like the human gut must be investigated by employing both sequencing methodologies and possibly supplemented with metabolomics approaches. While metagenomic analyses are very useful for microbial classification aimed at unveiling key players driving microbiota balances, using these data to explain functionalities of the microbiota is not always warranted.
The cell wall lipoprotein CD1687 acts as a DNA binding protein during deoxycholate-induced biofilm formation in Clostridioides difficile
Authors: Auria Emile , Hunault Lise , England Patrick , Monot Marc , Pipoli Da Fonseca Juliana , Matondo Mariette , Duchateau Magalie , Tremblay Yannick D. N. , Dupuy Bruno
Published: May 2023

The ability of bacterial pathogens to establish recurrent and persistent infections is frequently associated with their ability to form biofilms. Clostridioides difficile infections have a high rate of recurrence and relapses and it is hypothesized that biofilms are involved in its pathogenicity and persistence. Biofilm formation by C. difficile is still poorly understood. It has been shown that specific molecules such as deoxycholate (DCA) or metronidazole induce biofilm formation, but the mechanisms involved remain elusive. In this study, we describe the role of the C. difficile lipoprotein CD1687 during DCA-induced biofilm formation. We showed that the expression of CD1687, which is part of an operon within the CD1685-CD1689 gene cluster, is controlled by multiple transcription starting sites and some are induced in response to DCA. Only CD1687 is required for biofilm formation and the overexpression of CD1687 is sufficient to induce biofilm formation. Using RNAseq analysis, we showed that CD1687 affects the expression of transporters and metabolic pathways and we identified several potential binding partners by pull-down assay, including transport-associated extracellular proteins. We then demonstrated that CD1687 is surface exposed in C. difficile, and that this localization is required for DCA-induced biofilm formation. Given this localization and the fact that C. difficile forms eDNA-rich biofilms, we confirmed that CD1687 binds DNA in a non-specific manner. We thus hypothesize that CD1687 is a component of the downstream response to DCA leading to biofilm formation by promoting interaction between the cells and the biofilm matrix by binding eDNA.
Glucocerebrosidase activity and lipid levels are related to protein pathologies in Parkinson’s disease
Authors: Leyns Cheryl E. G. , Prigent Alice , Beezhold Brenna , Yao Lihang , Hatcher Nathan G. , Tao Peining , Kang John , Suh EunRan , Van Deerlin Vivianna M. , Trojanowski John Q. , Lee Virginia M. Y. , Kennedy Matthew E. , Fell Matthew J. , Henderson Michael X.
Published: May 2023

Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are progressive neurodegenerative diseases characterized by the accumulation of misfolded α-synuclein in the form of Lewy pathology. While most cases are sporadic, there are rare genetic mutations that cause disease and more common variants that increase incidence of disease. The most prominent genetic mutations for PD and DLB are in the GBA1 and LRRK2 genes. GBA1 mutations are associated with decreased glucocerebrosidase activity and lysosomal accumulation of its lipid substrates, glucosylceramide and glucosylsphingosine. Previous studies have shown a link between this enzyme and lipids even in sporadic PD. However, it is unclear how the protein pathologies of disease are related to enzyme activity and glycosphingolipid levels. To address this gap in knowledge, we examined quantitative protein pathology, glucocerebrosidase activity and lipid substrates in parallel from 4 regions of 91 brains with no neurological disease, idiopathic, GBA1-linked, or LRRK2-linked PD and DLB. We find that several biomarkers are altered with respect to mutation and progression to dementia. We found mild association of glucocerebrosidase activity with disease, but a strong association of glucosylsphingosine with α-synuclein pathology, irrespective of genetic mutation. This association suggests that Lewy pathology precipitates changes in lipid levels related to progression to dementia.
Commensurate-to-incommensurate transition of charge-density-wave order and a possible quantum critical point in pressurized kagome metal CsV3Sb5
Authors: Feng X. Y. , Zhao Z. , Luo J. , Yang J. , Fang A. F. , Yang H. T. , Gao H. J. , Zhou R. , Zheng Guo-qing
Published: May 2023

Clarifying the interplay between charge-density waves (CDWs) and superconductivity is important in the kagome metal CsV3Sb5, and pressure (P) can play a crucial role. Here, we present121/123Sb nuclear quadrupole resonance (NQR) measurements under hydrostatic pressures up to 2.43 GPa in CsV3Sb5single crystals. We demonstrate that the CDW gradually changes from a commensurate modulation with a star-of-David (SoD) pattern to an incommensurate one with a superimposed SoD and Tri-hexagonal (TrH) pattern stacking along thec-axis. Moreover, the linewidthδνof121/123Sb-NQR spectra increases with cooling down toTCDW, indicating the appearance of a short-range CDW order due to CDW fluctuations pinned by quenched disorders. Theδνshows a Curie–Weiss temperature dependence and tends to diverge atPc ~ 1.9 GPa, suggesting that a CDW quantum critical point (QCP) exists atPcwhereTcshows the maximum. ForP > Pc, spin fluctuations are enhanced when the CDW is suppressed. Our results suggest that the maximalTcatPc ~ 1.9 GPa is related to the CDW QCP, and the presence of spin fluctuations prevents theTcfrom a rapid decrease otherwise, after the CDW is completely suppressed.
Picophotonic localization metrology beyond thermal fluctuations
Authors: Liu Tongjun , Chi Cheng-Hung , Ou Jun-Yu , Xu Jie , Chan Eng Aik , MacDonald Kevin F. , Zheludev Nikolay I.
Published: May 2023

Despite recent tremendous progress in optical imaging and metrology1–6, there remains a substantial resolution gap between atomic-scale transmission electron microscopy and optical techniques. Is optical imaging and metrology of nanostructures exhibiting Brownian motion possible with such resolution, beyond thermal fluctuations? Here we report on an experiment in which the average position of a nanowire with a thermal oscillation amplitude of ∼150 pm is resolved in single-shot measurements with subatomic precision of 92 pm, using light at a wavelength of λ = 488 nm, providing an example of such sub-Brownian metrology with ∼λ/5,300 precision. To localize the nanowire, we employ a deep-learning analysis of the scattering of topologically structured light, which is highly sensitive to the nanowire’s position. This non-invasive metrology with absolute errors down to a fraction of the typical size of an atom, opens a range of opportunities to study picometre-scale phenomena with light.
Chloroquine resistance evolution in Plasmodium falciparum is mediated by the putative amino acid transporter AAT1
Authors: Amambua-Ngwa Alfred , Button-Simons Katrina A. , Li Xue , Kumar Sudhir , Brenneman Katelyn Vendrely , Ferrari Marco , Checkley Lisa A. , Haile Meseret T. , Shoue Douglas A. , McDew-White Marina , Tindall Sarah M. , Reyes Ann , Delgado Elizabeth , Dalhoff Haley , Larbalestier James K. , Amato Roberto , Pearson Richard D. , Taylor Alexander B. , Nosten François H. , D’Alessandro Umberto , Kwiatkowski Dominic , Cheeseman Ian H. , Kappe Stefan H. I. , Avery Simon V. , Conway David J. , Vaughan Ashley M. , Ferdig Michael T. , Anderson Timothy J. C.
Published: May 2023

Malaria parasites break down host haemoglobin into peptides and amino acids in the digestive vacuole for export to the parasite cytoplasm for growth: interrupting this process is central to the mode of action of several antimalarial drugs. Mutations in the chloroquine (CQ) resistance transporter, pfcrt, located in the digestive vacuole membrane, confer CQ resistance in Plasmodium falciparum, and typically also affect parasite fitness. However, the role of other parasite loci in the evolution of CQ resistance is unclear. Here we use a combination of population genomics, genetic crosses and gene editing to demonstrate that a second vacuolar transporter plays a key role in both resistance and compensatory evolution. Longitudinal genomic analyses of the Gambian parasites revealed temporal signatures of selection on a putative amino acid transporter (pfaat1) variant S258L, which increased from 0% to 97% in frequency between 1984 and 2014 in parallel with the pfcrt1 K76T variant. Parasite genetic crosses then identified a chromosome 6 quantitative trait locus containing pfaat1 that is selected by CQ treatment. Gene editing demonstrated that pfaat1 S258L potentiates CQ resistance but at a cost of reduced fitness, while pfaat1 F313S, a common southeast Asian polymorphism, reduces CQ resistance while restoring fitness. Our analyses reveal hidden complexity in CQ resistance evolution, suggesting that pfaat1 may underlie regional differences in the dynamics of resistance evolution, and modulate parasite resistance or fitness by manipulating the balance between both amino acid and drug transport.
Signal peptide mimicry primes Sec61 for client-selective inhibition
Authors: Rehan Shahid , Tranter Dale , Sharp Phillip P. , Craven Gregory B. , Lowe Eric , Anderl Janet L. , Muchamuel Tony , Abrishami Vahid , Kuivanen Suvi , Wenzell Nicole A. , Jennings Andy , Kalyanaraman Chakrapani , Strandin Tomas , Javanainen Matti , Vapalahti Olli , Jacobson Matthew P. , McMinn Dustin , Kirk Christopher J. , Huiskonen Juha T. , Taunton Jack , Paavilainen Ville O.
Published: May 2023

Preventing the biogenesis of disease-relevant proteins is an attractive therapeutic strategy, but attempts to target essential protein biogenesis factors have been hampered by excessive toxicity. Here we describe KZR-8445, a cyclic depsipeptide that targets the Sec61 translocon and selectively disrupts secretory and membrane protein biogenesis in a signal peptide-dependent manner. KZR-8445 potently inhibits the secretion of pro-inflammatory cytokines in primary immune cells and is highly efficacious in a mouse model of rheumatoid arthritis. A cryogenic electron microscopy structure reveals that KZR-8445 occupies the fully opened Se61 lateral gate and blocks access to the lumenal plug domain. KZR-8445 binding stabilizes the lateral gate helices in a manner that traps select signal peptides in the Sec61 channel and prevents their movement into the lipid bilayer. Our results establish a framework for the structure-guided discovery of novel therapeutics that selectively modulate Sec61-mediated protein biogenesis.
3DFlex: determining structure and motion of flexible proteins from cryo-EM
Authors: Punjani Ali , Fleet David J.
Published: May 2023

Modeling flexible macromolecules is one of the foremost challenges in single-particle cryogenic-electron microscopy (cryo-EM), with the potential to illuminate fundamental questions in structural biology. We introduce Three-Dimensional Flexible Refinement (3DFlex), a motion-based neural network model for continuous molecular heterogeneity for cryo-EM data. 3DFlex exploits knowledge that conformational variability of a protein is often the result of physical processes that transport density over space and tend to preserve local geometry. From two-dimensional image data, 3DFlex enables the determination of high-resolution 3D density, and provides an explicit model of a flexible protein’s motion over its conformational landscape. Experimentally, for large molecular machines (tri-snRNP spliceosome complex, translocating ribosome) and small flexible proteins (TRPV1 ion channel, αVβ8 integrin, SARS-CoV-2 spike), 3DFlex learns nonrigid molecular motions while resolving details of moving secondary structure elements. 3DFlex can improve 3D density resolution beyond the limits of existing methods because particle images contribute coherent signal over the conformational landscape.
Early detection of Solanum lycopersicum diseases from temporally-aggregated hyperspectral measurements using machine learning
Authors: Tomaszewski Michał , Nalepa Jakub , Moliszewska Ewa , Ruszczak Bogdan , Smykała Krzysztof
Published: May 2023

Some plant diseases can significantly reduce harvest, but their early detection in cultivation may prevent those consequential losses. Conventional methods of diagnosing plant diseases are based on visual observation of crops, but the symptoms of various diseases may be similar. It increases the difficulty of this task even for an experienced farmer and requires detailed examination based on invasive methods conducted in laboratory settings by qualified personnel. Therefore, modern agronomy requires the development of non-destructive crop diagnosis methods to accelerate the process of detecting plant infections with various pathogens. This research pathway is followed in this paper, and an approach for classifying selected Solanum lycopersicum diseases (anthracnose, bacterial speck, early blight, late blight and septoria leaf) from hyperspectral data captured on consecutive days post inoculation (DPI) is presented. The objective of that approach was to develop a technique for detecting infection in less than seven days after inoculation. The dataset used in this study included hyperspectral measurements of plants of two cultivars of S. lycopersicum: Benito and Polfast, which were infected with five different pathogens. Hyperspectral reflectance measurements were performed using a high-spectral-resolution field spectroradiometer (350–2500 nm range) and they were acquired for 63 days after inoculation, with particular emphasis put on the first 17 day-by-day measurements. Due to a significant data imbalance and low representation of measurements on some days, the collective datasets were elaborated by combining measurements from several days. The experimental results showed that machine learning techniques can offer accurate classification, and they indicated the practical utility of our approaches.
Evaluation of microbial communities of Chinese Feng-flavor Daqu with effects of environmental factors using traceability analysis
Authors: Zhang Yongli , Xu Chen , Xing Gang , Yan Zongke , Chen Yaodong
Published: May 2023

Analysis of the changes of microorganisms during Chinese Feng-flavor Daqu fermentation, and the specific contribution of different environmental factors to Daqu microorganisms. High throughput sequencing technology and SourceTracker software were used to analyze the microbial diversity of Feng-flavor Daqu before and after fermentation. 85 fungal and 105 bacterial were detected in the newly pressed Feng-flavor Daqu, while 33 fungal and 50 bacterial in the mature Daqu, and 202 fungal and 555 bacterial in the environmental samples. After fermentation, the microbial community structure of Daqu changed and decreased significantly. 94.7% of fungi come from raw materials and 1.8% from outdoor ground, 60.95% of bacteria come from indoor ground, 20.44% from raw materials, and 8.98% from tools. By comparing the changes of microorganisms in Daqu before and after fermentation, the microorganisms in mature Daqu may mainly come from not only the enhanced strains but also the environment.The source of main microorganisms in Feng-flavor Daqu and the influence of environmental factors on the quality of Daqu were clarified, which provided a basis for improving the quality of Feng-flavor Daqu.
Distinct histopathological features are associated with molecular subtypes and outcome in low grade serous ovarian carcinoma
Authors: Hollis Robert L. , Thomson John P. , van Baal Juliette , Ilenkovan Narthana , Churchman Michael , van de Vijver Koen , Dijk Frederike , Meynert Alison M. , Bartos Clare , Rye Tzyvia , Croy Ian , Diana Patricia , van Gent Mignon , Creedon Helen , Nirsimloo Rachel , Lok Christianne , Gourley Charlie , Herrington C. Simon
Published: May 2023

Low grade serous ovarian carcinoma (LGSOC) demonstrates unique clinical and molecular features compared to other ovarian cancer types. The relationship between common histological features of LGSOC and molecular events, such as hormone receptor expression patterns and MAPK gene mutation status, remains poorly understood. Recent data suggest some of these molecular features may be biomarkers of response to recently introduced biologically-targeted therapies, namely endocrine therapy and MEK inhibitors. We utilize a cohort of 63 pathologically-confirmed LGSOC cases with whole exome sequencing and hormone receptor expression data to investigate these relationships. LGSOC cases demonstrated uniformly high oestrogen receptor (ER) expression, but variable progesterone receptor (PR) expression intensity. 60% and 37% of cases demonstrated micropapillary and macropapillary patterns of stromal invasion, respectively. 63% of cases demonstrated desmoplasia, which was significantly associated with advanced disease stage and visible residual disease after cytoreductive surgery. MAPK-mutant cases (KRAS,BRAF,NRAS) more frequently demonstrated macropapillary stromal invasion, while Chr1p loss was associated with desmoplasia and low PR expression. Presence of micropapillary stromal invasion and low PR expression were associated with significantly poorer survival after accounting for stage and residual disease status. Together, these data identify novel relationships between histopathological features and molecularly-defined subgroups in LGSOC.
Putative role of HLA polymorphism among a Brazilian HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) population
Authors: Schor Doris , Porto Luís Cristóvão , Roma Eric Henrique , Castro-Alves Julio , Villela Anna Paula , Araújo Abelardo Q. C. , Glória Bonecini-Almeida Maria
Published: May 2023

Around ten million people are infected with HTLV-1 worldwide, and 1–4% develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), characterized by an important degeneration of the spinal cord, which can lead to death. Distinct HLA alleles have been associated with either HAM/TSP susceptibility or protection. However, these HLA alleles set may change according to the population studied. Brazil is the second country in the number of HTLV-1-infected people and there are few reports addressing the HLA influence on HTLV-1 infection as well as on disease outcome. The objective of this study was to evaluate the influence of HLA alleles as a risk factor for HAM/TSP and the proviral load (PVL) levels, clinical progression, and death outcomes in an admixed Brazilian population. The HLA-A, -B, -C, and -DRB1 were genotyped in 375 unrelated HTLV-1-infected individuals divided into asymptomatic carriers (AC) (n = 165) and HAM/TSP (n = 210) in a longitudinal cohort from 8 to 22 years of follow-up. Because locus B deviated from Hardy–Weinberg Equilibrium for the study groups, the results represented for HLA-B alleles were inconclusive. The alleles HLA-A*68 and -C*07 were related to HAM/TSP risk in multivariate analysis. The alleles HLA-A*33, and -A*36 were associated with protection against disease progression in HAM/TSP patients, while -C*12, -C*14, and -DRB1*08 were associated with increased risk of death. In the AC group, the presence of, -C*06 and -DRB1*15 alleles influenced an increased PVL, in an adjusted linear regression model, while -A*30, -A*34, -C*06, -C*17 and -DRB1*09 alleles were associated with increased PVL in HAM/TSP group compared to HAM/TSP individuals not carrying these alleles. All these alleles were also related to increased PVL associated with clinical progression outcome. Increased PVL associated with the death outcome was linked to the presence of HLA-A*30. PVL has been associated with HLA, and several alleles were related in AC and HAM/TSP patients with or without interacting with clinical progression outcomes. Understanding the prognostic value of HLA in HAM/TSP pathogenesis can provide important biomarkers tools to improve clinical management and contribute to the discovery of new therapeutic interventions.
Brain activity underlying visual search in depth when viewing volumetric multiplanar images
Authors: Naderi Mehrdad , Pladere Tatjana , Alksnis Reinis , Krumina Gunta
Published: May 2023

The study investigated the cortical activity associated with 3D and 2D image perception on a volumetric multiplanar display by analyzing event-related potentials (ERPs) and power spectral density (PSD). In this study, we used a volumetric multiplanar display to present visual targets, and the brain signals were recorded via an EEG amplifier and analyzed using the EEGLAB toolbox on MATLAB. The study found no significant differences in amplitude between the 3D and 2D conditions across five occipital and parietal electrodes. However, there was a significant difference in latency of the P3 component on the Pz electrode. The analysis of PSD showed no significant differences between the two conditions, although there was a slightly higher alpha and beta activity observed in the 2D visualization. The study concluded that 3D image representation on a volumetric multiplanar display has no more sensory or cognitive load on the human brain than 2D representation, and that depth perception on a multiplanar display requires less brain activity.
Online quantum time series processing with random oscillator networks
Authors: Nokkala Johannes
Published: May 2023

Reservoir computing is a powerful machine learning paradigm for online time series processing. It has reached state-of-the-art performance in tasks such as chaotic time series prediction and continuous speech recognition thanks to its unique combination of high computational power and low training cost which sets it aside from alternatives such as traditionally trained recurrent neural networks, and furthermore is amenable to implementations in dedicated hardware, potentially leading to extremely compact and efficient reservoir computers. Recently the use of random quantum systems has been proposed, leveraging the complexity of quantum dynamics for classical time series processing. Extracting the output from a quantum system without disturbing its state too much is problematic however, and can be expected to become a bottleneck in such approaches. Here we propose a reservoir computing inspired approach to online processing of time series consisting of quantum information, sidestepping the measurement problem. We illustrate its power by generalizing two paradigmatic benchmark tasks from classical reservoir computing to quantum information and introducing a task without a classical analogue where a random system is trained to both create and distribute entanglement between systems that never directly interact. Finally, we discuss partial generalizations where only the input or only the output time series is quantum.
Polarization-insensitive planar patch antenna with large embedded serial capacitance for on-metal tag design
Authors: Murugesh Muthukannan , Lim Eng-Hock , Chee Pei-Song , Bong Fwee-Leong
Published: May 2023

A polarization-insensitive planar patch antenna, which has a large embedded serial capacitance, is proposed for constructing a metal mountable tag by using merely a single radiator. The proposed antenna structure itself contains two flaps of patches, which are very closely overlapped, for generating a large capacitive reactance for reducing the resonant frequency of the tag. It has been found that the surface currents in the overlapped region are in the reverse direction as the large capacitance is virtually placed in series. This feature has been tactfully employed for producing a pair of orthogonal currents for designing the polarization-insensitive tag antenna and it can generate orthogonal fields in a unique way, making it readable from almost all directions at all points above the metal surface. For analyzing the impedance properties, an equivalent circuit was also constructed. This tag antenna is compact, and it can be read from ~ 15 m with 4W EIRP. Furthermore, the tag resonant frequency is shown to be unaffected much by its backing material. The proposed tag antenna is polarization-insensitve as it can be accessible from almost all directions on the metal.
Neuronal selectivity for stimulus information determines prefrontal LFP gamma power regardless of task execution
Authors: Singh Balbir , Wang Zhengyang , Constantinidis Christos
Published: May 2023

Local field potential (LFP) power in the gamma frequency is modulated by cognitive variables during task execution. We sought to examine whether such modulations only emerge when task rules are established. We therefore analyzed neuronal firing and LFPs in different prefrontal subdivisions before and after the same monkeys were trained to perform cognitive tasks. Prior to task rule learning, sites containing neurons selective for stimuli already exhibited increased gamma power during and after the passive viewing of stimuli compared to the baseline period. Unexpectedly, when the same monkeys learned to maintain these stimuli in working memory, the elevation of gamma power above the baseline was diminished, despite an overall increase in firing rate. Learning and executing the task further decoupled LFP power from single neuron firing. Gamma power decreased at the time when subjects needed to make a judgment about whether two stimuli were the same or not, and differential gamma power was observed for matching and nonmatching stimuli. Our results indicate that prefrontal gamma power emerges spontaneously, not necessarily tied to a cognitive task being executed.
Inflammatory responses induced by synergistic actions between nanoplastics and typical heavy metal ions in human cells
Authors: Li Cong , Huang Xinxin , Min Weicui , Zhong Huoqing , Yan Xiliang , Gao Yan , Wang Jianqiao , Zhou Hongyu , Yan Bing
Published: May 2023

Nanoplastics (NPs) may transport heavy metal ions into organisms as vectors and induce synergistic inflammatory responses in different human cells through distinct pathways.
Diversity of dynamic voltage patterns in neuronal dendrites revealed by nanopipette electrophysiology
Authors: Mc Hugh Jeffrey , Makarchuk Stanislaw , Mozheiko Daria , Fernandez-Villegas Ana , Kaminski Schierle Gabriele S. , Kaminski Clemens F. , Keyser Ulrich F. , Holcman David , Rouach Nathalie
Published: May 2023

Using nanopipette electrophysiology, we reveal in neuronal dendrites a diversity of voltage dynamics comprising firing activity, bursting events and spontaneous voltage transients, including a novel class of events consisting of transient and sustained hyperpolarisations.
A biphenyl thiosemicarbazide based fluorogenic chemosensor for selective recognition of Cd2+: application in cell bioimaging
Authors: Biswas Amitav , Mitra Debarpan , Naskar Rahul , Maji Atanu , Das Akash , Murmu Nabendu , Mondal Tapan Kumar
Published: May 2023

A biphenyl thiosemicarbazide based chemosensor (HBMC) has been fabricated and reported for specific detection of Cd2+ in MeOH : H2O (4 : 1).
Heterogeneity of the vanadia phase dispersed on titania. Co-existence of distinct mono-oxo VOx sites
Authors: Kentri Theocharis , Tsevis Athanasios , Boghosian Soghomon
Published: May 2023

Three distinct VOx species are found in the vanadia phase dispersed on TiO2(P25): a majority mono-oxo species with CNV=4, a minority mono-oxo species with CNV=5 and a minority dioxo species. The relative species presence is temperature dependent.
Evaluation of triphenylene-based MOF ultrathin films for lithium batteries
Authors: Ciria-Ramos Isabel , Tejedor Inés , Caparros Lucía , Doñagueda Beatriz , Lacruz Oscar , Urtizberea Ainhoa , Roubeau Olivier , Gascón Ignacio , Haro Marta
Published: May 2023

Metal–organic frameworks (MOFs) are attractive candidates to meet the requirement of next-generation batteries, as functional materials with a high surface area, well-defined metal centers, and organic linkers through coordination bonds.
Synthesis, characterization and biological activity of novel copper complexes containing a β-carboline derivative and amino acids
Authors: Chen Bai-Hua , Pan Zheng-Yin , Feng Wen-Wen , Liu Qi-Yan , Liu Yingju , He Liang
Published: May 2023

Two new β-carboline copper(ii) complexes bind to DNA by insertion and induce apoptosis associated with mitochondrial damage and oxidative stress.
Carrageenan in meat: improvement in lipid metabolism due to Sirtuin1-mediated fatty acid oxidation and inhibited lipid bioavailability
Authors: Huang Zhiji , Ma Yafang , Xie Yunting , Zhao Di , Li Chunbao
Published: May 2023

κ-Carrageenan in pork-based high-fat diets decreased lipid accumulation by promoting Sirtuin1-mediated β-oxidation, which was associated with inhibited lipids bioavailability and decreased SCFAs and BAs concentration.
Application of lamellar nickel hydroxide membrane as a tunable platform for ionic thermoelectric studies
Authors: Gogoi Raktim , Ghosh Arnab , Deka Priyamjeet , Datta K. K. R. , Raidongia Kalyan
Published: May 2023

The Seebeck coefficient of the ionic thermoelectric membrane of β-Ni(OH)2 is tuned by choosing appropriate intercalating ions. Additional energy is harvested from ions accumulated around electrodes during prolonged exposure to temperature gradients.
Peptide condensation and hydrolysis mechanisms from a proton-transfer network perspective
Authors: Herriman Teddy , Szilagyi Robert K.
Published: May 2023

From a systematic mapping of the proton transfer network between two glycine molecules, density functional theory calculations identified an experimentally sound reaction mechanism for the peptide bond formation and hydrolysis.
Improvement of photocatalytic activity in the degradation of 4-chlorophenol and phenol in aqueous medium using tin-modified TiO2 photocatalysts
Authors: Rangel-Vázquez I. , Del Angel G. , Ramos-Ramírez E. , González F. , Acevedo-Peña Próspero , Gómez C. Martínez , Tzompantzi F. , Gutiérrez-Ortega Norma , Torres-Torres J. G.
Published: May 2023

The Sn1T was synthesized for photodegradation of phenolic compounds.
Visible-light-driven reactions for the synthesis of sulfur dioxide-inserted compounds: generation of S–F, S–O, and S–N bonds
Authors: Luu Truong Giang , Kim Hee-Kwon
Published: May 2023

A review of recent advances in visible-light-mediated synthetic strategies for generation of SO2-X (X = F, O, N) bonds to give sulfonyl compounds.
Nanomaterials for photothermal cancer therapy
Authors: Duan Shufan , Hu Yanling , Zhao Ying , Tang Kaiyuan , Zhang Zhijing , Liu Zilu , Wang Ying , Guo Haiyang , Miao Yuchen , Du Hengda , Yang Dongliang , Li Shengke , Zhang Junjie
Published: May 2023

This review summarizes the common inorganic and organic photothermal nanoagents and their applications in tumor therapy. Additionally, the challenges and future prospects of nanomaterial-based photothermal therapy in cancer treatment are discussed.
Lanthanide molecular cluster-aggregates as the next generation of optical materials
Authors: Gálico Diogo Alves , Santos Calado Claudia Manuela , Murugesu Muralee
Published: May 2023

In this perspective, we provide an overview of the recent achievements in luminescent lanthanide-based molecular cluster-aggregates (MCAs) and illustrate why MCAs can be seen as the next generation of highly efficient optical materials.
Puncturing of soft tissues: experimental and fracture mechanics-based study
Authors: Montanari Matteo , Brighenti Roberto , Terzano Michele , Spagnoli Andrea
Published: May 2023

Penetration of a rigid circular needle into soft target solids is studied combining closed-form solution based on linear elastic fracture mechanics, FEM simulations and experiments. The results provide a manageable tool to assess safety of soft materials against puncturing.