bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial stress activates YAP/TAZ through RhoA oxidation to promote liver injury
Authors: Kwon Ari , Lee Na Young , Yu Jae-Hyun , Choi Myeung Gi , Park Jeongwoo , Koo Ja Hyun
Published: January 2024

Yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1; also known as TAZ) are the main effectors of the Hippo pathway and their dysregulation contributes to diseases in tissues including the liver. Although mitochondria are capable of transmitting signals to change transcriptomic landscape of diseased hepatocytes, such retrograde signaling and the related nuclear machinery are largely unknown. Here, we show that increased YAP activity is associated with mitochondrial stress during liver injury; and this is required for secondary inflammation, promoting hepatocyte death. Mitochondrial stress inducers robustly promoted YAP/TAZ dephosphorylation, nuclear accumulation, and target gene transcription. RNA sequencing revealed that the majority of mitochondrial stress transcripts required YAP/TAZ. Mechanistically, direct oxidation of RhoA by mitochondrial superoxide was responsible for PP2A-mediated YAP/TAZ dephosphorylation providing a novel physiological input for the Hippo pathway. Hepatocyte-specific Yap/Taz ablation suppressed acetaminophen-induced liver injury and blunted transcriptomic changes associated with the pathology. Our observations uncover unappreciated pathway of mitochondrial stress signaling and reveal YAP/TAZ activation as the mechanistic basis for liver injury progression.
Episodic ataxia type 2 with a novel missense variant (Leu602Arg) in CACNA1A
Authors: Miura Shiroh , Watanabe Emina , Senzaki Kensuke , Hiruki Shigeyoshi , Matsumoto Sayaka , Morikawa Takuya , Uchiyama Yusuke , Kurata Seiji , Ochi Masayuki , Ohyagi Yasumasa , Shibata Hiroki
Published: January 2024

Autosomal dominant episodic ataxia type 2 (EA2) is caused by variants in CACNA1A. We examined a 20-year-old male with EA symptoms from a Japanese family with hereditary EA. Cerebellar atrophy was not evident, but single photon emission computed tomography showed cerebellar hypoperfusion. We identified a novel nonsynonymous variant in CACNA1A, NM_001127222.2:c.1805T>G (p.Leu602Arg), which is predicted to be functionally deleterious; therefore, this variant is likely responsible for EA2 in this pedigree.
Rare mosaic variant of GJA1 in a patient with a neurodevelopmental disorder
Authors: Shimomura Rina , Yanagishita Tomoe , Ishiguro Kumiko , Shichiji Minobu , Sato Takatoshi , Shimojima Yamamoto Keiko , Nagata Miho , Ishihara Yasuki , Miyashita Yohei , Ishigaki Keiko , Nagata Satoru , Asano Yoshihiro , Yamamoto Toshiyuki
Published: January 2024

GJA1 is the causative gene for oculodentodigital dysplasia (ODDD). A novel de novo GJA1 variant, NM 000165:c263C > T [p.P88L], was identified in a mosaic state in a patient with short stature, seizures, delayed myelination, mild hearing loss, and tooth enamel hypoplasia. Although the patient exhibited severe neurodevelopmental delay, other clinical features of ODDD, including limb anomalies, were mild. This may be due to differences in the mosaic ratios in different organs.
Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development
Authors: Shah Amil M. , Myhre Peder L. , Arthur Victoria , Dorbala Pranav , Rasheed Humaira , Buckley Leo F. , Claggett Brian , Liu Guning , Ma Jianzhong , Nguyen Ngoc Quynh , Matsushita Kunihiro , Ndumele Chiadi , Tin Adrienne , Hveem Kristian , Jonasson Christian , Dalen Håvard , Boerwinkle Eric , Hoogeveen Ron C. , Ballantyne Christie , Coresh Josef , Omland Torbjørn , Yu Bing
Published: January 2024

Heart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with diverse age, geography, and HF ascertainment to identify circulating proteins and protein networks associated with HF development. Parallel analyses in Atherosclerosis Risk in Communities study participants in mid-life and late-life and in Trøndelag Health Study participants identified 37 proteins consistently associated with incident HF independent of traditional risk factors. Mendelian randomization supported causal effects of 10 on HF, HF risk factors, or left ventricular size and function, including matricellular (e.g. SPON1, MFAP4), senescence-associated (FSTL3, IGFBP7), and inflammatory (SVEP1, CCL15, ITIH3) proteins. Protein co-regulation network analyses identified 5 modules associated with HF risk, two of which were influenced by genetic variants that implicated trans hotspots within the VTN and CFH genes.
Gas diffusion enhanced electrode with ultrathin superhydrophobic macropore structure for acidic CO2 electroreduction
Authors: Sun Mingxu , Cheng Jiamin , Yamauchi Miho
Published: January 2024

Carbon dioxide (CO2) electroreduction reaction (CO2RR) offers a promising strategy for the conversion of CO2 into valuable chemicals and fuels. CO2RR in acidic electrolytes would have various advantages due to the suppression of carbonate formation. However, its reaction rate is severely limited by the slow CO2 diffusion due to the absence of hydroxide that facilitates the CO2 diffusion in an acidic environment. Here, we design an optimal architecture of a gas diffusion electrode (GDE) employing a copper-based ultrathin superhydrophobic macroporous layer, in which the CO2 diffusion is highly enhanced. This GDE retains its applicability even under mechanical deformation conditions. The CO2RR in acidic electrolytes exhibits a Faradaic efficiency of 87% with a partial current density $$( {j}_{{{{\rm{C}}}}_{2+}})$$

(

j

C

2
+

)

of −1.6 A cm−2 for multicarbon products (C2+), and $$ {j}_{{{{{{\rm{C}}}}}}_{2+}}$$

j

C

2
+

of −0.34 A cm−2 when applying dilute 25% CO2. In a highly acidic environment, C2+ formation occurs via a second order reaction which is controlled by both the catalyst and its hydroxide.
Replicating shear-mediated self-assembly of spider silk through microfluidics
Authors: Chen Jianming , Tsuchida Arata , Malay Ali D. , Tsuchiya Kousuke , Masunaga Hiroyasu , Tsuji Yui , Kuzumoto Mako , Urayama Kenji , Shintaku Hirofumi , Numata Keiji
Published: January 2024

The development of artificial spider silk with properties similar to native silk has been a challenging task in materials science. In this study, we use a microfluidic device to create continuous fibers based on recombinant MaSp2 spidroin. The strategy incorporates ion-induced liquid-liquid phase separation, pH-driven fibrillation, and shear-dependent induction of β-sheet formation. We find that a threshold shear stress of approximately 72 Pa is required for fiber formation, and that β-sheet formation is dependent on the presence of polyalanine blocks in the repetitive sequence. The MaSp2 fiber formed has a β-sheet content (29.2%) comparable to that of native dragline with a shear stress requirement of 111 Pa. Interestingly, the polyalanine blocks have limited influence on the occurrence of liquid-liquid phase separation and hierarchical structure. These results offer insights into the shear-induced crystallization and sequence-structure relationship of spider silk and have significant implications for the rational design of artificially spun fibers.
Evolution of optimal growth temperature in Asgard archaea inferred from the temperature dependence of GDP binding to EF-1A
Authors: Lu Zhongyi , Xia Runyue , Zhang Siyu , Pan Jie , Liu Yang , Wolf Yuri I. , Koonin Eugene V. , Li Meng
Published: January 2024

The archaeal ancestor of eukaryotes apparently belonged to the phylum Asgardarchaeota, but the ecology and evolution of Asgard archaea are poorly understood. The optimal GDP-binding temperature of a translation elongation factor (EF-1A or EF-Tu) has been previously shown to correlate with the optimal growth temperature of diverse prokaryotes. Here, we reconstruct ancestral EF-1A sequences and experimentally measure the optimal GDP-binding temperature of EF-1A from ancient and extant Asgard archaea, to infer the evolution of optimal growth temperatures in Asgardarchaeota. Our results suggest that the Asgard ancestor of eukaryotes was a moderate thermophile, with an optimal growth temperature around 53 °C. The origin of eukaryotes appears to coincide with a transition from thermophilic to mesophilic lifestyle during the evolution of Asgard archaea.
Synthesis of inter-[60]fullerene conjugates with inherent chirality
Authors: Hashikawa Yoshifumi , Okamoto Shu , Murata Yasujiro
Published: January 2024

Coalescence of [60]fullerenes potentially produces hypothetical nanocarbon assemblies with non-naturally occurring topologies. Since the discovery of [60]fullerene in 1985, coalesced [60]fullerene oligomers have only been observed as transient species by transmission electron microscopy during an oligomerization process under a high electron acceleration voltage. Herein, we showcase the rational synthesis of covalent assemblies consisting of inherently chiral open-[60]fullerenes. The crystallographic analyses unveiled double-caged structures of non-conjugated and conjugated inter-[60]fullerene hybrids, in which the two [60]fullerene cages are bounds to each other through a covalent linkage. The former one further assembles via a heterochiral recognition so that four carbon cages are arranged in a tetrahedral manner both in solution and solid state. Reflecting radially-conjugated double π-surface nature, the inter-[60]fullerene conjugate exhibits strong electronic communication in its reduced states, intense absorption behavior, and chiroptical activity with a dissymmetry factor of 0.21 (at 674 nm) which breaks the record for known chiral organic molecules.
The phosphatase DUSP22 inhibits UBR2-mediated K63-ubiquitination and activation of Lck downstream of TCR signalling
Authors: Shih Ying-Chun , Chen Hsueh-Fen , Wu Chia-Ying , Ciou Yi-Ru , Wang Chia-Wen , Chuang Huai-Chia , Tan Tse-Hua
Published: January 2024

DUSP22 is a dual-specificity phosphatase that inhibits T cell activation by inactivating the kinase Lck. Here we show that the E3 ubiquitin ligase UBR2 is a positive upstream regulator of Lck during T-cell activation. DUSP22 dephosphorylates UBR2 at specific Serine residues, leading to ubiquitin-mediated UBR2 degradation. UBR2 is also modified by the SCF E3 ubiquitin ligase complex via Lys48-linked ubiquitination at multiple Lysine residues. Single-cell RNA sequencing analysis and UBR2 loss of function experiments showed that UBR2 is a positive regulator of proinflammatory cytokine expression. Mechanistically, UBR2 induces Lys63-linked ubiquitination of Lck at Lys99 and Lys276 residues, followed by Lck Tyr394 phosphorylation and activation as part of TCR signalling. Inflammatory phenotypes induced by TCR-triggered Lck activation or knocking out DUSP22, are attenuated by genomic deletion of UBR2. UBR2-Lck interaction and Lck Lys63-linked ubiquitination are induced in the peripheral blood T cells of human SLE patients, which demonstrate the relevance of the UBR2-mediated regulation of inflammation to human pathology. In summary, we show here an important regulatory mechanism of T cell activation, which finetunes the balance between T cell response and aggravated inflammation.
An updated PREDICT breast cancer prognostic model including the benefits and harms of radiotherapy
Authors: Grootes Isabelle , Wishart Gordon C. , Pharoah Paul David Peter
Published: January 2024

PREDICT Breast (www.breast .predict.nhs.uk) is a prognostication tool for early invasive breast cancer. The current version was based on cases diagnosed in 1999–2003 and did not incorporate the benefits of radiotherapy or the harms associated with therapy. Since then, there has been a substantial improvement in the outcomes for breast cancer cases. The aim of this study was to update PREDICT Breast to ensure that the underlying model is appropriate for contemporary patients. Data from the England National Cancer Registration and Advisory Service for invasive breast cancer cases diagnosed 2000–17 were used for model development and validation. Model development was based on 35,474 cases diagnosed and registered by the Eastern Cancer Registry. A Cox model was used to estimate the prognostic effects of the year of diagnosis, age at diagnosis, tumour size, tumour grade and number of positive nodes. Separate models were developed for ER-positive and ER-negative disease. Data on 32,408 cases from the West Midlands Cancer Registry and 100,551 cases from other cancer registries were used for validation. The new model was well-calibrated; predicted breast cancer deaths at 5-, 10- and 15-year were within 10 per cent of the observed validation data. Discrimination was also good: The AUC for 15-year breast cancer survival was 0.809 in the West Midlands data set and 0.846 in the data set for the other registries. The new PREDICT Breast model outperformed the current model and will be implemented in the online tool which should lead to more accurate absolute treatment benefit predictions for individual patients.
Hong-Ou-Mandel interference of single-photon-level pulses stored in independent room-temperature quantum memories
Authors: Gera Sonali , Wallace Chase , Flament Mael , Scriminich Alessia , Namazi Mehdi , Kim Youngshin , Sagona-Stophel Steven , Vallone Giuseppe , Villoresi Paolo , Figueroa Eden
Published: January 2024

Quantum repeater networks require independent absorptive quantum memories capable of storing and retrieving indistinguishable photons to perform high-repetition entanglement swapping operations. The ability to perform these coherent operations at room temperature is of prime importance for the realization of scalable quantum networks. We perform Hong-Ou-Mandel (HOM) interference between photonic polarization states and single-photon-level pulses stored and retrieved from two sets of independent room-temperature quantum memories. We show that the storage and retrieval of polarization states from quantum memories does not degrade the HOM visibility for few-photon-level polarization states in a dual-rail configuration. For single-photon-level pulses, we measure the HOM visibility with various levels of background in a single polarization, single-rail QM, and investigate its dependence on the signal-to-background ratio. We obtain an HOM visibility of 43%, compared to the 48% no-memory limit of our set-up. These results allow us to estimate a 33% visibility for polarization qubits under the same conditions. These demonstrations lay the groundwork for future applications using large-scale memory-assisted quantum networks.
Twice hidden string order and competing phases in the spin-1/2 Kitaev–Gamma ladder
Authors: Sørensen Erik S. , Kee Hae-Young
Published: January 2024

Finding the Kitaev spin liquid in candidate materials involves understanding the entire phase diagram, including other allowed interactions. One of these interactions, called the Gamma (Γ) interaction, causes magnetic frustration and its interplay with the Kitaev (K) interaction is crucial to comprehend Kitaev materials. Due to the complexity of the combined KΓ model, quasi-one-dimensional models have been investigated. While several disordered phases are found in the 2-leg ladder, the nature of the phases are yet to be determined. Here we focus on the disordered phase near the antiferromagnetic Γ limit (denoted by AΓ phase) next to the ferromagnetic Kitaev phase. We report a distinct non-local string order parameter characterizing the AΓ phase, different from the string order parameter in the Kitaev phase. This string order parameter becomes evident only after two unitary transformation, referred to as a twice hidden string order parameter. The related entanglement spectrum, edge states, magnetic field responses, and the symmetry protecting the phase are presented, and its relevance to the two-dimensional Kitaev materials is discussed. Two newly identified disordered phases in the phase diagram of KΓ ladder is also reported.
Observations of high-order multiplicity in a high-mass stellar protocluster
Authors: Li Shanghuo , Sanhueza Patricio , Beuther Henrik , Chen Huei-Ru Vivien , Kuiper Rolf , Olguin Fernando A. , Pudritz Ralph E. , Stephens Ian W. , Zhang Qizhou , Nakamura Fumitaka , Lu Xing , Kuruwita Rajika L. , Sakai Takeshi , Henning Thomas , Taniguchi Kotomi , Li Fei
Published: January 2024

The dominant mechanism forming multiple stellar systems in the high-mass regime (M* ≳ 8 M⊙) remained unknown because direct imaging of multiple protostellar systems at early phases of high-mass star formation is very challenging. High-mass stars are expected to form in clustered environments containing binaries and higher-order multiplicity systems. So far only a few high-mass protobinary systems, and no definitive higher-order multiples, have been detected. Here we report the discovery of one quintuple, one quadruple, one triple and four binary protostellar systems simultaneously forming in a single high-mass protocluster, G333.23–0.06, using Atacama Large Millimeter/submillimeter Array high-resolution observations. We present a new example of a group of gravitationally bound binary and higher-order multiples during their early formation phases in a protocluster. This provides the clearest direct measurement of the initial configuration of primordial high-order multiple systems, with implications for the in situ multiplicity and its origin. We find that the binary and higher-order multiple systems, and their parent cores, show no obvious sign of disk-like kinematic structure. We conclude that the observed fragmentation into binary and higher-order multiple systems can be explained by core fragmentation, indicating its crucial role in establishing the multiplicity during high-mass star cluster formation.
Detection of apatite in ferroan anorthosite indicative of a volatile-rich early lunar crust
Authors: Hayden Tara S. , Barrett Thomas J. , Anand Mahesh , Whitehouse Martin J. , Jeon Heejin , Zhao Xuchao , Franchi Ian A.
Published: January 2024

Determination of the systematics of volatile elements (for example, H, Cl, S) of the early Moon is one of the main objectives of lunar science. This has been hindered by the lack of the main volatile-bearing mineral, apatite, in ferroan anorthosites (FANs), which are thought to represent the primary products of the lunar magma ocean and the earliest lunar crust. Due to the absence of apatite, plagioclase and bulk samples of the FAN suite have been previously utilized for the studies of volatiles in samples representing the earliest-formed lunar crust. Here we provide evidence of apatite in a FAN clast in the lunar meteorite Arabian Peninsula 007. We report that Arabian Peninsula 007 has an ancient age, comparable to those of Apollo FAN samples, with lighter hydrogen (δD = −45‰) and heavier chlorine (δ37Cl = +44‰) isotopic compositions than FAN bulk and plagioclase data. These results suggest that the early lunar crust was significantly more volatile rich than previously thought.
Surface stratification determines the interfacial water structure of simple electrolyte solutions
Authors: Litman Yair , Chiang Kuo-Yang , Seki Takakazu , Nagata Yuki , Bonn Mischa
Published: January 2024

The distribution of ions at the air/water interface plays a decisive role in many natural processes. Several studies have reported that larger ions tend to be surface-active, implying ions are located on top of the water surface, thereby inducing electric fields that determine the interfacial water structure. Here we challenge this view by combining surface-specific heterodyne-detected vibrational sum-frequency generation with neural network-assisted ab initio molecular dynamics simulations. Our results show that ions in typical electrolyte solutions are, in fact, located in a subsurface region, leading to a stratification of such interfaces into two distinctive water layers. The outermost surface is ion-depleted, and the subsurface layer is ion-enriched. This surface stratification is a key element in explaining the ion-induced water reorganization at the outermost air/water interface.
Geographies of regulatory disparity underlying Australia’s energy transition
Authors: White Lee V. , Riley Bradley , Wilson Sally , Markham Francis , O’Neill Lily , Klerck Michael , Davis Vanessa Napaltjari
Published: January 2024

Disparities in electricity retail regulatory protections will see some consumers approaching energy transition from an uneven footing. Here we examine the spatial organization of regulatory inequities in Australia by mapping electricity legal protections for settlements nationwide. Multiple logistic regression (n = 2,996) identifies the geographic and socio-demographic characteristics of settlements likely to be underserved by regulations to: protect life-support customers, guarantee service levels, clarify connection requirements for rooftop solar, require disconnection reporting and set clear and independent complaints processes. Assessing whether communities receive fewer than four of five protections, we find that Indigenous communities are 15% more likely to be underserved across multiple metrics and remote communities are 18% more likely to be underserved. These groups overlap. Those communities whose lands are rich in resources necessary for energy transition are simultaneously at risk of non-recognition of their own energy needs under current regulation, requiring policy remedies for a just transition.
A collaborative realist review of remote measurement technologies for depression in young people
Authors: Walsh Annabel E. L. , Naughton Georgia , Sharpe Thomas , Zajkowska Zuzanna , Malys Mantas , van Heerden Alastair , Mondelli Valeria
Published: January 2024

Digital mental health is becoming increasingly common. This includes use of smartphones and wearables to collect data in real time during day-to-day life (remote measurement technologies, RMT). Such data could capture changes relevant to depression for use in objective screening, symptom management and relapse prevention. This approach may be particularly accessible to young people of today as the smartphone generation. However, there is limited research on how such a complex intervention would work in the real world. We conducted a collaborative realist review of RMT for depression in young people. Here we describe how, why, for whom and in what contexts RMT appear to work or not work for depression in young people and make recommendations for future research and practice. Ethical, data protection and methodological issues need to be resolved and standardized; without this, RMT may be currently best used for self-monitoring and feedback to the healthcare professional where possible, to increase emotional self-awareness, enhance the therapeutic relationship and monitor the effectiveness of other interventions.
Multi-ensemble metrology by programming local rotations with atom movements
Authors: Shaw Adam L. , Finkelstein Ran , Tsai Richard Bing-Shiun , Scholl Pascal , Yoon Tai Hyun , Choi Joonhee , Endres Manuel
Published: January 2024

Current optical atomic clocks do not utilize their resources optimally. In particular, an exponential gain in sensitivity could be achieved if multiple atomic ensembles were to be controlled or read out individually, even without entanglement. However, controlling optical transitions locally remains an outstanding challenge for neutral-atom-based clocks and quantum computing platforms. Here we show arbitrary, single-site addressing for an optical transition via sub-wavelength controlled moves of atoms trapped in tweezers. The scheme is highly robust as it relies only on the relative position changes of tweezers and requires no additional addressing beams. Using this technique, we implement single-shot, dual-quadrature readout of Ramsey interferometry using two atomic ensembles simultaneously, and show an enhancement of the usable interrogation time at a given phase-slip error probability. Finally, we program a sequence that performs local dynamical decoupling during Ramsey evolution to evolve three ensembles with variable phase sensitivities, a key ingredient of optimal clock interrogation. Our results demonstrate the potential of fully programmable quantum optical clocks even without entanglement and could be combined with metrologically useful entangled states in the future.
A new treatment for breast cancer using a combination of two drugs: AZD9496 and palbociclib
Authors: Nave Ophir , Shor Yehuda , Bar Raziel , Segal Eliezer Elimelech , Sigron Moriah
Published: January 2024

In this study, we examined a mathematical model of breast cancer (BC) treatment that combines an oral oestrogen receptor inhibitor, AZD9496 with Palbociclib, a selective inhibitor of cyclin- dependent kinases CDK4 and CDK6. Treatment is described by analytical functions that enable us to control the dosage and time interval of the treatment, thus personalising the treatment for each patient. Initially, we investigated the effect of each treatment separately, and finally, we investigated the combination of both treatments. By applying numerical simulations, we confirmed that the combination of AZD9496 with palbociclib was the optimal treatment for BC. The dosage of AZD9496 increased and decreased throughout the treatment period, while the intervals were constant between treatments. Palbociclib changed almost cyclically, whereas the time intervals remained constant. To investigate the mathematical model, we applied the singularly perturbed homotopy analysis method, which is a numerical algorithm. The significant advantage of this method is that the mathematical model does not have to contain a small parameter (as is standard in perturbation theory). However, it is possible to artificially introduce a small parameter into the system of equations, making it possible to study the model using asymptotic methods.
Idiopathic pulmonary fibrosis-specific Bayesian network integrating extracellular vesicle proteome and clinical information
Authors: Tomoto Mei , Mineharu Yohei , Sato Noriaki , Tamada Yoshinori , Nogami-Itoh Mari , Kuroda Masataka , Adachi Jun , Takeda Yoshito , Mizuguchi Kenji , Kumanogoh Atsushi , Natsume-Kitatani Yayoi , Okuno Yasushi
Published: January 2024

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by severe lung fibrosis and a poor prognosis. Although the biomolecules related to IPF have been extensively studied, molecular mechanisms of the pathogenesis and their association with serum biomarkers and clinical findings have not been fully elucidated. We constructed a Bayesian network using multimodal data consisting of a proteome dataset from serum extracellular vesicles, laboratory examinations, and clinical findings from 206 patients with IPF and 36 controls. Differential protein expression analysis was also performed by edgeR and incorporated into the constructed network. We have successfully visualized the relationship between biomolecules and clinical findings with this approach. The IPF-specific network included modules associated with TGF-β signaling (TGFB1 and LRC32), fibrosis-related (A2MG and PZP), myofibroblast and inflammation (LRP1 and ITIH4), complement-related (SAA1 and SAA2), as well as serum markers, and clinical symptoms (KL-6, SP-D and fine crackles). Notably, it identified SAA2 associated with lymphocyte counts and PSPB connected with the serum markers KL-6 and SP-D, along with fine crackles as clinical manifestations. These results contribute to the elucidation of the pathogenesis of IPF and potential therapeutic targets.
Development and psychometric evaluation of the questionnaire on the contributing factors of tendency towards voluntary single-childedness and childlessness: a mixed method study
Authors: Sharif-Nia Hamid , Ahmadzadeh Tori Neda , Behmanesh Fereshteh , Ghaffari Fatemeh , Pourreza Abolghasem
Published: January 2024

Couples’ tendency towards voluntary single-childedness and childlessness (VSCC) has turned into a major challenge in all societies and led to different problems such as population aging. A key step to VSCC management is to determine its contributing factors through valid and reliable instruments. This exploratory sequential mixed method study (qualitative-quantitative) was conducted in 2020–2021. Phases of qualitative consists of all couples aged 15–49 in Babol, Iran, who were single or childless. Sampling is based on the purpose, and the number of samples is 20 couples. To collect data, face-to-face and semi-structured interviews were conducted with the participants. Sampling continued until data saturation. The data were analyzed by the conventional content analysis method and quantitative phase. Initially, a qualitative study was conducted on twenty couples, and were analyzed through conventional content analysis. Findings were used to develop QFT-VSCC and then, the face, content, and construct validity as well as reliability were assessed. Construct validity was assessed through exploratory and confirmatory factor analyses and reliability was assessed through internal consistency and stability assessments. The results of the qualitative part analysis consist of 140 codes, 30 primary categories, and nine main categories and two themes (individual limitations and social limitations). The primary QFT-VSCC had 78 items. Fifty-eight items were omitted during validity assessment and the remaining twenty-two items were loaded on five factors during factor analysis. These factors were threatened priorities, inappropriate familial context for childbearing, sense of occupational and social insecurity for the child, social modeling of childlessness, and tendency towards change or stability in marital life. The five factors explained 52.56% of the total variance. All model fit indices in confirmatory factor analysis were acceptable and the Cronbach’s alpha values of QFT-VSCC and all its factors were more than 0.70. The results of convergent validity analysis revealed that all factors had an AVE value greater than 0.5, and the HTMT index for all factors was less than 0.85. This indicated that discriminant validity had been achieved. QFT-VSCC is a simple valid and reliable instrument for VSCC assessment among both men and women.
Mechanical energy flow analysis in athletes with and without anterior cruciate ligament reconstruction during single-leg drop landing
Authors: Zanguie Hamidreza , Sheikhhoseini Rahman , Yousefi Mohammad , Hides Julie A.
Published: January 2024

Techniques that reduce mechanical energy have been linked to lower chances of experiencing an Anterior Cruciate Ligament (ACL) injury. Although there is evidence that movement patterns are altered in athletes who have undergone Anterior Cruciate Ligament Reconstruction (ACLR), energy transfer mechanisms have not been examined. This study aimed to compare energy flow mechanisms during single-leg drop landing between athletes with and without history of ACLR. A total of 20 female athletes were included in this study. Ten participants underwent ACLR 12 months ago (mean age, 21.57 ± 0.41 years) and 10 were healthy controls (mean age, 20.89 ± 0.21 years). Participants executed the single-leg drop landing (SLL) maneuver by descending from a 30 cm wooden box and landing on the tested leg on an embedded force plate. Information collected during the SLL trials was refined using rigid-body analysis and inverse dynamics within Nexus software, ultimately allowing construction of skeletal models of the athletes. Ankle and knee mechanical energy expenditure (MEE) was higher in the control participants during landing. However, the result for the hip MEE demonstrated that MEE of the control group was significantly lower compared with the ACLR group, but MEE of the control subjects was higher as compared to ACLR group (p ˂ 0.05). Results suggest the avoidant use of the quadriceps muscle post ACLR leads to knee-avoidant mechanics and loss of knee joint power generation during a SLL task.
Benefits of thermal and distance-filtered imaging for wayfinding with prosthetic vision
Authors: Sadeghi Roksana , Kartha Arathy , Barry Michael P. , Gibson Paul , Caspi Avi , Roy Arup , Geruschat Duane R. , Dagnelie Gislin
Published: January 2024

Visual prostheses such as the Argus II provide partial vision for individuals with limited or no light perception. However, their effectiveness in daily life situations is limited by scene complexity and variability. We investigated whether additional image processing techniques could improve mobility performance in everyday indoor environments. A mobile system connected to the Argus II provided thermal or distance-filtered video stimulation. Four participants used the thermal camera to locate a person and the distance filter to navigate a hallway with obstacles. The thermal camera allowed for finding a target person in 99% of trials, while unfiltered video led to confusion with other objects and a success rate of only 55% ($$p<0.01$$

p
<
0.01

). Similarly, the distance filter enabled participants to detect and avoid 88% of obstacles by removing background clutter, whereas unfiltered video resulted in a detection rate of only 10% ($$p<0.01$$

p
<
0.01

). For any given elapsed time, the success rate with filtered video was higher than with unfiltered video. After 90 s, participants’ success rate reached above 50% with filtered video and 24% and 3% with normal camera in the first and second tasks, respectively. Despite individual variations, all participants showed significant improvement when using the thermal and distance filters compared to unfiltered video. Adding a thermal and distance filter to a visual prosthesis system can enhance the performance of mobility activities by removing clutter in the background, showing people and warm objects with the thermal camera, or nearby obstacles with the distance filter.
Novel lncRNA regulatory elements in milk somatic cells of Holstein dairy cows associated with mastitis
Authors: Asselstine Victoria , Medrano Juan F. , Muniz Malane M. M. , Mallard Bonnie A. , Karrow Niel A. , Cánovas Angela
Published: January 2024

Despite regulatory elements such as long non - coding RNAs representing most of the transcriptome, the functional understanding of long non - coding RNAs in relation to major health conditions including bovine mastitis is limited. This study examined the milk somatic cell transcriptome from udder quarters of 6 Holstein dairy cows to identify differentially expressed long non - coding RNAs using RNA - Sequencing. Ninety - four differentially expressed long non - coding RNAs are identified, 5 of which are previously annotated for gene name and length, 11 are annotated for gene name and 78 are novel, having no gene name or length previously annotated. Significant inflammatory response and regulation of immune response pathways (false discovery rate < 0.05) are associated with the differentially expressed long non - coding RNAs. QTL annotation analysis revealed 31 QTL previously annotated in the genomic regions of the 94 differentially expressed long non - coding RNAs, and the majority are associated with milk traits. This research provides a better understanding of long non - coding RNAs regulatory elements in milk somatic cells, which may enhance current breeding strategies for more adaptable or high mastitis resistant cattle.
Chern dartboard insulator: sub-Brillouin zone topology and skyrmion multipoles
Authors: Chen Yun-Chung , Lin Yu-Ping , Kao Ying-Jer
Published: January 2024

Topology plays a crucial role in many physical systems, leading to interesting states at the surface. A paradigmatic example is the Chern number defined in the Brillouin zone that leads to robust gapless edge states. Here we introduce the reduced Chern number, defined in the subregions of Brillouin zone, and construct a family of Chern dartboard insulators with quantized reduced Chern numbers but with trivial bulk topology. Chern dartboard insulators are protected by the mirror symmetries and exhibit distinct pseudospin textures, including (anti)skyrmions, inside the sub-Brillouin zone. These Chern dartboard insulators host exotic gapless edge states, such as Möbius fermions and midgap corner states, and can be realized in the photonic crystals. Our work opens up new possibilities for exploring sub-Brillouin zone topology and nontrivial surface responses in topological systems.
Generalized acoustic impedance metasurface
Authors: Tian Yu-Ze , Wang Yan-Feng , Laude Vincent , Wang Yue-Sheng
Published: January 2024

Impedance theory has become a favorite method for metasurface design as it allows perfect control of wave properties. However, its functionality is strongly limited by the condition of strict continuity of normal power flow. In this paper, it is shown that acoustic impedance theory can be generalized under the integral equivalence principle without imposing the continuity of power flow. Equivalent non-local power flow transmission is instead realized through local design of metasurface unit cells that are characterized by a passive, asymmetric impedance matrix. Based on this strategy, a beam splitter loosely respecting local power flow is designed and demonstrated experimentally. It is concluded that arbitrary wave fields can be connected through arbitrarily shaped boundaries, i.e. transformed into one another. Generalized impedance metasurface theory is expected to extend the possible design of metasurfaces and the manipulation of acoustic waves.
Generation of 3D molecules in pockets via a language model
Authors: Feng Wei , Wang Lvwei , Lin Zaiyun , Zhu Yanhao , Wang Han , Dong Jianqiang , Bai Rong , Wang Huting , Zhou Jielong , Peng Wei , Huang Bo , Zhou Wenbiao
Published: January 2024

Generative models for molecules based on sequential line notation (for example, the simplified molecular-input line-entry system) or graph representation have attracted an increasing interest in the field of structure-based drug design, but they struggle to capture important three-dimensional (3D) spatial interactions and often produce undesirable molecular structures. To address these challenges, we introduce Lingo3DMol, a pocket-based 3D molecule generation method that combines language models and geometric deep learning technology. A new molecular representation, the fragment-based simplified molecular-input line-entry system with local and global coordinates, was developed to assist the model in learning molecular topologies and atomic spatial positions. Additionally, we trained a separate non-covalent interaction predictor to provide essential binding pattern information for the generative model. Lingo3DMol can efficiently traverse drug-like chemical spaces, preventing the formation of unusual structures. The Directory of Useful Decoys-Enhanced dataset was used for evaluation. Lingo3DMol outperformed state-of-the-art methods in terms of drug likeness, synthetic accessibility, pocket binding mode and molecule generation speed.
Myosin-independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actin
Authors: Mittal Nikhil , Michels Etienne B. , Massey Andrew E. , Qiu Yunxiu , Royer-Weeden Shaina P. , Smith Bryan R. , Cartagena-Rivera Alexander X. , Han Sangyoon J.
Published: January 2024

The stiffness of the extracellular matrix induces differential tension within integrin-based adhesions, triggering differential mechanoresponses. However, it has been unclear if the stiffness-dependent differential tension is induced solely by myosin activity. Here, we report that in the absence of myosin contractility, 3T3 fibroblasts still transmit stiffness-dependent differential levels of traction. This myosin-independent differential traction is regulated by polymerizing actin assisted by actin nucleators Arp2/3 and formin where formin has a stronger contribution than Arp2/3 to both traction and actin flow. Intriguingly, despite only slight changes in F-actin flow speed observed in cells with the combined inhibition of Arp2/3 and myosin compared to cells with sole myosin inhibition, they show a 4-times reduction in traction than cells with myosin-only inhibition. Our analyses indicate that traditional models based on rigid F-actin are inadequate for capturing such dramatic force reduction with similar actin flow. Instead, incorporating the F-actin network’s viscoelastic properties is crucial. Our new model including the F-actin viscoelasticity reveals that Arp2/3 and formin enhance stiffness sensitivity by mechanically reinforcing the F-actin network, thereby facilitating more effective transmission of flow-induced forces. This model is validated by cell stiffness measurement with atomic force microscopy and experimental observation of model-predicted stiffness-dependent actin flow fluctuation.
Giant offshore pumice deposit records a shallow submarine explosive eruption of ancestral Santorini
Authors: Druitt Tim , Kutterolf Steffen , Ronge Thomas A. , Hübscher Christian , Nomikou Paraskevi , Preine Jonas , Gertisser Ralf , Karstens Jens , Keller Jörg , Koukousioura Olga , Manga Michael , Metcalfe Abigail , McCanta Molly , McIntosh Iona , Pank Katharina , Woodhouse Adam , Beethe Sarah , Berthod Carole , Chiyonobu Shun , Chen Hehe , Clark Acacia , DeBari Susan , Johnston Raymond , Peccia Ally , Yamamoto Yuzuru , Bernard Alexis , Perez Tatiana Fernandez , Jones Christopher , Joshi Kumar Batuk , Kletetschka Günther , Li Xiaohui , Morris Antony , Polymenakou Paraskevi , Tominaga Masako , Papanikolaou Dimitrios , Wang Kuo-Lung , Lee Hao-Yang
Published: January 2024

Large explosive volcanic eruptions from island arcs pour pyroclastic currents into marine basins, impacting ecosystems and generating tsunamis that threaten coastal communities and infrastructures. Risk assessments require robust records of such highly hazardous events, which is challenging as most of the products lie buried under the sea. Here we report the discovery by IODP Expedition 398 of a giant rhyolitic pumice deposit emplaced 520 ± 10 ky ago at water depths of 200 to 1000 m during a high-intensity, shallow submarine eruption of ancestral Santorini Volcano. Pyroclastic currents discharged into the sea transformed into turbidity currents and slurries, forming a >89 ± 8 km3volcaniclastic megaturbidite up to 150 m thick in the surrounding marine basins, while breaching of the sea surface by the eruption column laid down veneers of ignimbrite on three islands. The eruption is one of the largest recorded on the South Aegean Volcanic Arc, and highlights the hazards from submarine explosive eruptions.
Systematic discovery of protein interaction interfaces using AlphaFold and experimental validation
Authors: Lee Chop Yan , Hubrich Dalmira , Varga Julia K , Schäfer Christian , Welzel Mareen , Schumbera Eric , Djokic Milena , Strom Joelle M , Schönfeld Jonas , Geist Johanna L , Polat Feyza , Gibson Toby J , Keller Valsecchi Claudia Isabelle , Kumar Manjeet , Schueler-Furman Ora , Luck Katja
Published: January 2024

Structural resolution of protein interactions enables mechanistic and functional studies as well as interpretation of disease variants. However, structural data is still missing for most protein interactions because we lack computational and experimental tools at scale. This is particularly true for interactions mediated by short linear motifs occurring in disordered regions of proteins. We find that AlphaFold-Multimer predicts with high sensitivity but limited specificity structures of domain-motif interactions when using small protein fragments as input. Sensitivity decreased substantially when using long protein fragments or full length proteins. We delineated a protein fragmentation strategy particularly suited for the prediction of domain-motif interfaces and applied it to interactions between human proteins associated with neurodevelopmental disorders. This enabled the prediction of highly confident and likely disease-related novel interfaces, which we further experimentally corroborated for FBXO23-STX1B, STX1B-VAMP2, ESRRG-PSMC5, PEX3-PEX19, PEX3-PEX16, and SNRPB-GIGYF1 providing novel molecular insights for diverse biological processes. Our work highlights exciting perspectives, but also reveals clear limitations and the need for future developments to maximize the power of Alphafold-Multimer for interface predictions.
Bacteria colonization in tumor microenvironment creates a favorable niche for immunogenic chemotherapy
Authors: Lim See-Khai , Lin Wen-Ching , Huang Sin-Wei , Pan Yi-Chung , Hu Che-Wei , Mou Chung-Yuan , Hu Che-Ming Jack , Mou Kurt Yun
Published: January 2024

The tumor microenvironment (TME) presents differential selective pressure (DSP) that favors the growth of cancer cells, and monovalent therapy is often inadequate in reversing the cancer cell dominance in the TME. In this work, we introduce bacteria as a foreign species to the TME and explore combinatorial treatment strategies to alter DSP for tumor eradication. We show that cancer-selective chemotherapeutic agents and fasting can provide a strong selection pressure against tumor growth in the presence of bacteria. Moreover, we show that an immunogenic drug (oxaliplatin), but not a non-immunogenic one (5-FU), synergizes with the bacteria to activate both the innate and adaptive immunity in the TME, resulting in complete tumor remission and a sustained anti-tumor immunological memory in mice. The combination of oxaliplatin and bacteria greatly enhances the co-stimulatory and antigen-presenting molecules on antigen-presenting cells, which in turn bridge the cytotoxic T cells for cancer-cell killing. Our findings indicate that rational combination of bacterial therapy and immunogenic chemotherapy can promote anticancer immunity against the immunosuppressive TME.
Hindering the unlimited proliferation of tumor cells synergizes with destroying tumor blood vessels for effective cancer treatment
Authors: Liu Ya , Xu Yajun , Wang Ying , Lv Jianlin , Wang Kun , Tang Zhaohui
Published: January 2024

The rational combination of chemotherapy drugs can improve the curative effect of cancer treatment.
Microwave-assisted synthesis of Co-free Li[Li0.2Ni0.2Mn0.6]O2 cathodes with a spinel-layered coherent structure for high-power Li-ion batteries
Authors: Wang Shenggui , Chen Jinniu , Zhao Tian , Yang Xiaoxia , Qiu Lang , Wang Yuankui , Song Yang , Wu Zhonghua , Guo Xiaodong , Yu Kun
Published: January 2024

A hydroxide co-precipitation method combined with a microwave heating process is proposed to synthesize cobalt-free Li[Li0.2Ni0.2Mn0.6]O2 with a layered/spinel heterostructure, which could deliver excellent electrochemical performance.
Self-assembly of peptide nanomaterials at biointerfaces: molecular design and biomedical applications
Authors: Guo Xin-Yuan , Yi Li , Yang Jia , An Hong-Wei , Yang Zi-Xin , Wang Hao
Published: January 2024

Self-assembly of peptides at biointerfaces for drug delivery, antibacterial strategies, cancer therapy, etc.
Quantum tunneling instability of the mythical hexazine and pentazine
Authors: Sedgi Itzhak , Kozuch Sebastian
Published: January 2024

Pentazine and Hexazine, two hypothetical high-energy density materials, exhibit inherent instability due to quantum tunneling effects.
Backbone-enabled modification of peptides with benzoquinone via palladium-catalyzed δ-C(sp2)–H functionalization
Authors: Lu Fengjie , Sun Yi , Liu Ya-ning , Geng Yujie , Zhang Ensheng , Tang Jian
Published: January 2024

Backbone-enabled site-selective modification of peptides with benzoquinone via Pd-catalyzed δ-C(sp2)–H functionalization has been achieved.
Low-valent titanium(ii) mediated intramolecular and regioselective alkyne/alkoxyallene reductive coupling reactions
Authors: Bodinier Florent , Lannou Marie-Isabelle , Sorin Geoffroy
Published: January 2024

Low-valent titanium(ii) complexes turned out to be suitable reagents in the promotion of alkyne/alkoxyallene coupling reactions in an intramolecular fashion.
Multi-stimuli responsive behavior of two Zn(ii) complexes based on a Schiff base with high contrast
Authors: Xia Zhong-Gang , Shi Yong-Sheng , Xiao Tong , Zheng Xiang-Jun
Published: January 2024

Two zinc(ii) complexes, [Zn(HL)X2]·CH3OH (X = I, Br) prepared through one-pot method exhibit high contrast NH3-induced discoloration properties, acidochromic properties and mechanochromic luminescence properties, and are made into test papers capable of detecting HCl and NH3 vapor.