bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-Small Cell Lung Cancer Epigenomes Exhibit Altered DNA Methylation in Smokers and Never-Smokers
Authors: Karlow Jennifer A. , Pehrsson Erica C. , Xing Xiaoyun , Watson Mark , Devarakonda Siddhartha , Govindan Ramaswamy , Wang Ting
Published: September 2023

Epigenetic alterations are widespread in cancer and can complement genetic alterations to influence cancer progression and treatment outcome. To determine the potential contribution of DNA  methylation alterations to tumor phenotype in non-small cell lung cancer (NSCLC) in both smoker and never-smoker patients, we performed genome-wide profiling of DNA methylation in 17 primary NSCLC tumors and 10 matched normal lung samples using the complementary assays, methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation sensitive restriction enzyme sequencing (MRE-seq). We reported recurrent methylation changes in the promoters of several genes, many previously implicated in cancer, including FAM83A and SEPT9 (hypomethylation), as well as PCDH7, NKX2-1, and SOX17 (hypermethylation). Although many methylation changes between tumors and their paired normal samples were shared across patients, several were specific to a particular smoking status. For example, never-smokers displayed a greater proportion of hypomethylated differentially methylated regions (hypoDMRs) and a greater number of recurrently hypomethylated promoters, including those of ASPSCR1, TOP2A, DPP9, and USP39, all previously linked to cancer. Changes outside of promoters were also widespread and often recurrent, particularly methylation loss over repetitive elements, highly enriched for ERV1 subfamilies. Recurrent hypoDMRs were enriched for several transcription factor binding motifs, often for genes involved in signaling and cell proliferation. For example, 71% of recurrent promoter hypoDMRs contained a motif for NKX2-1. Finally, the majority of DMRs were located within an active chromatin state in tissues profiled using the Roadmap Epigenomics data, suggesting that methylation changes may contribute to altered regulatory programs through the adaptation of cell type-specific expression programs.
The Oklahoma Public Archaeology Network (OKPAN)
Authors: Pitblado Bonnie L. , Cooley Delaney , Deere Bobi , Dudley Meghan , McLeod Allison , Moore Kaylyn , Palacios Horvey
Published: September 2023

As the venues for professional training and education, universities have always shaped the future of the archaeological discipline—for better but also, in important ways, for worse. Historically, university structures promoted practitioner homogeneity and social inequity and, at the largest research-intensive universities, even managed to turn “service” into a dirty word. However, using the same structures that perpetuated damaging practices in the past, universities can just as readily transform archaeology into the inclusive, community-engaged discipline it should always have been—while serving communities in ways that matter to them. This article explains and illustrates how and why we have tried to do this through the founding and operation of the Oklahoma Public Archaeology Network (OKPAN) at the University of Oklahoma. OKPAN seeks to improve relationships among diverse Oklahoma communities by framing archaeology as a tool that that can serve communities’ interests while creating pathways within universities for members of historically excluded groups to join and help further transform the discipline.
Normative Inference Tickets
Authors: Foster Jen , Ichikawa Jonathan
Published: September 2023

We argue that stereotypes associated with concepts likehe-said–she-said,conspiracy theory,sexual harassment, and those expressed by paradigmatic slurs provide “normative inference tickets”: conceptual permissions to automatic, largely unreflective normative conclusions. These “mental shortcuts” are underwritten by associated stereotypes. Because stereotypes admit of exceptions, normative inference tickets are highly flexible and productive, but also liable to create serious epistemic and moral harms. Epistemically, many are unreliable, yielding false beliefs which resist counterexample; morally, many perpetuate bigotry and oppression. Still, some normative inference tickets, like some activated bysexual harassment, constitute genuine moral and hermeneutical advances. For example, our framework helps explain Miranda Fricker's notion of “hermeneutical lacunae”: what early victims of “sexual harassment” – as well as their harassers – lacked before the term was coined was a communal normative inference ticket – one that could take us, collectively, from “this is happening” to “this is wrong.”
Management and publication of scientific data on traditional mycological and lichenological knowledge in Africa
Authors: Kinge Tonjock Rosemary , Jefwa Joyce Mnyazi , Houdanon Roël D. , Kamalebo Héritier Milenge , Abdel-Azeem Ahmed M. , Gryzenhout Marieka , Triebel Dagmar , Weibulat Tanja , Rambold Gerhard
Published: September 2023

Africa is an important global reservoir for biological, cultural and traditional knowledge about fungi and lichens, which are used as food, medicine and in mythology, among other things. African human populations are undergoing highly significant changes and adaptation processes, which are accompanied by rapid urbanization, meeting with western civilization, high rural migration and the loss of natural ecosystems. Indigenous knowledge is being lost, including that concerning fungi and lichens. Ethnomycology and ethnolichenology provide a diversity of knowledge about beneficial and poisonous fungi and lichens, and give insights into their sociological impact on human behaviour and use. Here we present a working and publishing environment established with the Diversity Workbench software in line with national and international initiatives for FAIR guided provision of research data. The database application called ‘EthnoMycAfrica’ contains published ethnomycological and ethnolichenological information from Africa. The content is created and curated by team partners from Central, East, West, North and Southern Africa. Data entry is performed both online and offline, optionally via a mobile device. Currently, the system with the tools DiversityDescriptions and DiversityNaviKey contains a total of 1350 well-structured and freely and openly accessible data records. EthnoMycAfrica is the first database with a data schema, standard descriptors and data content created mainly by African scholars. The data can be useful for researchers, students, conservationists, policy makers, and others. It will also provide a basis for facilitating hypothesis generation and meta-analysis.
The importance of a transformative biodiversity education for perceiving, appreciating and supporting lichen diversity in German urban environments
Authors: Zedda Luciana
Published: September 2023

Urban green spaces are indispensable for the conservation of biodiversity in Germany. In addition, the availability of green areas often provides citizens with the only opportunity to experience nature. Lichens are an important component of urban environments in terms of both species diversity, and ecosystem functions and services. However, they are rarely the subject of biodiversity education. To bolster awareness on their diversity and appreciation, a transformative biodiversity education in both the formal and informal sectors is necessary. This transformative biodiversity education should not only provide knowledge about species and habitats, but also on all dimensions of biodiversity, viz., the three levels of biodiversity, drivers of biodiversity loss, and ecosystem services. For this reason, the design of biodiversity education may be particularly challenging for educators and teachers. This paper shows how biodiversity education projects on urban lichens can be developed in accordance with the principles of transformative education, supporting nature experience, knowledge transfer (species knowledge in a broad sense and interdisciplinary aspects), participation and cooperation, as well as the use of digital media. Two best-case projects, tested in Germany, are presented as examples for the design and implementation of a transformative lichen education in urban areas. A similar approach can be easily applied in other education systems beyond national boundaries.
High diversity of Bacidia (Ramalinaceae, Lecanorales) species in the Caucasus as revealed by molecular and morphological analyses
Authors: Gerasimova Julia V. , Otte Volker , Urbanavichene Irina N. , Urbanavichus Gennadii P. , Beck Andreas
Published: September 2023

During a study of the incompletely known lichen flora of the Caucasus, we analyzed 237 specimens of corticolous Bacidia s. str. collected in the Northern and Southern Caucasus, including Armenia, Azerbaijan, Georgia, and Russia. Of these, 54 specimens belonging to 11 species of Bacidia s. str. were selected for molecular studies, representing the observed morphological variability of the genus. We obtained 142 sequences from three RNA-coding genes (nrITS, nrLSU, and mtSSU) and two protein-coding genes (RPB1 and RPB2). The single and concatenated datasets were complemented with Bacidia s. str. sequences from GenBank and subjected to Bayesian inference and two maximum likelihood analyses (RAxML and IQ-TREE). The resulting trees yielded highly concordant topologies of the groups and corresponded with previous results, supporting two main clades correlating with apothecia pigmentation. Our analyses are the first to reveal the presence of Bacidia heterochroa in the Caucasus. An exceptionally high degree of morphological plasticity was found in the Rubella and Suffusa groups. As a result of morphological examination and phylogenetic results, B. caucasica (Suffusa group) was described as new to science. Furthermore, two putative taxa in the Rubella group, Bacidia inconspicua ined. and B. maritima ined., were introduced. This study furthers our understanding and documentation of the understudied lichen flora of the Caucasus, bringing the total number of Bacidia species for the region to 13.
Pier Luigi Nimis: a life for lichens
Authors: Tretiach Mauro
Published: September 2023

There are people who leave their mark in their field. Without doubt, Pier Luigi Nimis (for the registry office, Pierluigi; for friends, Pier; for family members, Pil; for me and a few colleagues, PL) is such a person. On the threshold of retirement but no less active than ever, Pier Luigi is about to begin a new phase of his life, a life dedicated entirely to science and, in particular, to lichenology.
Pertussis outbreak mainly in unvaccinated young children in ultra-orthodox Jewish groups, Jerusalem, Israel 2023
Authors: Stein-Zamir Chen , Shoob Hanna , Abramson Nitza , Brown Emilie Hannah , Zimmermann Yael
Published: September 2023

Despite being a vaccine-preventable disease for decades, pertussis control is still a public health challenge. A pertussis outbreak emerged in Jerusalem (n = 257 cases, January to June 2023). Most cases were young children (median age 1.5 years), and 100 were infants under 1 year. The hospitalisation rate of infants was 24%, which was considerably higher than that of cases aged 1 year and above (3.8%). There was one fatality in an unvaccinated, 10-week-old infant whose mother had not received pertussis vaccination during pregnancy. Most children were unvaccinated and resided in Jewish ultra-orthodox neighbourhoods in Jerusalem district. An intervention programme and vaccination campaign are ongoing.
What’s in the mind’s eye of individuals with bipolar disorders: an exploration of the content and characteristics of mental images in different thymic phases
Authors: M’Bailara K. , Echegaray F. , Di Simplicio M.
Published: September 2023

Background:

Mental imagery, or ‘seeing with the mind’s eye’ (Kosslyn et al. 2001), provokes strong emotional responses (Ji et al., 2016). To date, there is a lack of data on the content and clinical characteristics (e.g. vividness, likelihood, emotional effects) of spontaneous mental images (MI) in people with bipolar disorder (BD) according to their thymic states.

Aim:

The current study sought to assess the characteristics associated with the contents of MI in people with BD.

Method:

Forty-two euthymic individuals diagnosed with BD (American Psychiatric Association, 2013) were asked to self-report their MI during depression, (hypo)mania and euthymia. Participants also rated levels of vividness, likelihood and emotional activation related to MI (i.e. valence, arousal, type of emotion).

Results:

The contents of the MI revealed phenomenological aspects of BD. Different themes were associated with each thymic phase. In (hypo)mania and in euthymia, the mental images were assessed as being as vivid as probable (p>.05). (Hypo)manic and euthymic-related MI activated more pleasure than displeasure (p<.001) and were mainly associated with joy. In depression, MI were assessed as more vivid than likely (p<.05). In depression, MI activated more displeasure than pleasure (p<.0001) and induced mainly sadness.

Discussion:

Overall, a congruence between the contents of images and the three thymic phases was found. The content of the MI was related to self-reported emotional effects that were congruent with the thymic phases concerned. The results add new clinical information for the use of imagery-based cognitive therapy in individuals with BD.
Psychometric properties of the Interpersonal Emotion Regulation Questionnaire in a community sample of the Portuguese population
Authors: Faustino Bruno , Pascoal Patricia M.
Published: September 2023

Background:

Intrapersonal aspects of emotion regulation have been at the forefront of research, while interpersonal aspects have received less attention. The Interpersonal Emotion Regulation Questionnaire (IERQ) was developed to address this issue. However, this scale was neither adapted nor validated for European Portuguese.

Aims:

The present study aims to adapt the IERQ to European Portuguese and explore the preliminary psychometric properties of the IERQ in a community sample, through confirmatory factor analysis (CFA). Construct validity was further supported by examining convergent validity with ERQ subscales.

Method:

Using a cross-sectional design, individuals were recruited online. Self-report questionnaires were used, namely the IERQ and the Emotion Regulation Questionnaire (ERQ).

Results:

The four-factor structure was confirmed through CFA. IERQ subscales correlated positively with the dimensions of the ERQ of cognitive reappraisal and correlated negatively with experiential suppression.

Conclusions:

This preliminary study showed that the IERQ has adequate psychometric properties in a Portuguese sample and supports that this instrument can be used to assess interpersonal emotion regulation strategies in non-clinical samples.
Auswirkungen der Corona-Pandemie
Authors: Häfner Angelika , Witzmann Markus
Published: September 2023

Was ist zu diesem Thema bereits bekannt?

Studien und Veröffentlichungen des Robert-Koch-Instituts (RKI) (2021) zum Thema „Psychische Gesundheit der erwachsenen Bevölkerung in Deutschland während der COVID-19-Pandemie“ zeigen eine wesentliche Verschlechterung psychischer Gesundheit in der Allgemeinbevölkerung auf.

Wie beurteilen wir Public-Health-Maßnahmen, wie Kontakteinschränkungen und welche Perspektiven sind relevant?

Das Begründungsmodell nach Strech und Marckmann (2010) bietet Kriterien zur ethischen Reflexion von Public-Health-Maßnahmen.

Welche Auswirkungen zeigen sich in der Praxis?

Kontakteinschränkende Maßnahmen haben vielfältige negative Auswirkungen auf bereits psychisch erkrankte Menschen und beeinflussen den Erhalt und die Förderung eines selbstbestimmten Lebens sowie die Teilhabe der psychisch erkrankten Personen.
Overlooked Long‐Term Atmospheric Chemical Feedbacks Alter the Impact of Solar Geoengineering: Implications for Tropospheric Oxidative Capacity
Authors: Moch Jonathan M. , Mickley Loretta J. , Eastham Sebastian D. , Lundgren Elizabeth W. , Shah Viral , Buonocore Jonathan J. , Pang Jacky Y. S. , Sadiq Mehliyar , Tai Amos P. K.
Published: September 2023

Studies of the impacts of solar geoengineering have mostly ignored tropospheric chemistry. By decreasing the sunlight reaching Earth's surface, geoengineering may help mitigate anthropogenic climate change, but changing sunlight also alters the rates of chemical reactions throughout the troposphere. Using the GEOS‐Chem atmospheric chemistry model, we show that stratospheric aerosol injection (SAI) with sulfate, a frequently studied solar geoengineering method, can perturb tropospheric composition over a span of 10 years, increasing tropospheric oxidative capacity by 9% and reducing methane lifetime. SAI decreases the overall flux of shortwave radiation into the troposphere, but increases flux at certain UV wavelengths due to stratospheric ozone depletion. These radiative changes, in turn, perturb tropospheric photochemistry, driving chemical feedbacks that can substantially influence the seasonal and spatial patterns of radiative forcing beyond what is caused by enhanced stratospheric aerosol concentrations alone. For example, chemical feedbacks decrease the radiative effectiveness of geoengineering in northern high latitude summer by 20%. Atmospheric chemical feedbacks also imply the potential for net global public health benefits associated with stratospheric ozone depletion, as the decreases in mortality resulting from SAI‐induced improvements in air quality outweigh the increases in mortality due to increased UV radiation exposure. Such chemical feedbacks also lead to improved plant growth. Our results show the importance of including fuller representations of atmospheric chemistry in studies of solar geoengineering and underscore the risk of surprises from this technology that could carry unexpected consequences for Earth's climate, the biosphere, and human health.
Exploring the Mantle Through Microseisms
Authors: Owen Rebecca
Published: September 2023

A new method for examining the tiny vibrations of Earth caused by ocean swells could help reveal details of deep-Earth structure.
Formation of Banded Chorus Waves by Propagation From Multiple Sources
Authors: Tao Xin
Published: September 2023

Chorus waves are electromagnetic emissions in the magnetosphere and play a crucial role in energetic electron dynamics. Observations show that these waves often exhibit a two‐band structure with a power gap near half the electron cyclotron frequency. However, the mechanism behind this gap remains an open question, despite the existence of multiple theories. Here we propose a model to explain the banded structure by the different propagation properties of the lower and upper band waves within a density crest. This requires independent sources for lower and upper band waves, and unducted propagation of upper band waves to the observing location. The model naturally generates a gap near half the electron cyclotron frequency and can be extended to explain lower‐band‐only, upper‐band‐only, and no‐gap whistler waves. The model calls for further research on density irregularities in the magnetosphere and their effects on shaping wave properties.
Hemispheric Asymmetries in Thermospheric Composition and Temperature: GOLD Observations
Authors: Wang Zihan , Zou Shasha , Cai Xuguang
Published: September 2023

With the launch of the Global‐scale Observations of the Limb and Disk (GOLD) mission, spatial variations of the thermospheric composition (ΣO/N2) and temperature can be investigated. In this work, we defined the hemispheric asymmetry indexes of thermospheric composition and temperature and investigated their local time (LT), latitude, and seasonal variations. For the first time, it is found that the hemispheric asymmetry of the thermosphere is weaker toward the duskside statistically. In addition, the hemispheric asymmetry of the thermosphere is found to be weaker toward lower latitudes, and the northern hemisphere has a longer duration with lower ΣO/N2 and higher temperature.
Seismological Indicators of Geologically Inferred Fault Maturity
Authors: Guo Huiyun , Lay Thorne , Brodsky Emily E.
Published: September 2023

Variations in fault zone maturity have intermittently been invoked to explain variations in some seismological observations for large earthquakes. However, the lack of a unified geological definition of fault maturity makes quantitative assessment of its importance difficult. We evaluate the degree of empirical correlation between geological and geometric measurements commonly invoked as indicative of fault zone maturity and remotely measured seismological source parameters of 34MW ≥ 6.0 shallow strike‐slip events. Metrics based on surface rupture segmentation, such as number of segments and surface rupture azimuth changes, correlate best with seismic source attributes while the correlations with cumulative fault slip are weaker. Average rupture velocity shows the strongest correlation with metrics of maturity, followed by relative aftershock productivity. Mature faults have relatively lower aftershock productivity and higher rupture velocity. A more complex relation is found with moment‐scaled radiated energy. There appears to be distinct behavior of very immature events which radiate modest seismic energy, while intermediate mature faults have events with higher moment‐scaled radiated energy and very mature faults with increasing cumulative slip tend to have events with reduced moment‐scaled radiated energy. These empirical comparisons establish that there are relationships between remote seismological observations and fault system maturity that can help to understand variations in seismic hazard among different fault environments and to assess the relative maturity of inaccessible or blind fault systems for which direct observations of maturity are very limited.
GRIN2A (NR2A): a gene contributing to glutamatergic involvement in schizophrenia
Authors: Harrison Paul J. , Bannerman David M.
Published: September 2023

Involvement of the glutamate system, particularly N-methyl-D-aspartate (NMDA) receptor hypofunction, has long been postulated to be part of the pathophysiology of schizophrenia. An important development is provided by recent data that strongly implicate GRIN2A, the gene encoding the NR2A (GluN2A) NMDA receptor subunit, in the aetiology of the disorder. Rare variants and common variants are both robustly associated with genetic risk for schizophrenia. Some of the rare variants are point mutations likely affecting channel function, but most are predicted to cause protein truncation and thence result, like the common variants, in reduced gene expression. We review the genomic evidence, and the findings from Grin2a mutant mice and other models which give clues as to the likely phenotypic impacts of GRIN2A genetic variation. We suggest that one consequence of NR2A dysfunction is impairment in a form of hippocampal synaptic plasticity, producing deficits in short-term habituation and thence elevated and dysregulated levels of attention, a phenotype of relevance to schizophrenia and its cognitive aspects.
Two-tiered mutualism improves survival and competitiveness of cross-feeding soil bacteria
Authors: Ge Zhan-Biao , Zhai Zhi-Qiang , Xie Wan-Ying , Dai Jun , Huang Ke , Johnson David R , Zhao Fang-Jie , Wang Peng
Published: September 2023

Metabolic cross-feeding is a pervasive microbial interaction type that affects community stability and functioning and directs carbon and energy flows. The mechanisms that underlie these interactions and their association with metal/metalloid biogeochemistry, however, remain poorly understood. Here, we identified two soil bacteria, Bacillus sp. BP-3 and Delftia sp. DT-2, that engage in a two-tiered mutualism. Strain BP-3 has low utilization ability of pyruvic acid while strain DT-2 lacks hexokinase, lacks a phosphotransferase system, and is defective in glucose utilization. When strain BP-3 is grown in isolation with glucose, it releases pyruvic acid to the environment resulting in acidification and eventual self-killing. However, when strain BP-3 is grown together with strain DT-2, strain DT-2 utilizes the released pyruvic acid to meet its energy requirements, consequently rescuing strain BP-3 from pyruvic acid-induced growth inhibition. The two bacteria further enhance their collective competitiveness against other microbes by using arsenic as a weapon. Strain DT-2 reduces relatively non-toxic methylarsenate [MAs(V)] to highly toxic methylarsenite [MAs(III)], which kills or suppresses competitors, while strain BP-3 detoxifies MAs(III) by methylation to non-toxic dimethylarsenate [DMAs(V)]. These two arsenic transformations are enhanced when strains DT-2 and BP-3 are grown together. The two strains, along with their close relatives, widely co-occur in soils and their abundances increase with the soil arsenic concentration. Our results reveal that these bacterial types employ a two-tiered mutualism to ensure their collective metabolic activity and maintain their ecological competitive against other soil microbes. These findings shed light on the intricateness of bacterial interactions and their roles in ecosystem functioning.
Mitochondrial IRG1 traps MCL-1 to induce hepatocyte apoptosis and promote carcinogenesis
Authors: Zhang Liyuan , Dong Yue , Zhang Luxin , Wang Minjun , Zhou Ye , Jia Kaiwei , Wang Suyuan , Wang Mu , Li Yunhui , Luo Shudan , Lu Shan , Fan Yiwen , Zhang Dingji , Yang Yingyun , Li Nan , Yu Yizhi , Cao Xuetao , Hou Jin
Published: September 2023

Hepatocarcinogenesis is initiated by repeated hepatocyte death and liver damage, and the underlying mechanisms mediating cell death and the subsequent carcinogenesis remain to be fully investigated. Immunoresponsive gene 1 (IRG1) and its enzymatic metabolite itaconate are known to suppress inflammation in myeloid cells, and its expression in liver parenchymal hepatocytes is currently determined. However, the potential roles of IRG1 in hepatocarcinogenesis are still unknown. Here, using the diethylnitrosamine (DEN)-induced hepatocarcinogenesis mouse model, we found that IRG1 expression in hepatocytes was markedly induced upon DEN administration. The DEN-induced IRG1 was then determined to promote the intrinsic mitochondrial apoptosis of hepatocytes and liver damage, thus enhancing the subsequent hepatocarcinogenesis. Mechanistically, the mitochondrial IRG1 could associate and trap anti-apoptotic MCL-1 to inhibit the interaction between MCL-1 and pro-apoptotic Bim, thus promoting Bim activation and downstream Bax mitochondrial translocation, and then releasing cytochrome c and initiating apoptosis. Thus, the inducible mitochondrial IRG1 promotes hepatocyte apoptosis and the following hepatocarcinogenesis, which provides mechanistic insight and a potential target for preventing liver injury and HCC.
Erectile device insertion following phalloplasty in transgender and non-binary individuals assigned female at birth: a narrative review
Authors: Chiriaco Giovanni , Looney Aisling , Christopher Andrew Nim , Ralph David , Lee Wai Gin
Published: September 2023

Genital gender affirmation surgery (gGAS) for individuals assigned female at birth (AFAB) is complex and requires the staged insertion of an erectile device to permit penetrative intercourse. This final stage of gGAS is challenging, owing to the variable anatomy and lack of supportive structures within the neophallus when compared with erectile device insertion for individuals assigned male at birth. There is a paucity in the literature at present regarding erectile device insertion in trans-sex AFAB patients. Hence, a narrative review following a literature review and supplemented by expert opinion from a high-volume centre of expertise is presented. The choices available for erectile device in this patient cohort are discussed. Principle surgical steps required for this complex surgery is outlined along with the recommended postoperative management of the patient. Postoperative outcomes and complications are also summarised in this fast-developing surgical procedure.
Strong structuring arising from weak cooperative O-H···π and C-H···O hydrogen bonding in benzene-methanol solution
Authors: Di Mino Camilla , Seel Andrew G. , Clancy Adam J. , Headen Thomas F. , Földes Támas , Rosta Edina , Sella Andrea , Skipper Neal T.
Published: September 2023

Weak hydrogen bonds, such as O-H···π and C-H···O, are thought to direct biochemical assembly, molecular recognition, and chemical selectivity but are seldom observed in solution. We have used neutron diffraction combined with H/D isotopic substitution to obtain a detailed spatial and orientational picture of the structure of benzene-methanol mixtures. Our analysis reveals that methanol fully solvates and surrounds each benzene molecule. The expected O-H···π interaction is highly localised and directional, with the methanol hydroxyl bond aligned normal to the aromatic plane and the hydrogen at a distance of 2.30 Å from the ring centroid. Simultaneously, the tendency of methanol to form chain and cyclic motifs in the bulk liquid is manifest in a highly templated solvation structure in the plane of the ring. The methanol molecules surround the benzene so that the O-H bonds are coplanar with the aromatic ring while the oxygens interact with C-H groups through simultaneous bifurcated hydrogen bonds. This demonstrates that weak hydrogen bonding can modulate existing stronger interactions to give rise to highly ordered cooperative structural motifs that persist in the liquid phase.
Determining subunit-subunit interaction from statistics of cryo-EM images: observation of nearest-neighbor coupling in a circadian clock protein complex
Authors: Han Xu , Zhang Dongliang , Hong Lu , Yu Daqi , Wu Zhaolong , Yang Tian , Rust Michael , Tu Yuhai , Ouyang Qi
Published: September 2023

Biological processes are typically actuated by dynamic multi-subunit molecular complexes. However, interactions between subunits, which govern the functions of these complexes, are hard to measure directly. Here, we develop a general approach combining cryo-EM imaging technology and statistical modeling and apply it to study the hexameric clock protein KaiC in Cyanobacteria. By clustering millions of KaiC monomer images, we identify two major conformational states of KaiC monomers. We then classify the conformational states of (>160,000) KaiC hexamers by the thirteen distinct spatial arrangements of these two subunit states in the hexamer ring. We find that distributions of the thirteen hexamer conformational patterns for two KaiC phosphorylation mutants can be fitted quantitatively by an Ising model, which reveals a significant cooperativity between neighboring subunits with phosphorylation shifting the probability of subunit conformation. Our results show that a KaiC hexamer can respond in a switch-like manner to changes in its phosphorylation level.
YAP silencing by RB1 mutation is essential for small-cell lung cancer metastasis
Authors: Wu Zhengming , Su Junhui , Li Fu-long , Chen Tao , Mayner Jaimie , Engler Adam , Ma Shenghong , Li Qingquan , Guan Kun-Liang
Published: September 2023

Small cell lung cancer (SCLC) is highly lethal due to its prevalent metastasis. Most SCLCs have inactivating mutations in TP53 and RB1. We find that loss of YAP expression is key for SCLC cells to acquire rapid ameboid migration and high metastatic potential. YAP functions through its target genes CCN1/CCN2 to inhibit SCLC ameboid migration. RB1 mutation contributes to YAP transcriptional silencing via E2F7, which recruits the RCOR co-repressor complex to YAP promoter. We discover that benzamide family HDAC inhibitors stimulate YAP expression by inhibiting the RCOR-HDAC complex, thereby suppressing SCLC metastasis and improving survival in a mouse model. Our study unveils the molecular and cellular basis underlying SCLC’s high metastatic potential, the previously unrecognized role of YAP in suppressing ameboid migration and tumor metastasis, and the mechanism of YAP transcription regulation involving E2F7, RCOR, and Sin3 HDAC. This study reveals a therapeutic potential of benzamides for SCLC treatment.
SCARB2 drives hepatocellular carcinoma tumor initiating cells via enhanced MYC transcriptional activity
Authors: Wang Feng , Gao Yang , Xue Situ , Zhao Luyao , Jiang Huimin , Zhang Tingting , Li Yunxuan , Zhao Chenxi , Wu Fan , Siqin Tana , Liu Ying , Wu Jie , Yan Yechao , Yuan Jian , Jiang Jian-dong , Li Ke
Published: September 2023

CSCs (Cancer stem cells) with distinct metabolic features are considered to cause HCC (hepatocellular carcinoma) initiation, metastasis and therapeutic resistance. Here, we perform a metabolic gene CRISPR/Cas9 knockout library screen in tumorspheres derived from HCC cells and find that deletion of SCARB2 suppresses the cancer stem cell-like properties of HCC cells. Knockout of Scarb2 in hepatocytes attenuates HCC initiation and progression in both MYC-driven and DEN (diethylnitrosamine)-induced HCC mouse models. Mechanistically, binding of SCARB2 with MYC promotes MYC acetylation by interfering with HDCA3-mediated MYC deacetylation on lysine 148 and subsequently enhances MYC transcriptional activity. Screening of a database of FDA (Food and Drug Administration)-approved drugs shows Polymyxin B displays high binding affinity for SCARB2 protein, disrupts the SCARB2-MYC interaction, decreases MYC activity, and reduces the tumor burden. Our study identifies SCARB2 as a functional driver of HCC and suggests Polymyxin B-based treatment as a targeted therapeutic option for HCC.
High-resolution single-photon imaging with physics-informed deep learning
Authors: Bian Liheng , Song Haoze , Peng Lintao , Chang Xuyang , Yang Xi , Horstmeyer Roarke , Ye Lin , Zhu Chunli , Qin Tong , Zheng Dezhi , Zhang Jun
Published: September 2023

High-resolution single-photon imaging remains a big challenge due to the complex hardware manufacturing craft and noise disturbances. Here, we introduce deep learning into SPAD, enabling super-resolution single-photon imaging with enhancement of bit depth and imaging quality. We first studied the complex photon flow model of SPAD electronics to accurately characterize multiple physical noise sources, and collected a real SPAD image dataset (64 × 32 pixels, 90 scenes, 10 different bit depths, 3 different illumination flux, 2790 images in total) to calibrate noise model parameters. With this physical noise model, we synthesized a large-scale realistic single-photon image dataset (image pairs of 5 different resolutions with maximum megapixels, 17250 scenes, 10 different bit depths, 3 different illumination flux, 2.6 million images in total) for subsequent network training. To tackle the severe super-resolution challenge of SPAD inputs with low bit depth, low resolution, and heavy noise, we further built a deep transformer network with a content-adaptive self-attention mechanism and gated fusion modules, which can dig global contextual features to remove multi-source noise and extract full-frequency details. We applied the technique in a series of experiments including microfluidic inspection, Fourier ptychography, and high-speed imaging. The experiments validate the technique’s state-of-the-art super-resolution SPAD imaging performance.
Structural insights into FSP1 catalysis and ferroptosis inhibition
Authors: Lv Yun , Liang Chunhui , Sun Qichao , Zhu Jing , Xu Haiyan , Li Xiaoqing , Li Yao-yao , Wang Qihai , Yuan Huiqing , Chu Bo , Zhu Deyu
Published: September 2023

Ferroptosis suppressor protein 1 (FSP1, also known as AIMF2, AMID or PRG3) is a recently identified glutathione-independent ferroptosis suppressor1–3, but its underlying structural mechanism remains unknown. Here we report the crystal structures of Gallus gallus FSP1 in its substrate-free and ubiquinone-bound forms. The structures reveal a FAD-binding domain and a NAD(P)H-binding domain, both of which are shared with AIF and NADH oxidoreductases4–9, and a characteristic carboxy-terminal domain as well. We demonstrate that the carboxy-terminal domain is crucial for the catalytic activity and ferroptosis inhibition of FSP1 by mediating the functional dimerization of FSP1, and the formation of two active sites located on two sides of FAD, which are responsible for ubiquinone reduction and a unique FAD hydroxylation respectively. We also identify that FSP1 can catalyze the production of H2O2 and the conversion of FAD to 6-hydroxy-FAD in the presence of oxygen and NAD(P)H in vitro, and 6-hydroxy-FAD directly inhibits ferroptosis in cells. Together, these findings further our understanding on the catalytic and ferroptosis suppression mechanisms of FSP1 and establish 6-hydroxy-FAD as an active cofactor in FSP1 and a potent radical-trapping antioxidant in ferroptosis inhibition.
Molecular characterization of the N-terminal half of TasA during amyloid-like assembly and its contribution to Bacillus subtilis biofilm formation
Authors: Cámara-Almirón Jesús , Domínguez-García Laura , El Mammeri Nadia , Lends Alons , Habenstein Birgit , de Vicente Antonio , Loquet Antoine , Romero Diego
Published: September 2023

Biofilms are bacterial communities that result from a cell differentiation process leading to the secretion of an extracellular matrix (ECM) by part of the population. In Bacillus subtilis, the main protein component of the ECM is TasA, which forms a fiber-based scaffold that confers structure to the ECM. The N-terminal half of TasA is strongly conserved among Bacillus species and contains a protein domain, the rigid core (RcTasA), which is critical for the structural and functional properties of the recombinant protein. In this study, we demonstrate that recombinantly purified RcTasA in vitro retains biochemical properties previously observed for the entire protein. Further analysis of the RcTasA amino acid sequence revealed two aggregation-prone stretches and a region of imperfect amino acid repeats, which are known to contribute to functional amyloid assembly. Biochemical characterization of these stretches found in RcTasA revealed their amyloid-like capacity in vitro, contributing to the amyloid nature of RcTasA. Moreover, the study of the imperfect amino acid repeats revealed the critical role of residues D64, K68 and D69 in the structural function of TasA. Experiments with versions of TasA carrying the substitutions D64A and K68AD69A demonstrated a partial loss of function of the protein either in the assembly of the ECM or in the stability of the core and amyloid-like properties. Taken together, our findings allow us to better understand the polymerization process of TasA during biofilm formation and provide knowledge into the sequence determinants that promote the molecular behavior of protein filaments in bacteria.
BioNetGMMFit: estimating parameters of a BioNetGen model from time-stamped snapshots of single cells
Authors: Wu John , Stewart William C. L. , Jayaprakash Ciriyam , Das Jayajit
Published: September 2023

Mechanistic models are commonly employed to describe signaling and gene regulatory kinetics in single cells and cell populations. Recent advances in single-cell technologies have produced multidimensional datasets where snapshots of copy numbers (or abundances) of a large number of proteins and mRNA are measured across time in single cells. The availability of such datasets presents an attractive scenario where mechanistic models are validated against experiments, and estimated model parameters enable quantitative predictions of signaling or gene regulatory kinetics. To empower the systems biology community to easily estimate parameters accurately from multidimensional single-cell data, we have merged a widely used rule-based modeling software package BioNetGen, which provides a user-friendly way to code for mechanistic models describing biochemical reactions, and the recently introduced CyGMM, that uses cell-to-cell differences to improve parameter estimation for such networks, into a single software package: BioNetGMMFit. BioNetGMMFit provides parameter estimates of the model, supplied by the user in the BioNetGen markup language (BNGL), which yield the best fit for the observed single-cell, time-stamped data of cellular components. Furthermore, for more precise estimates, our software generates confidence intervals around each model parameter. BioNetGMMFit is capable of fitting datasets of increasing cell population sizes for any mechanistic model specified in the BioNetGen markup language. By streamlining the process of developing mechanistic models for large single-cell datasets, BioNetGMMFit provides an easily-accessible modeling framework designed for scale and the broader biochemical signaling community.
A Dataset for Electricity Market Studies on Western and Northeastern Power Grids in the United States
Authors: Zhang Qiwei , Li Fangxing
Published: September 2023

Efficient electricity market operations and cost-effective electricity generations are fundamental to a low-carbon energy future. The Western Electricity Coordinating Council (WECC) and Northeast Power Coordinating Council (NPCC) systems were built to provide efficient electrical grid simulation solutions for their respective U.S. regions. Data reuse for electricity economic studies remains a challenge due to the lack of credible and realistic economic data. This paper delivers a comprehensive dataset containing generator aggregations, generator costs, transmission limits, load distributions, and electricity prices for the WECC and NPCC systems based on real-world grid operation data at year 2020, including power plant geographic locations, generation profiles, regional power flow interchanges, and load distributions in both regions. The electricity price from the developed dataset is simulated based on the other items in the dataset, and we show that the variation of the simulated electricity price reasonably aligns with the real-world electricity price in both the WECC and NPCC regions. Overall, the developed dataset is of interest for various electricity market and economic studies, such as the economic dispatch and locational marginal price (LMP) analysis.
Texture feature analysis of MRI-ADC images to differentiate glioma grades using machine learning techniques
Authors: Vijithananda Sahan M. , Jayatilake Mohan L. , Gonçalves Teresa C. , Rato Luis M. , Weerakoon Bimali S. , Kalupahana Tharindu D. , Silva Anil D. , Dissanayake Karuna , Hewavithana P. B.
Published: September 2023

Apparent diffusion coefficient (ADC) of magnetic resonance imaging (MRI) is an indispensable imaging technique in clinical neuroimaging that quantitatively assesses the diffusivity of water molecules within tissues using diffusion-weighted imaging (DWI). This study focuses on developing a robust machine learning (ML) model to predict the aggressiveness of gliomas according to World Health Organization (WHO) grading by analyzing patients’ demographics, higher-order moments, and grey level co-occurrence matrix (GLCM) texture features of ADC. A population of 722 labeled MRI-ADC brain image slices from 88 human subjects was selected, where gliomas are labeled as glioblastoma multiforme (WHO-IV), high-grade glioma (WHO-III), and low-grade glioma (WHO I-II). Images were acquired using 3T-MR systems and a region of interest (ROI) was delineated manually over tumor areas. Skewness, kurtosis, and statistical texture features of GLCM (mean, variance, energy, entropy, contrast, homogeneity, correlation, prominence, and shade) were calculated using ADC values within ROI. The ANOVA f-test was utilized to select the best features to train an ML model. The data set was split into training (70%) and testing (30%) sets. The train set was fed into several ML algorithms and selected most promising ML algorithm using K-fold cross-validation. The hyper-parameters of the selected algorithm were optimized using random grid search technique. Finally, the performance of the developed model was assessed by calculating accuracy, precision, recall, and F1 values reported for the test set. According to the ANOVA f-test, three attributes; patient gender (1.48), GLCM energy (9.48), and correlation (13.86) that performed minimum scores were excluded from the dataset. Among the tested algorithms, the random forest classifier(0.8772 ± 0.0237) performed the highest mean-cross-validation score and selected to build the ML model which was able to predict tumor categories with an accuracy of 88.14% over the test set. The study concludes that the developed ML model using the above features except for patient gender, GLCM energy, and correlation, has high prediction accuracy in glioma grading. Therefore, the outcomes of this study enable to development of advanced tumor classification applications that assist in the decision-making process in a real-time clinical environment.
Molecular dynamics simulations of methane adsorption and displacement from graphenylene shale reservoir nanochannels
Authors: Hajianzadeh Maryam , Mahmoudi Jafar , Sadeghzadeh Sadegh
Published: September 2023

Methane is the main component of shale gas and is adsorbed in shale pores. Methane adsorption not only affects the estimation of shale gas reserves but also reduces extraction efficiency. Therefore, investigating the behavior of methane adsorption in shale reservoirs is important for evaluating shale gas resources, as well as understanding its desorption and displacement from the nanochannels of shale gas reservoirs. In this research, molecular dynamics simulations were used to investigate the adsorption behavior of methane gas in organic shale pores made of graphenylene, followed by its displacement by CO2 and N2 injection gases. The effects of pore size, pressure, and temperature on adsorption were examined. It was observed that increasing the pore size at a constant pressure led to a decrease in the density of adsorbed methane molecules near the pore surface, while a stable free phase with constant density formed in the central region of the nanopore. Moreover, adsorption increased with increasing pressure, and at pressures ranging from 0 to 3 MPa, 15 and 20 Å pores exhibited lower methane adsorption compared to other pores. The amount of adsorption decreased with increasing temperature, and the observed adsorption isotherm followed the Langmuir adsorption isotherm. The mechanism of methane displacement by the two injected gases differed. Carbon dioxide filled both vacant adsorption sites and directly replaced the adsorbed methane. On the other hand, nitrogen only adsorbed onto the vacant sites and, by reducing the partial pressure of methane, facilitated the displacement of methane.