bluuebunny/crossref_metadata_2025_split huggingface dataset:
A dimensionless framework for predicting submarine fan morphology
Authors: Wahab Abdul , Hoyal David C. , Shringarpure Mrugesh , Straub Kyle M. 
Published: December 2022

AbstractObservations of active turbidity currents at field scale offers a limited scope which challenges the development of theory that links flow dynamics to the morphology of submarine fans. Here we offer a framework for predicting submarine fan morphologies by simplifying critical environmental forcings such as regional slopes and properties of sediments, through densimetric Froude (ratio of inertial to gravitational forces) and Rouse numbers (ratio of settling velocity of sediments to shear velocity) of turbidity currents. We leverage a depth-average process-based numerical model to simulate an array of submarine fans and measure rugosity as a proxy for their morphological complexity. We show a systematic increase in rugosity by either increasing the densimetric Froude number or decreasing the Rouse number of turbidity currents. These trends reflect gradients in the dynamics of channel migration on the fan surface and help discriminate submarine fans that effectively sequester organic carbon rich mud in deep ocean strata.
Low Pt loading for high-performance fuel cell electrodes enabled by hydrogen-bonding microporous polymer binders
Authors: Tang Hongying , Geng Kang , Aili David , Ju Qing , Pan Ji , Chao Ge , Yin Xi , Guo Xiang , Li Qingfeng , Li Nanwen 
Published: December 2022

AbstractA key challenge for fuel cells based on phosphoric acid doped polybenzimidazole membranes is the high Pt loading, which is required due to the low electrode performance owing to the poor mass transport and severe Pt poisoning via acid absorption on the Pt surface. Herein, these issues are well addressed by design and synthesis of effective catalyst binders based on polymers of intrinsic microporosity (PIMs) with strong hydrogen-bonding functionalities which improve phosphoric acid binding energy, and thus preferably uphold phosphoric acid in the vicinity of Pt catalyst particles to mitigate the adsorption of phosphoric acid on the Pt surface. With combination of the highly mass transport microporosity, strong hydrogen-bonds and high phosphoric acid binding energy, the tetrazole functionalized PIM binder enables an H2-O2 cell to reach a high Pt-mass specific peak power density of 3.8 W mgPt−1 at 160 °C with a low Pt loading of only 0.15 mgPt cm−2.
Slow growing behavior in African trypanosomes during adipose tissue colonization
Authors: Trindade Sandra , De Niz Mariana , Costa-Sequeira Mariana , Bizarra-Rebelo Tiago , Bento Fábio , Dejung Mario , Narciso Marta Valido , López-Escobar Lara , Ferreira João , Butter Falk , Bringaud Frédéric , Gjini Erida , Figueiredo Luisa M. 
Published: December 2022

AbstractWhen Trypanosoma brucei parasites, the causative agent of sleeping sickness, colonize the adipose tissue, they rewire gene expression. Whether this adaptation affects population behavior and disease treatment remained unknown. By using a mathematical model, we estimate that the population of adipose tissue forms (ATFs) proliferates slower than blood parasites. Analysis of the ATFs proteome, measurement of protein synthesis and proliferation rates confirm that the ATFs divide on average every 12 h, instead of 6 h in the blood. Importantly, the population of ATFs is heterogeneous with parasites doubling times ranging between 5 h and 35 h. Slow-proliferating parasites remain capable of reverting to the fast proliferation profile in blood conditions. Intravital imaging shows that ATFs are refractory to drug treatment. We propose that in adipose tissue, a subpopulation of T. brucei parasites acquire a slow growing behavior, which contributes to disease chronicity and treatment failure.
Identifying antibiotics based on structural differences in the conserved allostery from mitochondrial heme-copper oxidases
Authors: Nishida Yuya , Yanagisawa Sachiko , Morita Rikuri , Shigematsu Hideki , Shinzawa-Itoh Kyoko , Yuki Hitomi , Ogasawara Satoshi , Shimuta Ken , Iwamoto Takashi , Nakabayashi Chisa , Matsumura Waka , Kato Hisakazu , Gopalasingam Chai , Nagao Takemasa , Qaqorh Tasneem , Takahashi Yusuke , Yamazaki Satoru , Kamiya Katsumasa , Harada Ryuhei , Mizuno Nobuhiro , Takahashi Hideyuki , Akeda Yukihiro , Ohnishi Makoto , Ishii Yoshikazu , Kumasaka Takashi , Murata Takeshi , Muramoto Kazumasa , Tosha Takehiko , Shiro Yoshitsugu , Honma Teruki , Shigeta Yasuteru , Kubo Minoru , Takashima Seiji , Shintani Yasunori 
Published: December 2022

AbstractAntimicrobial resistance (AMR) is a global health problem. Despite the enormous efforts made in the last decade, threats from some species, including drug-resistant Neisseria gonorrhoeae, continue to rise and would become untreatable. The development of antibiotics with a different mechanism of action is seriously required. Here, we identified an allosteric inhibitory site buried inside eukaryotic mitochondrial heme-copper oxidases (HCOs), the essential respiratory enzymes for life. The steric conformation around the binding pocket of HCOs is highly conserved among bacteria and eukaryotes, yet the latter has an extra helix. This structural difference in the conserved allostery enabled us to rationally identify bacterial HCO-specific inhibitors: an antibiotic compound against ceftriaxone-resistant Neisseria gonorrhoeae. Molecular dynamics combined with resonance Raman spectroscopy and stopped-flow spectroscopy revealed an allosteric obstruction in the substrate accessing channel as a mechanism of inhibition. Our approach opens fresh avenues in modulating protein functions and broadens our options to overcome AMR.
A multicenter phase 2 trial of camrelizumab plus famitinib for women with recurrent or metastatic cervical squamous cell carcinoma
Authors: Xia Lingfang , Zhou Qi , Gao Yunong , Hu Wenjing , Lou Ge , Sun Hong , Zhu Jianqing , Shu Jin , Zhou Xianfeng , Sun Rong , Wu Xiaohua 
Published: December 2022

AbstractThis phase 2 study assesses the efficacy and safety of camrelizumab (an anti-PD-1 antibody) plus famitinib (anti-angiogenic agent) in women with pretreated recurrent or metastatic cervical cancer (ClinicalTrials.gov NCT03827837). Patients with histologically or cytologically confirmed cervical squamous cell carcinoma experiencing relapse or progression during or after 1–2 lines of systemic therapy for recurrent or metastatic disease are enrolled. Eligible patients receive camrelizumab 200 mg intravenously on day 1 of each 3-week cycle plus famitinib 20 mg orally once daily. The primary endpoint is the objective response rate. Secondary endpoints are duration of response, disease control rate, time to response, progression-free survival, overall survival, and safety. The trial has met pre-specified endpoint. Thirty-three patients are enrolled; median follow-up lasts for 13.6 months (interquartile range: 10.0–23.6). Objective responses are observed in 13 (39.4%, 95% confidence interval [CI]: 22.9–57.9) patients; the 12-month duration of response rate is 74.1% (95% CI: 39.1–90.9). Median progression-free survival is 10.3 months (95% CI: 3.5–not reached) and the 12-month overall survival rate is 77.7% (95% CI: 58.9–88.7). All patients experience treatment-related adverse events; grade ≥3 events occur in 26 (78.8%) patients. Treatment-related serious adverse events and deaths are observed in 9 (27.3%) and 2 (6.1%) patients, respectively. Camrelizumab plus famitinib shows promising antitumor activity with a manageable and tolerable safety profile in patients with pretreated recurrent or metastatic cervical squamous cell carcinoma. This combination may represent a treatment option for this population.
Giant spin ensembles in waveguide magnonics
Authors: Wang Zi-Qi , Wang Yi-Pu , Yao Jiguang , Shen Rui-Chang , Wu Wei-Jiang , Qian Jie , Li Jie , Zhu Shi-Yao , You J. Q. 
Published: December 2022

AbstractThe dipole approximation is usually employed to describe light-matter interactions under ordinary conditions. With the development of artificial atomic systems, ‘giant atom’ physics is possible, where the scale of atoms is comparable to or even greater than the wavelength of the light they interact with, and the dipole approximation is no longer valid. It reveals interesting physics impossible in small atoms and may offer useful applications. Here, we experimentally demonstrate the giant spin ensemble (GSE), where a ferromagnetic spin ensemble interacts twice with the meandering waveguide, and the coupling strength between them can be continuously tuned from finite (coupled) to zero (decoupled) by varying the frequency. In the nested configuration, we investigate the collective behavior of two GSEs and find extraordinary phenomena that cannot be observed in conventional systems. Our experiment offers a new platform for ‘giant atom’ physics.
Ultrahigh-responsivity waveguide-coupled optical power monitor for Si photonic circuits operating at near-infrared wavelengths
Authors: Ochiai Takaya , Akazawa Tomohiro , Miyatake Yuto , Sumita Kei , Ohno Shuhei , Monfray Stéphane , Boeuf Frederic , Toprasertpong Kasidit , Takagi Shinichi , Takenaka Mitsuru 
Published: December 2022

AbstractA phototransistor is a promising candidate as an optical power monitor in Si photonic circuits since the internal gain of photocurrent enables high responsivity. However, state-of-the-art waveguide-coupled phototransistors suffer from a responsivity of lower than 103 A/W, which is insufficient for detecting very low power light. Here, we present a waveguide-coupled phototransistor operating at a 1.3 μm wavelength, which consists of an InGaAs ultrathin channel on a Si waveguide working as a gate electrode to increase the responsivity. The Si waveguide gate underneath the InGaAs ultrathin channel enables the effective control of transistor current without optical absorption by the gate metal. As a result, our phototransistor achieved the highest responsivity of approximately 106 A/W among the waveguide-coupled phototransistors, allowing us to detect light of 621 fW propagating in the Si waveguide. The high responsivity and the reasonable response time of approximately 100 μs make our phototransistor promising as an effective optical power monitor in Si photonic circuits.
TBX2 specifies and maintains inner hair and supporting cell fate in the Organ of Corti
Authors: Kaiser Marina , Lüdtke Timo H. , Deuper Lena , Rudat Carsten , Christoffels Vincent M. , Kispert Andreas , Trowe Mark-Oliver 
Published: December 2022

AbstractThe auditory function of the mammalian cochlea relies on two types of mechanosensory hair cells and various non-sensory supporting cells. Recent studies identified the transcription factors INSM1 and IKZF2 as regulators of outer hair cell (OHC) fate. However, the transcriptional regulation of the differentiation of inner hair cells (IHCs) and their associated inner supporting cells (ISCs) has remained enigmatic. Here, we show that the expression of the transcription factor TBX2 is restricted to IHCs and ISCs from the onset of differentiation until adulthood and examine its function using conditional deletion and misexpression approaches in the mouse. We demonstrate that TBX2 acts in prosensory progenitors as a patterning factor by specifying the inner compartment of the sensory epithelium that subsequently gives rise to IHCs and ISCs. Hair cell-specific inactivation or misexpression causes transdifferentiation of hair cells indicating a cell-autonomous function of TBX2 in inducing and maintaining IHC fate.
Theory of optical axion electrodynamics and application to the Kerr effect in topological antiferromagnets
Authors: Ahn Junyeong , Xu Su-Yang , Vishwanath Ashvin 
Published: December 2022

AbstractEmergent axion electrodynamics in magneto-electric media is expected to provide novel ways to detect and control material properties with electromagnetic fields. However, despite being studied intensively for over a decade, its theoretical understanding remains mostly confined to the static limit. Here, we introduce a theory of axion electrodynamics at general frequencies. We define a proper optical axion magneto-electric coupling through its relation to optical surface Hall conductivity and provide ways to calculate it in lattice systems. By employing our formulas, we show that axion electrodynamics can lead to a significant Kerr effect in thin-film antiferromagnets at wavelengths that are seemingly too long to resolve the spatial modulation of magnetism. We identify the wavelength scale above which the Kerr effect is suppressed. Our theory is particularly relevant to materials like MnBi2Te4, a topological antiferromagnet whose magneto-electric response is shown here to be dominated by the axion contribution even at optical frequencies.
Differential IL18 signaling via IL18 receptor and Na-Cl co-transporter discriminating thermogenesis and glucose metabolism regulation
Authors: Zhang Xian , Luo Songyuan , Wang Minjie , Cao Qiongqiong , Zhang Zhixin , Huang Qin , Li Jie , Deng Zhiyong , Liu Tianxiao , Liu Cong-Lin , Meppen Mathilde , Vromman Amelie , Flavell Richard A. , Hotamışlıgil Gökhan S. , Liu Jian , Libby Peter , Liu Zhangsuo , Shi Guo-Ping 
Published: December 2022

AbstractWhite adipose tissue (WAT) plays a role in storing energy, while brown adipose tissue (BAT) is instrumental in the re-distribution of stored energy when dietary sources are unavailable. Interleukin-18 (IL18) is a cytokine playing a role in T-cell polarization, but also for regulating energy homeostasis via the dimeric IL18 receptor (IL18r) and Na-Cl co-transporter (NCC) on adipocytes. Here we show that IL18 signaling in metabolism is regulated at the level of receptor utilization, with preferential role for NCC in brown adipose tissue (BAT) and dominantly via IL18r in WAT. In Il18r−/−Ncc−/− mice, high-fat diet (HFD) causes more prominent body weight gain and insulin resistance than in wild-type mice. The WAT insulin resistance phenotype of the double-knockout mice is recapitulated in HFD-fed Il18r−/− mice, whereas decreased thermogenesis in BAT upon HFD is dependent on NCC deletion. BAT-selective depletion of either NCC or IL18 reduces thermogenesis and increases BAT and WAT inflammation. IL18r deletion in WAT reduces insulin signaling and increases WAT inflammation. In summary, our study contributes to the mechanistic understanding of IL18 regulation of energy metabolism and shows clearly discernible roles for its two receptors in brown and white adipose tissues.
The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii
Authors: Wang Jin-Lei , Li Ting-Ting , Elsheikha Hany M. , Liang Qin-Li , Zhang Zhi-Wei , Wang Meng , Sibley L. David , Zhu Xing-Quan 
Published: December 2022

AbstractPhenotypic switching between tachyzoite and bradyzoite is the fundamental mechanism underpinning the pathogenicity and adaptability of the protozoan parasite Toxoplasma gondii. Although accumulation of cytoplasmic starch granules is a hallmark of the quiescent bradyzoite stage, the regulatory factors and mechanisms contributing to amylopectin storage in bradyzoites are incompletely known. Here, we show that T. gondii protein phosphatase 2A (PP2A) holoenzyme is composed of a catalytic subunit PP2A-C, a scaffold subunit PP2A-A and a regulatory subunit PP2A-B. Disruption of any of these subunits increased starch accumulation and blocked the tachyzoite-to-bradyzoite differentiation. PP2A contributes to the regulation of amylopectin metabolism via dephosphorylation of calcium-dependent protein kinase 2 at S679. Phosphoproteomics identified several putative PP2A holoenzyme substrates that are involved in bradyzoite differentiation. Our findings provide novel insight into the role of PP2A as a key regulator of starch metabolism and bradyzoite differentiation in T. gondii.
Catalytic direct hydrocarboxylation of styrenes with CO2 and H2
Authors: Jin Yushu , Caner Joaquim , Nishikawa Shintaro , Toriumi Naoyuki , Iwasawa Nobuharu 
Published: December 2022

AbstractA three-component hydrocarboxylation of an olefin with CO2 and H2 could be regarded as a dream reaction, since it would provide a straightforward approach for the synthesis of aliphatic carboxylic acids in perfect atom economy. However, this transformation has not been realized in a direct manner under mild conditions, because boosting the carboxylation with thermodynamically stable CO2 while suppressing the rapid hydrogenation of olefin remains a challenging task. Here, we report a rhodium-catalysed reductive hydrocarboxylation of styrene derivatives with CO2 and H2 under mild conditions, in which H2 served as the terminal reductant. In this approach, the carboxylation process was largely accelerated by visible light irradiation, which was proved both experimentally and by computational studies. Hydrocarboxylation of various kinds of styrene derivatives was achieved in good yields without additional base under ambient pressure of CO2/H2 at room temperature. Mechanistic investigations revealed that use of a cationic rhodium complex was critical to achieve high hydrocarboxylation selectivity.
Conserved degronome features governing quality control associated proteolysis
Authors: Mashahreh Bayan , Armony Shir , Johansson Kristoffer Enøe , Chappleboim Alon , Friedman Nir , Gardner Richard G. , Hartmann-Petersen Rasmus , Lindorff-Larsen Kresten , Ravid Tommer 
Published: December 2022

AbstractThe eukaryotic proteome undergoes constant surveillance by quality control systems that either sequester, refold, or eliminate aberrant proteins by ubiquitin-dependent mechanisms. Ubiquitin-conjugation necessitates the recognition of degradation determinants, termed degrons, by their cognate E3 ubiquitin-protein ligases. To learn about the distinctive properties of quality control degrons, we performed an unbiased peptidome stability screen in yeast. The search identify a large cohort of proteome-derived degrons, some of which exhibited broad E3 ligase specificity. Consequent application of a machine-learning algorithm establishes constraints governing degron potency, including the amino acid composition and secondary structure propensities. According to the set criteria, degrons with transmembrane domain-like characteristics are the most probable sequences to act as degrons. Similar quality control degrons are present in viral and human proteins, suggesting conserved degradation mechanisms. Altogether, the emerging data indicate that transmembrane domain-like degron features have been preserved in evolution as key quality control determinants of protein half-life.
Divergent self-association properties of paralogous proteins TRIM2 and TRIM3 regulate their E3 ligase activity
Authors: Esposito Diego , Dudley-Fraser Jane , Garza-Garcia Acely , Rittinger Katrin 
Published: December 2022

AbstractTripartite motif (TRIM) proteins constitute a large family of RING-type E3 ligases that share a conserved domain architecture. TRIM2 and TRIM3 are paralogous class VII TRIM members that are expressed mainly in the brain and regulate different neuronal functions. Here we present a detailed structure-function analysis of TRIM2 and TRIM3, which despite high sequence identity, exhibit markedly different self-association and activity profiles. We show that the isolated RING domain of human TRIM3 is monomeric and inactive, and that this lack of activity is due to a few placental mammal-specific amino acid changes adjacent to the core RING domain that prevent self-association but not E2 recognition. We demonstrate that the activity of human TRIM3 RING can be restored by substitution with the relevant region of human TRIM2 or by hetero-dimerization with human TRIM2, establishing that subtle amino acid changes can profoundly affect TRIM protein activity. Finally, we show that TRIM2 and TRIM3 interact in a cellular context via their filamin and coiled-coil domains, respectively.
Suicidal chemotaxis in bacteria
Authors: Oliveira Nuno M. , Wheeler James H. R. , Deroy Cyril , Booth Sean C. , Walsh Edmond J. , Durham William M. , Foster Kevin R. 
Published: December 2022

AbstractBacteria commonly live in surface-associated communities where steep gradients of antibiotics and other chemical compounds can occur. While many bacterial species move on surfaces, we know surprisingly little about how such antibiotic gradients affect cell motility. Here, we study the behaviour of the opportunistic pathogen Pseudomonas aeruginosa in stable spatial gradients of several antibiotics by tracking thousands of cells in microfluidic devices as they form biofilms. Unexpectedly, these experiments reveal that bacteria use pili-based (‘twitching’) motility to navigate towards antibiotics. Our analyses suggest that this behaviour is driven by a general response to the effects of antibiotics on cells. Migrating bacteria reach antibiotic concentrations hundreds of times higher than their minimum inhibitory concentration within hours and remain highly motile. However, isolating cells - using fluid-walled microfluidic devices - reveals that these bacteria are terminal and unable to reproduce. Despite moving towards their death, migrating cells are capable of entering a suicidal program to release bacteriocins that kill other bacteria. This behaviour suggests that the cells are responding to antibiotics as if they come from a competing colony growing nearby, inducing them to invade and attack. As a result, clinical antibiotics have the potential to lure bacteria to their death.
The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction
Authors: Hu Guanlan , Ling Catriona , Chi Lijun , Thind Mehakpreet K. , Furse Samuel , Koulman Albert , Swann Jonathan R. , Lee Dorothy , Calon Marjolein M. , Bourdon Celine , Versloot Christian J. , Bakker Barbara M. , Gonzales Gerard Bryan , Kim Peter K. , Bandsma Robert H. J. 
Published: December 2022

AbstractMortality in children with severe malnutrition is strongly related to signs of metabolic dysfunction, such as hypoglycemia. Lower circulating tryptophan levels in children with severe malnutrition suggest a possible disturbance in the tryptophan-nicotinamide adenine dinucleotide (TRP-NAD+) pathway and subsequently in NAD+  dependent metabolism regulator sirtuin1 (SIRT1). Here we show that severe malnutrition in weanling mice, induced by 2-weeks of low protein diet feeding from weaning, leads to an impaired TRP-NAD+  pathway with decreased NAD+ levels and affects hepatic mitochondrial turnover and function. We demonstrate that stimulating the TRP-NAD+  pathway with NAD+  precursors improves hepatic mitochondrial and overall metabolic function through SIRT1 modulation. Activating SIRT1 is sufficient to induce improvement in metabolic functions. Our findings indicate that modulating the TRP-NAD+  pathway can improve liver metabolic function in a mouse model of severe malnutrition. These results could lead to the development of new interventions for children with severe malnutrition.