bluuebunny/crossref_metadata_2025 huggingface dataset:
Methyl-CpG binding domain 2 (Mbd2) is an epigenetic regulator of autism-risk genes and cognition
Authors: Lax Elad , Do Carmo Sonia , Enuka Yehoshua , Sapozhnikov Daniel M. , Welikovitch Lindsay A. , Mahmood Niaz , Rabbani Shafaat A. , Wang Liqing , Britt Jonathan P. , Hancock Wayne W. , Yarden Yosef , Szyf Moshe
Published: July 2023

The Methyl-CpG-Binding Domain Protein family has been implicated in neurodevelopmental disorders. The Methyl-CpG-binding domain 2 (Mbd2) binds methylated DNA and was shown to play an important role in cancer and immunity. Some evidence linked this protein to neurodevelopment. However, its exact role in neurodevelopment and brain function is mostly unknown. Here we show that Mbd2-deficiency in mice (Mbd2−/−) results in deficits in cognitive, social and emotional functions. Mbd2 binds regulatory DNA regions of neuronal genes in the hippocampus and loss of Mbd2 alters the expression of hundreds of genes with a robust down-regulation of neuronal gene pathways. Further, a genome-wide DNA methylation analysis found an altered DNA methylation pattern in regulatory DNA regions of neuronal genes in Mbd2−/− mice. Differentially expressed genes significantly overlap with gene-expression changes observed in brains of Autism Spectrum Disorder (ASD) individuals. Notably, downregulated genes are significantly enriched for human ortholog ASD risk genes. Observed hippocampal morphological abnormalities were similar to those found in individuals with ASD and ASD rodent models. Hippocampal Mbd2 knockdown partially recapitulates the behavioral phenotypes observed in Mbd2−/− mice. These findings suggest that Mbd2 is a novel epigenetic regulator of genes that are associated with ASD in humans. Mbd2 loss causes behavioral alterations that resemble those found in ASD individuals.
A Dhdds K42E knock-in RP59 mouse model shows inner retina pathology and defective synaptic transmission
Authors: Nguyen Mai N. , Chakraborty Dibyendu , Rao Sriganesh Ramachandra , Onysk Agnieszka , Radkiewicz Mariusz , Surmacz Liliana , Swiezewska Ewa , Soubeyrand Eric , Akhtar Tariq A. , Kraft Timothy W. , Sherry David M. , Fliesler Steven J. , Pittler Steven J.
Published: July 2023

Retinitis pigmentosa (RP) defines a group of hereditary progressive rod-cone degenerations that exhibit a common phenotype caused by variants in over 70 genes. While most variants in thedehydrodolichyldiphosphatesynthase (DHDDS) gene result in syndromic abnormalities, some variants cause non-syndromic RP (RP59). DHDDS encodes one subunit of the enzymecis-prenyltransferase (CPT), which is required for the synthesis of dolichol (Dol), that is a necessary protein glycosylation cofactor. We previously reported the creation and initial characterization of a knock-in (KI) mouse model harboring the most prevalent RP59-associatedDHDDSvariant (K42E) to understand how defects in DHDDS lead to retina-specific pathology. This model exhibited no profound retinal degeneration, nor proteinN-glycosylation defects. Here, we report that the Dol isoprenylogue species in retina, liver, and brain of the K42E mouse model are statistically shorter than in the corresponding tissues of age-matched controls, as reported in blood and urine of RP59 patients. Retinal transcriptome analysis demonstrated elevation of many genes encoding proteins involved in synaptogenesis and synaptic function. Quantitative retinal cell layer thickness measurements demonstrated a significant reduction in the inner nuclear layer (INL) and total retinal thickness (TRT) beginning at postnatal (PN) ∼2 months, progressively increasing to PN 18-mo. Histological analysis revealed cell loss in the INL, outer plexiform layer (OPL) disruption, and ectopic localization of outer nuclear layer (ONL) nuclei into the OPL of K42E mutant retinas, relative to controls. Electroretinograms (ERGs) of mutant mice exhibited reduced b-wave amplitudes beginning at PN 1-mo, progressively declining through PN 18-mo, without appreciable a-wave attenuation, relative to controls. Our results suggest that the underlying cause ofDHDDSK42E variant driven RP59 retinal pathology is defective synaptic transmission from outer to inner retina.
TM4SF1-AS1 inhibits apoptosis by promoting stress granule formation in cancer cells
Authors: Kitajima Hiroshi , Maruyama Reo , Niinuma Takeshi , Yamamoto Eiichiro , Takasawa Akira , Takasawa Kumi , Ishiguro Kazuya , Tsuyada Akihiro , Suzuki Ryo , Sudo Gota , Kubo Toshiyuki , Mitsuhashi Kei , Idogawa Masashi , Tange Shoichiro , Toyota Mutsumi , Yoshido Ayano , Kumegawa Kohei , Kai Masahiro , Yanagihara Kazuyoshi , Tokino Takashi , Osanai Makoto , Nakase Hiroshi , Suzuki Hiromu
Published: July 2023

Long noncoding RNAs (lncRNAs) play pivotal roles in tumor development. To identify dysregulated lncRNAs in gastric cancer (GC), we analyzed genome-wide trimethylation of histone H3 lysine 4 (H3K4me3) to screen for transcriptionally active lncRNA genes in the non-tumorous gastric mucosa of patients with GC and healthy individuals. We found that H3K4me3 at TM4SF1-AS1 was specifically upregulated in GC patients and that the expression of TM4SF1-AS1 was significantly elevated in primary and cultured GC cells. TM4SF1-AS1 contributes to GC cell growth in vitro and in vivo, and its oncogenic function is mediated, at least in part, through interactions with purine-rich element-binding protein α (Pur-α) and Y-box binding protein 1 (YB-1). TM4SF1-AS1 also activates interferon signaling in GC cells, which is dependent on Pur-α and RIG-I. Chromatin isolation by RNA purification (ChIRP)-mass spectrometry demonstrated that TM4SF1-AS1 was associated with several stress granule (SG)-related proteins, including G3BP2, RACK1, and DDX3. Notably, TM4SF1-AS1 promoted SG formation and inhibited apoptosis in GC cells by sequestering RACK1, an activator of the stress-responsive MAPK pathway, within SGs. TM4SF1-AS1-induced SG formation and apoptosis inhibition are dependent on Pur-α and YB-1. These findings suggested that TM4SF1-AS1 contributes to tumorigenesis by enhancing SG-mediated stress adaptation.
Macrophage DCLK1 promotes obesity-induced cardiomyopathy via activating RIP2/TAK1 signaling pathway
Authors: Yang Bin , Zhao Yunjie , Luo Wu , Zhu Weiwei , Jin Leiming , Wang Minxiu , Ye Lin , Wang Yi , Liang Guang
Published: July 2023

Obesity increases the risk for cardiovascular diseases and induces cardiomyopathy. Chronic inflammation plays a significant role in obesity-induced cardiomyopathy and may provide new therapeutic targets for this disease. Doublecortin-like kinase 1 (DCLK1) is an important target for cancer therapy and the role of DCLK1 in obesity and cardiovascular diseases is unclear. Herein, we showed that DCLK1 was overexpressed in the cardiac tissue of obese mice and investigated the role of DCLK1 in obesity-induced cardiomyopathy. We generated DCLK1-deleted mice and showed that macrophage-specific DCLK1 knockout, rather than cardiomyocyte-specific DCLK1 knockout, prevented high-fat diet (HFD)-induced heart dysfunction, cardiac hypertrophy, and fibrosis. RNA sequencing analysis showed that DCLK1 deficiency exerted cardioprotective effects by suppressing RIP2/TAK1 activation and inflammatory responses in macrophages. Upon HFD/palmitate (PA) challenge, macrophage DCLK1 mediates RIP2/TAK1 phosphorylation and subsequent inflammatory cytokine release, which further promotes hypertrophy in cardiomyocytes and fibrogenesis in fibroblasts. Finally, a pharmacological inhibitor of DCLK1 significantly protects hearts in HFD-fed mice. Our study demonstrates a novel role and a pro-inflammatory mechanism of macrophage DCLK1 in obesity-induced cardiomyopathy and identifies DCLK1 as a new therapeutic target for the treatment of this disease.
Targeting Wnt/β-catenin-mediated upregulation of oncogenic NLGN3 suppresses cancer stem cells in glioblastoma
Authors: Yun Eun-Jin , Kim Donghwi , Kim Sangwoo , Hsieh Jer-Tsong , Baek Seung Tae
Published: July 2023

Glioblastoma (GBM) is the most malignant tumor in brain and is highly resistant to therapy. Clinical evidence suggests increased number of cancer stem cells (CSCs) may contribute to the failure of conventional therapies, but the mechanisms associated with acquisition of CSC properties in GBM are not fully understood. We found that DAB2IP suppresses CSC properties by targeting the synaptic proteins neuroligin 3 (NLGN3) in GBM. Furthermore, we showed that GBM-derived NLGN3 has an oncogenic function by inducing CSC properties within GBM. Moreover, elevated NLGN3 transcription mediated by Wnt/β-catenin signaling pathway resulted in increased secretion of NLGN3 into the surrounding tumor microenvironment. Both condition media containing NLGN3 and recombinant NLGN3 transformed neighboring cells to CSCs, suggesting NLGN3 as a critical component inducing CSC properties. Furthermore, targeting NLGN3-bearing CSCs using upstream Wnt/β-catenin inhibitors synergistically enhances the efficacy of conventional treatment. Hence, we unveiled the series of regulatory mechanisms for acquisition of CSC properties in GBM progression by Wnt/β-catenin-mediated NLGN3. These results may provide a new targeting strategy to improve the therapeutic efficacy of GBM treatments.
Waning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination
Authors: Tong X. , McNamara R. P. , Avendaño M. J. , Serrano E. F. , García-Salum T. , Pardo-Roa C. , Bertera H. L. , Chicz T. M. , Levican J. , Poblete E. , Salinas E. , Muñoz A. , Riquelme A. , Alter G. , Medina R. A.
Published: July 2023

Since the emergence of SARS-CoV-2, vaccines targeting COVID-19 have been developed with unprecedented speed and efficiency. CoronaVac, utilising an inactivated form of the COVID-19 virus and the mRNA26 based Pfizer/BNT162b2 vaccines are widely distributed. Beyond the ability of vaccines to induce production of neutralizing antibodies, they might lead to the generation of antibodies attenuating the disease by recruiting cytotoxic and opsonophagocytic functions. However, the Fc-effector functions of vaccine induced antibodies are much less studied than virus neutralization. Here, using systems serology, we follow the longitudinal Fc-effector profiles induced by CoronaVac and BNT162b2 up until five months following the two-dose vaccine regimen. Compared to BNT162b2, CoronaVac responses wane more slowly, albeit the levels remain lower than that of BNT162b2 recipients throughout the entire observation period. However, mRNA vaccine boosting of CoronaVac responses, including response to the Omicron variant, induce significantly higher peak of antibody functional responses with increased humoral breadth. In summary, we show that vaccine platform-induced humoral responses are not limited to virus neutralization but rather utilise antibody dependent effector functions. We demonstrate that this functionality wanes with different kinetics and can be rescued and expanded via boosting with subsequent homologous and heterologous vaccination.
Scalable graphene sensor array for real-time toxins monitoring in flowing water
Authors: Maity Arnab , Pu Haihui , Sui Xiaoyu , Chang Jingbo , Bottum Kai J. , Jin Bing , Zhou Guihua , Wang Yale , Lu Ganhua , Chen Junhong
Published: July 2023

Risk management for drinking water often requires continuous monitoring of various toxins in flowing water. While they can be readily integrated with existing water infrastructure, two-dimensional (2D) electronic sensors often suffer from device-to-device variations due to the lack of an effective strategy for identifying faulty devices from preselected uniform devices based on electronic properties alone, resulting in sensor inaccuracy and thus slowing down their real-world applications. Here, we report the combination of wet transfer, impedance and noise measurements, and machine learning to facilitate the scalable nanofabrication of graphene-based field-effect transistor (GFET) sensor arrays and the efficient identification of faulty devices. Our sensors were able to perform real-time detection of heavy-metal ions (lead and mercury) and E. coli bacteria simultaneously in flowing tap water. This study offers a reliable quality control protocol to increase the potential of electronic sensors for monitoring pollutants in flowing water.
Cell-type-specific plasticity of inhibitory interneurons in the rehabilitation of auditory cortex after peripheral damage
Authors: Kumar Manoj , Handy Gregory , Kouvaros Stylianos , Zhao Yanjun , Brinson Lovisa Ljungqvist , Wei Eric , Bizup Brandon , Doiron Brent , Tzounopoulos Thanos
Published: July 2023

Peripheral sensory organ damage leads to compensatory cortical plasticity that is associated with a remarkable recovery of cortical responses to sound. The precise mechanisms that explain how this plasticity is implemented and distributed over a diverse collection of excitatory and inhibitory cortical neurons remain unknown. After noise trauma and persistent peripheral deficits, we found recovered sound-evoked activity in mouse A1 excitatory principal neurons (PNs), parvalbumin- and vasoactive intestinal peptide-expressing neurons (PVs and VIPs), but reduced activity in somatostatin-expressing neurons (SOMs). This cell-type-specific recovery was also associated with cell-type-specific intrinsic plasticity. These findings, along with our computational modelling results, are consistent with the notion that PV plasticity contributes to PN stability, SOM plasticity allows for increased PN and PV activity, and VIP plasticity enables PN and PV recovery by inhibiting SOMs.
Aggregation-regulated room-temperature phosphorescence materials with multi-mode emission, adjustable excitation-dependence and visible-light excitation
Authors: You Jingxuan , Zhang Xin , Nan Qinying , Jin Kunfeng , Zhang Jinming , Wang Yirong , Yin Chunchun , Yang Zhiyong , Zhang Jun
Published: July 2023

Constructing room-temperature phosphorescent materials with multiple emission and special excitation modes is fascinating and challenging for practical applications. Herein, we demonstrate a facile and general strategy to obtain ecofriendly ultralong phosphorescent materials with multi-mode emission, adjustable excitation-dependence, and visible-light excitation using a single organic component, cellulose trimellitate. Based on the regulation of the aggregation state of anionic cellulose trimellitates, such as CBtCOONa, three types of phosphorescent materials with different emission modes are fabricated, including blue, green and color-tunable phosphorescent materials with a strong excitation-dependence. The separated molecularly-dispersed CBtCOONa exhibits blue phosphorescence while the aggregated CBtCOONa emits green phosphorescence; and the CBtCOONa with a coexistence state of single molecular chains and aggregates exhibits color-tunable phosphorescence depending on the excitation wavelength. Moreover, aggregated cellulose trimellitates demonstrate unique visible-light excitation phosphorescence, which emits green or yellow phosphorescence after turning off the visible light. The aggregation-regulated phenomenon provides a simple principle for designing the proof-of-concept and on-demand phosphorescent materials by using a single organic component. Owing to their excellent processability and environmental friendliness, the aforementioned cellulose-based phosphorescent materials are demonstrated as advanced phosphorescence inks to prepare various disposable complex anticounterfeiting patterns and information codes.
Cytochrome c lysine acetylation regulates cellular respiration and cell death in ischemic skeletal muscle
Authors: Morse Paul T. , Pérez-Mejías Gonzalo , Wan Junmei , Turner Alice A. , Márquez Inmaculada , Kalpage Hasini A. , Vaishnav Asmita , Zurek Matthew P. , Huettemann Philipp P. , Kim Katherine , Arroum Tasnim , De la Rosa Miguel A. , Chowdhury Dipanwita Dutta , Lee Icksoo , Brunzelle Joseph S. , Sanderson Thomas H. , Malek Moh H. , Meierhofer David , Edwards Brian F. P. , Díaz-Moreno Irene , Hüttemann Maik
Published: July 2023

Skeletal muscle is more resilient to ischemia-reperfusion injury than other organs. Tissue specific post-translational modifications of cytochromec(Cytc) are involved in ischemia-reperfusion injury by regulating mitochondrial respiration and apoptosis. Here, we describe an acetylation site of Cytc, lysine 39 (K39), which was mapped in ischemic porcine skeletal muscle and removed by sirtuin5 in vitro. Using purified protein and cellular double knockout models, we show that K39 acetylation and acetylmimetic K39Q replacement increases cytochromecoxidase (COX) activity and ROS scavenging while inhibiting apoptosis via decreased binding to Apaf-1, caspase cleavage and activity, and cardiolipin peroxidase activity. These results are discussed with X-ray crystallography structures of K39 acetylated (1.50 Å) and acetylmimetic K39Q Cytc(1.36 Å) and NMR dynamics. We propose that K39 acetylation is an adaptive response that controls electron transport chain flux, allowing skeletal muscle to meet heightened energy demand while simultaneously providing the tissue with robust resilience to ischemia-reperfusion injury.
Impact of misclassified defective proviruses on HIV reservoir measurements
Authors: Reeves Daniel B. , Gaebler Christian , Oliveira Thiago Y. , Peluso Michael J. , Schiffer Joshua T. , Cohn Lillian B. , Deeks Steven G. , Nussenzweig Michel C.
Published: July 2023

Most proviruses persisting in people living with HIV (PWH) on antiretroviral therapy (ART) are defective. However, rarer intact proviruses almost always reinitiate viral rebound if ART stops. Therefore, assessing therapies to prevent viral rebound hinges on specifically quantifying intact proviruses. We evaluated the same samples from 10 male PWH on ART using the two-probe intact proviral DNA assay (IPDA) and near full length (nfl) Q4PCR. Both assays admitted similar ratios of intact to total HIV DNA, but IPDA found ~40-fold more intact proviruses. Neither assay suggested defective proviruses decay over 10 years. However, the mean intact half-lives were different: 108 months for IPDA and 65 months for Q4PCR. To reconcile this difference, we modeled additional longitudinal IPDA data and showed that decelerating intact decay could arise from very long-lived intact proviruses and/or misclassified defective proviruses: slowly decaying defective proviruses that are intact in IPDA probe locations (estimated up to 5%, in agreement with sequence library based predictions). The model also demonstrates how misclassification can lead to underestimated efficacy of therapies that exclusively reduce intact proviruses. We conclude that sensitive multi-probe assays combined with specific nfl-verified assays would be optimal to document absolute and changing levels of intact HIV proviruses.
Discovery and mechanism-guided engineering of BHET hydrolases for improved PET recycling and upcycling
Authors: Li Anni , Sheng Yijie , Cui Haiyang , Wang Minghui , Wu Luxuan , Song Yibo , Yang Rongrong , Li Xiujuan , Huang He
Published: July 2023

Although considerable research achievements have been made to address the plastic crisis using enzymes, their applications are limited due to incomplete degradation and low efficiency. Herein, we report the identification and subsequent engineering of BHETases, which have the potential to improve the efficiency of PET recycling and upcycling. Two BHETases (ChryBHETase and BsEst) are identified from the environment via enzyme mining. Subsequently, mechanism-guided barrier engineering is employed to yield two robust and thermostable ΔBHETases with up to 3.5-fold enhanced kcat/KM than wild-type, followed by atomic resolution understanding. Coupling ΔBHETase into a two-enzyme system overcomes the challenge of heterogeneous product formation and results in up to 7.0-fold improved TPA production than seven state-of-the-art PET hydrolases, under the conditions used here. Finally, we employ a ΔBHETase-joined tandem chemical-enzymatic approach to valorize 21 commercial post-consumed plastics into virgin PET and an example chemical (p-phthaloyl chloride) for achieving the closed-loop PET recycling and open-loop PET upcycling.
Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types
Authors: Driessens Stan L. W. , Galakhova Anna A. , Heyer Djai B. , Pieterse Isabel J. , Wilbers René , Mertens Eline J. , Waleboer Femke , Heistek Tim S. , Coenen Loet , Meijer Julia R. , Idema Sander , de Witt Hamer Philip C. , Noske David P. , de Kock Christiaan P. J. , Lee Brian R. , Smith Kimberly , Ting Jonathan T. , Lein Ed S. , Mansvelder Huibert D. , Goriounova Natalia A.
Published: July 2023

GWAS have identified numerous genes associated with human cognition but their cell type expression profiles in the human brain are unknown. These genes overlap with human accelerated regions (HARs) implicated in human brain evolution and might act on the same biological processes. Here, we investigated whether these gene sets are expressed in adult human cortical neurons, and how their expression relates to neuronal function and structure. We find that these gene sets are preferentially expressed in L3 pyramidal neurons in middle temporal gyrus (MTG). Furthermore, neurons with higher expression had larger total dendritic length (TDL) and faster action potential (AP) kinetics, properties previously linked to intelligence. We identify a subset of genes associated with TDL or AP kinetics with predominantly synaptic functions and high abundance of HARs.
The host–guest inclusion driven by host-stabilized charge transfer for construction of sequentially red-shifted mechanochromic system
Authors: Sun Dongdong , Wu Yong , Han Xie , Liu Simin
Published: July 2023

Developing more extensive methods to understand the underlying structure-property relationship of mechanochromic luminescent molecules is demanding but remains challenging. Herein, the effect of host-guest interaction on the mechanochromic properties of organic molecules is illustrated. A series of pyridinium-functionalized triphenylamine derivatives show bathochromic-shifted emission upon mechanical stimulation. These derivatives bind to cucurbit[8]uril to form homoternary host-guest inclusion complexes through host-stabilized intermolecular charge transfer interactions. Remarkably, the homoternary complexes exhibit longer emission than that of free guests in the solid state (even longer than ground guests), and a further bathochromic-shifted emission is observed upon grinding. Additionally, a heteroternary complex constructed through the encapsulation of pyrene (donor) and pyridinium (acceptor) guest pair in cucurbit[8]uril also displays the mechanochromic luminescent property. This work not only discloses the effect of host-guest inclusion on the mechanochromic property of organic molecules, but also provides a principle and a facile way to design the sequentially red-shifted mechanochromic materials.
High-throughput design of perpendicular magnetic anisotropy at quaternary Heusler and MgO interfaces
Authors: Jiang Sicong , Yang Kesong
Published: July 2023

Heusler alloys combined with MgO interfaces exhibit interfacial perpendicular magnetic anisotropy, making them attractive for energy-efficient spintronic technologies. However, finding suitable Heusler/MgO heterostructures with desired properties is challenging due to the vast range of compositions available and the complexity of interfacial structures, particularly for the emerging quaternary Heusler compounds. In this study, we report a high-throughput screening of quaternary-Heusler/MgO heterostructures for spintronic applications. By analyzing various materials descriptors, including formation energy, convex hull distance, magnetic ordering, lattice misfit, magnetic anisotropy constant, tunnel magnetoresistance, Curie temperature, and atomic site disordering, we identified 5 promising compounds out of 27,000 quaternary Heusler compounds. These compounds, namely IrCrAlTi, IrCrGaTi, IrMnZnTi, OsCrAlTa, and TaGaOsCr, show potential for designing energy-efficient perpendicular magnetic tunnel junctions. This work demonstrates an efficient approach using open quantum materials repositories, effective materials descriptors, and high-throughput computational techniques to accelerate the discovery of quaternary-Heusler-based functional materials.
Spectroscopic characterization of the quantum linear-zigzag transition in trapped ions
Authors: Zhang J. , Chow B. T. , Ejtemaee S. , Haljan P. C.
Published: July 2023

While engineered quantum systems are a general route to the manipulation of multipartite quantum states, access in a physical system to a continuous quantum phase transition under sufficient control offers the possibility of an intrinsic source of entangled states. To this end we realize the quantum version of the linear-zigzag structural transition for arrays of up to five ground state-cooled ions held in a linear Paul trap and we demonstrate several of the control requirements towards entangled-state interferometry near the critical point. Using in situ spectroscopy we probe the energy level structure and occupation of the soft mode associated with the structural transition, and show a stable critical point and majority ground state occupation crossing the transition. We resolve biases arising from trap electrode asymmetries that change the nature of the transition, show that they can be suppressed by varying the ion number, and demonstrate control of the transition bias using optical dipole forces.
Thiophosphate photochemistry enables prebiotic access to sugars and terpenoid precursors
Authors: Ritson Dougal J. , Sutherland John D.
Published: July 2023

Over the past few years, evidence has accrued that demonstrates that terrestrial photochemical reactions could have provided numerous (proto)biomolecules with implications for the origin of life. This chemistry simply relies on UV light, inorganic sulfur species and hydrogen cyanide. Recently, we reported that, under the same conditions, reduced phosphorus species, such as those delivered by meteorites, can be oxidized to orthophosphate, generating thiophosphate in the process. Here we describe an investigation of the properties of thiophosphate as well as additional possible means for its formation on primitive Earth. We show that several reported prebiotic reactions, including the photoreduction of thioamides, carbonyl groups and cyanohydrins, can be markedly improved, and that tetroses and pentoses can be accessed from hydrogen cyanide through a Kiliani–Fischer-type process without progressing to higher sugars. We also demonstrate that thiophosphate allows photochemical reductive aminations, and that thiophosphate chemistry allows a plausible prebiotic synthesis of the C5 moieties used in extant terpene and terpenoid biosynthesis, namely dimethylallyl alcohol and isopentenyl alcohol.
Present-day North Atlantic salinity constrains future warming of the Northern Hemisphere
Authors: Park In-Hong , Yeh Sang-Wook , Cai Wenju , Wang Guojian , Min Seung-Ki , Lee Sang-Ki
Published: July 2023

Earth system models exhibit considerable intermodel spread in Atlantic Meridional Overturning Circulation intensity and its carbon uptake, resulting in great uncertainty in future climate. Here we show that present-day sea surface salinity (SSS) in the North Atlantic subpolar region modulates anthropogenic carbon uptake in the North Atlantic, and thus can be used to constrain future warming. Specifically, models that generate a present-day higher SSS in the North Atlantic subpolar region generate a greater uptake of anthropogenic carbon in the future, suppressing the greenhouse effect and resulting in slower warming, and vice versa in models with a present-day lower SSS. Emergent constraints based on the observed SSS greatly reduce the uncertainty of the Northern Hemisphere surface temperature warming and accumulative carbon uptake by about 30% and 53%, respectively, by the end of the twenty-first century under the Shared Socioeconomic Pathways 5–8.5 scenario.
Positive and Negative Affect Schedule in early COVID-19 pandemic
Authors: Andreu-Sánchez Celia , Martín-Pascual Miguel Ángel
Published: July 2023

The COVID-19 pandemic is the first pandemic in the Information Age. It started in Asia and spread rapidly around the world. As a consequence, millions of people were subject to lockdowns, and traditional media and social media reached more people. Our study, carried out during the lockdown, asked people about their feelings and emotions and included a Positive and Negative Affect Schedule (PANAS). Here, we present the data resulting from that study, which could potentially be reused by psychologists interested in learning about the emotional effects of the COVID-19 pandemic as well as to make comparisons before and after the lockdown period in 2020.
An extinct deep-snouted Alligator species from the Quaternary of Thailand and comments on the evolution of crushing dentition in alligatorids
Authors: Darlim Gustavo , Suraprasit Kantapon , Chaimanee Yaowalak , Tian Pannipa , Yamee Chotima , Rugbumrung Mana , Kaweera Adulwit , Rabi Márton
Published: July 2023

Fossil Alligator remains from Asia are critical for tracing the enigmatic evolutionary origin of the Chinese alligator, Alligator sinensis, the only living representative of Alligatoridae outside the New World. The Asian fossil record is extremely scarce and it remains unknown whether A. sinensis is an anagenetic lineage or alternatively, extinct divergent species were once present. We provide a detailed comparative description of a morphologically highly distinct Alligator skull from the Quaternary of Thailand. Several autapomorphic characters warrant the designation of a new species. Alligator munensis sp. nov. shares obvious derived features with A. sinensis but autapomorphies imply a cladogenetic split, possibly driven by the uplift of the southeastern Tibetan plateau. The presence of enlarged posterior alveoli in Alligator munensis is most consistent with a reversal to the alligatorine ancestral condition of having crushing dentition, a morphology strikingly absent among living alligatorids. Crushing dentition has been previously considered to indicate an ecological specialisation in early alligatorines that was subsequently lost in Alligator spp. However, we argue that there is yet no evidence for crushing dentition reflecting an adaptation for a narrower niche, while opportunistic feeding, including seasonal utilisation of hard-shelled preys, is a reasonable alternative interpretation of its function.
Treatment effects of Herbst appliance in skeletal Class II cases during pre-pubertal and post-pubertal periods: a cone-beam computed tomographic study
Authors: Farouk Khaled , Eissa Osama , Ghoneima Ahmed , El-Bedwehi Ashraf , Abdel-Fattah Ezzat , Hussein Farouk , El-Bialy Tarek
Published: July 2023

In the present study, Thirty-six Class patients II (A condition in which the upper jaw is larger than the lower jaw) were randomly selected and assigned to one of two groups based on their maturation stage: the pre-pubertal group (18 patients, mean age 9.15 ± 1.5 years) and post-pubertal group (18 patients, mean age 16.3 ± 1.0 years). All patients were treated with a metallic splint-supported Herbst IV appliance (An appliance that acts like artificial joint working between the upper and power jaws that keeps the lower jaw in a forward position, thus improving the Class II condition). Pretreatment (T1) and post-Herbst IV treatment (T2) scans were obtained for both groups. Dental and skeletal measurements were made on the scans and statistically analyzed using paired and independent t-tests. The study hypothesis was that; the dentoskeletal changes in Class II malocclusion treatment using Herbst appliance in the Pre-pubertal is more than the Post-pubertal growth stage due to the remaining growth potential for the pre-pubertal patients. The comparison between the two groups revealed statistically significant differences in horizontal skeletal parameters in the lower jaw only, while other readings were similar.
Channeling is a distinct class of dissolution in complex porous media
Authors: Menke Hannah P. , Maes Julien , Geiger Sebastian
Published: July 2023

The traditional model of solid dissolution in porous media consists of three dissolution regimes (uniform, compact, wormhole)—or patterns—that are established depending on the relative dominance of reaction rate, flow, and diffusion. In this work, we investigate the evolution of pore structure using numerical simulations during acid injection on two models of increasing complexity. We investigate the boundaries between dissolution regimes and characterize the existence of a fourth dissolution regime called channeling, where initially fast flow pathways are preferentially widened by dissolution. Channeling occurs in cases where the distribution in pore throat size results in orders of magnitude differences in flow rate for different flow pathways. This focusing of dissolution along only dominant flow paths induces an immediate, large change in permeability with a comparatively small change in porosity, resulting in a porosity–permeability relationship unlike any that has been previously seen. This work suggests that the traditional conceptual model of dissolution regimes must be updated to incorporate the channeling regime for reliable forecasting of dissolution in applications like geothermal energy production and geologic carbon storage.
Growth factors and mechano-regulated reciprocal crosstalk with extracellular matrix tune the keratocyte–fibroblast/myofibroblast transition
Authors: Pot Simon A. , Lin Zhe , Shiu Jauye , Benn Mario C. , Vogel Viola
Published: July 2023

Improper healing of the cornea after injury, infections or surgery can lead to corneal scar formation, which is associated with the transition of resident corneal keratocytes into activated fibroblasts and myofibroblasts (K–F/M). Myofibroblasts can create an extracellular matrix (ECM) niche in which fibrosis is promoted and perpetuated, resulting in progressive tissue opacification and vision loss. As a reversion back to quiescent keratocytes is essential to restore corneal transparency after injury, we characterized how growth factors with demonstrated profibrotic effects (PDGF, FGF, FBS, TGFβ1) induce the K–F/M transition, and whether their withdrawal can revert it. Indeed, the upregulated expression of αSMA and the associated changes in cytoskeletal architecture correlated with increases in cell contractility, fibronectin (Fn) and collagen matrix density and Fn fiber strain, as revealed by 2D cell culture, nanopillar cellular force mapping and a FRET-labeled Fn tension probe. Substrate mechanosensing drove a more complete K–F/M transition reversal following growth factor withdrawal on nanopillar arrays than on planar glass substrates. Using decellularized ECM scaffolds, we demonstrated that the K–F/M transition was inhibited in keratocytes reseeded onto myofibroblast-assembled, and/or collagen-1-rich ECM. This supports the presence of a myofibroblast-derived ECM niche that contains cues favoring tissue homeostasis rather than fibrosis.
Early Mesozoic burst of morphological disparity in the slow-evolving coelacanth fish lineage
Authors: Ferrante Christophe , Cavin Lionel
Published: July 2023

Since the split of the coelacanth lineage from other osteichthyans 420 million years ago, the morphological disparity of this clade has remained remarkably stable. Only few outliers with peculiar body shape stood out over the evolutionary history, but they were phylogenetically and stratigraphically independent of each other. Here, we report the discovery of a new clade of ancient latimeriid coelacanths representing a small flock of species present in the Western Tethys between 242 and 241 million years ago. Among the four species, two show highly derived anatomy. A new genus shows reversal to plesiomorphic conditions in its skull and caudal fin organisation. The new genus and its sister Foreyia have anatomical modules that moved from the general coelacanth Bauplau either in the same direction or in opposite direction that affect proportions of the body, opercle and fins. Comparisons with extant genetic models shows that changes of the regulatory network of the Hedgehog signal gene family may account for most of the altered anatomy. This unexpected, short and confined new clade represents the only known example of a burst of morphological disparity over the long history of coelacanths at a recovery period after the Permian–Triassic Mass Extinction.
9000 years of change in coral community structure and accretion in Belize reefs, western Atlantic
Authors: Gischler Eberhard , Hudson J. Harold , Eisenhauer Anton , Parang Soran , Deveaux Michael
Published: July 2023

Tropical coral reefs, as prominent marine diversity hotspots, are in decline, and long-term studies help to improve understanding of the effects of global warming, sea-level rise, ocean acidification, deterioration of water quality, and disease. Here, we evaluated relative coral abundance and reef accretion rates over the past 9000 years in Belize barrier and atoll reefs, the largest reef system in the Atlantic Ocean.Acropora palmataandOrbicellaspp. have been the most common corals. The abundance of competitive, fast-growing acroporids was constant over multi-millennial timescales. A decline inA. cervicornisabundance, however, and three centennial-scale gaps inA. palmataoccurrence, suggest that the modern decline in acroporids was not unprecedented. Stress-tolerant corals predominate at the beginning of Holocene successions. Following the improvement of environmental conditions after inundation of the reef pedestal, their abundance has decreased. The abundance of weedy corals has increased during the Holocene underlining the importance of fecundity for the coral community. Reef-accretion rate, as calculated based on 76 new U-series age dates, has decreased over the Holocene and the mean value of 3.36 m kyr−1is at the lower end of global reef growth compilations and predicted future rates of rise in sea level.
Life cycle assessment of microgreen production: effects of indoor vertical farm management on yield and environmental performance
Authors: Parkes Michael G. , Azevedo Duarte Leal , Cavallo Ana Celeste , Domingos Tiago , Teixeira Ricardo F. M.
Published: July 2023

The global production of plant-based foods is a significant contributor to greenhouse gas emissions. Indoor vertical farms (IVFs) have emerged as a promising approach to urban agriculture. However, their environmental performance is not well understood, particularly in relation to operational choices where global warming potentials (GWP) can vary between 0.01–54 kg CO2e/kg−1 of leafy greens produced. We conducted a life cycle assessment (LCA) of a building-integrated IVF for microgreen production to analyse a range of operational conditions for cultivation: air temperature, CO2 concentration, and photoperiod. We analyzed a dynamic LCA inventory that combined a process-based plant growth model and a mass balance model for air and heat exchange between the chamber and the outside. Results showed that the GWP of IVFs can vary greatly depending on the operation conditions set, ranging from 3.3 to 63.3 kg CO2e/kg−1. The optimal conditions for minimizing GWP were identified as 20 ℃, maximum CO2 concentration in the chamber, and maximum photoperiod, which led to a minimum GWP of 3.3 kg CO2e/kg−1 and maximum production of 290.5 kg fresh weight week-1. Intensification of production thus led to lower impacts because the marginal increase in yield due to increased resource use was larger than the marginal increase in impact. Therefore, adjusting growing conditions is essential for the sustainability of urban food production.
A diagnostic classification of lung nodules using multiple-scale residual network
Authors: Wang Hongfeng , Zhu Hai , Ding Lihua , Yang Kaili
Published: July 2023

Computed tomography (CT) scans have been shown to be an effective way of improving diagnostic efficacy and reducing lung cancer mortality. However, distinguishing benign from malignant nodules in CT imaging remains challenging. This study aims to develop a multiple-scale residual network (MResNet) to automatically and precisely extract the general feature of lung nodules, and classify lung nodules based on deep learning. The MResNet aggregates the advantages of residual units and pyramid pooling module (PPM) to learn key features and extract the general feature for lung nodule classification. Specially, the MResNet uses the ResNet as a backbone network to learn contextual information and discriminate feature representation. Meanwhile, the PPM is used to fuse features under four different scales, including the coarse scale and the fine-grained scale to obtain more general lung features of the CT image. MResNet had an accuracy of 99.12%, a sensitivity of 98.64%, a specificity of 97.87%, a positive predictive value (PPV) of 99.92%, and a negative predictive value (NPV) of 97.87% in the training set. Additionally, its area under the receiver operating characteristic curve (AUC) was 0.9998 (0.99976–0.99991). MResNet's accuracy, sensitivity, specificity, PPV, NPV, and AUC in the testing set were 85.23%, 92.79%, 72.89%, 84.56%, 86.34%, and 0.9275 (0.91662–0.93833), respectively. The developed MResNet performed exceptionally well in estimating the malignancy risk of pulmonary nodules found on CT. The model has the potential to provide reliable and reproducible malignancy risk scores for clinicians and radiologists, thereby optimizing lung cancer screening management.
Comparison of in silico predicted Mycobacterium tuberculosis spoligotypes and lineages from whole genome sequencing data
Authors: Napier Gary , Couvin David , Refrégier Guislaine , Guyeux Christophe , Meehan Conor J. , Sola Christophe , Campino Susana , Phelan Jody , Clark Taane G.
Published: July 2023

Bacterial strain-types in the Mycobacterium tuberculosis complex underlie tuberculosis disease, and have been associated with drug resistance, transmissibility, virulence, and host–pathogen interactions. Spoligotyping was developed as a molecular genotyping technique used to determine strain-types, though recent advances in whole genome sequencing (WGS) technology have led to their characterization using SNP-based sub-lineage nomenclature. Notwithstanding, spoligotyping remains an important tool and there is a need to study the congruence between spoligotyping-based and SNP-based sub-lineage assignation. To achieve this, an in silico spoligotype prediction method (“Spolpred2”) was developed and integrated into TB-Profiler. Lineage and spoligotype predictions were generated for > 28 k isolates and the overlap between strain-types was characterized. Major spoligotype families detected were Beijing (25.6%), T (18.6%), LAM (13.1%), CAS (9.4%), and EAI (8.3%), and these broadly followed known geographic distributions. Most spoligotypes were perfectly correlated with the main MTBC lineages (L1-L7, plus animal). Conversely, at lower levels of the sub-lineage system, the relationship breaks down, with only 65% of spoligotypes being perfectly associated with a sub-lineage at the second or subsequent levels of the hierarchy. Our work supports the use of spoligotyping (membrane or WGS-based) for low-resolution surveillance, and WGS or SNP-based systems for higher-resolution studies.
Characterization of a novel and active temperate phage vB_AbaM_ABMM1 with antibacterial activity against Acinetobacter baumannii infection
Authors: Mardiana Meity , Teh Soon-Hian , Tsai Yun-Chan , Yang Hsueh-Hui , Lin Ling-Chun , Lin Nien-Tsung
Published: July 2023

Acinetobacter baumannii is an opportunistic pathogen that significantly causes hospital-acquired infections. Due to its multidrug resistance, treating infections caused by this pathogen is challenging. Recently, phages have gained attention as a potential alternative to antibiotics in treating bacterial infections. While lytic phages are preferred in therapy, the use of temperate phages for this purpose has received less attention. This study characterized a novel temperate phage vB_AbaM_ABMM1 (ABMM1) with antibacterial activity toward A. baumannii. ABMM1 adsorbs quickly, has short latent periods, and is relatively stable at various temperatures and neutral pH. ABMM1 has an icosahedral head and a contractile tail. It has a 75,731 kb circular permuted dsDNA genome containing 86 gene products with 37.3% G + C content and a mosaic arrangement typical of temperate phages. Genomic analysis confirmed that ABMM1 does not have antibiotic-resistance genes or virulence-related factors. The packaging strategy was predicted in silico, suggesting that ABMM1 represents a headful phage. Only truncated ABMM1 prophage was detected and has similarity in the genome of several A. baumannii strains. Despite its ability to integrate into the host chromosome, the high MOI of ABMM1 (MOI 10) effectively killed the host bacterial cells and reduced the fatality rate of bacterial infection in the zebrafish model. These findings indicate that ABMM1 can be an alternative treatment for A. baumannii infection.
Effect of intervention based on the 5A self-management model on the improvement of behaviors related to women's reproductive health after legal abortion
Authors: Mirian Zahra , AbdiShahshahani Mahshid , Noroozi Mahnaz , Mostafavi Firozeh , Beigi Marjan
Published: July 2023

Legal abortion has adopted many beneficial measures to prevent the birth of fetuses with congenital anomalies and maintain the health of high-risk mothers. However, abortion has its own complications and, thus, most mothers need care in this regard. The aim of this study was to determine the effect of self-management model on behaviors related to the reproductive health of mothers after legal abortion. This clinical trial study was conducted on 72 women who had legal abortion with the permission from Isfahan forensic medicine. The intervention was conducted using the 5A self-management model. The control group received the usual health system cares. Data collection tool was a researcher-made questionnaire of behaviors related to reproductive health, which was completed before and two months after the intervention by the two groups. The total mean score of the behavior (P < 0.001) and its dimensions (Prevention of post-abortion complications with P = 0.01, Prevention of sexually transmitted infections, satisfactory sexual function and family planning with P < 0.001) in the intervention group two months after the outset of the intervention was significantly higher than before the intervention. The total mean score of the behavior (P < 0.001) and its dimensions (Prevention of post-abortion complications with P = 0.002, Prevention of sexually transmitted infections, satisfactory sexual function and family planning with P < 0.001) two months after the outset of the intervention in the intervention group was significantly higher than the control group. Based on the results, this educational model can be emphasized to promote reproductive health behaviors of women after abortion.

Clinical trial protocol link: https://www.irct.ir/user/trial/55184/view.