bluuebunny/crossref_metadata_2025_split huggingface dataset:
Location of NMDARs and co-agonist control the generation of bursts in nigral dopamine neurons
Authors: Ringlet Sofian , Motta Zoraide , Vandries Laura , Seutin Vincent , Jehasse Kevin , Caldinelli Laura , Pollegioni Loredano , Engel Dominique 
Published: June 2024

AbstractNMDA receptor activation in pars compacta substantia nigra dopamine neurons is central to the generation of bursting activity, a key signal temporally associated to movement initiation. The site of the NMDAR pool (synaptic and/or extrasynaptic) as well as the identity of the co-agonist involved in the ignition of this phasic activity remains unknown. Usingex vivoelectrophysiological recordings, we demonstrate that NMDARs located outside synapses are preponderant for this firing. This pool of receptors is recruited during intense synaptic activity via spillover of glutamate and require the binding of NMDAR co-agonist glycine for their full activation. Synaptic NMDARs are not directly involved in bursting and are activated by D-serine, a distinct co-agonist. Location dependency of NMDARs and co-agonist underlying burst generation may serve as a guideline in understanding the physiological role of dopamine neurons in health and disease.TeaserExtrasynaptic NMDARs recruited by spillover and glycine allow the generation of bursts in dopamine neurons.
DNA binding is rate-limiting for natural transformation
Authors: Ellison Taylor J. , Ellison Courtney K. 
Published: June 2024

AbstractBacteria take up environmental DNA using dynamic appendages called type IV pili (T4P) to elicit horizontal gene transfer in a process called natural transformation. Natural transformation is widespread amongst bacteria yet determining how different factors universally contribute to or limit this process across species has remained challenging. Here we show thatAcinetobacter baylyi, the most naturally transformable species, is highly transformable due to its ability to robustly bind nonspecific DNA via a dedicated orphan minor pilin, FimT. We show that, compared to its homologues,A. baylyiFimT contains multiple positively charged residues that additively promote DNA binding efficiency. Expression ofA. baylyiFimT in a closely relatedAcinetobacterpathogen is sufficient to substantially improve its capacity for natural transformation, demonstrating that T4P-DNA binding is a rate-limiting step in this process. These results demonstrate the importance of T4P-DNA binding efficiency in driving natural transformation, establishing a key factor limiting horizontal gene transfer.ImportanceNatural transformation is a multi-step, broadly conserved mechanism for horizontal gene transfer in which bacteria take up exogenous DNA from the environment and integrate it into their genome by homologous recombination. A complete picture of the factors that limit this behavior remain unclear due to variability between bacterial systems. In this manuscript, we provide clear and direct evidence that DNA binding by type IV pili prior to DNA uptake is a rate-limiting step of natural transformation. We show that increasing DNA binding in antibiotic resistant Acinetobacter pathogens can boost their transformation rates by 100-fold. In addition to expanding our understanding of the factors that limit transformation in the environment, these results will also contribute to a deeper understanding of the spread of antibiotic resistance genes in relevant human pathogens.
Structures of the human transcription factor brachyury offer insights into DNA recognition, and identify small molecule binders for the development of degraders for cancer therapy
Authors: Newman Joseph A , Gavard Angeline E , Imprachim Nergis , Aitkenhead Hazel , Sheppard Hadley E. , Clarke Paul A. , Hossain Mohammad Anwar , Temme Louisa , Oh Hans J. , Wells Carrow I. , Davis-Gilbert Zachary W. , Workman Paul , Gileadi Opher , Drewry David H. 
Published: June 2024

AbstractThe transcription factor brachyury is a member of the T-Box family of transcription factors. It is active during embryogenesis and is required for the formation of the posterior mesoderm and the notochord in vertebrates. Aside from its role in embryogenesis, brachyury plays an essential role in tumour growth of the rare chordoma bone cancer and is implicated in other solid tumours. Given that brachyury is minimally expressed in healthy tissues, these findings suggest that brachyury is a potential therapeutic target in cancer. Unfortunately, as a ligandless transcription factor, brachyury has historically been considered undruggable. To investigate direct targeting of brachyury by small molecules, we initially determined the structure of human brachyury both in complex with its cognate DNA and in the absence of DNA. Analysis of these structures provided insights into brachyury DNA binding and the structural context of the G177D variant which is strongly associated with chordoma risk. We used these structures to perform a crystallographic fragment screen of brachyury and identify hotspot regions on numerous pockets on the brachyury surface. Finally, we have performed follow-up chemistry on fragment hits and describe the structure-based progression of a thiazole-containing chemical series. Excitingly, we have produced brachyury binders with low µM potency that can serve as starting point for further medicinal chemistry efforts. These data show that brachyury is ligandable and provides an example of how crystallographic fragment screening may be used to find ligands to target protein classes that are traditionally difficult to address using other approaches.
Vasopressin differentially modulates the excitability of rat olfactory bulb neuron subtypes
Authors: Suyama Hajime , Bianchini Gaia , Lukas Michael 
Published: June 2024

AbstractVasopressin (VP) is essential for social memory already at the level of the olfactory bulb (OB), and OB VP cells are activated by social interaction. However, it remains unclear how VP modulates olfactory processing to enable enhanced discrimination of very similar odors, e.g., rat body odors. So far, it has been shown that VP reduces firing rates in mitral cells (MCs) during odor presentationin-vivoand decreases the amplitudes of olfactory nerve-evoked excitatory postsynaptic potentials (ON-evoked EPSPs) in external tufted cellsin-vitro. We performed whole-cell patch-clamp recordings and population Ca2+imaging on acute rat OB slices. We recorded ON-evoked EPSPs as well as spontaneous inhibitory postsynaptic currents (IPSCs) from two types of projection neurons, middle tufted cells (mTCs) and MCs. VP bath-application reduced the amplitudes of ON-evoked EPSPs and the frequencies of spontaneous IPSCs in mTCs but did not change those in MCs. Therefore, we analyzed ON evoked-EPSPs in inhibitory interneurons, i.e., periglomerular cells (PGCs) and granule cells (GCs), to search for the origin of increased inhibition in mTCs. However, VP did not increase the amplitudes of evoked EPSPs in either type of interneurons. We next performed two-photon population Ca2+imaging in the glomerular layer and the superficial GC layer of responses to stronger ON stimulation than during patch-clamp experiments that should evoke action potentials in the measured cells. We observed that VP application increased ON-evoked Ca2+influx in juxtaglomerular cell and GC somata and decreased it in the intraglomerular neuropil. Thus, our findings indicate inhibition by VP on projection neurons via strong ON input-mediated inhibitory interneuron activity.
Shedding Light onH. pyloriDetection: A Fusion Protein Approach Unveiled through LIPS Method
Authors: Farzanfar Seyedeh Mahsa , Asad Sedigheh 
Published: June 2024

ABSTRACTThe Luciferase Immunoprecipitation Systems (LIPS) method serves as a highly sensitive approach for quantitatively detecting antibodies to antigens, offering potential in identifying viral and bacterial infections. However, the substantial size of the luciferase-antigen fusion protein presents challenges in both production and folding. An alternative strategy employing epitopes rather than full length antigenic protein may circumvent issues associated with recombinant expression.Helicobacter pylori, a gram-negative bacterium, poses a risk of gastric cancer if untreated over time. This study focuses on the recombinant production of a fusion protein comprising in silico designed antigenic epitopes from theH. pyloriurease protein and luciferase, aiming to reduce the fusion protein’s size and thus augment its expression in theE. colisystem. By employing bioinformatic analysis, sequences encoding the antigenic regions were pinpointed and subsequently amplified via PCR. A luciferase-linker-epitope construct was devised and constructed accordingly. TheE. coliBl21 (DE3) strain was utilized to express the recombinant chimeric protein, which was subsequently purified to achieve a state of homogeneity. The molecular weight of the fusion protein was estimated to be 75 kilodalton. Verification of the chimeric protein’s proper folding and functionality was confirmed, as evidenced by a bioluminescence assay yielding an emission of 13.7 × 106(RLU/s). Furthermore, western blot analysis authenticated the fusion protein’s capability to bind specifically toH. pyloriantibodies. These findings underscore the potential of the resultant protein as a promising candidate forH. pyloridetection while also streamlining the recombinant production of LIPS fusion proteins.Key PointsEpitope-driven protein design boostsE. coliexpression for LIPS advancement.ImprovedH. pyloridetection aids early gastric cancer identification.
Characterization of the calmodulin-like protein family inChara brauniiand their conserved interaction with the calmodulin-binding transcription activator family
Authors: Symonds Kyle , Wali Udo , Duff Liam , Snedden Wayne A. 
Published: June 2024

AbstractCalcium sensor proteins play important roles by detecting changes in intracellular calcium and relaying that information onto downstream targets through protein-protein interaction. Very little is known about calcium sensors from plant species that predate land colonization and the evolution of embryophytes. Here, we examined the genome of the multicellular algae,Chara braunii, for orthologs to the evolutionarily-conserved calcium sensor calmodulin (CaM), and for CaM-like proteins (CMLs). We identified one CaM and eight CML isoforms which rang in size from 16.4 to 21.3 kDa and are predicted to have between two to four calcium-binding (EF-hand) domains. Using recombinant protein, we tested whether CbCaM and CbCMLs1-7 possess biochemical properties of typical calcium sensors. CbCaM and the CbCMLs all displayed high-affinity calcium binding with estimated globalKDvalues in the physiological µM range. In response to calcium binding, CbCaM and the CbCMLs exhibited varying degrees of increase in exposed hydrophobicity, suggesting different calcium-induced conformational changes occur among isoforms. We found many examples of putative CaM targets encoded in theC. brauniigenome and explored the ability of CbCaM and CbCMLs to interactin plantawith a representative putative target, aC. brauniiCaM-binding transcription factor (CbCAMTA1). CbCaM, CbCML2, and CbCML4 associated with the C-terminal region of CbCAMTA1. Collectively, our data support the hypothesis that complex calcium signaling and sensing networks involving CaM and CMLs evolved early in the green lineage. Similarly, it seems likely that calcium-mediated regulation of transcription occurs inC. brauniivia CAMTAs and is an ancient trait predating embryophytic emergence.HighlightsAlthough calmodulin (CaM) and calmodulin-like (CML) proteins are well studied in vascular plants, little is known about their orthologs in ancient lineages. We characterized CaM and CMLs fromChara braunii, and assessed their ability to bind a representative target protein, a calmodulin-binding transcription factor, CbCAMTA1.
Dupilumab dampens mucosal type 2 response during acetylsalicylic acid challenge in N-ERD patients
Authors: Eckl-Dorna J. , Morgenstern C. , Poglitsch K. , Arnoldner T. , Gangl K. , Bartosik T. , Campion N.J. , Tu A. , Stanek V. , Schneider S. , Bangert C. 
Published: June 2024

ABSTRACTRationaleNon-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is characterized by the clinical triad of hypersensitivity to NSAIDs, nasal polyposis, and asthma. The cells and mediators causing acute symptoms when driving the hypersensitivity reaction to acetylsalicylic acid (ASA) ingestion, remain poorly defined.ObjectivesTo investigate the dynamics of nasal mediators during ASA provocation in N-ERD patients before and twenty-four weeks after therapy with the IL-4 receptor alpha-blocking antibody dupilumab.MethodsNasal mucosal lining fluids of patients with N-ERD, chronic rhinosinusitis patients with nasal polyp (CRSwNP) and healthy disease controls were collected at selected time points up to two hours after ASA provocation. Analysis of thirty-three different inflammatory mediators as well as transcriptomic profiling was performed. In N-ERD patients, provocation was repeated after twenty-four weeks of dupilumab therapy.Measurements and Main ResultsSixty minutes after provocation with ASA, N-ERD patients showed a significant increase in type 2 associated cytokines (i.e., TSLP, IL-5, and eotaxin-3) as compared to the other patient groups. This effect was diminished after twenty-four weeks of dupilumab therapy and was independent of the development of ASA tolerance. Transcriptomics revealed dampened upregulation of type 2 associated pathways genes (i.e.,AREG) as well as enhanced downregulation of lipid (i.e.,ALOX15) and peroxisome metabolisms (i.e.,NOS2) at ASA provocation after dupilumab therapy.ConclusionsTreatment with dupilumab leads to reduced nasal type 2 cytokine secretion and distinct changes in transcriptomic profile during ASA provocation, but changes in type 2 mediators show no association with tolerance development.
Production of the
ΞN
dibaryon as a weakly bound system in
pp
collisions
Authors: Wu Tian-Chen , Hosaka Atsushi , Geng Li-Sheng 
Published: June 2024

The ΞN interaction plays an important role in understanding the long-anticipated H dibaryon. Recent lattice QCD calculations verified the attractive nature of the ΞN interaction. On the other hand, whether it is strong enough to generate a bound state remains inconclusive. In this work, assuming it can generate a weakly bound state, we study the yields of the ΞN dibaryon for different binding energies in pp collisions at 7 TeV using the coalescence model and the transport model PACIAE. The yields are estimated first numerically and then analytically, adopting a Yukawa-type wave function. In particular, we find that in the weak binding limit, there exists a universal relation between the yield and the binding energy, valid for pp collisions.

Published by the American Physical Society
2024
Decoding the
B→Kνν
excess at Belle II: Kinematics, operators, and masses
Authors: Fridell Kåre , Ghosh Mitrajyoti , Okui Takemichi , Tobioka Kohsaku 
Published: June 2024

An excess in the branching fraction for B+→K+νν recently measured at Belle II may be a hint of new physics. We perform thorough likelihood analyses for different new physics scenarios such as B→KX with a new invisible particle X, or B→Kχχ through a scalar, vector, or tensor current with χ being a new invisible particle or a neutrino. We find that vector-current three-body decay with mX≃0.6 GeV—which may be dark matter—is most favored, while two-body decay with mX≃2  GeV is also competitive. The best-fit branching fractions for the scalar and tensor cases are a few times larger than for the two-body and vector cases. Past measurements provide further discrimination, although the best-fit parameters stay similar.

Published by the American Physical Society
2024
Quantum Hall effect in InAsSb quantum wells at elevated temperatures
Authors: Bal M. E. , Cheah E. , Lei Z. , Schott R. , Lehner C. A. , Engelkamp H. , Wegscheider W. , Zeitler U. 
Published: June 2024

We have characterized the electronic properties of a high-mobility two-dimensional electron system in modulation doped InAsSb quantum wells and compare them to InSb quantum wells grown in a similar fashion. Using temperature-dependent Shubnikov-de Haas experiments as well as FIR transmission, we find an effective mass of m*≈0.022me, which is lower than in the investigated InSb quantum well, but due to a rather strong confinement still higher than in the corresponding bulk compound. The effective g-factor was determined to be g*≈24.1. These results are also corroborated by k·p band structure calculations. When spin polarizing the electrons in a tilted magnetic field, the g-factor is significantly enhanced by electron-electron interactions, reaching a value as large as g*=60 at a spin polarization P=0.75. Finally, we show that due to the low effective mass, the quantum Hall effect in our particular sample can be observed up to a temperature of 60 K.

Published by the American Physical Society
2024
Numerical investigation and performance comparison of UAV propeller with varying duct configuration
Authors: R. Jagan Raj , G. Gowtham 
Published: June 2024

PurposeThe purpose of this study is to investigate the effects of propeller thrust with two different duct configurations. Propellers in a quadcopter play an indispensable role in generating the necessary thrust and torque to keep the drone flying and manoeuvring. Based on the specific purpose of the unmanned aerial vehicle, both the altitude and attitude can be varied by the amount of thrust produced.Design/methodology/approachThis paper deals with the generation of three numerical models such as plain rotor, rotor with fixed duct and rotor with rotating duct and the comparison of their amount of generated thrust. The plain rotor numerical analysis was compared with the experimental results. The rotor taken for the analysis was 15 mm*5.5 mm TAROT 650. Thrust was measured for all models at four different angular speeds, such as 2,500 rpm, 4,000 rpm, 5,500 rpm and 7,000 rpm.FindingsDue to the suction pressure gradient on the duct inlet surface, the additional amount of lift is produced, and it is the best way of increasing propulsion efficiency and its aerodynamic performance as it reduces the tip loss at the tip of the propeller. The turbulence model taken for the numerical analysis wask−ε.Originality/valueThe rotating duct is expected to provide additional thrust by the increased upward force due to the rotation of duct. The rotating duct produced the optimal results between the plain model and ducted model. At the highest speed of 7,000 rpm, the ducted propeller produced 24.97 N, and the rotating duct propeller produced 23.89 N, whereas the plain propeller produced 23 N thrust. Nearly 8.6% of the thrust improvement is observed in duct and 3.87% in rotating duct.
Assessing the accountability mechanisms in the 2015 Nepal earthquakes housing reconstruction: a case study of Bungamati, Lalitpur Metropolitan city, Nepal
Authors: Rimal Govind Bahadur , Koedsin Werapong , Techato Kuaanan , Rimal Naresh N. 
Published: June 2024

PurposeThis research examined the accountability measures put into practice during the housing reconstruction following the 2015 Nepal earthquakes. Additionally, it aimed to identify gaps in accountability practices and suggest approaches for improving their efficacy.Design/methodology/approachThe research methodology encompassed a qualitative approach. Around 30 research participants were selected for in-depth interviews using a purposive sampling strategy to ensure data richness and relevance. The interviews were recorded, transcribed and then iteratively analysed using thematic framework analysis. This analytical technique involved identifying recurrent themes and patterns within the transcriptions of the participants' articulation.FindingsThe study showed the pivotal role of meetings and interactive forums in promoting transparency and disseminating vital information during housing reconstruction. Additionally, it underscored the contributions of nongovernmental organizations (NGOs) and community-based organizations (CBOs) in information dissemination within affected communities. Policy challenges centre on identifying vulnerable populations, local support mechanisms and contextualizing reconstruction policies, specifically focusing on urban heritage settlements. Strengthening local service delivery and complaint mechanisms, capacity building and defining the roles and responsibilities of actors and beneficiaries are suggestive measures for a participatory and inclusive reconstruction process.Originality/valueResearch holds distinctive value due to its recent inception and its focus on both the subject matter and the specific geographical context. It contributes novel insights into the principles and practices of accountability mechanisms during the housing reconstruction process following a major disaster.
Yoorrook: truth telling in the Victorian Treaty process
Authors: Moore Kevin James , Stanton Pauline , Fan Shea X. , Rose Mark , Jones Mark 
Published: June 2024

PurposeThe purpose of this paper is to explore this process through reviewing key reports and literature through an Indigenous standpoint lens. We identify three key challenges facing the Yoorrook Commission in its journey. First, the continued resistance of influential sections of the Australian community to look backwards and accept responsibility for the violence of the colonial project. Second, the trauma facing those who speak out and remember and the real danger of expectations dashed. Third, the continuance of the colonial pandemic and underlying and invisible racism that infects and poisons all Australians.Design/methodology/approachThis paper has drawn on key literature and secondary data through an Indigenous Lens.FindingsWe identify three challenges facing Yoorrook. First, the resistance of influential sections of the Australian community to accept responsibility for the violence of the colonial project. Second, the trauma facing those who speak out and remember and the danger of expectations dashed. Third, the continuance of underlying and invisible racism that infects and poisons the hearts and minds of non-Indigenous Australia. Despite these challenges we argue that the ability of Yoorrook to capture the lived experience of First Peoples in Victoria and the ability to hold key government officials to account presents a unique opportunity to advance the self determination of all First Peoples in Australia.Originality/valueThis is the first Treaty in Victoria and there has been no study of it before.