bluuebunny/crossref_metadata_2025_split huggingface dataset:
From interaction networks to interfaces, scanning intrinsically disordered regions using AlphaFold2
Authors: Bret Hélène , Gao Jinmei , Zea Diego Javier , Andreani Jessica , Guerois Raphaël 
Published: January 2024

AbstractThe revolution brought about by AlphaFold2 opens promising perspectives to unravel the complexity of protein-protein interaction networks. The analysis of interaction networks obtained from proteomics experiments does not systematically provide the delimitations of the interaction regions. This is of particular concern in the case of interactions mediated by intrinsically disordered regions, in which the interaction site is generally small. Using a dataset of protein-peptide complexes involving intrinsically disordered regions that are non-redundant with the structures used in AlphaFold2 training, we show that when using the full sequences of the proteins, AlphaFold2-Multimer only achieves 40% success rate in identifying the correct site and structure of the interface. By delineating the interaction region into fragments of decreasing size and combining different strategies for integrating evolutionary information, we manage to raise this success rate up to 90%. We obtain similar success rates using a much larger dataset of protein complexes taken from the ELM database. Beyond the correct identification of the interaction site, our study also explores specificity issues. We show the advantages and limitations of using the AlphaFold2 confidence score to discriminate between alternative binding partners, a task that can be particularly challenging in the case of small interaction motifs.
Discovery of plant chemical defence mediated by a two-component system involving β-glucosidase in Panax species
Authors: Ma Li-Juan , Liu Xiao , Guo Liwei , Luo Yuan , Zhang Beibei , Cui Xiaoxue , Yang Kuan , Cai Jing , Liu Fang , Ma Ni , Yang Feng-Qing , He Xiahong , Shi She-Po , Wan Jian-Bo 
Published: January 2024

AbstractPlants usually produce defence metabolites in non-active forms to minimize the risk of harm to themselves and spatiotemporally activate these defence metabolites upon pathogen attack. This so-called two-component system plays a decisive role in the chemical defence of various plants. Here, we discovered that Panax notoginseng, a valuable medicinal plant, has evolved a two-component chemical defence system composed of a chloroplast-localized β-glucosidase, denominated PnGH1, and its substrates 20(S)-protopanaxadiol ginsenosides. The β-glucosidase and its substrates are spatially separated in cells under physiological conditions, and ginsenoside hydrolysis is therefore activated only upon chloroplast disruption, which is caused by the induced exoenzymes of pathogenic fungi upon exposure to plant leaves. This activation of PnGH1-mediated hydrolysis results in the production of a series of less-polar ginsenosides by selective hydrolysis of an outer glucose at the C-3 site, with a broader spectrum and more potent antifungal activity in vitro and in vivo than the precursor molecules. Furthermore, such β-glucosidase-mediated hydrolysis upon fungal infection was also found in the congeneric species P. quinquefolium and P. ginseng. Our findings reveal a two-component chemical defence system in Panax species and offer insights for developing botanical pesticides for disease management in Panax species.
Alternative dosing regimen of exemestane in a randomized presurgical trial: the role of obesity in biomarker modulation
Authors: Johansson Harriet , Guerrieri-Gonzaga Aliana , Gandini Sara , Bertelsen Bjørn-Erik , Macis Debora , Serrano Davide , Mellgren Gunnar , Lazzeroni Matteo , Thomas Parijatham S. , Crew Katherine D. , Kumar Nagi B. , Briata Irene Maria , Galimberti Viviana , Viale Giuseppe , Vornik Lana A. , Aristarco Valentina , Buttiron Webber Tania , Spinaci Stefano , Brown Powel H. , Heckman-Stoddard Brandy M. , Szabo Eva , Bonanni Bernardo , DeCensi Andrea 
Published: January 2024

AbstractIn a 3-arm presurgical trial, four-six weeks exemestane 25 mg three times/week (TIW) was non-inferior to 25 mg/day (QD) in suppressing circulating estradiol in postmenopausal women with ER-positive breast cancer. Since obesity may decrease exemestane efficacy, we analyzed changes in sex steroids, adipokines, Ki-67, and drug levels in relation to obesity. Postmenopausal women with early-stage ER-positive breast cancer were randomized to either exemestane 25 mg QD (n = 57), 25 mg TIW (n = 57), or 25 mg/week (QW, n = 62) for 4–6 weeks before breast surgery. Serum and tissue pre- and post-treatment biomarkers were stratified by body mass index (BMI)< or ≥30 kg/m2. Post-treatment median exemestane and 17-OH exemestane levels were 5–6 times higher in the QD arm compared to the TIW arm. For obese women, TIW maintained comparable reductions to QD in systemic estradiol levels, although the reduction in estrone was less with the TIW regimen. There was less suppression of SHBG with the TIW versus the QD dose schedule in obese women which should result in less systemic bioavailable estrogens. Metabolically, the effect of the TIW regimen was similar to the QD regimen for obese women in terms of leptin suppression and increase in the adiponectin-leptin ratio. Reduction in tissue Ki-67 was less for obese women on the TIW regimen than QD, although changes were similar for non-obese women. Our findings suggest that TIW exemestane should be explored further for primary cancer prevention in both normal weight and obese cohorts.
Deciphering Lyman-α emission deep into the epoch of reionization
Authors: Witten Callum , Laporte Nicolas , Martin-Alvarez Sergio , Sijacki Debora , Yuan Yuxuan , Haehnelt Martin G. , Baker William M. , Dunlop James S. , Ellis Richard S. , Grogin Norman A. , Illingworth Garth , Katz Harley , Koekemoer Anton M. , Magee Daniel , Maiolino Roberto , McClymont William , Pérez-González Pablo G. , Puskás Dávid , Roberts-Borsani Guido , Santini Paola , Simmonds Charlotte 
Published: January 2024

AbstractDuring the epoch of reionization, the first galaxies were enshrouded in pristine neutral gas, with one of the brightest emission lines in star-forming galaxies, Lyman α (Lyα), expected to remain undetected until the Universe became ionized. Providing an explanation for the surprising detection of Lyα in these early galaxies is a major challenge for extragalactic studies. Recent James Webb Space Telescope observations have reignited the debate about whether residence in an overdensity of galaxies is a sufficient and necessary condition for Lyα to escape. Here, we take unique advantage of both high-resolution and high-sensitivity images from the James Webb Space Telescope Near Infrared Camera to show that all galaxies in a sample of Lyα emitters with redshift >7 have close companions. We exploit on-the-fly radiative-transfer magnetohydrodynamical simulations with cosmic ray feedback to show that galaxies with frequent mergers have very bursty star formation histories that drives episodes of high intrinsic Lyα emission and facilitates the escape of Lyα photons along channels cleared of neutral gas. We conclude that the rapid buildup of stellar mass through mergers presents a compelling solution to the long-standing puzzle of the detection of Lyα emission deep in the epoch of reionization.
Yersinia entomophaga Tc toxin is released by T10SS-dependent lysis of specialized cell subpopulations
Authors: Sitsel Oleg , Wang Zhexin , Janning Petra , Kroczek Lara , Wagner Thorsten , Raunser Stefan 
Published: January 2024

AbstractDisease-causing bacteria secrete numerous toxins to invade and subjugate their hosts. Unlike many smaller toxins, the secretion machinery of most large toxins remains enigmatic. By combining genomic editing, proteomic profiling and cryo-electron tomography of the insect pathogen Yersinia entomophaga, we demonstrate that a specialized subset of these cells produces a complex toxin cocktail, including the nearly ribosome-sized Tc toxin YenTc, which is subsequently exported by controlled cell lysis using a transcriptionally coupled, pH-dependent type 10 secretion system (T10SS). Our results dissect the Tc toxin export process by a T10SS, identifying that T10SSs operate via a previously unknown lytic mode of action and establishing them as crucial players in the size-insensitive release of cytoplasmically folded toxins. With T10SSs directly embedded in Tc toxin operons of major pathogens, we anticipate that our findings may model an important aspect of pathogenesis in bacteria with substantial impact on agriculture and healthcare.
Microglia regulate sleep through calcium-dependent modulation of norepinephrine transmission
Authors: Ma Chenyan , Li Bing , Silverman Daniel , Ding Xinlu , Li Anan , Xiao Chi , Huang Ganghua , Worden Kurtresha , Muroy Sandra , Chen Wei , Xu Zhengchao , Tso Chak Foon , Huang Yixuan , Zhang Yufan , Luo Qingming , Saijo Kaoru , Dan Yang 
Published: January 2024

AbstractSleep interacts reciprocally with immune system activity, but its specific relationship with microglia—the resident immune cells in the brain—remains poorly understood. Here, we show in mice that microglia can regulate sleep through a mechanism involving Gi-coupled GPCRs, intracellular Ca2+ signaling and suppression of norepinephrine transmission. Chemogenetic activation of microglia Gi signaling strongly promoted sleep, whereas pharmacological blockade of Gi-coupled P2Y12 receptors decreased sleep. Two-photon imaging in the cortex showed that P2Y12–Gi activation elevated microglia intracellular Ca2+, and blockade of this Ca2+ elevation largely abolished the Gi-induced sleep increase. Microglia Ca2+ level also increased at natural wake-to-sleep transitions, caused partly by reduced norepinephrine levels. Furthermore, imaging of norepinephrine with its biosensor in the cortex showed that microglia P2Y12–Gi activation significantly reduced norepinephrine levels, partly by increasing the adenosine concentration. These findings indicate that microglia can regulate sleep through reciprocal interactions with norepinephrine transmission.
A ubiquitous spectrolaminar motif of local field potential power across the primate cortex
Authors: Mendoza-Halliday Diego , Major Alex James , Lee Noah , Lichtenfeld Maxwell J. , Carlson Brock , Mitchell Blake , Meng Patrick D. , Xiong Yihan , Westerberg Jacob A. , Jia Xiaoxuan , Johnston Kevin D. , Selvanayagam Janahan , Everling Stefan , Maier Alexander , Desimone Robert , Miller Earl K. , Bastos André M. 
Published: January 2024

AbstractThe mammalian cerebral cortex is anatomically organized into a six-layer motif. It is currently unknown whether a corresponding laminar motif of neuronal activity patterns exists across the cortex. Here we report such a motif in the power of local field potentials (LFPs). Using laminar probes, we recorded LFPs from 14 cortical areas across the cortical hierarchy in five macaque monkeys. The laminar locations of recordings were histologically identified by electrolytic lesions. Across all areas, we found a ubiquitous spectrolaminar pattern characterized by an increasing deep-to-superficial layer gradient of high-frequency power peaking in layers 2/3 and an increasing superficial-to-deep gradient of alpha-beta power peaking in layers 5/6. Laminar recordings from additional species showed that the spectrolaminar pattern is highly preserved among primates—macaque, marmoset and human—but more dissimilar in mouse. Our results suggest the existence of a canonical layer-based and frequency-based mechanism for cortical computation.
Projected income data under different shared socioeconomic pathways for Washington state
Authors: Wan Heng , Ganguli Sumitrra , Mohankumar Narmadha Meenu , Jain Milan , Wilson Kyle , Anderson David 
Published: January 2024

AbstractHigh-resolution income projections under different Shared Socioeconomic Pathways (SSPs) are essential for the climate change research communities to devise climate change adaptation and mitigation strategies. To generate income projections for Washington state, we obtain state-level GDP per capita projections and convert them into projected annual household income. The resulting state-level income projections are subsequently downscaled to the census block-level based on the Longitudinal Origin-Destination Employment Statistics (LODES) dataset. For accuracy assessment, we downscale historical income data from state- level to block- and block group-level and compare the downscaled results against the actual income data from LODES. County-level accuracy assessment is also conducted based on American Community Survey. The results demonstrate a good agreement (Average R2 of 0.67, 0.8, and 0.99 for block-, block group-, and county-level, respectively) between the downscaled income data and the reference data, thereby validating the methodology employed. Our approach is applicable to other states for income projections, which can be utilized by a broader audience, including those involved in demographic analysis, economic research, and urban planning.
Pumpkin seeds (Cucurbita pepo subsp. ovifera) decoction promotes Trichinella spiralis expulsion during intestinal phase via “Weep and Sweep” mechanism
Authors: Saleh Aml S. , El-Newary Samah A. , Mohamed Walaa A. , Elgamal Abdelbaset M. , Farah Mona A. 
Published: January 2024

AbstractTrichinosis is a zoonotic disease of communal health concern as it instigated human outbreaks in several countries. Besides, the development of resistance, traditional therapy has numerous antagonistic effects. Thereby, finding efficient natural alternatives is required. In comparison to albendazole, this study evaluated the impact of pumpkin decoction on Trichinella spiralis in experimentally infected mice. The anthelmintic action of pumpkin decoction (500 mg/kg) was determined using T. spiralis infected mice in enteric phase for 5 days. Pumpkin decoction anthelmintic activity fortified by mixing with honey (1:1). Pumpkin decoction and Pumpkin decoction-honey mixture were evaluated by comprising with reference drug, albendazole (50 mg/kg). The T. spiralis adult count was significantly lower in all treated groups, with the pumpkin decoction-honey mixture showing the largest reduction (83.2%) when compared to the infected group (P ≤ 0.001). The intestinal histological changes and the level of COX-2 expression in the intestinal tissue were both significantly reduced in the same group. The pumpkin decoction improved the immune response, as evidenced by a significant decrease in nitric oxide (NO) and tumor necrosis factor (TNF-α) and a significant increase in the expression of the transforming growth factor (TGF-1β) and interleukin-17 (IL-17). The pumpkin decoction's anthelmintic action was facilitated by the TGF-1β and IL-17-driven Weep and Sweep mechanism. Both administration of pumpkin decoction beside honey showed the best treatment group that resulted in high infection reduction besides amelioration of biochemical markers and restoration of histological to normal state. In conclusion, pumpkin decoction is highly effective against T. spiralis which could be a promising alternative herbal drug and the pumpkin decoction effect was higher in the case of combination with honey.
Space object identification and classification from hyperspectral material analysis
Authors: Vasile Massimiliano , Walker Lewis , Campbell Andrew , Marto Simão , Murray Paul , Marshall Stephen , Savitski Vasili 
Published: January 2024

AbstractThis paper presents a data processing pipeline designed to extract information from the hyperspectral signature of unknown space objects. The methodology proposed in this paper determines the material composition of space objects from single pixel images. Two techniques are used for material identification and classification: one based on machine learning and the other based on a least square match with a library of known spectra. From this information, a supervised machine learning algorithm is used to classify the object into one of several categories based on the detection of materials on the object. The behaviour of the material classification methods is investigated under non-ideal circumstances, to determine the effect of weathered materials, and the behaviour when the training library is missing a material that is present in the object being observed. Finally the paper will present some preliminary results on the identification and classification of space objects.
In vitro investigation of the blood flow downstream of a 3D-printed aortic valve
Authors: Zeugin Till , Coulter Fergal B. , Gülan Utku , Studart André R. , Holzner Markus 
Published: January 2024

AbstractThe hemodynamics in the aorta as well as the durability of aortic valve prostheses vary greatly between different types of devices. Although placement and sizing of surgical aortic valve prostheses are excellent, the valve geometry of common devices cannot be customized to fit the patient’s anatomy perfectly. Similarly, transcatheter aortic valve implantation (TAVI) devices are not customizable and may be orientated unfavorably during implantation. Imperfect fit of an aortic valve prosthesis may result in suboptimal performance and in some cases the need for additional surgery. Leveraging the advent of precision, multi-material 3D-printing, a bioinspired silicone aortic valve was developed. The manufacturing technique makes it fully customizable and significantly cheaper to develop and produce than common prostheses. In this study, we assess the hemodynamic performance of such a 3D-printed aortic valve and compare it to two TAVI devices as well as to a severely stenosed valve. We investigate the blood flow distal to the valve in an anatomically accurate, compliant aorta model via three-dimensional particle tracking velocimetry measurements. Our results demonstrate that the 3D-printed aortic valve induces flow patterns and topology compatible with the TAVI valves and showing similarity to healthy aortic blood flow. Compared to the stenosis, the 3D-printed aortic valve reduces turbulent kinetic energy levels and irreversible energy losses by over 75%, reaching values compatible with healthy subjects and conventional TAVIs. Our study substantiates that the 3D-printed heart valve displays a hemodynamic performance similar to established devices and underscores its potential for driving innovation towards patient specific valve prostheses.
Light pollution and habitat fragmentation in the grey mouse lemur
Authors: Le Tallec Thomas , Hozer Clara , Perret Martine , Théry Marc 
Published: January 2024

AbstractLight pollution, by changing organisms’ behavior, affects locomotion, migration and can ultimately fragment the habitat. To investigate the effects of light pollution on habitat fragmentation, we conducted an experimental study on a nocturnal and photosensitive primate, the grey mouse lemur (Microcebus murinus). Twelve males were housed individually in an apparatus with two cages connected by two corridors, opaque and transparent. During 4 nights, the transparent corridor was illuminated by specific light intensities: 0 lx, 0.3 lx, 20 lx and 51.5 lx corresponding respectively to total darkness, full moon, minimal intensity recommended by the European standard EN-13201 on public lighting, and to light pollution recorded in an urban area. Each night, general activity, use of corridors and cage occupancy were recorded using an infrared camera. For the first time in a nocturnal primate, results demonstrate that light pollution changes the preference of use of corridors, modifies the locomotor pattern and limits the ability of animals to efficiently exploit their environment according to a light intensity-dependent relationship. However, results indicate that a dark corridor allows partial compensation partly preserving general activities. This study highlights the necessity to consider light pollution during the implementation of conservation plans and the relevance of nocturnal frames.
Standardized analysis of syndesmosis stability in ankle trauma with an innovative syndesmosis-test-tool: a biomechanical study
Authors: Kohler Felix Christian , Hallbauer Jakob , Herrmann Lea , Ullrich Bernhard Wilhelm , Biedermann Uta , Wildemann Britt , Hofmann Gunther Olaf , Ramm Roland , Lenz Mark , Marintschev Ivan , Schenk Philipp 
Published: January 2024

AbstractWhen treating ankle fractures, the question of syndesmosis complex involvement often arises. So far, there is no standardized method to reliably detect syndesmosis injuries in the surgical treatment of ankle fractures. For this reason, an intraoperative syndesmosis-test-tool (STT) was developed and compared to the recommended and established hook-test (HT). Tests were performed on cadaveric lower legs (n = 20) and the diastasis was visualized by 3D camera. Tests were performed at 50, 80, and 100 N in native conditions and four instability levels. Instability was induced from anterior to posterior and the reverse on the opposite side. The impact on diastasis regarding the direction, the force level, the instability level, and the device used was checked using a general linear model for repeated measurement. The direction of the induced instability showed no influence on the diastasis during the stability tests. The diastasis measured with the STT increased from 0.5 to 3.0 mm depending on the instability, while the range was lower with the HT (1.1 to 2.3 mm). The results showed that the differentiation between the instability levels was statistically significantly better for the developed STT. The last level of maximum instability was significantly better differentiable with the STT compared to the HT. An average visualizable diastasis of more than 2 mm could only be achieved at maximum instability. In conclusion, the newly developed STT was superior to the commonly used HT to detect instability.
The use of information technology to improve interdisciplinary communication during infectious diseases ward rounds on the paediatric intensive care unit
Authors: Willems Jef , Heyndrickx Adeline , Schelstraete Petra , Gadeyne Bram , De Cock Pieter , Vandendriessche Stien , Depuydt Pieter 
Published: January 2024

AbstractProspective audit with feedback during infectious diseases ward rounds (IDWR) is a common antimicrobial stewardship (AMS) practice on the Paediatric Intensive Care Unit (PICU). These interdisciplinary meetings rely on the quality of handover, with high risk of omission of information. We developed an electronic platform integrating infection-related patient data (COSARAPed). In the mixed PICU of a Belgian tertiary hospital we conducted an observational prospective cohort study comparing patient handovers during IDWRs using the COSARAPed-platform to those with access only to conventional resources. The quality of handover was investigated directly by assessment if the narrative was in accordance with Situation-Background-Assessment-Recommendation principles and if adequate demonstration of diagnostic information occurred, and also indirectly by registration if this was only achieved after intervention by the non-presenting AMS team members. We also recorded all AMS-recommendations. During a 6-month study period, 24 IDWRs and 82 patient presentations were assessed. We could only find a statistically significant advantage in favor of COSARAPed by indirect evaluation. We registered 92 AMS-recommendations, mainly resulting in reduced antibiotic pressure. We concluded that the IDWR is an appropriate platform for AMS on the PICU and that the utilisation of COSARAPed may enhance the quality of patient handover.