bluuebunny/crossref_metadata_2025 huggingface dataset:
Staphylococcus aureus functional amyloids catalyze degradation of β-lactam antibiotics
Authors: Arad Elad , Pedersen Kasper B. , Malka Orit , Mambram Kunnath Sisira , Golan Nimrod , Aibinder Polina , Schiøtt Birgit , Rapaport Hanna , Landau Meytal , Jelinek Raz
Published: December 2023

Antibiotic resistance of bacteria is considered one of the most alarming developments in modern medicine. While varied pathways for bacteria acquiring antibiotic resistance have been identified, there still are open questions concerning the mechanisms underlying resistance. Here, we show that alpha phenol-soluble modulins (PSMαs), functional bacterial amyloids secreted by Staphylococcus aureus, catalyze hydrolysis of β-lactams, a prominent class of antibiotic compounds. Specifically, we show that PSMα2 and, particularly, PSMα3 catalyze hydrolysis of the amide-like bond of the four membered β-lactam ring of nitrocefin, an antibiotic β-lactam surrogate. Examination of the catalytic activities of several PSMα3 variants allowed mapping of the active sites on the amyloid fibrils’ surface, specifically underscoring the key roles of the cross-α fibril organization, and the combined electrostatic and nucleophilic functions of the lysine arrays. Molecular dynamics simulations further illuminate the structural features of β-lactam association upon the fibril surface. Complementary experimental data underscore the generality of the functional amyloid-mediated catalytic phenomenon, demonstrating hydrolysis of clinically employed β-lactams by PSMα3 fibrils, and illustrating antibiotic degradation in actual S. aureus biofilms and live bacteria environments. Overall, this study unveils functional amyloids as catalytic agents inducing degradation of β-lactam antibiotics, underlying possible antibiotic resistance mechanisms associated with bacterial biofilms.
Dissecting the basis for differential substrate specificity of ADAR1 and ADAR2
Authors: Zambrano-Mila Marlon S. , Witzenberger Monika , Rosenwasser Zohar , Uzonyi Anna , Nir Ronit , Ben-Aroya Shay , Levanon Erez Y. , Schwartz Schraga
Published: December 2023

Millions of adenosines are deaminated throughout the transcriptome by ADAR1 and/or ADAR2 at varying levels, raising the question of what are the determinants guiding substrate specificity and how these differ between the two enzymes. We monitor how secondary structure modulates ADAR2 vs ADAR1 substrate selectivity, on the basis of systematic probing of thousands of synthetic sequences transfected into cell lines expressing exclusively ADAR1 or ADAR2. Both enzymes induce symmetric, strand-specific editing, yet with distinct offsets with respect to structural disruptions: −26 nt for ADAR2 and −35 nt for ADAR1. We unravel the basis for these differences in offsets through mutants, domain-swaps, and ADAR homologs, and find it to be encoded by the differential RNA binding domain (RBD) architecture. Finally, we demonstrate that this offset-enhanced editing can allow an improved design of ADAR2-recruiting therapeutics, with proof-of-concept experiments demonstrating increased on-target and potentially decreased off-target editing.
Projecting future carbon emissions from cement production in developing countries
Authors: Cheng Danyang , Reiner David M. , Yang Fan , Cui Can , Meng Jing , Shan Yuli , Liu Yunhui , Tao Shu , Guan Dabo
Published: December 2023

Achieving low-carbon development of the cement industry in the developing countries is fundamental to global emissions abatement, considering the local construction industry’s rapid growth. However, there is currently a lack of systematic and accurate accounting and projection of cement emissions in developing countries, which are characterized with lower basic economic country condition. Here, we provide bottom-up quantifications of emissions from global cement production and reveal a regional shift in the main contributors to global cement CO2 emissions. The study further explores cement emissions over 2020-2050 that correspond to different housing and infrastructure conditions and emissions mitigation options for all developing countries except China. We find that cement emissions in developing countries except China will reach 1.4-3.8 Gt in 2050 (depending on different industrialization trajectories), compared to their annual emissions of 0.7 Gt in 2018. The optimal combination of low-carbon measures could contribute to reducing annual emissions by around 65% in 2050 and cumulative emissions by around 48% over 2020-2050. The efficient technological paths towards a low carbon future of cement industry vary among the countries and infrastructure scenarios. Our results are essential to understanding future emissions patterns of the cement industry in the developing countries and can inform policies in the cement sector that contribute to meeting the climate targets set out in the Paris Agreement.
Nanophotonics for pair production
Authors: Di Giulio Valerio , García de Abajo F. Javier
Published: December 2023

The transformation of electromagnetic energy into matter represents a fascinating prediction of relativistic quantum electrodynamics that is paradigmatically exemplified by the creation of electron-positron pairs out of light. However, this phenomenon has a very low probability, so positron sources rely instead on beta decay, which demands elaborate monochromatization and trapping schemes to achieve high-quality beams. Here, we propose to use intense, strongly confined optical near fields supported by a nanostructured material in combination with high-energy photons to create electron-positron pairs. Specifically, we show that the interaction between near-threshold γ-rays and polaritons yields higher pair-production cross sections, largely exceeding those associated with free-space photons. Our work opens an unexplored avenue toward generating tunable pulsed positrons from nanoscale regions at the intersection between particle physics and nanophotonics.
The emergence of modern zoogeographic regions in Asia examined through climate–dental trait association patterns
Authors: Liu Liping , Galbrun Esther , Tang Hui , Kaakinen Anu , Zhang Zhongshi , Zhang Zijian , Žliobaitė Indrė
Published: December 2023

The complex and contrasted distribution of terrestrial biota in Asia has been linked to active tectonics and dramatic climatic changes during the Neogene. However, the timings of the emergence of these distributional patterns and the underlying climatic and tectonic mechanisms remain disputed. Here, we apply a computational data analysis technique, called redescription mining, to track these spatiotemporal phenomena by studying the associations between the prevailing herbivore dental traits of mammalian communities and climatic conditions during the Neogene. Our results indicate that the modern latitudinal zoogeographic division emerged after the Middle Miocene climatic transition, and that the modern monsoonal zoogeographic pattern emerged during the late Late Miocene. Furthermore, the presence of a montane forest biodiversity hotspot in the Hengduan Mountains alongside Alpine fauna on the Tibetan Plateau suggests that the modern distribution patterns may have already existed since the Pliocene.
The 5α condensate state in 20Ne
Authors: Zhou Bo , Funaki Yasuro , Horiuchi Hisashi , Ma Yu-Gang , Röpke Gerd , Schuck Peter , Tohsaki Akihiro , Yamada Taiichi
Published: December 2023

The formed 4He (α) clusters consisting of two neutrons and two protons can be a building block in light nuclear systems. Intriguingly, these alpha clusters could potentially form alpha condensate states within the nuclear system. The Hoyle state at 7.65 MeV in 12C, which plays an essential role in stellar nucleosynthesis, is now considered to be a phase transition, namely the 3α Bose-Einstein condensate. Confirming the existence of Hoyle-analog states in Nα nuclei (N > 3) remains a major challenge. Here we show microscopic five-body calculations for the 20Ne nucleus. We find that one excited 0+ state has a distinct gas-like characteristic and represents the condensate state. Identifying the 5α condensate state is an important step in establishing the concept of α condensation in nuclear fermion systems.
Nearly complete structure of bacteriophage DT57C reveals architecture of head-to-tail interface and lateral tail fibers
Authors: Ayala Rafael , Moiseenko Andrey V. , Chen Ting-Hua , Kulikov Eugene E. , Golomidova Alla K. , Orekhov Philipp S. , Street Maya A. , Sokolova Olga S. , Letarov Andrey V. , Wolf Matthias
Published: December 2023

The T5 family of viruses are tailed bacteriophages characterized by a long non-contractile tail. The bacteriophage DT57C is closely related to the paradigmal T5 phage, though it recognizes a different receptor (BtuB) and features highly divergent lateral tail fibers (LTF). Considerable portions of T5-like phages remain structurally uncharacterized. Here, we present the structure of DT57C determined by cryo-EM, and an atomic model of the virus, which was further explored using all-atom molecular dynamics simulations. The structure revealed a unique way of LTF attachment assisted by a dodecameric collar protein LtfC, and an unusual composition of the phage neck constructed of three protein rings. The tape measure protein (TMP) is organized within the tail tube in a three-stranded parallel α-helical coiled coil which makes direct contact with the genomic DNA. The presence of the C-terminal fragment of the TMP that remains within the tail tip suggests that the tail tip complex returns to its original state after DNA ejection. Our results provide a complete atomic structure of a T5-like phage, provide insights into the process of DNA ejection as well as a structural basis for the design of engineered phages and future mechanistic studies.
Nonuniversal impact of cholesterol on membranes mobility, curvature sensing and elasticity
Authors: Pöhnl Matthias , Trollmann Marius F. W. , Böckmann Rainer A.
Published: December 2023

Biological membranes, composed mainly of phospholipids and cholesterol, play a vital role as cellular barriers. They undergo localized reshaping in response to environmental cues and protein interactions, with the energetics of deformations crucial for exerting biological functions. This study investigates the non-universal role of cholesterol on the structure and elasticity of saturated and unsaturated lipid membranes. Our study uncovers a highly cooperative relationship between thermal membrane bending and local cholesterol redistribution, with cholesterol showing a strong preference for the compressed membrane leaflet. Remarkably, in unsaturated membranes, increased cholesterol mobility enhances cooperativity, resulting in membrane softening despite membrane thickening and lipid compression caused by cholesterol. These findings elucidate the intricate interplay between thermodynamic forces and local molecular interactions that govern collective properties of membranes.
An archetype and scaling of developmental tissue dynamics across species
Authors: Morishita Yoshihiro , Lee Sang-Woo , Suzuki Takayuki , Yokoyama Hitoshi , Kamei Yasuhiro , Tamura Koji , Kawasumi-Kita Aiko
Published: December 2023

Morphometric studies have revealed the existence of simple geometric relationships among various animal shapes. However, we have little knowledge of the mathematical principles behind the morphogenetic dynamics that form the organ/body shapes of different species. Here, we address this issue by focusing on limb morphogenesis in Gallus gallus domesticus (chicken) and Xenopus laevis (African clawed frog). To compare the deformation dynamics between tissues with different sizes/shapes as well as their developmental rates, we introduce a species-specific rescaled spatial coordinate and a common clock necessary for cross-species synchronization of developmental times. We find that tissue dynamics are well conserved across species under this spacetime coordinate system, at least from the early stages of development through the phase when basic digit patterning is established. For this developmental period, we also reveal that the tissue dynamics of both species are mapped with each other through a time-variant linear transformation in real physical space, from which hypotheses on a species-independent archetype of tissue dynamics and morphogenetic scaling are proposed.
DeepRTAlign: toward accurate retention time alignment for large cohort mass spectrometry data analysis
Authors: Liu Yi , Yang Yun , Chen Wendong , Shen Feng , Xie Linhai , Zhang Yingying , Zhai Yuanjun , He Fuchu , Zhu Yunping , Chang Cheng
Published: December 2023

Retention time (RT) alignment is a crucial step in liquid chromatography-mass spectrometry (LC-MS)-based proteomic and metabolomic experiments, especially for large cohort studies. The most popular alignment tools are based on warping function method and direct matching method. However, existing tools can hardly handle monotonic and non-monotonic RT shifts simultaneously. Here, we develop a deep learning-based RT alignment tool, DeepRTAlign, for large cohort LC-MS data analysis. DeepRTAlign has been demonstrated to have improved performances by benchmarking it against current state-of-the-art approaches on multiple real-world and simulated proteomic and metabolomic datasets. The results also show that DeepRTAlign can improve identification sensitivity without compromising quantitative accuracy. Furthermore, using the MS features aligned by DeepRTAlign, we trained and validated a robust classifier to predict the early recurrence of hepatocellular carcinoma. DeepRTAlign provides an advanced solution to RT alignment in large cohort LC-MS studies, which is currently a major bottleneck in proteomics and metabolomics research.
Interactions between climate change, urban infrastructure and mobility are driving dengue emergence in Vietnam
Authors: Gibb Rory , Colón-González Felipe J. , Lan Phan Trong , Huong Phan Thi , Nam Vu Sinh , Duoc Vu Trong , Hung Do Thai , Dong Nguyễn Thanh , Chien Vien Chinh , Trang Ly Thi Thuy , Kien Quoc Do , Hoa Tran Minh , Tai Nguyen Hữu , Hang Tran Thi , Tsarouchi Gina , Ainscoe Eleanor , Harpham Quillon , Hofmann Barbara , Lumbroso Darren , Brady Oliver J. , Lowe Rachel
Published: December 2023

Dengue is expanding globally, but how dengue emergence is shaped locally by interactions between climatic and socio-environmental factors is not well understood. Here, we investigate the drivers of dengue incidence and emergence in Vietnam, through analysing 23 years of district-level case data spanning a period of significant socioeconomic change (1998-2020). We show that urban infrastructure factors (sanitation, water supply, long-term urban growth) predict local spatial patterns of dengue incidence, while human mobility is a more influential driver in subtropical northern regions than the endemic south. Temperature is the dominant factor shaping dengue’s distribution and dynamics, and using long-term reanalysis temperature data we show that warming since 1950 has expanded transmission risk throughout Vietnam, and most strongly in current dengue emergence hotspots (e.g., southern central regions, Ha Noi). In contrast, effects of hydrometeorology are complex, multi-scalar and dependent on local context: risk increases under either short-term precipitation excess or long-term drought, but improvements in water supply mitigate drought-associated risks except under extreme conditions. Our findings challenge the assumption that dengue is an urban disease, instead suggesting that incidence peaks in transitional landscapes with intermediate infrastructure provision, and provide evidence that interactions between recent climate change and mobility are contributing to dengue’s expansion throughout Vietnam.
Ultrafast THz probing of nonlocal orbital current in transverse multilayer metallic heterostructures
Authors: Kumar Sandeep , Kumar Sunil
Published: December 2023

THz generation from femtosecond photoexcited spintronic heterostructures has become a versatile tool for investigating ultrafast spin-transport and transient charge-current in a non-contact and non-invasive manner. The equivalent effect from the orbital degree of freedom is still in the primitive stage. Here, we experimentally demonstrate orbital-to-charge current conversion in metallic heterostructures, consisting of a ferromagnetic layer adjacent to either a light or a heavy metal layer, through detection of the emitted THz pulses. Our temperature-dependent experiments help to disentangle the orbital and spin components that are manifested in the respective Hall-conductivities, contributing to THz emission. NiFe/Nb shows the strongest inverse orbital Hall effect with an experimentally extracted value of effective intrinsic Hall-conductivity, $${({\sigma }_{{SOH}}^{{{{{\mathrm{int}}}}}})}^{{eff}} \sim 195{\varOmega }^{-1}{{cm}}^{-1}$$

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, while CoFeB/Pt shows maximum contribution from the inverse spin Hall effect. In addition, we observe a nearly ten-fold enhancement in the THz emission due to pronounced orbital-transport in W-insertion heavy metal layer in CoFeB/W/Ta heterostructure as compared to CoFeB/Ta bilayer counterpart.
The formation of the Indo-Pacific montane avifauna
Authors: Reeve Andrew Hart , Kennedy Jonathan David , Pujolar José Martín , Petersen Bent , Blom Mozes P. K. , Alström Per , Haryoko Tri , Ericson Per G. P. , Irestedt Martin , Nylander Johan A. A. , Jønsson Knud Andreas
Published: December 2023

The processes generating the earth’s montane biodiversity remain a matter of debate. Two contrasting hypotheses have been advanced to explain how montane populations form: via direct colonization from other mountains, or, alternatively, via upslope range shifts from adjacent lowland areas. We seek to reconcile these apparently conflicting hypotheses by asking whether a species’ ancestral geographic origin determines its mode of mountain colonization. Island-dwelling passerine birds at the faunal crossroads between Eurasia and Australo-Papua provide an ideal study system. We recover the phylogenetic relationships of the region’s montane species and reconstruct their ancestral geographic ranges, elevational ranges, and migratory behavior. We also perform genomic population studies of three super-dispersive montane species/clades with broad island distributions. Eurasian-origin species populated archipelagos via direct colonization between mountains. This mode of colonization appears related to ancestral adaptations to cold and seasonal climates, specifically short-distance migration. Australo-Papuan-origin mountain populations, by contrast, evolved from lowland ancestors, and highland distribution mostly precludes their further colonization of island mountains. Our study explains much of the distributional variation within a complex biological system, and provides a synthesis of two seemingly discordant hypotheses for montane community formation.
Immunoproximity biotinylation reveals the axon initial segment proteome
Authors: Zhang Wei , Fu Yu , Peng Luxin , Ogawa Yuki , Ding Xiaoyun , Rasband Anne , Zhou Xinyue , Shelly Maya , Rasband Matthew N. , Zou Peng
Published: December 2023

The axon initial segment (AIS) is a specialized neuronal compartment required for action potential generation and neuronal polarity. However, understanding the mechanisms regulating AIS structure and function has been hindered by an incomplete knowledge of its molecular composition. Here, using immuno-proximity biotinylation we further define the AIS proteome and its dynamic changes during neuronal maturation. Among the many AIS proteins identified, we show that SCRIB is highly enriched in the AIS both in vitro and in vivo, and exhibits a periodic architecture like the axonal spectrin-based cytoskeleton. We find that ankyrinG interacts with and recruits SCRIB to the AIS. However, loss of SCRIB has no effect on ankyrinG. This powerful and flexible approach further defines the AIS proteome and provides a rich resource to elucidate the mechanisms regulating AIS structure and function.
Dispersal from the Qinghai-Tibet plateau by a high-altitude butterfly is associated with rapid expansion and reorganization of its genome
Authors: Zhao Youjie , Su Chengyong , He Bo , Nie Ruie , Wang Yunliang , Ma Junye , Song Jingyu , Yang Qun , Hao Jiasheng
Published: December 2023

Parnassius glacialis is a typical “Out of the QTP” alpine butterfly that originated on the Qinghai-Tibet Plateau (QTP) and dispersed into relatively low-altitude mountainous. Here we assemble a chromosome-level genome of P. glacialis and resequence 9 populations in order to explore the genome evolution and local adaptation of this species. These results indicated that the rapid accumulation and slow unequal recombination of transposable elements (TEs) contributed to the formation of its large genome. Several ribosomal gene families showed extensive expansion and selective evolution through transposon-mediated processed pseudogenes. Additionally, massive structural variations (SVs) of TEs affected the genetic differentiation of low-altitude populations. These low-altitude populations might have experienced a genetic bottleneck in the past and harbor genes with selective signatures which may be responsible for the potential adaptation to low-altitude environments. These results provide a foundation for understanding genome evolution and local adaptation for “Out of the QTP” of P. glacialis.
Carbonate chemistry and carbon sequestration driven by inorganic carbon outwelling from mangroves and saltmarshes
Authors: Reithmaier Gloria M. S. , Cabral Alex , Akhand Anirban , Bogard Matthew J. , Borges Alberto V. , Bouillon Steven , Burdige David J. , Call Mitchel , Chen Nengwang , Chen Xiaogang , Cotovicz Luiz C. , Eagle Meagan J. , Kristensen Erik , Kroeger Kevin D. , Lu Zeyang , Maher Damien T. , Pérez-Lloréns J. Lucas , Ray Raghab , Taillardat Pierre , Tamborski Joseph J. , Upstill-Goddard Rob C. , Wang Faming , Wang Zhaohui Aleck , Xiao Kai , Yau Yvonne Y. Y. , Santos Isaac R.
Published: December 2023

Mangroves and saltmarshes are biogeochemical hotspots storing carbon in sediments and in the ocean following lateral carbon export (outwelling). Coastal seawater pH is modified by both uptake of anthropogenic carbon dioxide and natural biogeochemical processes, e.g., wetland inputs. Here, we investigate how mangroves and saltmarshes influence coastal carbonate chemistry and quantify the contribution of alkalinity and dissolved inorganic carbon (DIC) outwelling to blue carbon budgets. Observations from 45 mangroves and 16 saltmarshes worldwide revealed that >70% of intertidal wetlands export more DIC than alkalinity, potentially decreasing the pH of coastal waters. Porewater-derived DIC outwelling (81 ± 47 mmol m−2 d−1 in mangroves and 57 ± 104 mmol m−2 d−1 in saltmarshes) was the major term in blue carbon budgets. However, substantial amounts of fixed carbon remain unaccounted for. Concurrently, alkalinity outwelling was similar or higher than sediment carbon burial and is therefore a significant but often overlooked carbon sequestration mechanism.
Interleukin 31 receptor α promotes smooth muscle cell contraction and airway hyperresponsiveness in asthma
Authors: Akkenepally Santhoshi V. , Yombo Dan J. K. , Yerubandi Sanjana , Reddy Geereddy Bhanuprakash , Deshpande Deepak A. , McCormack Francis X. , Madala Satish K.
Published: December 2023

Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. Multiple cytokines, including IFNγ, IL-4, and IL-13 are associated with asthma; however, the mechanisms underlying the effects of these cytokines remain unclear. Here, we report a significant increase in the expression of IL-31RA, but not its cognate ligand IL-31, in mouse models of allergic asthma. In support of this, IFNγ, IL-4, and IL-13 upregulated IL-31RA but not IL-31 in both human and mice primary airway smooth muscle cells (ASMC) isolated from the airways of murine and human lungs. Importantly, the loss of IL-31RA attenuated AHR but had no effect on inflammation and goblet cell hyperplasia in mice challenged with allergens or treated with IL-13 or IFNγ. We show that IL-31RA functions as a positive regulator of muscarinic acetylcholine receptor 3 expression, augmenting calcium levels and myosin light chain phosphorylation in human and murine ASMC. These findings identify a role for IL-31RA in AHR that is distinct from airway inflammation and goblet cell hyperplasia in asthma.
An allele-selective inter-chromosomal protein bridge supports monogenic antigen expression in the African trypanosome
Authors: Faria Joana R. C. , Tinti Michele , Marques Catarina A. , Zoltner Martin , Yoshikawa Harunori , Field Mark C. , Horn David
Published: December 2023

UPF1-like helicases play roles in telomeric heterochromatin formation and X-chromosome inactivation, and also in monogenic variant surface glycoprotein (VSG) expression via VSG exclusion-factor-2 (VEX2), a UPF1-related protein in the African trypanosome. We show that VEX2 associates with chromatin specifically at the single active VSG expression site on chromosome 6, forming an allele-selective connection, via VEX1, to the trans-splicing locus on chromosome 9, physically bridging two chromosomes and the VSG transcription and splicing compartments. We further show that the VEX-complex is multimeric and self-regulates turnover to tightly control its abundance. Using single cell transcriptomics following VEX2-depletion, we observed simultaneous derepression of many other telomeric VSGs and multi-allelic VSG expression in individual cells. Thus, an allele-selective, inter-chromosomal, and self-limiting VEX1-2 bridge supports monogenic VSG expression and multi-allelic VSG exclusion.
In operando cryo-STEM of pulse-induced charge density wave switching in TaS2
Authors: Hart James L. , Siddique Saif , Schnitzer Noah , Funni Stephen D. , Kourkoutis Lena F. , Cha Judy J.
Published: December 2023

The charge density wave material 1T-TaS2 exhibits a pulse-induced insulator-to-metal transition, which shows promise for next-generation electronics such as memristive memory and neuromorphic hardware. However, the rational design of TaS2 devices is hindered by a poor understanding of the switching mechanism, the pulse-induced phase, and the influence of material defects. Here, we operate a 2-terminal TaS2 device within a scanning transmission electron microscope at cryogenic temperature, and directly visualize the changing charge density wave structure with nanoscale spatial resolution and down to 300 μs temporal resolution. We show that the pulse-induced transition is driven by Joule heating, and that the pulse-induced state corresponds to the nearly commensurate and incommensurate charge density wave phases, depending on the applied voltage amplitude. With our in operando cryogenic electron microscopy experiments, we directly correlate the charge density wave structure with the device resistance, and show that dislocations significantly impact device performance. This work resolves fundamental questions of resistive switching in TaS2 devices, critical for engineering reliable and scalable TaS2 electronics.
UniKP: a unified framework for the prediction of enzyme kinetic parameters
Authors: Yu Han , Deng Huaxiang , He Jiahui , Keasling Jay D. , Luo Xiaozhou
Published: December 2023

Prediction of enzyme kinetic parameters is essential for designing and optimizing enzymes for various biotechnological and industrial applications, but the limited performance of current prediction tools on diverse tasks hinders their practical applications. Here, we introduce UniKP, a unified framework based on pretrained language models for the prediction of enzyme kinetic parameters, including enzyme turnover number (kcat), Michaelis constant (Km), and catalytic efficiency (kcat / Km), from protein sequences and substrate structures. A two-layer framework derived from UniKP (EF-UniKP) has also been proposed to allow robust kcat prediction in considering environmental factors, including pH and temperature. In addition, four representative re-weighting methods are systematically explored to successfully reduce the prediction error in high-value prediction tasks. We have demonstrated the application of UniKP and EF-UniKP in several enzyme discovery and directed evolution tasks, leading to the identification of new enzymes and enzyme mutants with higher activity. UniKP is a valuable tool for deciphering the mechanisms of enzyme kinetics and enables novel insights into enzyme engineering and their industrial applications.
Neuronal substrates of egg-laying behaviour at the abdominal ganglion of Drosophila melanogaster
Authors: Oliveira-Ferreira Cristina , Gaspar Miguel , Vasconcelos Maria Luísa
Published: December 2023

Egg-laying in Drosophila is the product of post-mating physiological and behavioural changes that culminate in a stereotyped sequence of actions. Egg-laying harbours a great potential as a paradigm to uncover how the appropriate motor circuits are organized and activated to generate behaviour. To study this programme, we first describe the different phases of the egg-laying programme and the specific actions associated with each phase. Using a combination of neuronal activation and silencing experiments, we identify neurons (OvAbg) in the abdominal ganglion as key players in egg-laying. To generate and functionally characterise subsets of OvAbg, we used an intersectional approach with neurotransmitter specific lines—VGlut, Cha and Gad1. We show that OvAbg/VGlut neurons promote initiation of egg deposition in a mating status dependent way. OvAbg/Cha neurons are required in exploration and egg deposition phases, though activation leads specifically to egg expulsion. Experiments with the OvAbg/Gad1 neurons show they participate in egg deposition. We further show a functional connection of OvAbg neurons with brain neurons. This study provides insight into the organization of neuronal circuits underlying complex motor behaviour.
Pyridine-mediated B–B bond cleavage of tetrahydroxydiboron to synthesize n-doped SWCNTs with long-term air stability
Authors: Tanaka Naoki , Hamasuna Aoi , Yamaguchi Itsuki , Kato Koichiro , Fujigaya Tsuyohiko
Published: December 2023

Neutral radicals, including carbon radicals, are highly useful chemical species for the functionalization of semiconducting materials to change their electrical and optical properties owing to their high reactivity. However, boron radicals have been limited to synthetic and reaction chemistry, with rare utilization in materials science. In this study, a mixture of tetrahydroxydiboron (B2(OH)4) and pyridine derivatives was found to act as an electron dopant for single-walled carbon nanotubes (SWCNTs) because of the electron transfer from pyridine-mediated boron radicals generated by B–B bond dissociation to neutral radicals. In particular, the radical formed from a mixture of B2(OH)4 and 4-phenylpyridine ((4-Phpy)B(OH)2·) efficiently doped electrons into the SWCNT films; thus, n-type SWCNTs with long-term air stability for more than 50 days at room temperature were prepared. Furthermore, the experimental and theoretical surface analyses revealed that the formation of stable cations from ((4-Phpy)B(OH)2·) and the efficient interaction with SWCNTs due to their high planarity served as the mechanism for their stable doping.
Characteristics of brain glucose metabolism and metabolic connectivity in noise-induced hearing loss
Authors: Shin Seunghyeon , Nam Hyun-Yeol
Published: December 2023

The purpose of this study was to evaluate the differences in cerebral glucose metabolism and metabolic connectivity between noise-induced hearing loss (NIHL) subjects and normal subjects. Eighty-nine subjects who needed close observation for NIHL or were diagnosed with NIHL and 89 normal subjects were enrolled. After pre-processing of positron emission tomography images including co-registration, spatial normalization, and smoothing, a two-sample t-test was conducted to compare cerebral glucose metabolism between the two groups. To evaluate metabolic connectivity between two groups, BRAPH–BRain Analysis using graPH theory, a software package to perform graph theory analysis of the brain connectome was used. NIHL subjects showed hypometabolism compared to normal subjects in both insulae (x − 38, y − 18, z 4; × 42, y − 12, z 4) and right superior temporal gyrus (× 44, y 16, z − 20). No brain regions showed hypermetabolism in the NIHL subjects. In metabolic connectivity analysis, NIHL subjects showed decreased average strength, global efficiency, local efficiency, and mean clustering coefficient when compared with normal subjects. Decreased glucose metabolism and metabolic connectivity in NIHL subject might reflect decreased auditory function. It might be characteristic of sensorineural hearing loss.
Characterization of a new mouse line triggering transient oligodendrocyte progenitor depletion
Authors: Brousse B. , Mercier O. , Magalon K. , Gubellini P. , Malapert P. , Cayre M. , Durbec P.
Published: December 2023

Oligodendrocyte progenitor cells (OPC) are the main proliferative cells in the healthy adult brain. They produce new myelinating oligodendrocytes to ensure physiological myelin remodeling and regeneration after various pathological insults. Growing evidence suggests that OPC have other functions. Here, we aimed to develop an experimental model that allows the specific ablation of OPC at the adult stage to unravel possible new functions. We generated a transgenic mouse expressing a floxed human diphtheria toxin receptor under the control of the PDGFRa promoter, crossed with an Olig2Cre mouse to limit the recombination to the oligodendrocyte lineage in the central nervous system. We determined a diphtheria toxin dose to substantially decrease OPC density in the cortex and the corpus callosum without triggering side toxicity after a few daily injections. OPC density was normalized 7 days post-treatment, showing high repopulation capacity from few surviving OPC. We took advantage of this strong but transient depletion to show that OPC loss was associated with behavioral impairment, which was restored by OPC recovery, as well as disruption of the excitation/inhibition balance in the sensorimotor cortex, reinforcing the hypothesis of a neuromodulatory role of OPC in the adult brain.
Smartphone based colorimetric approach for quantitative determination of uric acid using Image J
Authors: Elagamy Samar H. , Adly Latifa , Abdel Hamid Mohamed Ahmed
Published: December 2023

Recently, significant attention has been directed towards digital image colorimetry DIC using mobile applications or available software programs, which offer the advantage of analyzing samples without the need for sophisticated instruments. One such image processing program is Image J, widely used for obtaining quantitative information from scientific images. Image J could measure the color intensities by quantifying of the RGB (red–green–blue) gray levels across the images of colored substances. These values are correlated to the color intensities through conversion to CMY (cyan–magenta–yellow) values which are proportional to the color intensities. The objective of this study is to develop an innovative analytical method for the quantitative determination of uric acid using Image J for color quantification. Image J was utilized to analyze images captured by smart phone for successive concentrations of uric acid that were previously treated with phosphotungstate to develop a blue color. The proposed method has been applied for determination of uric acid in real urine using standard addition method and the results were compared with UV/VIS spectrophotometry as a reference method. In this research, we will also assess the effectiveness of quantitative analysis using Image J in comparison to a mobile application, namely RGB Color Detector.
Investigation of genetic diversity and polyandry of Leptinotarsa decemlineata using X-linked microsatellite markers
Authors: Sedlák P. , Sedláková V. , Vašek J. , Melounová M. , Čílová D. , Vejl P. , Habuštová O. Skoková , Doležal P. , Hausvater E.
Published: December 2023

A panel of X-linked microsatellite markers was newly designed using the data from a previous sequencing project available in NCBI and used for a study of the Colorado potato beetle (CPB, Leptinotarsa decemlineata) X-haplotype variability. The analysis of scaffolds 49 and 61 (newly identified as fragments of CPB chromosome X) found ten high-quality markers, which were arranged in two PCR multiplexes and evaluated in both 420 CPB adults, collected from 14 localities of Czechia and Slovakia, and 866 larvae from five single-female families from two more Czech localities. Length polymorphisms found in 6 loci have predicted 192 potential X-haplotypes, however, only 36 combinations were detected in the adult males (N = 189), and seven additional ones in the larvae. The X-haplotypes were also generally unevenly distributed; five of the most frequent haplotypes were detected in 55% of males, 19 repeating up to ten-times in 38.7% of males and the remained 12 occurred uniquely in 6.3% of males. Bulk analysis of X-haplotypes dissimilarity indicated seven haplotype groups diversified by mutations and recombinations. Two haplotypes showed a distinctive regional distribution, which indicates an east–west disruption of CPB migration probably caused by different environments of localities in the South Bohemia region and Vysocina region. On the contrary, the results indicate a south–north migration corridor alongside the Vltava River. In the single-female families, from 6 to 13 distinct paternal haplotypes were detected, which proved and quantified a frequented polyandry in CPB.
Molecular data representation based on gene embeddings for cancer drug response prediction
Authors: Park Sejin , Lee Hyunju
Published: December 2023

Cancer drug response prediction is a crucial task in precision medicine, but existing models have limitations in effectively representing molecular profiles of cancer cells. Specifically, when these models represent molecular omics data such as gene expression, they employ a one-hot encoding-based approach, where a fixed gene set is selected for all samples and omics data values are assigned to specific positions in a vector. However, this approach restricts the utilization of embedding-vector-based methods, such as attention-based models, and limits the flexibility of gene selection. To address these issues, our study proposes gene embedding-based fully connected neural networks (GEN) that utilizes gene embedding vectors as input data for cancer drug response prediction. The GEN allows for the use of embedding-vector-based architectures and different gene sets for each sample, providing enhanced flexibility. To validate the efficacy of GEN, we conducted experiments on three cancer drug response datasets. Our results demonstrate that GEN outperforms other recently developed methods in cancer drug prediction tasks and offers improved gene representation capabilities. All source codes are available at https://github.com/DMCB-GIST/GEN/.
Optimizing daylight in west-facing facades for LEED V4.1 compliance using metaheuristic approach
Authors: Son Pham Vu Hong , Huyen Vo Thi Bich
Published: December 2023

This study introduces an optimized design approach for west-facing room façades to improve daylighting while adhering to LEED v4.1 sustainability criteria. Employing parametric modeling, metaheuristic optimization, and validated daylight simulations, the research highlights the African Vulture Optimization Algorithm's success in achieving 100% LEED compliance and superior performance over random models in daylight sufficiency and glare reduction. Light-colored materials and transparent glazing emerged as beneficial for LEED points. Despite computational limitations and the need for empirical validation, this method offers architects versatile and sustainable design solutions. Comparative analysis reveals the algorithm's strong performance, although opportunities exist for refinement. Future research directions include contrasting this algorithm with other optimization methods, focusing on empirical backing, assessing environmental and human-centric impacts, adapting to varied building types and conditions, and examining diverse geographical and material factors. This work advances daylight-integrated façade design, suggesting a more comprehensive framework for building performance optimization.
In-situ directed energy deposition of Al based low density steel for automotive applications
Authors: Rott Matěj , Li Ying , Koukolíková Martina , Šípová Martina , Salvetr Pavel , Nový Zbyšek , Wolf Gerhard , Džugan Jan
Published: December 2023

This work deals with the fabrication of one low density steel by mixing AISI S2 tool steel and AlSi10Mg powders using powder-based directed energy deposition (P-DED) technique. Two approaches of mixing powders were compared-continuous mixing during the process (in-situ) and mixing the powder prior to the process (premixed). The P-DED sample was characterised by a variety of techniques such as optical microscopy, scanning electron microscopy, electron backscatter diffraction, X-ray diffraction, and hardness measurement. Our findings demonstrate the successful achievement of steel with a 8 wt. % AlSi10Mg addition when two dissimilar powders are premixed, resulting in approximately 12% reduction in the density of S2 steel. Optimizing the powder feed rate and the ratio of AlSi10Mg powder contribute to an improvement of printability, eliminating materials separation, leading to a homogenous deposited part. Compared to the in-situ mixing case, the premixed process within the current process window generates a more homogeneous microstructure consisting of three phases: Ferrite, Fe3Al and Fe3AlC carbide. Whereas, the in-situ sample exhibits only two phases Ferrite and Fe3Al. The hardness of the premixed sample is found to be slightly higher compared to the in-situ sample.
A novel lifting point location optimization method of transmission line tower based on improved grey wolf optimizer
Authors: Wang Guolin , Ding Pengjie , Huang Chaosheng , Yu Zhongliang
Published: December 2023

In the erection process of transmission line tower, the appropriate lifting point position is an important factor in ensuring the stability and balance of the lifting process and preventing deformation and damage to the towers. In this paper, a improved grey wolf optimization algorithm is proposed to solve the issues of low optimization efficiency and easily getting trapped in local minima when optimizing the lifting point position of transmission line towers. The improved algorithm includes the use of a good point-set strategy to enhance the initialization method of grey wolf individuals, ensuring a more uniform distribution of the population and reducing ineffective searches in the early stages of optimization. Furthermore, two random operators are utilized to combine and mutate the optimal grey wolf position, thereby enhancing the algorithm's ability to escape local optima. Finally, the trend information of the optimization process is considered, and the median value of the population is used to improve the stability of the optimization algorithm. Experimental results demonstrate that the proposed algorithm has better optimization performance and faster convergence speed compared to genetic algorithm, particle swarm optimization algorithm, and artificial fish swarm algorithm. It effectively addresses the optimization problem of lifting point position for transmission line towers.
AAV capsid bioengineering in primary human retina models
Authors: Westhaus Adrian , Eamegdool Steven S. , Fernando Milan , Fuller-Carter Paula , Brunet Alicia A. , Miller Annie L. , Rashwan Rabab , Knight Maddison , Daniszewski Maciej , Lidgerwood Grace E. , Pébay Alice , Hewitt Alex , Santilli Giorgia , Thrasher Adrian J. , Carvalho Livia S. , Gonzalez-Cordero Anai , Jamieson Robyn V. , Lisowski Leszek
Published: December 2023

Adeno-associated viral (AAV) vector-mediated retinal gene therapy is an active field of both pre-clinical as well as clinical research. As with other gene therapy clinical targets, novel bioengineered AAV variants developed by directed evolution or rational design to possess unique desirable properties, are entering retinal gene therapy translational programs. However, it is becoming increasingly evident that predictive preclinical models are required to develop and functionally validate these novel AAVs prior to clinical studies. To investigate if, and to what extent, primary retinal explant culture could be used for AAV capsid development, this study performed a large high-throughput screen of 51 existing AAV capsids in primary human retina explants and other models of the human retina. Furthermore, we applied transgene expression-based directed evolution to develop novel capsids for more efficient transduction of primary human retina cells and compared the top variants to the strongest existing benchmarks identified in the screening described above. A direct side-by-side comparison of the newly developed capsids in four different in vitro and ex vivo model systems of the human retina allowed us to identify novel AAV variants capable of high transgene expression in primary human retina cells.
Biomechanical and histomorphological analysis of the mandible in rats with chronic kidney disease
Authors: Hu Ta-la , Chen Jun , Shao Shen-quan , Li Le-le , Lai Can , Gao Wu-niri , Xu Rui-feng , Meng Yan
Published: December 2023

The present study aimed to investigate the biomechanical and histomorphological features of mandibles in an adenine-induced chronic kidney disease–mineral and bone disorder (CKD-MBD) rat model of CKD. A total of 14 Sprague-Dawley rats were randomized into the following two groups: control group and CKD group. At the end of the sixth week, all rats were euthanized, and serum was collected for biochemical marker tests. Macroscopic bone growth and biomechanical parameters were measured in the right hemimandible, while the left hemimandible was used for bone histomorphometric analysis. Compared to the control group, the CKD group showed a significant increase in serum creatinine, blood urea nitrogen, and serum parathyroid hormone at the end of the sixth week. The biomechanical structural properties significantly decreased in the CKD group compared to the control group. Bone histomorphometric analysis indicated that the trabecular bone volume of rats in the CKD group was significantly lower than that of the control group. In the CKD groups, the bone formation parameters of the trabecular bone were significantly increased, while the bone mineralization apposition rates of both the trabecular bone and periosteal cortical bone were significantly increased. The rat CKD model showed deteriorated structural mechanics, low trabecular bone volume, high trabecular bone formation, increased trabecular bone mineralization apposition rate, and increased cortical bone mineralization apposition rate, which met the characteristics of osteitis fibrosa, indicating that this model is a useful tool for the study of mandible diseases in CKD patients.