bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible role of lncRNAs in amelioration of Parkinson’s disease symptoms by transplantation of dopaminergic cells
Authors: Amini A. , Esmaeili F. , Golpich M.
Published: March 2024

Long non-coding RNAs (lncRNAs) are biomarkers for diagnosis and treatment of Parkinson’s disease (PD). Since dopaminergic cell transplantation is a clinical method to treat PD, this study investigated the effects of dopaminergic cell therapy on the expression of some lncRNAs and genes related to PD. In this study, Twenty-eight rats were randomly assigned to four experimental groups. The control group (Sal group) received saline injections. The Par group was a PD rat model with 6-hydroxydopamine (6-OHDA) injection in right striatum (ST). PD animals were transplanted by undifferentiated P19 stem cells (Par-E group), and P19-derived dopaminergic cells (Par-N group). Cell transplant effects were evaluated using behavioral tests (cylinder, open field, and rotarod tests), and histological methods (H&E and Nissl staining, and immunohistochemistry). Moreover, the expression of lncRNAs MALAT1, MEG3, and SNHG1, alongside specific neuronal (synaptophysin) and dopaminergic (tyrosine hydroxylase) markers was evaluated by qRT-PCR. Behavioral and histopathological examinations revealed that cell transplantation partially compensated dopaminergic cell degeneration in ST and substantia nigra (SN) of PD rats. The expression of MALAT1, SNHG1, and MEG3 was decreased in the ST of the Par group, while MEG3 and SNHG1 gene expression was increased in PBMC relative to the Sal group. In PBMC of the Par-N group, all three lncRNAs showed a reduction in their expression. Conversely, MALAT1 and SNHG1 expression was increased in ST tissue, while MEG3 gene expression was decreased compared to the Sal group. In conclusion, dopaminergic cell transplantation could change the lncRNAs expression. Furthermore, it partially improves symptoms in PD rats.
Adsorption and DFT investigations of Cr(VI) removal using nanocrystals decorated with graphene oxide
Authors: Singh Simranjeet , Anil Amith G. , Uppara Basavaraju , Behera Sushant K. , Nath Bidisha , N Pavithra , Bhati Shipra , Singh Joginder , Khan Nadeem A. , Ramamurthy Praveen C.
Published: March 2024

In this research, a solvothermal approach is introduced to synthesize a metal-organic frameworks (MOFs) nanocomposite (GO/UiO-66-NDC) for the removal of Cr(VI) from water. A comprehensive analysis was performed to understand the physical, chemical, and structural properties of the MOF nanocomposite. The adsorption behavior of Cr(VI) was investigated by changing various parameters, such as pH, dosage, and concentration, to determine isotherms, thermodynamics, and kinetics. The results showed that the nanocomposite had a high tolerance to pH and thermal stability, with a high adsorption capacity of 157.23 mg g−1 for Cr(VI) at pH 3 due to the presence of zirconium oxide clusters. The density functional theory simulations showed that the nanocomposite had ten times more dynamic delocalized surface states, which enhanced the adsorption capacity and agreed with the experimental results. Furthermore, the nanocomposite exhibited better regeneration performance compared to previously reported materials, making it a promising super-adsorbent for removing Cr(VI) from water.
Peptidoglycan synthesis drives a single population of septal cell wall synthases during division in Bacillus subtilis
Authors: Whitley Kevin D. , Grimshaw James , Roberts David M. , Karinou Eleni , Stansfeld Phillip J. , Holden Séamus
Published: March 2024

Bacterial cell division requires septal peptidoglycan (sPG) synthesis by the divisome complex. Treadmilling of the essential tubulin homologue FtsZ has been implicated in septal constriction, though its precise role remains unclear. Here we used live-cell single-molecule imaging of the divisome transpeptidase PBP2B to investigate sPG synthesis dynamics in Bacillus subtilis. In contrast to previous models, we observed a single population of processively moving PBP2B molecules whose motion is driven by peptidoglycan synthesis and is not associated with FtsZ treadmilling. However, despite the asynchronous motions of PBP2B and FtsZ, a partial dependence of PBP2B processivity on FtsZ treadmilling was observed. Additionally, through single-molecule counting experiments we provide evidence that the divisome synthesis complex is multimeric. Our results support a model for B. subtilis division where a multimeric synthesis complex follows a single track dependent on sPG synthesis whose activity and dynamics are asynchronous with FtsZ treadmilling.
Penning micro-trap for quantum computing
Authors: Jain Shreyans , Sägesser Tobias , Hrmo Pavel , Torkzaban Celeste , Stadler Martin , Oswald Robin , Axline Chris , Bautista-Salvador Amado , Ospelkaus Christian , Kienzler Daniel , Home Jonathan
Published: March 2024

Trapped ions in radio-frequency traps are among the leading approaches for realizing quantum computers, because of high-fidelity quantum gates and long coherence times1–3. However, the use of radio-frequencies presents several challenges to scaling, including requiring compatibility of chips with high voltages4, managing power dissipation5 and restricting transport and placement of ions6. Here we realize a micro-fabricated Penning ion trap that removes these restrictions by replacing the radio-frequency field with a 3 T magnetic field. We demonstrate full quantum control of an ion in this setting, as well as the ability to transport the ion arbitrarily in the trapping plane above the chip. This unique feature of the Penning micro-trap approach opens up a modification of the quantum charge-coupled device architecture with improved connectivity and flexibility, facilitating the realization of large-scale trapped-ion quantum computing, quantum simulation and quantum sensing.
De novo-designed transmembrane proteins bind and regulate a cytokine receptor
Authors: Mravic Marco , He Li , Kratochvil Huong T. , Hu Hailin , Nick Sarah E. , Bai Weiya , Edwards Anne , Jo Hyunil , Wu Yibing , DiMaio Daniel , DeGrado William F.
Published: March 2024

Transmembrane (TM) domains as simple as a single span can perform complex biological functions using entirely lipid-embedded chemical features. Computational design has the potential to generate custom tool molecules directly targeting membrane proteins at their functional TM regions. Thus far, designed TM domain-targeting agents have been limited to mimicking the binding modes and motifs of natural TM interaction partners. Here, we demonstrate the design of de novo TM proteins targeting the erythropoietin receptor (EpoR) TM domain in a custom binding topology competitive with receptor homodimerization. The TM proteins expressed in mammalian cells complex with EpoR and inhibit erythropoietin-induced cell proliferation. In vitro, the synthetic TM domain complex outcompetes EpoR homodimerization. Structural characterization reveals that the complex involves the intended amino acids and agrees with our designed molecular model of antiparallel TM helices at 1:1 stoichiometry. Thus, membrane protein TM regions can now be targeted in custom-designed topologies.
EUPRO - A reference database on project-based R&D collaboration networks
Authors: Scherngell Thomas , Barber Michael , Zahradnik Georg , Wolfmayr Anna , Bilalli Shkodra Xheneta
Published: March 2024

The EUPRO database enables the analysis of participation patterns of organisations in and across different European R&D funding initiatives and the investigation of resulting collaborative R&D network structures and dynamics. The perimeter of EUPRO is currently more than 600,000 R&D projects funded by European (EU, transnational or national) research funding organisations, comprising systematic information about contents of the R&D projects, their participating organizations (including organisation type and location), and a number of additional characteristics (e.g. underlying policy instrument and programme). This scientific data descriptor serves as illustrative information source for users, both from science as well as from policy. It discusses the conceptual background and derives respective analytical opportunities for different actual, highly relevant debates in innovation studies and related fields. Moreover, the data collection process is described in a compact manner, as well as how the collected data are harmonized and aggregated into a suitable data model for analytical purposes. Finally, we put forward issues of technical validation, data quality and enrichment, and usage notes on how to access EUPRO.
Administrative data ICD-10 diagnostic codes identifies most lab-confirmed SARS-CoV-2 admissions but misses many discharged from the Emergency Department
Authors: Moura Cristiano S. , Morrison Laurie J. , Hohl Corinne M. , Grant Lars , Pilote Louise , Neville Autumn , Hau Jeffrey P. , Bernatsky Sasha ,   and the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) investigators,   for the Network of Canadian Emergency Researchers,   the Canadian Critical Care Trials Group
Published: March 2024

We estimated the operating characteristics of ICD-10 code U07.1, introduced by the World Health Organization in 2020, to identify lab-confirmed SARS-CoV-2. CCEDRRN is a national research registry of adults (March 2020–August 2021) with suspected/confirmed SARS-CoV-2 identified in Canadian emergency departments (EDs) using chart review (symptoms, clinical information, and lab test results including SARS-CoV-2 polymerase chain reaction, PCR results). CCEDRRN data were linked to administrative hospitalization discharge and ED ICD-10 diagnostic codes (accessed centrally via the Canadian Institute for Health Information). We identified ICD-10 diagnostic codes in CCEDRRN participants. We defined lab-confirmed SARS-CoV-2 based on at least one positive PCR in the 0–14 days before the ED presentation and/or during hospitalization (in those admitted from ED). We performed separate analyses for CCEDRRN participants discharged from ED and those hospitalized from the ED. Additional analyses were stratified by province, sex, age, and (for hospitalized patients) timing of the first PCR test. The sensitivity of ICD-10 code U07.1 for a positive SARS-CoV-2 test was 93.6% (95% CI 93.0–94.1%) in those hospitalized from ED and 83.0% (95% CI 82.1–83.9%) in those discharged from the ED. Sensitivity was similar across provinces and demographics, but in each stratified analysis, values were higher in those hospitalized versus those discharged from ED. The ICD-10 diagnostic code for U07.1 within administrative data identified most lab-confirmed SARS-CoV-2 within persons hospitalized from ED, although a significant number of cases discharged from ED were missed. This should be considered when using administrative data for research and public health planning.
Improving our understanding of future tropical cyclone intensities in the Caribbean using a high-resolution regional climate model
Authors: Dullaart Job C. M. , de Vries Hylke , Bloemendaal Nadia , Aerts Jeroen C. J. H. , Muis Sanne
Published: March 2024

The Caribbean region is prone to the strong winds and low air pressures of tropical cyclones and their corresponding storm surge that driving coastal flooding. To protect coastal communities from the impacts of tropical cyclones, it is important to understand how this impact of tropical cyclones might change towards the future. This study applies the storyline approach to show what tropical cyclones Maria (2017) and Dorian (2019) could look like in a 2 °C and 3.4 °C warmer future climate. These two possible future climates are simulated with a high-resolution regional climate model using the pseudo global warming approach. Using the climate response from these simulations we apply a Delta-quantile mapping technique to derive future changes in wind speed and mean sea level pressure. We apply this Delta technique to tropical cyclones Maria and Dorian’s observed wind and pressure fields to force a hydrodynamic model for simulating storm surge levels under historical and future climate conditions. Results show that the maximum storm surge heights of Maria and Dorian could increase by up to 0.31 m and 0.56 m, respectively. These results clearly show that future changes in storm surge heights are not negligible compared to end-of-the-century sea level rise projections, something that is sometimes overlooked in large-scale assessments of future coastal flood risk.
Quantum error mitigation via quantum-noise-effect circuit groups
Authors: Hama Yusuke , Nishi Hirofumi
Published: March 2024

Near-term quantum computers have been built as intermediate-scale quantum devices and are fragile against quantum noise effects, namely, NISQ devices. Traditional quantum-error-correcting codes are not implemented on such devices and to perform quantum computation in good accuracy with these machines we need to develop alternative approaches for mitigating quantum computational errors. In this work, we propose quantum error mitigation (QEM) scheme for quantum computational errors which occur due to couplings with environments during gate operations, i.e., decoherence. To establish our QEM scheme, first we estimate the quantum noise effects on single-qubit states and represent them as groups of quantum circuits, namely, quantum-noise-effect circuit groups. Then our QEM scheme is conducted by subtracting expectation values generated by the quantum-noise-effect circuit groups from those obtained by the quantum circuits for the quantum algorithms under consideration. As a result, the quantum noise effects are reduced, and we obtain approximately the ideal expectation values via the quantum-noise-effect circuit groups and the numbers of elementary quantum circuits composing them scale polynomial with respect to the products of the depths of quantum algorithms and the numbers of register bits. To numerically demonstrate the validity of our QEM scheme, we run noisy quantum simulations of qubits under amplitude damping effects for four types of quantum algorithms. Furthermore, we implement our QEM scheme on IBM Q Experience processors and examine its efficacy. Consequently, the validity of our scheme is verified via both the quantum simulations and the quantum computations on the real quantum devices. Our QEM scheme is solely composed of quantum-computational operations (quantum gates and measurements), and thus, it can be conducted by any type of quantum device. In addition, it can be applied to error mitigation for many other types of quantum noise effects as well as noisy quantum computing of long-depth quantum algorithms.
Description and management of Aspergillus section Nigri causing post-harvest bulbs rot of onion
Authors: El-Dawy Eman G. A. M. , Hussein Mohamed A. , El‑Nahas Safaa
Published: March 2024

When onions are improperly stored, a post-harvest disease known as black mold of onion bulbs can result in considerable economic losses. Aspergillus section Nigri, one of many species, has been implicated in the development of black mold. In the present study, rot onion bulbs were collected from markets in Qena, Egypt. Thirteen Aspergillus section Nigri isolates were obtained and identified by morphological and molecular characterization. The ochratoxins potential of isolated A. section Nigri was tested, and three isolates were producers at the range of 1.5–15 ppm. For the presence of pks gene, no amplification product was detected. Using the fungal growth inhibition test, the isolates of A. niger were inhibited by eco-friendly materials Cement and Zeolite. Cement exhibited maximum percentage growth inhibition against the tested isolates at 74.7–86.7%. The pathogenicity activity of the A. niger isolates was tested by inoculation of healthy onion bulbs, other onion bulbs covered with Cement and Zeolite before inoculation by A. niger was used. The two treatments significantly reduced bulbs rot disease of onion than untreated bulbs. Seven and nine isolates showed 0% rot on covered bulbs by Cement and Zeolite, respectively as compared with inoculated onions, which exhibited rot ranging from 55 to 80%. Using eco-friendly materials with efficiency against post-harvest bulbs rot of onion was evaluated in this study.
Vibrio natriegens as a superior host for the production of c-type cytochromes and difficult-to-express redox proteins
Authors: Fuchs Helena , Ullrich Sophie R. , Hedrich Sabrina
Published: March 2024

C-type cytochromes fulfil many essential roles in both aerobic and anaerobic respiration. Their characterization requires large quantities of protein which can be obtained through heterologous production. Heterologous production of c-type cytochromes in Escherichia coli is hindered since the ccmABCDEFGH genes necessary for incorporation of heme c are only expressed under anaerobic conditions. Different strategies were devised to bypass this obstacle, such as co-expressing the ccm genes from the pEC86 vector. However, co-expression methods restrict the choice of expression host and vector. Here we describe the first use of Vibrio natriegens Vmax X2 for the recombinant production of difficult-to-express redox proteins from the extreme acidophile Acidithiobacillus ferrooxidans CCM4253, including three c-type cytochromes. Co-expression of the ccm genes was not required to produce holo-c-type cytochromes in Vmax X2. E. coli T7 Express only produced holo-c-type cytochromes during co-expression of the ccm genes and was not able to produce the inner membrane cytochrome CycA. Additionally, Vmax X2 cell extracts contained higher portions of recombinant holo-proteins than T7 Express cell extracts. All redox proteins were translocated to the intended cell compartment in both hosts. In conclusion, V. natriegens represents a promising alternative for the production of c-type cytochromes and difficult-to-express redox proteins.
Morphological differences of the neuroretinal rim between temporally tilted and non-tilted optic discs in healthy eyes
Authors: Joo Chan Woong , Choi Youn Joo , Kim Han Ul , Park Sung Pyo , Na Kyeong Ik
Published: March 2024

This study aimed to compare morphological differences of the neuroretinal rim between the temporally tilted and non-tilted optic discs in healthy eyes. We prospectively enrolled participants aged 20–40 years with temporally tilted or non-tilted optic discs. The optic nerve head parameters were analyzed using spectral domain-optical coherence tomography. The angle between the Bruch’s membrane opening (BMO) plane and BMO-minimum rim width (BMO-MRW) was termed “BMO-MRW angle”. Peripapillary retinal nerve fiber layer thickness (pRNFLT) and BMO-based parameters were compared between the temporally tilted and non-tilted disc groups. As a result, 55 temporally tilted disc eyes and 38 non-tilted disc eyes were analyzed. Global pRNFLT, global BMO-MRW, and total BMO-minimum rim area (BMO-MRA) were similar between the two groups (p = 0.138, 0.161, and p = 0.410, respectively). In the sectoral analysis, temporally tilted disc group exhibited thicker BMO-MRW in the temporal sector (p = 0.032) and thinner in the nasal superior and nasal sectors (p = 0.025 and p = 0.002, respectively). Temporally tilted disc group showed larger BMO-MRA in the temporal, temporal superior, and temporal inferior sectors (p < 0.001, p < 0.001, and p < 0.016, respectively), alongside a higher BMO-MRW angle in the temporal sector and lower in the nasal superior and nasal sectors. In conclusion, the neuroretinal rim, represented by BMO-MRW and BMO-MRA, showed morphological differences between temporally tilted and non-tilted optic discs in healthy eyes. BMO-MRW and BMO-MRA showed temporalization in the same manner as pRNFLT in the temporally tilted disc eyes. The BMO-MRW angle showed that in temporally tilted disc eyes, optic nerve fibers met the BMO plane steeply in the nasal sector and gently in the temporal sector than in non-tilted disc eyes, suggesting potential stress region of optic nerve fibers in temporally tilted disc eyes.
Timing of first abdominal operation in Crohn’s disease based on a diagnostic model
Authors: Yang Lichao , Zhang Yawei , Yao Baojia , Wu Qiang , Peng Liangxin , Yuan Lianwen
Published: March 2024

This study aims to develop a clinical diagnostic model for assessing the need for initial abdominal surgery in patients diagnosed with Crohn's disease (CD) and create a nomogram to facilitate clinical decision-making. A total of 164 surgical CD patients and 230 control CD patients were included in this retrospective analysis. Least Absolute Shrinkage and Selection Operator (Lasso) regression and binomial logistic regression were employed to select clinical variables. The 394 CD patients were randomly allocated to a training set and a validation set in a 7:3 ratio. The filtered variables were used to establish a diagnostic model and nomogram in the training set, subsequently validated in the testing set. Decision Curve Analysis (DCA) and clinical impact curve were constructed to validate the clinical applicability of the model. Binomial logistic regression analysis identified seven clinical variables with a p-value less than 0.01, including Biomarker (B), Waist-to-Height Ratio (WHtR), Intestinal obstruction, Albumin (ALB), Crohn's Disease Activity Index (CDAI), Myocardial Flow Index (MFI), and C-reactive protein (CRP). These variables were utilized to establish the diagnostic model. Calibration curves showed good alignment, with a C-index of 0.996 in the training set and 0.990 in the testing set. DCA and clinical impact curve demonstrated that the diagnostic model had good clinical efficiency and could provide clinical benefits. A validated diagnostic model for determining the timing of the first abdominal operation in CD patients was established and evaluated, showing high discriminative ability, calibration, and clinical efficiency. It can be utilized by clinicians to assess the optimal timing for transitioning CD patients from medical treatment to surgical intervention, providing valuable references for individualized treatment decisions for CD patients.
The Impact of Russia-Ukraine geopolitical conflict on the air quality and toxicological properties of ambient PM2.5 in Milan, Italy
Authors: Aghaei Yashar , Badami Mohammad Mahdi , Tohidi Ramin , Subramanian P. S. Ganesh , Boffi Roberto , Borgini Alessandro , De Marco Cinzia , Contiero Paolo , Ruprecht Ario Alberto , Verma Vishal , Chatila Talal , Sioutas Constantinos
Published: March 2024

The geopolitical conflict between Russia and Ukraine has disrupted Europe’s natural gas supplies, driving up gas prices and leading to a shift towards biomass for residential heating during colder months. This study assessed the consequent air quality and toxicological impacts in Milan, Italy, focusing on fine particulate matter (PM2.5, dp < 2.5 μm) emissions. PM2.5 samples were analyzed for their chemical composition and assessed for their oxidative potential using the dithiothreitol (DTT) assay across three periods reflecting residential heating deployment (RHD): pre-RHD, intra-RHD, and post-RHD periods. During the intra-RHD period, PM2.5 levels were significantly higher than those in other periods, with concentrations reaching 57.94 ± 7.57 μg/m3, indicating a deterioration in air quality. Moreover, levoglucosan was 9.2 times higher during the intra-RHD period compared to the pre-RHD period, correlating with elevated levels of elemental carbon (EC) and polycyclic aromatic hydrocarbons (PAHs). These findings were compared with previous local studies before the conflict, underscoring a significant rise in biomass-related emissions. DTT assay levels during the intra-RHD were 2.1 times higher than those observed during the same period in 2022, strongly correlating with biomass burning emissions. Our findings highlight the necessity for policies to mitigate the indirect health effects of increased biomass burning emissions due to the energy crisis triggered by the geopolitical conflict.
Facile synthesis of Fe2O3, Fe2O3@CuO and WO3 nanoparticles: characterization, structure determination and evaluation of their biological activity
Authors: Mohamed Asmaa T. , Hameed Reda Abdel , EL-Moslamy Shahira H. , Fareid Mohamed , Othman Mohamad , Loutfy Samah A. , Kamoun Elbadawy A. , Elnouby Mohamed
Published: March 2024

Due to their high specific surface area and its characteristic’s functionalized nanomaterials have great potential in medical applications specialty, as an anticancer. Herein, functional nanoparticles (NPs) based on iron oxide Fe2O3, iron oxide modified with copper oxide Fe2O3@CuO, and tungsten oxide WO3 were facile synthesized for biomedical applications. The obtained nanomaterials have nanocrystal sizes of 35.5 nm for Fe2O3, 7 nm for Fe2O3@CuO, and 25.5 nm for WO3. In addition to octahedral and square nanoplates for Fe2O3, and WO3; respectively. Results revealed that Fe2O3, Fe2O3@CuO, and WO3 NPs showed remarked anticancer effects versus a safe effect on normal cells through cytotoxicity test using MTT-assay. Notably, synthesized NPs e.g. our result demonstrated that Fe2O3@CuO exhibited the lowest IC50 value on the MCF-7 cancer cell line at about 8.876 µg/ml, compared to Fe2O3 was 12.87 µg/ml and WO3 was 9.211 µg/ml which indicate that the modification NPs Fe2O3@CuO gave the highest antiproliferative effect against breast cancer. However, these NPs showed a safe mode toward the Vero normal cell line, where IC50 were monitored as 40.24 µg/ml for Fe2O3, 21.13 µg/ml for Fe2O3@CuO, and 25.41 µg/ml for WO3 NPs. For further evidence. The antiviral activity using virucidal and viral adsorption mechanisms gave practiced effect by viral adsorption mechanism and prevented the virus from replicating inside the cells. Fe2O3@CuO and WO3 NPs showed a complete reduction in the viral load synergistic effect of combinations between the tested two materials copper oxide instead of iron oxide alone. Interestingly, the antimicrobial efficiency of Fe2O3@CuO NPs, Fe2O3NPs, and WO3NPs was evaluated using E. coli, S. aureus, and C. albicans pathogens. The widest microbial inhibition zone (ca. 38.45 mm) was observed with 250 mg/ml of WO3 NPs against E. coli, whereas using 40 mg/ml of Fe2O3@CuO NPS could form microbial inhibition zone ca. 32.86 mm against S. aureus. Nevertheless, C. albicans was relatively resistant to all examined NPs. The superior biomedical activities of these nanostructures might be due to their unique features and accepted evaluations.
Pathogenic mutations in UBQLN2 exhibit diverse aggregation propensity and neurotoxicity
Authors: Safren Nathaniel , Dao Thuy P. , Mohan Harihar Milaganur , Huang Camellia , Trotter Bryce , Castañeda Carlos A. , Paulson Henry , Barmada Sami , Sharkey Lisa M.
Published: March 2024

The ubiquitin-adaptor protein UBQLN2 promotes degradation of several aggregate-prone proteins implicated in neurodegenerative diseases. Missense UBQLN2 mutations also cause X-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Previously we demonstrated that the liquid-like properties of UBQLN2 molecular assemblies are altered by a specific pathogenic mutation, P506T, and that the propensity of UBQLN2 to aggregate correlated with neurotoxicity. Here, we systematically assess the effects of multiple, spatially distinct ALS/FTD-linked missense mutations on UBQLN2 aggregation propensity, neurotoxicity, phase separation, and autophagic flux. In contrast to what we observed for the P506T mutation, no other tested pathogenic mutant exhibited a clear correlation between aggregation propensity and neurotoxicity. These results emphasize the unique nature of pathogenic UBQLN2 mutations and argue against a generalizable link between aggregation propensity and neurodegeneration in UBQLN2-linked ALS/FTD.
Enhancing coevolutionary signals in protein–protein interaction prediction through clade-wise alignment integration
Authors: Fang Tao , Szklarczyk Damian , Hachilif Radja , von Mering Christian
Published: March 2024

Protein–protein interactions (PPIs) play essential roles in most biological processes. The binding interfaces between interacting proteins impose evolutionary constraints that have successfully been employed to predict PPIs from multiple sequence alignments (MSAs). To construct MSAs, critical choices have to be made: how to ensure the reliable identification of orthologs, and how to optimally balance the need for large alignments versus sufficient alignment quality. Here, we propose a divide-and-conquer strategy for MSA generation: instead of building a single, large alignment for each protein, multiple distinct alignments are constructed under distinct clades in the tree of life. Coevolutionary signals are searched separately within these clades, and are only subsequently integrated using machine learning techniques. We find that this strategy markedly improves overall prediction performance, concomitant with better alignment quality. Using the popular DCA algorithm to systematically search pairs of such alignments, a genome-wide all-against-all interaction scan in a bacterial genome is demonstrated. Given the recent successes of AlphaFold in predicting direct PPIs at atomic detail, a discover-and-refine approach is proposed: our method could provide a fast and accurate strategy for pre-screening the entire genome, submitting to AlphaFold only promising interaction candidates—thus reducing false positives as well as computation time.
Research on driving mechanism and prediction of electric power carbon emission in Gansu Province under dual-carbon target
Authors: Qiao Fuwei , Yang Qinzhe , Shi Wei , Yang Xuedi , Ouyang Guanwen , Zhao Lulu
Published: March 2024

The electric power industry is a key industry for the country to achieve the double carbon target. Its low carbon development has a double effect on this industry and helps other industries to achieve the carbon peak target. This paper firstly uses the IPCC inventory method to calculate carbon emissions in the production phase of the power industry in Gansu Province from 2000 to 2019, followed by the ridge regression method and the STIRPAT model to analyse the quantitative impact of six major drivers on carbon emissions, and finally, the scenario analysis method is used to forecast carbon emissions in this phase. The results show that the carbon emissions of Gansu Province show a trend of rising and then falling, and reached a peak of 65.66 million tons in 2013. For every 1% increase in population effect, urbanisation level, affluence, clean energy generation share, technology level and industrial structure, carbon emissions will grow by 4.939%, 0.625%, 0.224%, − 0.259%, 0.063% and 0.022% respectively. Because of the clean energy advantage in Gansu Province, the low-carbon development scenario will continue to have low carbon emissions during the scenario cycle, which can be reduced to 53.454 million tons in 2030; the baseline scenario will achieve a carbon peak in 2025, with a peak of 62.627 million tons; the economic development scenario has not achieved carbon peak during the scenario cycle, and carbon emissions will increase to 73.223 million tons in 2030.
Exploring cell-free assays for COVID-19 serosurvey
Authors: Inchauste Lucia , Nurtop Elif , Brisbarre Nadège , Ninove Laetitia , Gallian Pierre , de Lamballerie Xavier , Priet Stéphane
Published: March 2024

Serosurveys to monitor immunity toward COVID-19 in the population are primarily performed using an ELISA to screen samples for SARS-CoV-2 antibodies, followed by confirmation by a virus neutralization test, which is considered the Gold Standard. However, virus neutralization test may not be feasible for some laboratories because of the requirement for specific facilities and trained personnel. In an attempt to address this limitation, we evaluated three cell-free methods as potential alternatives for assessing SARS-CoV-2 seroprevalence in human population from plasma. We report the establishment of two inhibition ELISAs designed to detect anti-Spike RBD IgG antibodies and a microsphere quantitative suspension array technology assay, based on the Luminex xMAP platform, to measure the presence of antibodies against various SARS-CoV-2 antigens, including anti-RBD. These methods were also compared to a commercial chemiluminescent immunoassay designed for anti-RBD antibodies detection and to the combined ELISA + virus neutralization test strategy. These cell-free assays performed equally to estimate the percentage of positive and negative samples and could be used to determine the prevalence of SARS-CoV-2 antibodies in human population, at least in cohort with high-expected prevalence, without the use of seroneutralization assay.
Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease
Authors: Martinelli Filippo , Heinken Almut , Henning Ann-Kristin , Ulmer Maria A. , Hensen Tim , González Antonio , Arnold Matthias , Asthana Sanjay , Budde Kathrin , Engelman Corinne D. , Estaki Mehrbod , Grabe Hans-Jörgen , Heston Margo B. , Johnson Sterling , Kastenmüller Gabi , Martino Cameron , McDonald Daniel , Rey Federico E. , Kilimann Ingo , Peters Olive , Wang Xiao , Spruth Eike Jakob , Schneider Anja , Fliessbach Klaus , Wiltfang Jens , Hansen Niels , Glanz Wenzel , Buerger Katharina , Janowitz Daniel , Laske Christoph , Munk Matthias H. , Spottke Annika , Roy Nina , Nauck Matthias , Teipel Stefan , Knight Rob , Kaddurah-Daouk Rima F. , Bendlin Barbara B. , Hertel Johannes , Thiele Ines
Published: March 2024

In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and controls, revealing decreased formate and fumarate concentrations in AD. Additionally, we utilised whole-genome sequencing (WGS) data obtained from a separate group of individuals with AD and controls. This information allowed us to create and investigate host-microbiome personalised whole-body metabolic models. We predicted microbial formate as well as other microbial metabolites, which could alter urine formate production in the host-microbiome personalised models. Additionally, we identified specific reactions responsible for the production of formate in the host, and interestingly, these reactions were linked to genes that have correlations with AD. This study suggests formate as a possible early AD marker and highlights genetic and microbiome contributions to its production. The reduced formate secretion and its genetic associations point to a complex connection between gut microbiota and AD. This holistic understanding might pave the way for novel diagnostic and therapeutic avenues in AD management.
Novel pheromone-mediated reproductive behaviour in the stag beetle, Lucanus cervus
Authors: Harvey Deborah J. , Vuts József , Hooper Antony , Caulfield John C. , Finch Paul , Woodcock Christine M. , Gange Alan C. , Chapman Jason W. , Birkett Michael A. , Pickett John A.
Published: March 2024

The iconic European stag beetle (Lucanus cervus) (Coleoptera: Lucanidae) is one of the largest terrestrial beetles in Europe. Due to decreasing population numbers, thought to be a consequence of habitat loss, this beetle has become a near-threatened species across much of Europe, and a reliable monitoring system is required to measure its future population trends. As part of a programme aimed at conserving UK populations, we have investigated the chemical ecology of the beetle, with a view to developing an efficient semiochemical-based monitoring system. Such a scheme will be beneficial not only in the UK but across the European range of the species, where the beetle is of conservation concern. Here, we report on a surprising discovery of a male-produced pheromone, which provokes initial sexual receptivity in females, and which has not been previously identified in the animal kingdom. Furthermore, we assign sex pheromone function to a previously described female-specific compound.
A pilot observation using ultrasonography and vowel articulation to investigate the influence of suspected obstructive sleep apnea on upper airway
Authors: Saha Shumit , Rattansingh Anand , Martino Rosemary , Viswanathan Keerthana , Saha Anamika , Montazeri Ghahjaverestan Nasim , Yadollahi Azadeh
Published: March 2024

Failure to employ suitable measures before administering full anesthesia to patients with obstructive sleep apnea (OSA) who are undergoing surgery may lead to developing complications after surgery. Therefore, it is very important to screen OSA before performing a surgery, which is currently done by subjective questionnaires such as STOP-Bang, Berlin scores. These questionnaires have 10–36% specificity in detecting sleep apnea, along with no information given on anatomy of upper airway, which is important for intubation. To address these challenges, we performed a pilot study to understand the utility of ultrasonography and vowel articulation in screening OSA. Our objective was to investigate the influence of OSA risk factors in vowel articulation through ultrasonography and acoustic features analysis. To accomplish this, we recruited 18 individuals with no risk of OSA and 13 individuals with high risk of OSA and asked them to utter vowels, such as /a/ (as in “Sah”), /e/ (as in “See”). An expert ultra-sonographer measured the parasagittal anterior–posterior (PAP) and transverse diameter of the upper airway. From the recorded vowel sounds, we extracted 106 features, including power, pitch, formant, and Mel frequency cepstral coefficients (MFCC). We analyzed the variation of the PAP diameters and vowel features from "See: /i/" to "Sah /a/" between control and OSA groups by two-way repeated measures ANOVA. We found that, there was a variation of upper airway diameter from “See” to “Sah” was significantly smaller in OSA group than control group (OSA: ∆12.8 ± 5.3 mm vs. control: ∆22.5 ± 3.9 mm OSA, p < 0.01). Moreover, we found several vowel features showed the exact same or opposite trend as PAP diameter variation, which led us to build a machine learning model to estimate PAP diameter from vowel features. We found a correlation coefficient of 0.75 between the estimated and measured PAP diameter after applying four estimation models and combining their output with a random forest model, which showed the feasibility of using acoustic features of vowel sounds to monitor upper airway diameter. Overall, this study has proven the concept that ultrasonography and vowel sounds analysis may be useful as an easily accessible imaging tool of upper airway.
Synthesis of biologically active Shiga toxins in cell-free systems
Authors: Ramm Franziska , Kaser Danny , König Irina , Fellendorf Juliane , Wenzel Dana , Zemella Anne , Papatheodorou Panagiotis , Barth Holger , Schmidt Herbert
Published: March 2024

Shiga toxins (Stx) produced by pathogenic bacteria can cause mild to severe diseases in humans. Thus, the analysis of such toxins is of utmost importance. As an AB5 toxin, Stx consist of a catalytic A-subunit acting as a ribosome-inactivating protein (RIP) and a B-pentamer binding domain. In this study we synthesized the subunits and holotoxins from Stx and Stx2a using different cell-free systems, namely an E. coli- and CHO-based cell-free protein synthesis (CFPS) system. The functional activity of the protein toxins was analyzed in two ways. First, activity of the A-subunits was assessed using an in vitro protein inhibition assay. StxA produced in an E. coli cell-free system showed significant RIP activity at concentrations of 0.02 nM, whereas toxins synthesized in a CHO cell-free system revealed significant activity at concentrations of 0.2 nM. Cell-free synthesized StxA2a was compared to StxA2a expressed in E. coli cells. Cell-based StxA2a had to be added at concentrations of 20 to 200 nM to yield a significant RIP activity. Furthermore, holotoxin analysis on cultured HeLa cells using an O-propargyl-puromycin assay showed significant protein translation reduction at concentrations of 10 nM and 5 nM for cell-free synthesized toxins derived from E. coli and CHO systems, respectively. Overall, these results show that Stx can be synthesized using different cell-free systems while remaining functionally active. In addition, we were able to use CFPS to assess the activity of different Stx variants which can further be used for RIPs in general.
Optimization of pacing parameters to entrain slow wave activity in the pig jejunum
Authors: Nagahawatte Nipuni D. , Avci Recep , Paskaranandavadivel Niranchan , Cheng Leo K.
Published: March 2024

Pacing has been proposed as a therapy to restore function in motility disorders associated with electrical dysrhythmias. The spatial response of bioelectrical activity in the small intestine to pacing is poorly understood due to a lack of high-resolution investigations. This study systematically varied pacing parameters to determine the optimal settings for the spatial entrainment of slow wave activity in the jejunum. An electrode array was developed to allow simultaneous pacing and high-resolution mapping of the small intestine. Pacing parameters including pulse-width (50, 100 ms), pulse-amplitude (2, 4, 8 mA) and pacing electrode orientation (antegrade, retrograde, circumferential) were systematically varied and applied to the jejunum (n = 15 pigs). Pulse-amplitudes of 4 mA (p = 0.012) and 8 mA (p = 0.002) were more effective than 2 mA in achieving spatial entrainment while pulse-widths of 50 ms and 100 ms had comparable effects (p = 0.125). A pulse-width of 100 ms and a pulse-amplitude of 4 mA were determined to be most effective for slow wave entrainment when paced in the antegrade or circumferential direction with a success rate of greater than 75%. These settings can be applied in chronic studies to evaluate the long-term efficacy of pacing, a critical aspect in determining its therapeutic potential.
Social and economic variables explain COVID-19 diffusion in European regions
Authors: Cancedda Christian , Cappellato Alessio , Maninchedda Luigi , Meacci Leonardo , Peracchi Sofia , Salerni Claudia , Baralis Elena , Giobergia Flavio , Ceri Stefano
Published: March 2024

At the beginning of 2020, Italy was the country with the highest number of COVID-19 cases, not only in Europe, but also in the rest of the world, and Lombardy was the most heavily hit region of Italy. The objective of this research is to understand which variables have determined the prevalence of cases in Lombardy and in other highly-affected European regions. We consider the first and second waves of the COVID-19 pandemic, using a set of 22 variables related to economy, population, healthcare and education. Regions with a high prevalence of cases are extracted by means of binary classifiers, then the most relevant variables for the classification are determined, and the robustness of the analysis is assessed. Our results show that the most meaningful features to identify high-prevalence regions include high number of hours spent in work environments, high life expectancy, and low number of people leaving from education and neither employed nor educated or trained.
Deep learning-based label-free imaging of lymphatics and aqueous veins in the eye using optical coherence tomography
Authors: Gong Peijun , Tang Xiaolan , Chen Junying , You Haijun , Wang Yuxing , Yu Paula K. , Yu Dao-Yi , Cense Barry
Published: March 2024

We demonstrate an adaptation of deep learning for label-free imaging of the micro-scale lymphatic vessels and aqueous veins in the eye using optical coherence tomography (OCT). The proposed deep learning-based OCT lymphangiography (DL-OCTL) method was trained, validated and tested, using OCT scans (23 volumetric scans comprising 19,736 B-scans) from 11 fresh ex vivo porcine eyes with the corresponding vessel labels generated by a conventional OCT lymphangiography (OCTL) method based on thresholding with attenuation compensation. Compared to conventional OCTL, the DL-OCTL method demonstrates comparable results for imaging lymphatics and aqueous veins in the eye, with an Intersection over Union value of 0.79 ± 0.071 (mean ± standard deviation). In addition, DL-OCTL mitigates the imaging artifacts in conventional OCTL where the OCT signal modelling was corrupted by the tissue heterogeneity, provides ~ 10 times faster processing based on a rough comparison and does not require OCT-related knowledge for correct implementation as in conventional OCTL. With these favorable features, DL-OCTL promises to improve the practicality of OCTL for label-free imaging of lymphatics and aqueous veins for preclinical and clinical imaging applications.
Narrow bandwidth, low-emittance positron beams from a laser-wakefield accelerator
Authors: Streeter M. J. V. , Colgan C. , Carderelli J. , Ma Y. , Cavanagh N. , Los E. E. , Ahmed H. , Antoine A. F. , Audet T. , Balcazar M. D. , Calvin L. , Kettle B. , Mangles S. P. D. , Najmudin Z. , Rajeev P. P. , Symes D. R. , Thomas A. G. R. , Sarri G.
Published: March 2024

The rapid progress that plasma wakefield accelerators are experiencing is now posing the question as to whether they could be included in the design of the next generation of high-energy electron-positron colliders. However, the typical structure of the accelerating wakefields presents challenging complications for positron acceleration. Despite seminal proof-of-principle experiments and theoretical proposals, experimental research in plasma-based acceleration of positrons is currently limited by the scarcity of positron beams suitable to seed a plasma accelerator. Here, we report on the first experimental demonstration of a laser-driven source of ultra-relativistic positrons with sufficient spectral and spatial quality to be injected in a plasma accelerator. Our results indicate, in agreement with numerical simulations, selection and transport of positron beamlets containing $$N_{e+}\ge 10^5$$

N

e
+

≥

10
5

positrons in a 5% bandwidth around 600 MeV, with femtosecond-scale duration and micron-scale normalised emittance. Particle-in-cell simulations show that positron beams of this kind can be guided and accelerated in a laser-driven plasma accelerator, with favourable scalings to further increase overall charge and energy using PW-scale lasers. The results presented here demonstrate the possibility of performing experimental studies of positron acceleration in a laser-driven wakefield accelerator.
Multiannual patterns of genetic structure and mating type ratios highlight the complex bloom dynamics of a marine planktonic diatom
Authors: Ruggiero Maria Valeria , Buffoli Marina , Wolf Klara K. E. , D’Alelio Domenico , Di Tuccio Viviana , Lombardi Ernestina , Manfellotto Francesco , Vitale Laura , Margiotta Francesca , Sarno Diana , John Uwe , Ferrante Maria Immacolata , Montresor Marina
Published: March 2024

Understanding the genetic structure of populations and the processes responsible for its spatial and temporal dynamics is vital for assessing species’ adaptability and survival in changing environments. We investigate the genetic fingerprinting of blooming populations of the marine diatom Pseudo-nitzschia multistriata in the Gulf of Naples (Mediterranean Sea) from 2008 to 2020. Strains were genotyped using microsatellite fingerprinting and natural samples were also analysed with Microsatellite Pool-seq Barcoding based on Illumina sequencing of microsatellite loci. Both approaches revealed a clonal expansion event in 2013 and a more stable genetic structure during 2017–2020 compared to previous years. The identification of a mating type (MT) determination gene allowed to assign MT to strains isolated over the years. MTs were generally at equilibrium with two notable exceptions, including the clonal bloom of 2013. The populations exhibited linkage equilibrium in most blooms, indicating that sexual reproduction leads to genetic homogenization. Our findings show that P. multistriata blooms exhibit a dynamic genetic and demographic composition over time, most probably determined by deeper-layer cell inocula. Occasional clonal expansions and MT imbalances can potentially affect the persistence and ecological success of planktonic diatoms.