bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct in situ photolithography of ultra-stable CsPbBr3 quantum dot arrays based on crosslinking polymerization
Authors: Wan Yanli , Zhao Yixing , Li Yaling , Zhang Zhenwei , Li Sen , Tian Tingfang , Wang Li
Published: December 2023

XBPO-treated CsPbBr3 perovskite quantum dots arrays were prepared by utilizing the waterproof properties of the PQDs under photopolymerization condition and the non-waterproof properties without photopolymerization.
Quaternary ammonium fluorides and difluorosilicates as nucleophilic fluorination reagents
Authors: Trojan Michal , Kučnirová Kateřina , Bouzková Šárka , Cvačka Josef , Čejka Jan , Tavčar Gašper , Rybáčková Markéta , Kvíčala Jaroslav
Published: December 2023

Fluorination reactivity and selectivity of TBAT and four new nucleophilic fluorination reagents were better than those of TBAF, TASF and other quaternary ammonium fluorides.
Synthesis of hollow sphere structured TiO2 loaded with Ag2O and its photocatalytic activity
Authors: Liu Hejin , Liu Ying , Wang Xueqin , Qiao Peng , Wang Wenyi , Zhang Mei , Liu Yanxiu , Song Hua
Published: December 2023

Owing to its high stability and catalytic activity, TiO2 has been widely used as a photocatalyst where its photocatalytic performance can be significantly improved by microstructure regulation and semiconductor loading.
Caustics and velocity caustics in the diffuse interstellar medium at high Galactic latitudes
Authors: Kalberla P. M. W.
Published: December 2023

Context. The far-infrared (FIR) distribution at high Galactic latitudes, observed with Planck, is filamentary with coherent structures in polarization. These structures are also closely related to H I filaments with coherent velocity structures. There is a long-standing debate about the physical nature of these structures. They are considered either as velocity caustics, fluctuations engraved by the turbulent velocity field or as cold three-dimensional density structures in the interstellar medium (ISM).

Aims. We discuss different approaches to data analysis and interpretation in order to work out the differences.

Methods. We considered mathematical preliminaries for the derivation of caustics that characterize filamentary structures in the ISM. Using the Hessian operator, we traced individual FIR filamentary structures in H I from channel maps as observed and alternatively from data that are provided by the velocity decomposition algorithm (VDA). VDA is claimed to separate velocity caustics from density effects.

Results. Based on the strict mathematical definition, the so-called velocity caustics are not actually caustics. These VDA data products may contain caustics in the same way as the original H I observations. Caustics derived by a Hessian analysis of both databases are nearly identical with a correlation coefficient of 98%. However, the VDA algorithm leads to a 30% increase in the alignment uncertainties when fitting FIR/H I orientation angles. Thus, the VDA velocity crowding concept fails to explain the alignment of FIR/H I filaments at |b| > 20°. We used H I absorption data to constrain the physical nature of FIR/H I filaments and determine spin temperatures and volume densities of FIR/H I filaments. H I filaments exist as cold neutral medium (CNM) structures; outside the filaments no CNM absorption is detectable.

Conclusions. The CNM in the diffuse ISM is exclusively located in filaments with FIR counterparts. These filaments at high Galactic latitudes exist as cold density structures; velocity crowding effects are negligible.
Availability of web servers significantly boosts citations rates of bioinformatics methods for protein function and disorder prediction
Authors: Song Jiangning , Kurgan Lukasz
Published: December 2023

Motivation

Development of bioinformatics methods is a long, complex and resource-hungry process. Hundreds of these tools were released. While some methods are highly cited and used, many suffer relatively low citation rates. We empirically analyze a large collection of recently released methods in three diverse protein function and disorder prediction areas to identify key factors that contribute to increased citations.

Results

We show that provision of a working web server significantly boosts citation rates. On average, methods with working web servers generate three times as many citations compared to tools that are available as only source code, have no code and no server, or are no longer available. This observation holds consistently across different research areas and publication years. We also find that differences in predictive performance are unlikely to impact citation rates. Overall, our empirical results suggest that a relatively low-cost investment into the provision and long-term support of web servers would substantially increase the impact of bioinformatics tools.
Mining literature and pathway data to explore the relations of ketamine with neurotransmitters and gut microbiota using a knowledge-graph
Authors: Liu Ting , Feenstra K Anton , Huang Zhisheng , Heringa Jaap
Published: December 2023

Motivation

Up-to-date pathway knowledge is usually presented in scientific publications for human reading, making it difficult to utilize these resources for semantic integration and computational analysis of biological pathways. We here present an approach to mining knowledge graphs by combining manual curation with automated named entity recognition and automated relation extraction. This approach allows us to study pathway-related questions in detail, which we here show using the ketamine pathway, aiming to help improve understanding of the role of gut microbiota in the antidepressant effects of ketamine.

Results

The thus devised ketamine pathway ‘KetPath’ knowledge graph comprises five parts: (i) manually curated pathway facts from images; (ii) recognized named entities in biomedical texts; (iii) identified relations between named entities; (iv) our previously constructed microbiota and pre-/probiotics knowledge bases; and (v) multiple community-accepted public databases. We first assessed the performance of automated extraction of relations between named entities using the specially designed state-of-the-art tool BioKetBERT. The query results show that we can retrieve drug actions, pathway relations, co-occurring entities, and their relations. These results uncover several biological findings, such as various gut microbes leading to increased expression of BDNF, which may contribute to the sustained antidepressant effects of ketamine. We envision that the methods and findings from this research will aid researchers who wish to integrate and query data and knowledge from multiple biomedical databases and literature simultaneously.

Availability and implementation

Data and query protocols are available in the KetPath repository at https://dx.doi.org/10.5281/zenodo.8398941 and https://github.com/tingcosmos/KetPath.
Vitamin D3 promotes fish oocyte development by directly regulating gonadal steroid hormone synthesis
Authors: Yang Gang , Cheng Ke , Huang Yanqing , Wang Chunfang
Published: December 2023

Vitamin D receptors and vitamin D3-metabolizing enzymes have been found to be highly expressed in the ovaries and spermatophores of fish. However, the role of vitamin D3 on fish gonadal development has rarely been reported. In this study, 2-month-old female zebrafish were fed with different concentrations of vitamin D3 diets (0, 700, 1400, and 11 200 IU/kg) to investigate the effects of vitamin D3 on ovarian development. The diet with 0 IU/kg vitamin D3 resulted in elevated interstitial spaces, follicular atresia, and reproductive toxicity in zebrafish ovaries. Supplementation with 700 and 1400 IU/kg of vitamin D3 significantly increased the oocyte maturation rate; upregulated ovarian gonadal steroid hormone synthesis capacity; and elevated plasma estradiol, testosterone, and ovarian vitellogenin levels. Furthermore, the current study identified a vitamin D response element in the cyp19a1a promoter and demonstrated that 1.25(OH)2D3-vitamin D response directly activated cyp19a1a production through activating the vitamin D response element. In conclusion, this study shows that an appropriate concentration of vitamin D3 can promote zebrafish ovarian development and affect vitellogenin synthesis through the vdr/cyp19a1a/er/vtg gene axis.
Pathological shifts in tryptophan metabolism in human term placenta exposed to LPS or poly I:C
Authors: Abad Cilia , Karahoda Rona , Orbisova Anna , Kastner Petr , Heblik Daniel , Kucera Radim , Portillo Ramon , Staud Frantisek
Published: December 2023

Maternal immune activation during pregnancy is a risk factor for offspring neuropsychiatric disorders. Among the mechanistic pathways by which maternal inflammation can affect fetal brain development and programming, those involving tryptophan (TRP) metabolism have drawn attention because various TRP metabolites have neuroactive properties. This study evaluates the effect of bacterial (lipopolysaccharides/LPS) and viral (polyinosinic:polycytidylic acid/poly I:C) placental infection on TRP metabolism using an ex vivo model. Human placenta explants were exposed to LPS or poly I:C, and the release of TRP metabolites was analyzed together with the expression of related genes and proteins and the functional activity of key enzymes in TRP metabolism. The rate-limiting enzyme in the serotonin pathway, tryptophan hydroxylase, showed reduced expression and functional activity in explants exposed to LPS or poly I:C. Conversely, the rate-limiting enzyme in the kynurenine pathway, indoleamine dioxygenase, exhibited increased activity, gene, and protein expression, suggesting that placental infection mainly promotes TRP metabolism via the kynurenine (KYN) pathway. Furthermore, we observed that treatment with LPS or poly I:C increased activity in the kynurenine monooxygenase branch of the KYN pathway. We conclude that placental infection impairs TRP homeostasis, resulting in decreased production of serotonin and an imbalance in the ratio between quinolinic acid and kynurenic acid. This disrupted homeostasis may eventually expose the fetus to suboptimal/toxic levels of neuroactive molecules and impair fetal brain development.
‘We Taught You How to Teach Us’: An Autoethnography of Decolonising of Social Work Education in a Programme for Bedouin-Arab Social Workers in Israel
Authors: Segev Einav , Allassad Alhuzail Nuzha
Published: December 2023

The need to decolonise social work education has become prominent in curricula developed over the past years. The curriculum in social work schools defines and shapes ways of knowing largely in terms of privileged Western knowledge. It is therefore necessary to change it and adopt pedagogical approaches more suitable for populations from different cultures. This article presents a study on a dedicated training programme for Bedouin-Arab social workers in Israel. Its pedagogies are informed by decolonised and culturally adapted social work education. This qualitative study was conducted in a teacher-researcher reflexive autoethnography approach, based on documentation of thirty-six lessons and reflections by the programme lecturers and on a thematic analysis of their experiences as social work educators. The findings present several pedagogies in terms of ‘bridge’: the pedagogic, the cultural sensitivity, the theory–practice and the safe space bridge. These expand the knowledge base in social work education beyond Western knowledge, demonstrating how knowledge practices unique to different cultures and identities may be adopted and adapted within it. Based on these findings, it is suggested to transform and enrich social work education by decolonising it to include new knowledge from diverse populations.
Expression and clinical diagnostic value of CCHE1 in breast cancer
Authors: Zhao Feng , Zhou Wenjuan , Xin Ran , Miao Xin
Published: December 2023

Objective

Breast cancer is a malignant tumor in the epithelial tissue of the breast gland. This study aimed to unveil the expression and clinical diagnostic value of lncRNA cervical cancer high-expressed 1 (CCHE1) in breast cancer.

Methods

CCHE1 expression in breast cancer tissues was evaluated by RT-qPCR. The relationship between the CCHE1 expression and clinicopathological features of breast cancer was analyzed with the chi-square test, and the survival of breast cancer patients was evaluated with the Kaplan–Meier method. The diagnostic value of CCHE1 expression for breast cancer was evaluated by using the receiver operating characteristics (ROC) curve. Breast cancer cell lines (SKBR3, T47D, BT474, and MCF-7) were cultured for detecting CCHE1 expression in the cells. MCF-7 cells were selected for the subsequent experiments, and the small interfering RNA of CCHE1 (si-CCHE1) and CCHE1 overexpression vector (pcDNA-CCHE1) were transfected into MCF-7 cells. The proliferation, migration, and invasive ability were assessed by CCK-8 and Transwell assays. The influence of CCHE1 on the growth of tumors was validated by nude mice xenograft assay.

Results

CCHE1 was up-regulated in breast cancer tissues and breast cancer cells. The high expression level of CCHE1 in cancer tissues of breast cancer patients was correlated with larger tumor size, advanced TNM stage, Ki-67 status, and lymph node metastasis. The area under the ROC curve for CCHE1 in the diagnosis of breast cancer was 0.983 (95% CI: 0.966–1.000), with a sensitivity of 95.00% and a specificity of 91.70%. The 5-year survival rate was higher in patients with low CCHE1 expression than those with high CCHE1 expression. Furthermore, restrained CCHE1 impeded proliferation, invasion, and migration of MCF-7 cells, as well as tumor growth in mice.

Conclusion

Our study highlights that elevated expression of CCHE1 in breast cancer tissues, which is closely related to clinicopathologic features, has some clinical value in the diagnosis of the disease.
Metabolome analysis reveals that cyclic adenosine diphosphate ribose contributes to the regulation of differentiation in mice adipocyte
Authors: Takahashi Haruya , Nishitani Kento , Kawarasaki Satoko , Martin‐Morales Agustin , Nagai Hiroyuki , Kuwata Hidetoshi , Tokura Motohiro , Okaze Haruka , Mohri Shinsuke , Ara Takeshi , Ito Tetsuro , Nomura Wataru , Jheng Huei‐Fen , Kawada Teruo , Inoue Kazuo , Goto Tsuyoshi
Published: December 2023

Adipocytes play a key role in energy storage and homeostasis. Although the role of transcription factors in adipocyte differentiation is known, the effect of endogenous metabolites of low molecular weight remains unclear. Here, we analyzed time‐dependent changes in the levels of these metabolites throughout adipocyte differentiation, using metabolome analysis, and demonstrated that there is a positive correlation between cyclic adenosine diphosphate ribose (cADPR) and Pparγ mRNA expression used as a marker of differentiation. We also found that the treatment of C3H10T1/2 adipocytes with cADPR increased the mRNA expression of those marker genes and the accumulation of triglycerides. Furthermore, inhibition of ryanodine receptors (RyR), which are activated by cADPR, caused a significant reduction in mRNA expression levels of the marker genes and triglyceride accumulation in adipocytes. Our findings show that cADPR accelerates adipocytic differentiation via RyR pathway.
MiR‐9 promotes G‐MDSC recruitment and tumor proliferation by targeting SOCS3 in breast cancer
Authors: Gu Xinyue , Wei Fang , Tong Jinzhe , Liu Yichen , Chen Simiao , Zheng Lufeng , Xing Yingying
Published: December 2023

Myeloid‐derived suppressor cells (MDSCs) are a heterogeneous group of cells that differentiate from myeloid cells, proliferate in cancer and inflammatory reactions, and mainly exert immunosuppressive functions. Nonetheless, the precise mechanisms that dictate both the accumulation and function of MDSCs remain only partially elucidated. In the course of our investigation, we observed a positive correlation between the content of MDSCs especially G‐MDSCs and miR‐9 level in the tumor tissues derived from miR‐9 knockout MMTV‐PyMT mice and 4T1 tumor‐bearing mice with miR‐9 overexpression. Combined with RNA‐seq analysis, we identified SOCS2 and SOCS3 as direct targets of miR‐9. Additionally, our research unveiled the pivotal role of the CCL5/CCR5 axis in orchestrating the chemotactic recruitment of G‐MDSCs within the tumor microenvironment, a process that is enhanced by miR‐9. These findings provide fresh insights into the molecular mechanisms governing the accumulation of MDSCs within the framework of breast cancer development.
Flatfoot Reconstruction for Painful Pediatric Idiopathic Flexible Flatfoot: Prospective Study Demonstrates Improved Alignment, Function, and Patient-reported Outcomes
Authors: DeFrancesco Christopher J. , Conti Matthew S. , Zanini Silvia , Blanco John , Dodwell Emily , Hillstrom Howard J. , Scher David M.
Published: December 2023

Background:

This prospective study was undertaken to report outcomes following reconstructive surgery for patients with painful pediatric idiopathic flexible flatfoot.

Methods:

Twenty-five patients with pediatric idiopathic flexible flatfoot were evaluated pre- and post flatfoot reconstruction with lateral column lengthening (LCL). All patients had lengthening of the Achilles or gastrocnemius, while 13 patients had medial side soft tissue (MSST) procedures, 7 underwent medial cuneiform plantarflexion osteotomy (MCPO), and 5 had medializing calcaneal osteotomy. Measures of static foot alignment—both radiographic parameters and clinical arch height indices—were compared, as were measures of dynamic foot alignment and loading, including arch height flexibility and pedobarography. Preoperative and postoperative patient-reported outcome (PRO) scores were compared between those treated with or without MSST procedures.

Results:

The median subject age was 13.8 years (range: 10.3 to 16.5) at the time of surgery. All radiographic parameters improved with surgery (P<0.001). The mean sitting arch height index showed a modest increase after surgery (P=0.023). Arch height flexibility was similar after surgery. The mean center-of-pressure excursion index increased from 14.1% to 24.0% (P<0.001), and the mean first metatarsal head (MH) peak pressure dropped (P<0.001), while the mean fifth MH peak pressure increased (P=0.018). The ratio of peak pressure in the fifth MH to peak pressure in the second MH increased (P=0.010). The ratio of peak pressure in the first MH to peak pressure in the second MH decreased when an MCPO was not used (P<0.002), but it remained stable when an MCPO was included. Mean scores in all PRO domains improved (P<0.001). Patients treated without MSST procedures showed no difference in PROMIS Pain Interference scores compared to those without MSST procedures.

Conclusions:

Flatfoot reconstruction surgery using an LCL with plantarflexor lengthening results in improved PROs. LCL changes but does not normalize the distribution of MH pressure loading. The addition of an MCPO can prevent a significant reduction in load-sharing by the first MH.
Emerging Futuristic Targeted Therapeutics
Authors: Mistry Tanuma , Nath Arijit , Pal Ranita , Ghosh Sushmita , Mahata Sutapa , Kumar Sahoo Pranab , Sarkar Sinjini , Choudhury Trisha , Nath Partha , Alam Neyaz , Nasare Vilas D.
Published: December 2023

Triple-negative breast cancer is characterized by high lethality attributed to factors such as chemoresistance, transcriptomic, and genomic heterogeneity, leading to a poor prognosis and limiting available targeted treatment options. While the identification of molecular targets remains pivotal for therapy involving chemo drugs, the current challenge lies in the poor response rates, low survival rates, and frequent relapses. Despite various clinical investigations exploring molecular targeted therapies in conjunction with conventional chemo treatment, the outcomes have been less than optimal. The critical need for more effective therapies underscores the urgency to discover potent novel treatments, including molecular and immune targets, as well as emerging strategies. This review provides a comprehensive analysis of conventional treatment approaches and explores emerging molecular and immune-targeted therapeutics, elucidating their mechanisms to address the existing obstacles for a more effective management of triple-negative breast cancer.
Discovery and characterization of novel inhibitors against ALS-related SOD1(A4V) aggregation through screening of a chemical library using Differerential Scanning Fluorimetry (DSF)
Authors: Giannakou Maria , Vorgias Constantinos , Hatzinikolaou Dimitris G.
Published: December 2023

Cu/Zn Superoxide Dismutase 1 (SOD1) is a 32-kDa cytosolic dimeric metalloenzyme that neutralizes superoxide anions into harmless oxygen and hydrogen peroxide. Mutations in SOD1 are associated with ALS, a disease causing motor neuron atrophy and subsequent mortality. These mutations exert their harmful effects through a gain of function mechanism, rather than loss of function. Despite extensive research, the specific mechanism causing selective motor neuron death still remains unclear. A defining feature of ALS pathogenesis is protein misfolding and aggregation, evidenced by ubiquitinated protein inclusions containing SOD1 in motor neurons. This work aims to identify compounds countering SOD1(A4V) misfolding and aggregation, potentially aiding ALS treatment. The approach employed is drug repurposing andin vitroscreening of a 1280 pharmacologically active compounds library, LOPAC®. Using Differential Scanning Fluorimetry Technique (DSF), compounds were tested for their impact on SOD1(A4V) thermal stability. Screening revealed one compound raising protein-ligand Tmby 7°C, eight inducing a higher second Tm, suggesting stabilzation effect, and five reducing Tmup to 18°C, suggesting possible interactions or non-specific binding.
Genetic modification strategies for electroporation and CRISPR-Cas-based technologies in the non-competent Gram-negative bacteriumAcinetobactersp. Tol 5
Authors: Ishikawa Masahito , Hori Katsutoshi
Published: December 2023

Environmental isolates are promising candidates for new chassis of synthetic biology because of their inherent conversion capabilities and resilience to environmental stresses; however, many remain genetically intractable and unamenable to established genetic tools tailored for model bacteria.Acinetobactersp. Tol 5 possesses intriguing properties for use in synthetic biology applications. However, genetic manipulation via electroporation is hindered by its low transformation efficiency. This study demonstrated the genetic refinement of the Tol 5 strain, achieving efficient transformation via electroporation. We deleted two genes encoding restriction enzymes. The resulting mutant strain not only exhibited marked efficiency of electrotransformation but also proved receptive to bothin vitroandin vivoDNA assembly technologies, thereby facilitating the construction of recombinant DNA. In addition, we successfully adapted a CRISPR-Cas9-based base-editing platform developed for otherAcinetobacterspecies. Our genetic modification strategy allows for the domestication of non-model bacteria, streamlining their utilization in synthetic biology applications.
MiniRead: a simple and inexpensive do-it-yourself device for multiple analyses of micro-organism growth kinetics
Authors: Falque Matthieu , Bourgais Aurélie , Dumas Fabrice , de Carvalho Mickaël , Diblasi Célian
Published: December 2023

Fitness in micro-organisms can be proxied by growth parameters on different media and/or temperatures. This is achieved done by measuring optical density at 600 nm using a spectrophotometer, which measures the effect of absorbance and side scattering due to turbidity of cells suspensions. However, when growth kinetics must be monitored in many 96-well plates at the same time, buying several 96-channels spectrophotometers is often beyond budgets. The MiniRead device presented here is a simple and inexpensive do-it-yourself 96-well temperature-controlled turbidimeter designed to measure the interception of white lightviaabsorption or side scattering through liquid culture medium. Turbidity is automatically recorded in each well at regular time intervals for up to several days or weeks. Output tabulated text files are recorded into a micro-SD memory card to be easily transferred to a computer. We propose also an R package which allows (1) to compute the non-linear calibration curves required to convert raw readings into cell concentration values, and (2) to analyze growth kinetics output files to automatically estimate growth parameters such as lag time, maximum growth rate, or cell concentration at the plateau.

The MiniRead project is freely available under GPL license fromhttps://forgemia.inra.fr/gqe-base/MiniRead. The project includes (1): user manual (Supplementary Material 1), firmware, list of electronic components and printed circuit board manufacturing files for the MiniRead device, and (2) a release containing the MiniRead R package for calibration and data analysis (Supplementary Material 2) with its tutorial (Supplementary Material 3). Detailed device building instructions are available athttps://moulon.inrae.fr/materiel_labo/miniread/.
An improved workflow for the quantification of orthohantavirus infection using automated imaging and flow cytometry
Authors: Menke Laura , Sieben Christian
Published: December 2023

Determination of the infectious titer is a central requirement when working with pathogenic viruses. The plaque or focus assay is commonly used but a labor- and time-consuming approach to determine the infectious titer of orthohantavirus samples. We have developed an optimized virus quantification approach that relies on the fluorescence-based detection of the orthohantavirus nucleocapsid protein (N) in infected cells with high sensitivity. We present the use of flow cytometry but highlight fluorescence microscopy in combination with automated data analysis as an attractive alternative to increase the information retrieved from an infection experiment. Additionally, we offer an open-source software equipped with a user-friendly graphical interface, eliminating the necessity for advanced programming skills.
Atypical Cell Cycle Regulation over Neural Stem Cell Expansion
Authors: Qemo Ingrid , Lubanska Dorota , Stringer Keith Franklin , Fifield Bre-Anne , Elabed Youshaa , Mahendran Hema Priya , Alrashed Sami , Boujeke Emmanuel , Rodzinka Alexander , Sorge Alexandra , Kandalam Srinath , Brown Jillian , Ghafoor Hasan , Arshad Maheen , Porter Lisa A.
Published: December 2023

Populations of quiescent adult neural stem cells (NSCs) that reside in the mammalian brain aid in neurogenesis throughout life and can be identified by molecular markers including Nestin, a type VI intermediate filament protein. Cell cycle regulation plays an important role in determining the fate of NSCs in the adult brain and maintaining a crucial balance between self-renewal and differentiation. Data from our group and others support that the atypical cyclin-like protein Spy1 (also called RingoA; geneSPDYA) plays a critical role in activating NSCs from a quiescent state. Elevated levels of Spy1 are found in aggressive human brain cancers, including glioblastoma. Using a conditional mouse model, we demonstrate that driving the expression of Spy1 in the Nestin-enriched NSC population of the brain directs the cells toward symmetric cellular division, increases stemness characteristics, decreases differentiation, and increases susceptibility to oncogenic transformation & drug resistance. This study contributes to better understanding of intricate cell cycle mechanisms which lead to deviation from the homeostatic state, promoting aberrant changes in adult NSCs.
Robust trigger wave speed inXenopuscytoplasmic extracts
Authors: Huang Jo-Hsi , Chen Yuping , Huang William Y. C. , Tabatabaee Saman , Ferrell James E.
Published: December 2023

Self-regenerating trigger waves can spread rapidly through the crowded cytoplasm without diminishing in amplitude or speed, providing consistent, reliable, long-range communication. The macromolecular concentration of the cytoplasm varies in response to physiological and environmental fluctuations, raising the question of how or if trigger waves can robustly operate in the face of such fluctuations. UsingXenopusextracts, we found that mitotic and apoptotic trigger wave speeds are remarkably invariant. We derived a model that accounts for this robustness and for the eventual slowing at extremely high and low cytoplasmic concentrations. The model implies that the positive and negative effects of cytoplasmic concentration (increased reactant concentration vs. increased viscosity) are nearly precisely balanced. Accordingly, artificially maintaining a constant cytoplasmic viscosity during dilution abrogates this robustness. The robustness in trigger wave speeds may contribute to the reliability of the extremely rapid embryonic cell cycle.
Glucocorticoids rapidly modulate CaV1.2-mediated calcium signals through Kv2.1 channel clusters in hippocampal neurons
Authors: Wan Di , Lu Tongchuang , Li Chenyang , Hu Changlong
Published: December 2023

The precise regulation of Ca2+signals plays a crucial role in the physiological functions of neurons. Here, we investigated the rapid effect of glucocorticoids on Ca2+signals in hippocampal neurons. In cultured hippocampal neurons, glucocorticoids inhibited the spontaneous somatic Ca2+spikes generated by Kv2.1-organized Ca2+microdomains. Furthermore, glucocorticoids rapidly reduced the cell surface expressions of Kv2.1 and CaV1.2 channels in hippocampal neurons. In HEK293 cells transfected with Kv2.1 alone, glucocorticoids significantly reduced the surface expression of Kv2.1 with little effect on K+currents. Glucocorticoids inhibited CaV1.2 currents but had no effect on the cell surface expression of CaV1.2 in HEK293 cells transfected with CaV1.2 alone. Notably, in the presence of wild-type Kv2.1, glucocorticoids caused a decrease in the surface expression of CaV1.2 channels in HEK293 cells. However, this effect was not observed in the presence of non-clustering Kv2.1S586A mutant channels. Live cell imaging showed that glucocorticoids rapidly decreased Kv2.1 clusters on the plasma membrane. Correspondingly, western blot results indicated a significant increase in the cytoplasmic level of Kv2.1, suggesting the endocytosis of Kv2.1 clusters. Glucocorticoids rapidly decreased the intracellular cAMP concentration and the phosphorylation level of PKA in hippocampal neurons. The PKA inhibitor H89 mimicked the effect of glucocorticoids on Kv2.1, while the PKA agonist forskolin abrogated the effect. In conclusion, glucocorticoids rapidly regulate CaV1.2-mediated Ca2+signals in hippocampal neurons by promoting the endocytosis of Kv2.1 channel clusters through reducing PKA activity.

Significance Statement

The rapid non-genomic effect of glucocorticoids on the central nervous system is not fully understood. CaV1.2-mediated Ca2+signaling microdomains control somatic Ca2+signals and regulate excitation-transcription coupling in hippocampal neurons. Here, we demonstrate that glucocorticoids rapidly inhibit CaV1.2-mediated somatic Ca2+spikes in hippocampal neurons. Glucocorticoids reduce the surface expression of Kv2.1 clusters but do not affect the surface expression of non-clustering Kv2.1. Moreover, glucocorticoids induce the endocytosis of CaV1.2 channels through wild-type Kv2.1. However, glucocorticoids cannot induce the endocytosis of CaV1.2 channels through Kv2.1S586A mutant channels, which cannot form clusters. This study sheds light on the intricate interplay between glucocorticoids, Kv2.1 channels, and CaV1.2 channels, unraveling a dual mechanism that influences both overall Ca2+signaling and the intricate organization of neural microdomains.
A Combination of Four Nuclear Targeted Effectors ProtectsToxoplasmaAgainst Interferon Gamma Driven Human Host Cell Death During Acute Infection
Authors: Henry Brittany , Sibley L. David , Rosenberg Alex
Published: December 2023

In both mice and humans, Type II interferon-gamma (IFNγ) is crucial for regulation ofToxoplasma gondii(T. gondii) infection, during acute or chronic phases. To thwart this defense,T. gondiisecretes protein effectors hindering the host’s immune response. For example,T. gondiirelies on the MYR translocon complex to deploy soluble dense granule effectors (GRAs) into the host cell cytosol or nucleus. Recent genome-wide loss-of-function screens in IFNγ-primed primary human fibroblasts identified MYR translocon components as crucial for parasite resistance against IFNγ driven vacuole clearance. However, these screens did not pinpoint specific MYR-dependent GRA proteins responsible for IFNγ signaling blockade, suggesting potential functional redundancy.

Our study reveals thatT. gondiidepends on the MYR translocon complex to prevent host cell death and parasite premature egress in human cells stimulated with IFNγ post-infection, a unique phenotype observed in various human cell lines but not in murine cells. Intriguingly, inhibiting parasite egress did not prevent host cell death, indicating this mechanism is distinct from those described previously. Genome-wide loss-of-function screens uncovered TgIST, GRA16, GRA24, and GRA28 as effectors necessary for a complete block of IFNγ response. GRA24 and GRA28 directly influenced IFNγ driven transcription, GRA24’s action depended on its interaction with p38 MAPK, while GRA28 disrupted histone acetyltransferase activity of CBP/p300. Given the intricate nature of the immune response toT. gondii, it appears that the parasite has evolved equally elaborate mechanisms to subvert IFNγ signaling, extending beyond direct interference with the JAK/STAT1 pathway, to encompass other signaling pathways as well.
Adaptation-induced sharpening of orientation tuning curves in the mouse visual cortex
Authors: Ouelhazi Afef , Bharmauria Vishal , Molotchnikoff Stéphane
Published: December 2023

Orientation selectivity is an emergent property of visual neurons across species with columnar and non-columnar organization of the visual cortex. To compute the orientation selectivity of a neuron, a tuning function is fit on the raw responses of a neuron and then a measure, termed orientation selectivity index (OSI), is derived from this fitted curve to determine the tuning of the neuron. Previously, it has been shown that adaptation (a protocol where a neuron under observation is presented a non-optimal stimulus for a specific time) has varying effects on the tuning properties of neurons, such as, orientation, spatial frequency, motion etc. The emergence of OSI is more established in columnar cortices than the non-columnar ones. However, how adaptation impinges upon the OSI of the latter has not been systematically investigated. Here, in the mouse primary visual cortex (V1), we show that a 12-min adaptation protocol sharpens the OSI (tuning) of the visual neurons, underlying a specific dendritic neural mechanism, potentially facilitating the learning of novel features.
Evidence of 14-3-3 proteins contributing to kinetochore integrity and chromosome congression during mitosis
Authors: Anbalagan Guhan Kaliyaperumal , Agarwal Prakhar , Ghosh Santanu Kumar
Published: December 2023

The 14-3-3 family of proteins are conserved across eukaryotes and serve myriad important regulatory functions of the cell. Homo/heterodimers of these protein homologs, majorly recognize their ligands via conserved motifs from a plethora of cellular proteins to modulate the localization and functions of those effector ligands. In most of the genetic backgrounds ofSaccharomyces cerevisiae, disruption of both 14-3-3 homologs (Bmh1 and Bmh2) are either lethal or survive with severe growth defects showing gross chromosomal missegregation and prolonged cell cycle arrest. To elucidate their contributions to chromosome segregation, in this work we investigated their centromere/kinetochore-related functions. Analysis of appropriate deletion mutants shows that Bmh isoforms have cumulative and unshared isoform-specific contributions in maintaining the proper integrity of the kinetochore ensemble. Consequently,bmhmutant cells exhibited perturbations in kinetochore-microtubule (KT-MT) dynamics, characterized by kinetochore declustering, mis-localization of kinetochore proteins, and Mad2-mediated transient G2/M arrest. These defects also caused an asynchronous chromosome congression inbmhmutants during metaphase. In summary, this report advances the knowledge on contributions of budding yeast 14-3-3 proteins in chromosome segregation by demonstrating their roles in kinetochore integrity and chromosome congression.
Immune-responsive gene-1: The mitochondrial Key to Th17 Cell Pathogenicity in CNS Autoimmunity
Authors: Nematullah Mohammad , Fatma Mena , Zhou Guoli , Rashid Faraz , Ayasolla Kameshwar , Ahmed Mohammad Ejaz , She Ruicong , Mir Sajad , Zahoor Insha , Hoda Nasrul , Rattan Ramandeep , Giri Shailendra
Published: December 2023

Pathogenic Th17 cells play crucial roles in CNS autoimmune diseases such as multiple sclerosis (MS), but their regulation by endogenous mechanisms remains unknown. Through RNA-seq analysis of primary brain glial cells, we identified immuno-responsive gene 1 (Irg1) as one of the highly upregulated gene under inflammatory conditions. Validation in the spinal cord of animals with experimental autoimmune encephalomyelitis (EAE), an MS model, confirmed elevatedIrg1levels in myeloid, CD4, and B cells in the EAE group raising the concern ifIrg1 is detrimental or protective.Irg1knockout (KO) mice exhibited severe EAE disease, increased mononuclear cell infiltration, and increased levels of triple-positive CD4+ T cells expressing IL17a, GM-CSF, and IFNγ. A lack ofIrg1in macrophages elevates Class II expression, promoting the polarization of myelin-primed CD4+ T cells into pathogenic Th17 cells via the NLRP3/IL-1β axis. Adoptive transfer in Rag-1 KO and single-cell RNA sequencing highlighted the crucial role ofIrg1in shaping pathogenic Th17 cells. Moreover, bone marrow chimeras revealed that immune cells lackingIrg1maintained pathogenic and inflammatory phenotypes, suggesting its protective role in autoimmune diseases, including MS.

Significance

Immunoresponsive gene 1 (Irg1) was identified as a significantly elevated gene under inflammatory conditions through in vitro and in vivo models. Using global knockout mice, we identifiedIrg1 as a protective endogenous gene that negatively regulates pathogenic Th17 cells. Single-cell RNA sequencing of infiltrating cells during EAE revealed thatIrg1 knockout enhanced the expression of pathogenic Th signatures in CD4+ T cells, indicating a robust proinflammatory environment.Irg1 negatively regulates IL-1β in macrophages, which is essential for the differentiation of pTh17 CD4+ T cells, potentially clarifying the exacerbation of EAE in knockout animals. Our study identifiedIrg1 as a negative regulator of both innate and adaptive immune responses in a CNS autoimmunity model.
Magnetoelectric Nanodiscs Enable Wireless Transgene-Free Neuromodulation
Authors: Kim Ye Ji , Driscoll Nicolette , Kent Noah , Paniagua Emmanuel Vargas , Tabet Anthony , Koehler Florian , Manthey Marie , Sahasrabudhe Atharva , Signorelli Lorenzo , Gregureć Danijela , Anikeeva Polina
Published: December 2023

Deep-brain stimulation (DBS) with implanted electrodes revolutionized treatment of movement disorders and empowered neuroscience studies. Identifying less invasive alternatives to DBS may further extend its clinical and research applications. Nanomaterial-mediated transduction of magnetic fields into electric potentials offers an alternative to invasive DBS. Here, we synthesize magnetoelectric nanodiscs (MENDs) with a core-double shell Fe3O4-CoFe2O4-BaTiO3architecture with efficient magnetoelectric coupling. We find robust responses to magnetic field stimulation in neurons decorated with MENDs at a density of 1 µg/mm2despite individual-particle potentials below the neuronal excitation threshold. We propose a model for repetitive subthreshold depolarization, which combined with cable theory, corroborates our findings in vitro and informs magnetoelectric stimulation in vivo. MENDs injected into the ventral tegmental area of genetically intact mice at concentrations of 1 mg/mL enable remote control of reward behavior, setting the stage for mechanistic optimization of magnetoelectric neuromodulation and inspiring its future applications in fundamental and translational neuroscience.
Deconer: A comprehensive and systematic evaluation toolkit for reference-based cell type deconvolution algorithms using gene expression data
Authors: Zhang Wei , Zhang Xianglin , Liu Qiao , Wei Lei , Qiao Xu , Gao Rui , Liu Zhiping , Wang Xiaowo
Published: December 2023

In recent years, computational methods for quantifying cell type proportions from transcription data have gained significant attention, particularly those reference-based methods which have demonstrated high accuracy. However, there is currently a lack of comprehensive evaluation and guidance for available reference-based deconvolution methods in cell proportion deconvolution analysis. In this study, we propose a comprehensive evaluation toolkit, called Deconer, specifically designed for reference-based deconvolution methods. Deconer provides various simulated and real gene expression datasets, including both bulk and single-cell sequencing data, and offers multiple visualization interfaces. By utilizing Deconer, we conducted systematic comparisons of 14 reference-based deconvolution methods from different perspectives, including method robustness, accuracy in deconvolving rare components, signature gene selection, and building external reference. We also performed an in-depth analysis of the application scenarios and challenges in cell proportion deconvolution methods. Finally, we provided constructive suggestions for users in selecting and developing cell proportion deconvolution algorithms. This work presents novel insights to researchers, assisting them in choosing appropriate toolkits, applying solutions in clinical contexts, and advancing the development of deconvolution tools tailored to gene expression data.
How the immune mousetrap works: structural evidence for the immunomodulatory action of a peptide from influenza NS1 protein
Authors: Zabrodskaya Yana , Tsvetkov Vladimir , Shurygina Anna-Polina , Vasyliev Kirill , Shaldzhyan Aram , Gorshkov Andrey , Kuklin Alexander , Fedorova Natalya , Egorov Vladimir
Published: December 2023

One of the critical stages of the T-cell immune response is the dimerization of the intramembrane domains of T-cell receptors (TCR). Structural similarities between the immunosuppressive domains of viral proteins and the transmembrane domains of TCR have led several authors to hypothesize the mechanism of immune response suppression by highly pathogenic viruses: viral proteins embed themselves in the membrane and act on the intramembrane domain of the TCRalpha subunit, hindering its functional oligomerization. It has also been suggested that this mechanism is used by influenza A virus in NS1-mediated immunosuppression. We have shown that the peptide corresponding to the primary structure of the potential immunosuppressive domain of NS1 protein (G51) can reduce concanavalin A-induced proliferation of PBMC cells, as well as in vitro, G51 can affect the oligomerization of the core peptide corresponding to the intramembrane domain of TCR, using AFM and small-angle neutron scattering.

The results obtained usingin celluloandin vitromodel systems suggest the presence of functional interaction between the NS1 fragment and the intramembrane domain of the TCR alpha subunit. We have proposed a possible scheme for such interaction obtained by computer modeling.

This suggests the existence of another NS1-mediated mechanism of immunosuppression in influenza.

Abstract Figure
Occupational stress in the construction industry: a bibliometric-qualitative analysis of literature and future research directions
Authors: Chiang Dephanie Cheok Ieng , Antwi-Afari Maxwell Fordjour , Anwer Shahnawaz , Mohandes Saeed Reza , Li Xiao
Published: December 2023

Purpose

Given the growing concern about employees' well-being, numerous researchers have investigated the causes and effects of occupational stress. However, a review study on identifying existing research topics and gaps is still deficient in the extant literature. To fill this gap, this review study aims to present a bibliometric and science mapping approach to review the state-of-the-art journal articles published on occupational stress in the construction industry.

Design/methodology/approach

A three-fold comprehensive review approach consisting of bibliometric review, scientometric analysis and in-depth qualitative discussion was employed to review 80 journal articles in Scopus.

Findings

Through qualitative discussions, mainstream research topics were summarized, research gaps were identified and future research directions were proposed as follows: versatile stressors and stress model; an extended subgroup of factors in safety behavior; adaptation of multiple biosensors and bio-feedbacks; evaluation and comparison of organizational stress interventions; and incorporation of artificial intelligence and smart technologies into occupational stress management in construction.

Originality/value

The findings of this review study present a well-rounded framework to identify the research gaps in this field to advance research in the academic community and enhance employees' well-being in construction.
From traditional to emerging technologies in supporting smart libraries. A bibliometric and thematic approach from 2013 to 2022
Authors: Khan Asad Ullah , Ma Zhiqiang , Li Mingxing , Zhi Liangze , Hu Weijun , Yang Xia
Published: December 2023

Purpose

The evolution from emerging technologies to smart libraries is thoroughly analyzed thematically and bibliometrically in this research study, spanning 2013 through 2022. Finding and analyzing the significant changes, patterns and trends in the subject as they are represented in academic papers is the goal of this research.

Design/methodology/approach

Using bibliometric methodologies, this study gathered and examined a large corpus of research papers, conference papers and related material from several academic databases.

Findings

Starting with Artificial Intelligence (AI), the Internet of Things (IoT), Big Data (BD), Augmentation Reality/Virtual Reality and Blockchain Technology (BT), the study discusses the advent of new technologies and their effects on libraries. Using bibliometric analysis, this study looks at the evolution of publications over time, the geographic distribution of research and the most active institutions and writers in the area. A thematic analysis is also carried out to pinpoint the critical areas of study and trends in emerging technologies and smart libraries. Some emerging themes are information retrieval, personalized recommendations, intelligent data analytics, connected library spaces, real-time information access, augmented reality/virtual reality applications in libraries and strategies, digital literacy and inclusivity.

Originality/value

This study offers a thorough overview of the research environment by combining bibliometric and thematic analysis, illustrating the development of theories and concepts during the last ten years. The results of this study helps in understanding the trends and future research directions in emerging technologies and smart libraries. This study is an excellent source of information for academics, practitioners and policymakers involved in developing and applying cutting-edge technology in library environments.
A bargaining perspective on vertical integration
Authors: Döpper Hendrik , Sapi Geza , Wey Christian
Published: December 2023

We analyze vertical integration incentives in a bilaterally duopolistic industry with bargaining in the input market. Vertical integration incentives are a combination of horizontal integration incentives upstream and downstream and depend on the strength of substitutability and complementarity and the shape of the unit cost function. Under particular circumstances, vertical integration can convey more bargaining power to the merged entity than a horizontal merger to monopoly. In a bidding game for an exogenously determined target firm, a vertical merger can dominate a horizontal one, while pre‐emption does not occur.