bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental Origins of Human Cortical Oligodendrocytes and Astrocytes
Authors: Yang Lin , Li Zhenmeiyu , Liu Guoping , Li Xiaosu , Yang Zhengang
Published: August 2021

Human cortical radial glial cells are primary neural stem cells that give rise to cortical glutaminergic projection pyramidal neurons, glial cells (oligodendrocytes and astrocytes) and olfactory bulb GABAergic interneurons. One of prominent features of the human cortex is enriched with glial cells, but there are major gaps in understanding how these glial cells are generated. Herein, by integrating analysis of published human cortical single-cell RNA-Seq datasets with our immunohistochemistical analyses, we show that around gestational week 18, EGFR-expressing human cortical truncated radial glial cells (tRGs) give rise to basal multipotent intermediate progenitors (bMIPCs) that express EGFR, ASCL1, OLIG2 and OLIG1. These bMIPCs undergo several rounds of mitosis and generate cortical oligodendrocytes, astrocytes and olfactory bulb interneurons. We also characterized molecular features of the cortical tRG. Integration of our findings suggests a general picture of the lineage progression of cortical radial glial cells, a fundamental process of the developing human cerebral cortex.
Active Inference as a Computational Framework for Consciousness
Authors: Vilas Martina G. , Auksztulewicz Ryszard , Melloni Lucia
Published: August 2021

Recently, the mechanistic framework of active inference has been put forward as a principled foundation to develop an overarching theory of consciousness which would help address conceptual disparities in the field (Wiese 2018; Hohwy and Seth 2020). For that promise to bear out, we argue that current proposals resting on the active inference scheme need refinement to become a process theory of consciousness. One way of improving a theory in mechanistic terms is to use formalisms such as computational models that implement, attune and validate the conceptual notions put forward. Here, we examine how computational modelling approaches have been used to refine the theoretical proposals linking active inference and consciousness, with a focus on the extent and success to which they have been developed to accommodate different facets of consciousness and experimental paradigms, as well as how simulations and empirical data have been used to test and improve these computational models. While current attempts using this approach have shown promising results, we argue they remain preliminary in nature. To refine their predictive and structural validity, testing those models against empirical data is needed i.e., new and unobserved neural data. A remaining challenge for active inference to become a theory of consciousness is to generalize the model to accommodate the broad range of consciousness explananda; and in particular to account for the phenomenological aspects of experience. Notwithstanding these gaps, this approach has proven to be a valuable avenue for theory advancement and holds great potential for future research.
Inhomogeneity detection in the rainfall series for the Mae Klong River Basin, Thailand
Authors: Khalil Alamgir
Published: August 2021

An accurate and complete rainfall record is prerequisite for climate studies. The purpose of this research study was to evaluate the homogeneity of the rainfall series for the Mae Klong River Basin in Thailand. Monthly rainfall data of eight stations in the Mae Klong River Basin for the period 1971–2015 were used. The double mass curve analysis was used to check the consistency of rainfall data, whereas the absolute homogeneity was assessed using the Pettitt test, standard normal homogeneity test, Buishand test, and von Neumann test at a 5% significance level. The results of these tests were qualitatively classified as ‘useful’, ‘doubtful’, and ‘suspect’ according to the null hypothesis. Results of the monthly time series indicated the rainfall data as ‘useful’ for 75% of the stations, while two stations’ data were classified as ‘doubtful’ (Stn130221) and ‘suspect’ (Stn376401). On an annual scale, seven out of eight stations data were classified as ‘useful,’ while one station (Stn376401) data were classified as ‘suspect’. Double mass curve analysis technique was used for the adjustment of inhomogeneous data. The results of this study can help provide reliable rainfall data for climate studies in the basin.
The Differential Metabolomes in Cumulus and Mural Granulosa Cells from Human Preovulatory Follicles
Authors: Gao Er-Meng , Turathum Bongkoch , Wang Ling , Zhang Di , Liu Yu-Bing , Tang Rong-Xin , Chian Ri-Cheng
Published: August 2021

This study evaluated the differences in metabolites between cumulus cells (CCs) and mural granulosa cells (MGCs) from human preovulatory follicles to understand the mechanism of oocyte maturation involving CCs and MGCs. CCs and MGCs were collected from women who were undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment. The differences in morphology were determined by immunofluorescence. The metabolomics of CCs and MGCs was measured by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) followed by quantitative polymerase chain reaction (qPCR) and western blot analysis to further confirm the genes and proteins involved in oocyte maturation. CCs and MGCs were cultured for 48 h in vitro, and the medium was collected for detection of hormone levels. There were minor morphological differences between CCs and MGCs. LC-MS/MS analysis showed that there were differences in 101 metabolites between CCs and MGCs: 7 metabolites were upregulated in CCs, and 94 metabolites were upregulated in MGCs. The metabolites related to cholesterol transport and estradiol production were enriched in CCs, while metabolites related to antiapoptosis were enriched in MGCs. The expression of genes and proteins involved in cholesterol transport (ABCA1, LDLR, and SCARB1) and estradiol production (SULT2B1 and CYP19A1) was significantly higher in CCs, and the expression of genes and proteins involved in antiapoptosis (CRLS1, LPCAT3, and PLA2G4A) was significantly higher in MGCs. The level of estrogen in CCs was significantly higher than that in MGCs, while the progesterone level showed no significant differences. There are differences between the metabolomes of CCs and MGCs. These differences may be involved in the regulation of oocyte maturation.
Association between stage and histopathological type of nasopharyngeal cancer on occurrence of postirradiation otitis media with effusion
Authors: Lasminingrum Lina , Boesoeri Shinta Fitri , Mahdiani Sally , Ranti Eveline Sabrina
Published: August 2021

ABSTRACT

Introduction:

Indonesia is one of the countries with the highest incidence of nasopharyngeal cancer (NPC), 6.2 out of 100,000 population/year. Radiotherapy is one of the main treatment options for NPC. Otitis media with effusion (OME) is the most common ear complication of radiotherapy for NPC patients.

Objective:

This study aimed to determine the association between the stage and histopathological type of NPC on the occurrence of OME.

Method:

This study used a cross-sectional method, data were taken retrospectively from medical records based on inclusion and exclusion criteria for the period January 2015–December 2019.

Results:

131 patients met the inclusion and exclusion criteria. There were 87 men and 44 women, with the largest age range being 46–55 years (49%). Most (51%) had stage III NPC, followed by stage IV A by 28%. The histopathological type is mostly undifferentiated non-keratinized NPC in 90 patients (69%) and 34 patients with differentiated nonkeratinized types (26%). The association between stage (p1) and histopathological type (p2) of NPC with the incidence of OME after radiotherapy showed insignificant results (p1 = 0.272 and p2 = 0.101).

Conclusion:

Otitis media with effusion in post irradiated nasopharyngeal carcinoma patients occurred in 18.3%. Postirradiation OME generally occurs in men with the age range of 46–55 years, NPC stage III and non-keratinizing undifferentiated histopathological type. There was no significant association between stage and histopathological type of NPC with the occurrence of postirradiation OME.

Highlights
Radiation-induced breast angiosarcoma: A case report
Authors: Hamza Kiram , Cheikh Telmoudi Ely , Maryem Bouab , Hicham Benaguida , Mustapha Benhessou , Mohamed Ennachit , Mohamed Elkarroumi
Published: August 2021

ABSTRACT

Introduction:

Breast angiosarcomas are rare and aggressive conjunctival malignancies. They represent 0.04% of malignant breast tumors and 8–10% of all breast sarcomas. There are two forms; a primary one with no known precursor, and one secondary to breast irradiation.

Case report:

Patient aged 63 years, mother of four, known hypertensive on treatment, operated 07 years ago by right breast conservative surgery with at pathology report; CMI type NOS, grade II SBR, endoluminal B, (0 N+/10 N). The patient received chemotherapy, radiotherapy and hormone therapy for 5 years.

Seven years later, she presented with a mass in the right axillary extension, near the lumpectomy scar, classified as ACR BI-RADS 4 on echomammography. The tru-cut biopsy objectified a radiation-induced breast angiosarcoma on immunohistochemistry. The patient underwent a right mastectomy.

Discussion:

Breast angiosarcoma is a rare and aggressive conjunctival tumor. There are two forms of angiosarcoma, primary with unknown precursor and secondary occurring after breast irradiation. The mode of revelation is the appearance of breast nodule rapidly increasing in volume. Histological confirmation of the sarcomatous component on the post-radiation lesion allows the diagnosis to be made. Surgery is the only treatment for radiation-induced angiosarcoma. The role of adjuvant therapies remains limited in the treatment of radiation-induced angiosarcoma.

Conclusion:

Radiation-induced angiosarcoma is a rare malignant tumour occurring in patients who have undergone breast conserving treatment. Its diagnosis is confirmed by histological study and surgery is the cornerstone of treatment.

Highlights
Computational Statistical Physics
Authors: Böttcher Lucas , Herrmann Hans J.
Published: August 2021

Providing a detailed and pedagogical account of the rapidly-growing field of computational statistical physics, this book covers both the theoretical foundations of equilibrium and non-equilibrium statistical physics, and also modern, computational applications such as percolation, random walks, magnetic systems, machine learning dynamics, and spreading processes on complex networks. A detailed discussion of molecular dynamics simulations is also included, a topic of great importance in biophysics and physical chemistry. The accessible and self-contained approach adopted by the authors makes this book suitable for teaching courses at graduate level, and numerous worked examples and end of chapter problems allow students to test their progress and understanding.
A comparison of Galactic electron density models using PyGEDM
Authors: Price D. C. , Flynn C. , Deller A.
Published: August 2021

Galactic electron density distribution models are crucial tools for estimating the impact of the ionised interstellar medium on the impulsive signals from radio pulsars and fast radio bursts. The two prevailing Galactic electron density models (GEDMs) are YMW16 (Yao et al. 2017, ApJ, 835, 29) and NE2001 (Cordes & Lazio 2002, arXiv e-prints, pp astro–ph/0207156). Here, we introduce a software packagePyGEDMwhich provides a unified application programming interface for these models and the YT20 (Yamasaki & Totani 2020, ApJ, 888, 105) model of the Galactic halo. We usePyGEDMto compute all-sky maps of Galactic dispersion measure (DM) for YMW16 and NE2001 and compare the large-scale differences between the two. In general, YMW16 predicts higher DM values towards the Galactic anticentre. YMW16 predicts higher DMs at low Galactic latitudes, but NE2001 predicts higher DMs in most other directions. We identify lines of sight for which the models are most discrepant, using pulsars with independent distance measurements. YMW16 performs better on average than NE2001, but both models show significant outliers. We suggest that future campaigns to determine pulsar distances should focus on targets where the models show large discrepancies, so future models can use those measurements to better estimate distances along those line of sight. We also suggest that the Galactic halo should be considered as a component in future GEDMs, to avoid overestimating the Galactic DM contribution for extragalactic sources such as FRBs.
Customised vestibular rehabilitation with the addition of virtual reality based therapy in the management of persistent postural-perceptual dizziness
Authors: Mempouo E , Lau K , Green F , Bowes C , Ray J
Published: August 2021

Objective

Visual-vestibular mismatch patients experience persistent postural and perceptual dizziness. Previous studies have shown the benefit of vestibular rehabilitation for visual desensitisation using gaze stabilisation exercises and optokinetic stimulation. This study assessed the benefit of customised vestibular rehabilitation with visual desensitisation and virtual reality based therapy rehabilitation in the management of patients with persistent postural-perceptual dizziness.

Methods

This retrospective study included 100 patients with Situational Characteristic Questionnaire scores of more than 0.9. All patients received virtual reality based therapy along with usual vestibular rehabilitation using gaze stabilisation exercises with a plain background followed by graded visual stimulation and optokinetic digital video disc stimulation. Patients’ symptoms were assessed before and after vestibular rehabilitation using the Situational Characteristic Questionnaire, Generalised Anxiety Disorder Assessment-7, Nijmegen Questionnaire and Dizziness Handicap Inventory.

Results

There were statistically significant improvements in Situational Characteristic Questionnaire scores, Nijmegen Questionnaire scores and Dizziness Handicap Inventory total score. However, there was a statistically insignificant difference in Generalised Anxiety Disorder Assessment-7 scores. There was a significant positive correlation between post-rehabilitation Situational Characteristic Questionnaire scores and other questionnaire results.

Conclusion

Incorporating virtual reality based therapy with customised vestibular rehabilitation exercises results in significant improvement in persistent postural-perceptual dizziness related symptoms.
Impact of lifestyle modifications on snoring and mild sleep apnoea patients
Authors: Sahni N , Arora K , Bansal S , Reddy G V N , Malhotra S , Virk R S
Published: August 2021

Objective

Behavioural modification through increasing nutritional awareness, along with customised dietary changes and education about physical inactivity, for obese snorers and mildly sleep apnoeic patients would help improve their quality of life.

Methods

A one-year prospective interventional study enrolled snorers and/or mild obstructive sleep apnoea sufferers, with 36 patients each in the test group and control group. Nutritional information and tailor-made diet charts were given to the 36 test subjects. The severity of snoring and daytime sleepiness after 6 and 12 months was compared using the Epworth Sleepiness Scale and Thornton Snoring Scale as measures of quality of life.

Results

Subjective scores on both scales showed highly significant improvement (p ≤ 0.001) in the test group. No significant improvement was seen in the control group.

Conclusion

Awareness of basic nutrition and customised diet plans help to achieve behavioural modification in the long term, resulting in a better quality of life.
Navigating trade-offs between dams and river conservation
Authors: Thieme M.L. , Tickner D. , Grill G. , Carvallo J.P. , Goichot M. , Hartmann J. , Higgins J. , Lehner B. , Mulligan M. , Nilsson C. , Tockner K. , Zarfl C. , Opperman J.
Published: August 2021

Non-technical summary

There has been a long history of conflicts, studies, and debate over how to both protect rivers and develop them sustainably. With a pause in new developments caused by the global pandemic, anticipated further implementation of the Paris Agreement and high-level global climate and biodiversity meetings in 2021, now is an opportune moment to consider the current trajectory of development and policy options for reconciling dams with freshwater system health.

Technical summary

We calculate potential loss of free-flowing rivers (FFRs) if proposed hydropower projects are built globally. Over 260,000 km of rivers, including Amazon, Congo, Irrawaddy, and Salween mainstem rivers, would lose free-flowing status if all dams were built. We propose a set of tested and proven solutions to navigate trade-offs associated with river conservation and dam development. These solution pathways are framed within the mitigation hierarchy and include (1) avoidance through either formal river protection or through exploration of alternative development options; (2) minimization of impacts through strategic or system-scale planning or re-regulation of downstream flows; (3) restoration of rivers through dam removal; and (4) mitigation of dam impacts through biodiversity offsets that include restoration and protection of FFRs. A series of examples illustrate how avoiding or reducing impacts on rivers is possible – particularly when implemented at a system scale – and can be achieved while maintaining or expanding benefits for climate resilience, water, food, and energy security.

Social media summary

Policy solutions and development pathways exist to navigate trade-offs to meet climate resilience, water, food, and energy security goals while safeguarding FFRs.
Continental‐Scale Geographic Trends in Barometric‐Pumping Efficiency Potential: A North American Case Study
Authors: Avendaño Sofia T. , Harp Dylan R. , Kurwadkar Sudarshan , Ortiz John P. , Stauffer Philip H.
Published: August 2021

Barometric pumping is a gas transport mechanism that has important implications for many applications involving subsurface gas seepage processes. This study provides the first continental‐scale analysis of barometric‐pumping efficiency potential based on meteorology. We quantified the barometric‐pumping efficiency potential at 1,257 locations across the continental US and Canada. The results provide continental‐scale geographic dependencies of barometric‐pumping efficiency potential, indicating a significant correlation with latitude and a nonlinear dependence on longitude. The analysis also indicates that variability in barometric‐pumping efficiency potential decreases with distance from the coast and as elevation increases. Locations far from the coastline are more likely to have upper mid‐range potentials, while higher elevation locations are more likely to have low potentials. The highest barometric‐pumping efficiency potentials are mostly found around the Gulf of St. Lawrence around 50°N. Locations along the Atlantic coast exhibit large‐scale variations in potentials with a clear increasing trend with latitude.
Atmospheric Rivers and Snow Accumulation in the Upper Colorado River Basin
Authors: Xiao Mu , Lettenmaier Dennis P.
Published: August 2021

We utilized a macroscale hydrology model in conjunction with an atmospheric river (AR) catalog to evaluate AR‐affected snow accumulation in the Upper Colorado River basin (UCRB) headwaters for water years 1951–2015. We find that there are on average 11.4 days during which AR‐originating snow accumulates in the UCRB each year, yielding 5.75 km3 of snow water equivalent (SWE). This AR‐originating SWE accounts for 30.8% of average annual peak SWE in the basin. Most of the ARs that reach the UCRB first intercept the Sierra Nevada region of California; 84% of days affected by ARs in the UCRB are also AR‐affected days in the Sierra Nevada. The pathways of the ARs reaching the UCRB do not have a great effect on snow accumulation, however ARs that first pass through the Sierra Nevada generally produce greater snow accumulations there than in the UCRB.
Reinforcement of Secondary Circulation by Aerosol Feedback and PM2.5 Vertical Exchange in the Atmospheric Boundary Layer
Authors: Li Jixiang , Wu Min , Li Yang , Ma Shuxin , Wang Zhanxiang , Zhao Yuan , Lian Lulu , Song Shijie , Huang Tao , Gao Hong , Tao Shu , Liu Junfeng , Mao Xiaoxuan , Ma Jianmin
Published: August 2021

The secondary circulation (SC) plays a vital role in the vertical exchange of meteorological variables and aerosol particles between the atmospheric boundary layer (ABL) and the free atmosphere. We show that, under favorable synoptic‐scale weather conditions aggravating PM2.5 pollution, heavy particle contaminations reduce wind speed in the low ABL via an aerosol feedback mechanism that perturbs the SCs. We examine the aerosol feedback impact on the reinforcement of SCs subject to heavy PM2.5 pollution occurring in Beijing and its surroundings in China. Results reveal that episodic and composite heavy PM2.5 events simulated by the aerosol feedback model runs reduce the ABL wind speeds and enhance the SC. We identify the SC signals by the differences of resultant wind speeds and PM2.5 concentrations between “feedback” and “nonfeedback” simulations under the presence of a hill topographic forcing, which is conducive to the vertical exchange of PM2.5 between the ABL and free atmosphere.
Nonlinear control of photonic higher-order topological bound states in the continuum
Authors: Hu Zhichan , Bongiovanni Domenico , Jukić Dario , Jajtić Ema , Xia Shiqi , Song Daohong , Xu Jingjun , Morandotti Roberto , Buljan Hrvoje , Chen Zhigang
Published: August 2021

Higher-order topological insulators (HOTIs) are recently discovered topological phases, possessing symmetry-protected corner states with fractional charges. An unexpected connection between these states and the seemingly unrelated phenomenon of bound states in the continuum (BICs) was recently unveiled. When nonlinearity is added to the HOTI system, a number of fundamentally important questions arise. For example, how does nonlinearity couple higher-order topological BICs with the rest of the system, including continuum states? In fact, thus far BICs in nonlinear HOTIs have remained unexplored. Here we unveil the interplay of nonlinearity, higher-order topology, and BICs in a photonic platform. We observe topological corner states that are also BICs in a laser-written second-order topological lattice and further demonstrate their nonlinear coupling with edge (but not bulk) modes under the proper action of both self-focusing and defocusing nonlinearities. Theoretically, we calculate the eigenvalue spectrum and analog of the Zak phase in the nonlinear regime, illustrating that a topological BIC can be actively tuned by nonlinearity in such a photonic HOTI. Our studies are applicable to other nonlinear HOTI systems, with promising applications in emerging topology-driven devices.
Gut microbial biomarkers for the treatment response in first-episode, drug-naïve schizophrenia: a 24-week follow-up study
Authors: Yuan Xiuxia , Wang Yunpeng , Li Xue , Jiang Jiajun , Kang Yulin , Pang Lijuan , Zhang Peifen , Li Ang , Lv Luxian , Andreassen Ole A. , Fan Xiaoduo , Hu Shaohua , Song Xueqin
Published: August 2021

Preclinical studies have shown that the gut microbiota can play a role in schizophrenia (SCH) pathogenesis via the gut-brain axis. However, its role in the antipsychotic treatment response is unclear. Here, we present a 24-week follow-up study to identify gut microbial biomarkers for SCH diagnosis and treatment response, using a sample of 107 first-episode, drug-naïve SCH patients, and 107 healthy controls (HCs). We collected biological samples at baseline (all participants) and follow-up time points after risperidone treatment (SCH patients). Treatment response was assessed using the Positive and Negative Symptoms Scale total (PANSS-T) score. False discovery rate was used to correct for multiple testing. We found that SCH patients showed lower α-diversity (the Shannon and Simpson’s indices) compared to HCs at baseline (p = 1.21 × 10−9, 1.23 × 10−8, respectively). We also found a significant difference in β-diversity between SCH patients and HCs (p = 0.001). At baseline, using microbes that showed different abundance between patients and controls as predictors, a prediction model can distinguish patients from HCs with an area under the curve (AUC) of 0.867. In SCH patients, after 24 weeks of risperidone treatment, we observed an increase of α-diversity toward the basal level of HCs. At the genus level, we observed decreased abundance of Lachnoclostridium (p = 0.019) and increased abundance Romboutsia (p = 0.067). Moreover, the treatment response in SCH patients was significantly associated with the basal levels of Lachnoclostridium and Romboutsia (p = 0.005 and 0.006, respectively). Our results suggest that SCH patients may present characteristic microbiota, and certain microbiota biomarkers may predict treatment response in this patient population.
Ferroptosis: the potential value target in atherosclerosis
Authors: Ouyang Siyu , You Jia , Zhi Chenxi , Li Pin , Lin Xiaoyan , Tan Xiaoqian , Ma Wentao , Li Liang , Xie Wei
Published: August 2021

In advanced atherosclerosis (AS), defective function-induced cell death leads to the formation of the characteristic necrotic core and vulnerable plaque. The forms and mechanisms of cell death in AS have recently been elucidated. Among them, ferroptosis, an iron-dependent form of necrosis that is characterized by oxidative damage to phospholipids, promotes AS by accelerating endothelial dysfunction in lipid peroxidation. Moreover, disordered intracellular iron causes damage to macrophages, vascular smooth muscle cells (VSMCs), vascular endothelial cells (VECs), and affects many risk factors or pathologic processes of AS such as disturbances in lipid peroxidation, oxidative stress, inflammation, and dyslipidemia. However, the mechanisms through which ferroptosis initiates the development and progression of AS have not been established. This review explains the possible correlations between AS and ferroptosis, and provides a reliable theoretical basis for future studies on its mechanism.
The Cardamine enshiensis genome reveals whole genome duplication and insight into selenium hyperaccumulation and tolerance
Authors: Huang Chuying , Ying Hongqin , Yang Xibiao , Gao Yuan , Li Tuo , Wu Bo , Ren Meng , Zhang Zixiong , Ding Jun , Gao Jianhua , Wen Dan , Ye Xingzhi , Liu Ling , Wang Huan , Sun Guogen , Zou Yi , Chen Nansheng , Wang Li
Published: August 2021

Cardamine enshiensis is a well-known selenium (Se)-hyperaccumulating plant. Se is an essential trace element associated with many health benefits. Despite its critical importance, genomic information of this species is limited. Here, we report a chromosome-level genome assembly of C. enshiensis, which consists of 443.4 Mb in 16 chromosomes with a scaffold N50 of 24 Mb. To elucidate the mechanism of Se tolerance and hyperaccumulation in C. enshiensis, we generated and analyzed a dataset encompassing genomes, transcriptomes, and metabolomes. The results reveal that flavonoid, glutathione, and lignin biosynthetic pathways may play important roles in protecting C. enshiensis from stress induced by Se. Hi-C analysis of chromatin interaction patterns showed that the chromatin of C. enshiensis is partitioned into A and B compartments, and strong interactions between the two telomeres of each chromosome were correlated with histone modifications, epigenetic markers, DNA methylation, and RNA abundance. Se supplementation could affect the 3D chromatin architecture of C. enshiensis at the compartment level. Genes with compartment changes after Se treatment were involved in selenocompound metabolism, and genes in regions with topologically associated domain insulation participated in cellular responses to Se, Se binding, and flavonoid biosynthesis. This multiomics research provides molecular insight into the mechanism underlying Se tolerance and hyperaccumulation in C. enshiensis.
Integrated single-cell analysis revealed immune dynamics during Ad5-nCoV immunization
Authors: Cao Qiqi , Wu Shipo , Xiao Chuanle , Chen Shuzhen , Chi Xiangyang , Cui Xiuliang , Tang Hao , Su Wenru , Zheng Yingfeng , Zhong Jiayong , Li Zhaomin , Li Fang , Chen Haijia , Hou Lihua , Wang Hongyang , Wen Wen
Published: August 2021

Coronavirus disease 2019 (COVID-19), driven by SARS-CoV-2, is a severe infectious disease that has become a global health threat. Vaccines are among the most effective public health tools for combating COVID-19. Immune status is critical for evaluating the safety and response to the vaccine, however, the evolution of the immune response during immunization remains poorly understood. Single-cell RNA sequencing (scRNA-seq) represents a powerful tool for dissecting multicellular behavior and discovering therapeutic antibodies. Herein, by performing scRNA/V(D)J-seq on peripheral blood mononuclear cells from four COVID-19 vaccine trial participants longitudinally during immunization, we revealed enhanced cellular immunity with concerted and cell type-specific IFN responses as well as boosted humoral immunity with SARS-CoV-2-specific antibodies. Based on the CDR3 sequence and germline enrichment, we were able to identify several potential binding antibodies. We synthesized, expressed and tested 21 clones from the identified lineages. Among them, one monoclonal antibody (P3V6-1) exhibited relatively high affinity with the extracellular domain of Spike protein, which might be a promising therapeutic reagent for COVID-19. Overall, our findings provide insights for assessing vaccine through the novel scRNA/V(D)J-seq approach, which might facilitate the development of more potent, durable and safe prophylactic vaccines.
Principles of seed banks and the emergence of complexity from dormancy
Authors: Lennon Jay T. , den Hollander Frank , Wilke-Berenguer Maite , Blath Jochen
Published: August 2021

Across the tree of life, populations have evolved the capacity to contend with suboptimal conditions by engaging in dormancy, whereby individuals enter a reversible state of reduced metabolic activity. The resulting seed banks are complex, storing information and imparting memory that gives rise to multi-scale structures and networks spanning collections of cells to entire ecosystems. We outline the fundamental attributes and emergent phenomena associated with dormancy and seed banks, with the vision for a unifying and mathematically based framework that can address problems in the life sciences, ranging from global change to cancer biology.
The evolution of hematopoietic cells under cancer therapy
Authors: Pich Oriol , Cortes-Bullich Albert , Muiños Ferran , Pratcorona Marta , Gonzalez-Perez Abel , Lopez-Bigas Nuria
Published: August 2021

Chemotherapies may increase mutagenesis of healthy cells and change the selective pressures in tissues, thus influencing their evolution. However, their contributions to the mutation burden and clonal expansions of healthy somatic tissues are not clear. Here, exploiting the mutational footprint of some chemotherapies, we explore their influence on the evolution of hematopoietic cells. Cells of Acute Myeloid Leukemia (AML) secondary to treatment with platinum-based drugs show the mutational footprint of these drugs, indicating that non-malignant blood cells receive chemotherapy mutations. No trace of the 5-fluorouracil (5FU) mutational signature is found in AMLs secondary to exposure to 5FU, suggesting that cells establishing the leukemia could be quiescent during treatment. Using the platinum-based mutational signature as a barcode, we determine that the clonal expansion originating the secondary AMLs begins after the start of the cytotoxic treatment. Its absence in clonal hematopoiesis cases is consistent with the start of the clonal expansion predating the exposure to platinum-based drugs.
Warm temperature triggers JOX and ST2A-mediated jasmonate catabolism to promote plant growth
Authors: Zhu Tingting , Herrfurth Cornelia , Xin Mingming , Savchenko Tatyana , Feussner Ivo , Goossens Alain , De Smet Ive
Published: August 2021

Plants respond to warm temperature by increased elongation growth of organs to enhance cooling capacity. Phytohormones, such as auxin and brassinosteroids, regulate this growth process. However, our view on the players involved in warm temperature-mediated growth remains fragmentary. Here, we show that warm temperature leads to an increased expression of JOXs and ST2A, genes controlling jasmonate catabolism. This leads to an elevated 12HSO4-JA level and consequently to a reduced level of bioactive jasmonates. Ultimately this results in more JAZ proteins, which facilitates plant growth under warm temperature conditions. Taken together, understanding the conserved role of jasmonate signalling during thermomorphogenesis contributes to ensuring food security under a changing climate.
Biomimetic chameleon soft robot with artificial crypsis and disruptive coloration skin
Authors: Kim Hyeonseok , Choi Joonhwa , Kim Kyun Kyu , Won Phillip , Hong Sukjoon , Ko Seung Hwan
Published: August 2021

Development of an artificial camouflage at a complete device level remains a vastly challenging task, especially under the aim of achieving more advanced and natural camouflage characteristics via high-resolution camouflage patterns. Our strategy is to integrate a thermochromic liquid crystal layer with the vertically stacked, patterned silver nanowire heaters in a multilayer structure to overcome the limitations of the conventional lateral pixelated scheme through the superposition of the heater-induced temperature profiles. At the same time, the weaknesses of thermochromic camouflage schemes are resolved in this study by utilizing the temperature-dependent resistance of the silver nanowire network as the process variable of the active control system. Combined with the active control system and sensing units, the complete device chameleon model successfully retrieves the local background color and matches its surface color instantaneously with natural transition characteristics to be a competent option for a next-generation artificial camouflage.
The developing mouse coronal suture at single-cell resolution
Authors: Farmer D’Juan T. , Mlcochova Hana , Zhou Yan , Koelling Nils , Wang Guanlin , Ashley Neil , Bugacov Helena , Chen Hung-Jhen , Parvez Riana , Tseng Kuo-Chang , Merrill Amy E. , Maxson Robert E. , Wilkie Andrew O. M. , Crump J. Gage , Twigg Stephen R. F.
Published: August 2021

Sutures separate the flat bones of the skull and enable coordinated growth of the brain and overlying cranium. The coronal suture is most commonly fused in monogenic craniosynostosis, yet the unique aspects of its development remain incompletely understood. To uncover the cellular diversity within the murine embryonic coronal suture, we generated single-cell transcriptomes and performed extensive expression validation. We find distinct pre-osteoblast signatures between the bone fronts and periosteum, a ligament-like population above the suture that persists into adulthood, and a chondrogenic-like population in the dura mater underlying the suture. Lineage tracing reveals an embryonic Six2+ osteoprogenitor population that contributes to the postnatal suture mesenchyme, with these progenitors being preferentially affected in a Twist1+/−; Tcf12+/− mouse model of Saethre-Chotzen Syndrome. This single-cell atlas provides a resource for understanding the development of the coronal suture and the mechanisms for its loss in craniosynostosis.
Seismicity at the Castor gas reservoir driven by pore pressure diffusion and asperities loading
Authors: Cesca Simone , Stich Daniel , Grigoli Francesco , Vuan Alessandro , López-Comino José Ángel , Niemz Peter , Blanch Estefanía , Dahm Torsten , Ellsworth William L.
Published: August 2021

The 2013 seismic sequence at the Castor injection platform offshore Spain, including three earthquakes of magnitude 4.1, occurred during the initial filling of a planned Underground Gas Storage facility. The Castor sequence is one of the most important cases of induced seismicity in Europe and a rare example of seismicity induced by gas injection into a depleted oil field. Here we use advanced seismological techniques applied to an enhanced waveform dataset, to resolve the geometry of the faults, develop a greatly enlarged seismicity catalog and record details of the rupture kinematics. The sequence occurred by progressive fault failure and unlocking, with seismicity initially migrating away from the injection points, triggered by pore pressure diffusion, and then back again, breaking larger asperities loaded to higher stress and producing the largest earthquakes. Seismicity occurred almost exclusively on a secondary fault, located below the reservoir, dipping opposite from the reservoir bounding fault.
CRISPR/Cas9-engineered inducible gametocyte producer lines as a valuable tool for Plasmodium falciparum malaria transmission research
Authors: Boltryk Sylwia D. , Passecker Armin , Alder Arne , Carrington Eilidh , van de Vegte-Bolmer Marga , van Gemert Geert-Jan , van der Starre Alex , Beck Hans-Peter , Sauerwein Robert W. , Kooij Taco W. A. , Brancucci Nicolas M. B. , Proellochs Nicholas I. , Gilberger Tim-Wolf , Voss Till S.
Published: August 2021

The malaria parasite Plasmodium falciparum replicates inside erythrocytes in the blood of infected humans. During each replication cycle, a small proportion of parasites commits to sexual development and differentiates into gametocytes, which are essential for parasite transmission via the mosquito vector. Detailed molecular investigation of gametocyte biology and transmission has been hampered by difficulties in generating large numbers of these highly specialised cells. Here, we engineer P. falciparum NF54 inducible gametocyte producer (iGP) lines for the routine mass production of synchronous gametocytes via conditional overexpression of the sexual commitment factor GDV1. NF54/iGP lines consistently achieve sexual commitment rates of 75% and produce viable gametocytes that are transmissible by mosquitoes. We also demonstrate that further genetic engineering of NF54/iGP parasites is a valuable tool for the targeted exploration of gametocyte biology. In summary, we believe the iGP approach developed here will greatly expedite basic and applied malaria transmission stage research.
Sondheimer oscillations as a probe of non-ohmic flow in WP2 crystals
Authors: van Delft Maarten R. , Wang Yaxian , Putzke Carsten , Oswald Jacopo , Varnavides Georgios , Garcia Christina A. C. , Guo Chunyu , Schmid Heinz , Süss Vicky , Borrmann Horst , Diaz Jonas , Sun Yan , Felser Claudia , Gotsmann Bernd , Narang Prineha , Moll Philip J. W.
Published: August 2021

As conductors in electronic applications shrink, microscopic conduction processes lead to strong deviations from Ohm’s law. Depending on the length scales of momentum conserving (lMC) and relaxing (lMR) electron scattering, and the device size (d), current flows may shift from ohmic to ballistic to hydrodynamic regimes. So far, an in situ methodology to obtain these parameters within a micro/nanodevice is critically lacking. In this context, we exploit Sondheimer oscillations, semi-classical magnetoresistance oscillations due to helical electronic motion, as a method to obtain lMR even when lMR ≫ d. We extract lMR from the Sondheimer amplitude in WP2, at temperatures up to T ~ 40 K, a range most relevant for hydrodynamic transport phenomena. Our data on μm-sized devices are in excellent agreement with experimental reports of the bulk lMR and confirm that WP2 can be microfabricated without degradation. These results conclusively establish Sondheimer oscillations as a quantitative probe of lMR in micro-devices.
A microRNA panel compared to environmental and polygenic scores for colorectal cancer risk prediction
Authors: Raut Janhavi R. , Schöttker Ben , Holleczek Bernd , Guo Feng , Bhardwaj Megha , Miah Kaya , Schrotz-King Petra , Brenner Hermann
Published: August 2021

Circulating microRNAs (miRNAs) could improve colorectal cancer (CRC) risk prediction. Here, we derive a blood-based miRNA panel and evaluate its ability to predict CRC occurrence in a population-based cohort of adults aged 50–75 years. Forty-one miRNAs are preselected from independent studies and measured by quantitative-real-time-polymerase-chain-reaction in serum collected at baseline of 198 participants who develop CRC during 14 years of follow-up and 178 randomly selected controls. A 7-miRNA score is derived by logistic regression. Its predictive ability, quantified by the optimism-corrected area-under-the-receiver-operating-characteristic-curve (AUC) using .632+ bootstrap is 0.794. Predictive ability is compared to that of an environmental risk score (ERS) based on known risk factors and a polygenic risk score (PRS) based on 140 previously identified single-nucleotide-polymorphisms. In participants with all scores available, optimism-corrected-AUC is 0.802 for the 7-miRNA score, while AUC (95% CI) is 0.557 (0.498–0.616) for the ERS and 0.622 (0.564–0.681) for the PRS.
Real space electron delocalization, resonance, and aromaticity in chemistry
Authors: Reuter Leonard , Lüchow Arne
Published: August 2021

Chemists explaining a molecule’s stability and reactivity often refer to the concepts of delocalization, resonance, and aromaticity. Resonance is commonly discussed within valence bond theory as the stabilizing effect of mixing different Lewis structures. Yet, most computational chemists work with delocalized molecular orbitals, which are also usually employed to explain the concept of aromaticity, a ring delocalization in cyclic planar systems which abide certain number rules. However, all three concepts lack a real space definition, that is not reliant on orbitals or specific wave function expansions. Here, we outline a redefinition from first principles: delocalization means that likely electron arrangements are connected via paths of high probability density in the many-electron real space. In this picture, resonance is the consideration of additional electron arrangements, which offer alternative paths. Most notably, the famous 4n + 2 Hückel rule is generalized and derived from nothing but the antisymmetry of fermionic wave functions.
Abrupt hippocampal remapping signals resolution of memory interference
Authors: Wanjia Guo , Favila Serra E. , Kim Ghootae , Molitor Robert J. , Kuhl Brice A.
Published: August 2021

Remapping refers to a decorrelation of hippocampal representations of similar spatial environments. While it has been speculated that remapping may contribute to the resolution of episodic memory interference in humans, direct evidence is surprisingly limited. We tested this idea using high-resolution, pattern-based fMRI analyses. Here we show that activity patterns in human CA3/dentate gyrus exhibit an abrupt, temporally-specific decorrelation of highly similar memory representations that is precisely coupled with behavioral expressions of successful learning. The magnitude of this learning-related decorrelation was predicted by the amount of pattern overlap during initial stages of learning, with greater initial overlap leading to stronger decorrelation. Finally, we show that remapped activity patterns carry relatively more information about learned episodic associations compared to competing associations, further validating the learning-related significance of remapping. Collectively, these findings establish a critical link between hippocampal remapping and episodic memory interference and provide insight into why remapping occurs.
Graded bulk-heterojunction enables 17% binary organic solar cells via nonhalogenated open air coating
Authors: Zhang Ying , Liu Kuan , Huang Jiaming , Xia Xinxin , Cao Jiupeng , Zhao Guangming , Fong Patrick W. K. , Zhu Ye , Yan Feng , Yang Yang , Lu Xinhui , Li Gang
Published: August 2021

Graded bulk-heterojunction (G-BHJ) with well-defined vertical phase separation has potential to surpass classical BHJ in organic solar cells (OSCs). In this work, an effective G-BHJ strategy via nonhalogenated solvent sequential deposition is demonstrated using nonfullerene acceptor (NFA) OSCs. Spin-coated G-BHJ OSCs deliver an outstanding 17.48% power conversion efficiency (PCE). Depth-profiling X-ray photoelectron spectroscopy (DP-XPS) and angle-dependent grazing incidence X-ray diffraction (GI-XRD) techniques enable the visualization of polymer/NFA composition and crystallinity gradient distributions, which benefit charge transport, and enable outstanding thick OSC PCEs (16.25% for 300 nm, 14.37% for 500 nm), which are among the highest reported. Moreover, the nonhalogenated solvent enabled G-BHJ OSC via open-air blade coating and achieved a record 16.77% PCE. The blade-coated G-BHJ has drastically different D-A crystallization kinetics, which suppresses the excessive aggregation induced unfavorable phase separation in BHJ. All these make G-BHJ a feasible and promising strategy towards highly efficient, eco- and manufacture friendly OSCs.
Evidence for ligand- and solvent-induced disproportionation of uranium(IV)
Authors: Du Jingzhen , Douair Iskander , Lu Erli , Seed John A. , Tuna Floriana , Wooles Ashley J. , Maron Laurent , Liddle Stephen T.
Published: August 2021

Disproportionation, where a chemical element converts its oxidation state to two different ones, one higher and one lower, underpins the fundamental chemistry of metal ions. The overwhelming majority of uranium disproportionations involve uranium(III) and (V), with a singular example of uranium(IV) to uranium(V/III) disproportionation known, involving a nitride to imido/triflate transformation. Here, we report a conceptually opposite disproportionation of uranium(IV)-imido complexes to uranium(V)-nitride/uranium(III)-amide mixtures. This is facilitated by benzene, but not toluene, since benzene engages in a redox reaction with the uranium(III)-amide product to give uranium(IV)-amide and reduced arene. These disproportionations occur with potassium, rubidium, and cesium counter cations, but not lithium or sodium, reflecting the stability of the corresponding alkali metal-arene by-products. This reveals an exceptional level of ligand- and solvent-control over a key thermodynamic property of uranium, and is complementary to isolobal uranium(V)-oxo disproportionations, suggesting a potentially wider prevalence possibly with broad implications for the chemistry of uranium.
NEK1-mediated retromer trafficking promotes blood–brain barrier integrity by regulating glucose metabolism and RIPK1 activation
Authors: Wang Huibing , Qi Weiwei , Zou Chengyu , Xie Zhangdan , Zhang Mengmeng , Naito Masanori Gomi , Mifflin Lauren , Liu Zhen , Najafov Ayaz , Pan Heling , Shan Bing , Li Ying , Zhu Zheng-Jiang , Yuan Junying
Published: August 2021

Loss-of-function mutations in NEK1 gene, which encodes a serine/threonine kinase, are involved in human developmental disorders and ALS. Here we show that NEK1 regulates retromer-mediated endosomal trafficking by phosphorylating VPS26B. NEK1 deficiency disrupts endosomal trafficking of plasma membrane proteins and cerebral proteome homeostasis to promote mitochondrial and lysosomal dysfunction and aggregation of α-synuclein. The metabolic and proteomic defects of NEK1 deficiency disrupts the integrity of blood–brain barrier (BBB) by promoting lysosomal degradation of A20, a key modulator of RIPK1, thus sensitizing cerebrovascular endothelial cells to RIPK1-dependent apoptosis and necroptosis. Genetic inactivation of RIPK1 or metabolic rescue with ketogenic diet can prevent postnatal lethality and BBB damage in NEK1 deficient mice. Inhibition of RIPK1 reduces neuroinflammation and aggregation of α-synuclein in the brains of NEK1 deficient mice. Our study identifies a molecular mechanism by which retromer trafficking and metabolism regulates cerebrovascular integrity, cerebral proteome homeostasis and RIPK1-mediated neuroinflammation.