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The article discusses the research conducted by Maarten Bebelman, Lenka Belicova, and Marino Zerial on hepatoblasts, which are progenitors of liver cells that differentiate into hepatocytes or cholangiocytes. The study reveals how hepatoblast polarization and lumen morphogenesis are linked to hepatocyte cell fate determination. The researchers investigated how inducing isotropic lumen growth instead of anisotropic lumen elongation affects gene expression and proper hepatocyte differentiation. The findings suggest that lumen morphology plays a crucial role in regulating gene expression during the differentiation of liver progenitors. [Extracted from the article]

[Display omitted] • A MIP paper-based electrochemical cell was developed for the determination of 5-hydroxymethylfurfural. • The linear concentration range was between 5.0 to 1000 µmol/L. • The device was successfully applied in different honey samples. The concentration of 5-hydroxymethylfurfural (HMF) has become one of the most useful parameters for the quality evaluation of honey − a crucial focus within the honey industry. In this work, a voltammetric molecularly imprinted polymer (MIP) paper-based electrochemical cell for the rapid quantification of HMF in honey is presented for the first time. Carbon ink was used to produce a custom-designed working electrode on chromatographic paper. The selected functional monomer was 4-aminobenzoic acid (ABA). MIP was obtained by electropolymerization directly on electrodes. The preparation process of the MIP, as well as the integrity of the paper platform, were investigated and optimized. Cyclic voltammetry was employed to characterize the sensor. Based on the optimized conditions, it revealed an imprinting factor of 13.5, a linear response in the range between 5.0 and 1000 µmol/L with a limit of detection of 0.608 mg kg−1. The sensor's practical applicability for the quantification of HMF in honey samples was successfully tested, demonstrating good performance compared with high performance liquid chromatography (HPLC). With the inherent sustainable properties of paper platforms, this cost-effective and disposable MIP paper-based electrochemical cell holds promise as a viable alternative for on-site monitoring of HMF in honey. [ABSTRACT FROM AUTHOR]

A new study in the journal Development has found that many mRNAs enriched in germ granules in Caenorhabditis elegans are not involved in germline development. The researchers were surprised to find that most of the transcripts in germ granules encode general housekeeping functions and are degraded before the formation of primordial germ cells (PGCs). Only a small number of transcripts are maintained in PGCs and are required for germ cell fate. The researchers hypothesize that the majority of transcripts in germ granules function as structural scaffolds to support the condensation of the protein MEG-3, while only a minority of transcripts enrich in PGCs and play a role in germ cell fate determination. [Extracted from the article]

Dental stem cells, with their exceptional proliferative capacity and multidirectional differentiation potential, hold significant promise for dental and oral tissue regeneration. Epigenetic inheritance, which involves stable and heritable changes in gene expression and function without alterations to the DNA sequence, plays a critical role in numerous biological processes. Environmental factors are particularly influential in epigenetic inheritance, as variations in exposure can lead to changes in epigenetic modifications that subsequently impact gene expression. Epigenetic mechanisms are widely involved in processes such as bone homeostasis, embryogenesis, stem cell fate determination, and disease development. Recently, the epigenetic regulation of dental stem cells has attracted considerable research attention. This paper reviews studies focused on the epigenetic mechanisms governing the multidirectional differentiation of dental stem cells. [ABSTRACT FROM AUTHOR]

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To construct a femtocell based ultra-dense network (UDN) is the important way to satisfy the ever-growing data traffic demands in the next generation mobile networks. However, it causes frequent handovers (HOs), thus leading to negative consequences such as increased power consumption and poor quality of service (QoS). This paper represents a research on the uplink handover (UL-HO) being watched recently and proposes a new method to further improve the energy efficient and QoS. First, we confirm the UL-HO mechanism, formulate the power consumption caused by UL-HO and compare downlink handover (DL-HO) with UL-HO in terms of the performance parameters including the power consumption, handover rate (HOR), handover failure rate (HOFR), ping-pong rate (PPR), delay, packet loss rate (PLR) and throughput during handover (HO). Then, it is proved through simulation that the reliable target cell determination scheme considering uplink reference signal received power (UL-RSRP), available bandwidth, direction of user equipment (UE), and admission control is lower in HOR, HOFR, PPR, power consumption, delay and PLR. In particular, we propose a new algorithm to determine the reasonable target cell considering UL-RSRP, available bandwidth and moving direction of UE, thus reducing HOR and PPR. The improved UL-HO scheme can be implemented easily by adding some functions besides the upper-layer protocol, while it can provide a lot of benefits such as reduced power consumption, delay, frequent HOs resulting in reducing HOR and PPR. Accordingly, this can be introduced into 5G as a HO scheme. [ABSTRACT FROM AUTHOR]

Performing measurements and compiling a power matrix (IEC 61853-1) is a useful tool for illustrating the energy production of a PV module at different levels of irradiance and temperature. At the European Solar Test Installation (ESTI) a steady-state solar simulator can be used to determine these matrices. The steady-state solar simulator irradiates the PV module from the front side, which heats the module to the desired temperature. However, this causes a temperature difference between the front surface of the module and the rear, where the temperature sensor is attached. This temperature difference, between the measured module temperature (Tm) and the temperature of the cell junction, gives rise to errors. In this paper, a correction procedure according to the determination of the equivalent cell temperature (ECT) of photovoltaic devices by the open-circuit voltage method in IEC 60904-5 is proposed and evaluated. In this study the difference between the Tm and the ECT was determined to about 1 °C to 3 °C, resulting in a deviation of the Pmax value in the power matrix up to about 1.5%, for a monocrystalline PV module. [ABSTRACT FROM AUTHOR]

Aquatic ecosystems polluted by heavy metals can affect microalgae growth when their concentrations overcome certain limits, depending on each involved heavy metal species. Yet, for heavy metal concentrations in the low range, microalgae exhibit metal tolerance and can accumulate a diversity of metal species from aqueous media. In particular, Spirulina platensis proved biosorption ability for heavy metals like Zn, Cd, Pb, or Cr, which can make it useful for the bioremediation of aquatic media polluted with heavy metals. This prokaryotic cyanobacteria from the microalgae species, which has a high protein, carbohydrate, and fats content, can interact with heavy metals through biosorption/bioaccumulation, leading to changes in the biomass yield, growth rate, and implicitly, biomass composition. This paper aims to investigate the influence of some heavy metal ions on the development and metabolic processes occurring in the cyanobacteria S. platensis, in order to establish its limitations in heavy metal bioremediation. In this regard, submerged cultures of S. platensis, involving standardized culture medium (Zarrouk), in the presence of nickel, cadmium, and lead ions in different concentrations (0.5 mg/L, 1.0 mg/L, and 1.5 mg/L, were considered. The cultivation of the microalgae was carried out for 28 days, with the determination of cell mass growth, dry biomass, protein accumulation, cell viability, and pH of the culture media, at certain time intervals (0, 3, 7, 13, 18, 24, and 28 days). Spirulina cultures were affected by the metal ions in different degrees, depending both on the type of metal ion and its concentration. The most toxic for cell growth and biomass accumulation were nickel and cadmium ions, at concentrations of 1.0 mg/L, and 1.5 mg/L, respectively. Cadmium, regardless of concentration, caused a decrease in dry biomass weight throughout the microalgae cultivation period. Instead, lead exhibited the lowest effect on the viability and integrity of spirulina cells, regardless of the concentration in which it was used. [ABSTRACT FROM AUTHOR]

Highly porous open-cell carbon materials have great potential for use as high-temperature thermal insulation for space vehicles due to a unique combination of properties: low density, high rigidity, sufficient compressive strength, and low thermal conductivity. The physical properties of these materials essentially depend on their microstructure. This implies the possibility of constructing a new advanced technique for the optimal design of multilayer thermal protection systems for aerospace vehicles, taking into account the dependence of materials' thermal properties on microstructure. The formulation of the optimization problem traditional to thermal design implies the determination of the layer thicknesses that provide a minimum specific mass of the thermal protection, subject to the specified constraints on the maximum temperatures in the layers. The novelty of this work lies in the fact that, along with the thickness of the layers, the design parameters include the cell diameter and porosity, which characterize the structure of highly porous cellular materials. The innovative part of the presented paper lies in the determination of cell diameter and the porosity of open-cell carbon foam together with the thickness of the layers for multilayer thermal insulation, ensuring the required operational temperature on the boundaries of the layers and a minimum of the total mass of the system. This article reveals new possibilities for using the numerical optimization method to determine the geometric parameters of the thermal protection system and the morphology of the materials used. A new methodology for designing heat-loaded structures based on the simultaneous selection of macro- and micro-parameters of the system is proposed. The basic principles of constructing an algorithm for designing a multilayer thermal protection system are outlined, taking into account the possibility of choosing the parameters of the highly porous materials' structure. The reliability of the developed optimization method was verified by comparing the results of mathematical modeling with experimental data obtained for highly porous cellular materials with known microstructure parameters. [ABSTRACT FROM AUTHOR]

The Epidermal Growth Factor Receptor (EGFR) signaling pathway plays a critical role in regulating tissue patterning. Drosophila EGFR signaling achieves specificity through multiple ligands and feedback loops to finetune signaling outcomes spatiotemporally. The principal Drosophila EGF ligand, cleaved Spitz, and the negative feedback regulator, Argos are diffusible and can act both in a cell autonomous and non-autonomous manner. The expression dose of Spitz and Argos early in photoreceptor cell fate determination has been shown to be critical in patterning the Drosophila eye, but the exact identity of the cells expressing these genes in the larval eye disc has been elusive. Using single molecule RNA Fluorescence in situ Hybridization (smFISH), we reveal an intriguing differential expression of spitz and argos mRNA in the Drosophila third instar eye imaginal disc indicative of directional non-autonomous EGFR signaling. By genetically tuning EGFR signaling, we show that rather than absolute levels of expression, the ratio of expression of spitz-to-argos to be a critical determinant of the final adult eye phenotype. Proximate effects on EGFR signaling in terms of cell cycle and differentiation markers are affected differently in the different perturbations. Proper ommatidial patterning is robust to thresholds around a tightly maintained wildtype spitz-to-argos ratio, and breaks down beyond. This provides a powerful instance of developmental buffering against gene expression fluctuations. Author summary: Sexual multicellular organisms start life as a single cell–the fertilized egg. One of the fundamental questions of Developmental Biology is to understand how cells proliferate and assume specific identities to faithfully reproduce the organismal tissue patterning. Cells communicate via signaling pathways to achieve complex patterning outcomes. Epidermal Growth Factor Receptor (EGFR) signaling is known to coordinate both cell division and fate choices in animals ranging from humans to the fruit-fly (Drosophila melanogaster). The fruit-fly eye with its strikingly patterned, hexagonally arranged units is a remarkable example of tissue patterning by EGFR signaling. In this paper, we investigate how expression levels of an activator (Spitz) and inhibitor (Argos) that tune the activation level of EGFR pathway regulate the patterning of the Drosophila eye. We find the activator-to-inhibitor ratio to be a critical factor in this process. The pattern is robust in a range around a tightly-controlled wildtype ratio. Beyond this biological range, both cell fate and cell division are affected producing different 'rough-eye' phenotypes. This is a striking example of how developmental patterning may be buffered against reasonable fluctuations in gene expression. [ABSTRACT FROM AUTHOR]

The cargo carried by extracellular vesicles (EVs) plays an important physiological role in their corresponding target organs or target tissue cells. Extracellular vesicles are classified into large extracellular vesicles (LEVs) and small extracellular vesicles (SEVs) according to their diameters. Since different subtypes contain different contents, their roles are also different. In this study, the morphology and size of LEVs were analyzed by transmission electron microscopy and nanoparticle size, and the marker proteins of LEVs (CD63, GP96, TSG101, ALB) were identified by western blot, and high-purity LEVs were obtained. Through the uptake of extracellular vesicles by purified ovarian granulosa cells and the determination of granulosa cell viability, cell apoptosis, and steroid hormone production, the result indicated that LEVs significantly enhanced cell viability (P < 0.05), reduced the rate of granulosa cell apoptosis (P < 0.05). Meanwhile, LEVs promoted the secretion of estradiol in granulosa cells (P < 0.05). This study provides a reference for the in-depth study of the function of follicular fluid extracellular vesicle subtypes and the research on the regulation of extracellular vesicles on follicle and oocyte development. [Display omitted] • This study is the first to compare the effects of LEVs and SEVs in bovine follicular fluid on granulosa cells. • This paper reveals that LEVs in bovine follicular fluid inhibit granulosa cell apoptosis and promote granulosa cell proliferation. • This paper investigates that LEVs in bovine follicular fluid promote estradiol secretion in granulosa cells. [ABSTRACT FROM AUTHOR]

Cytoskeleton proteins have been long recognized as structural proteins that provide the necessary mechanical architecture for cell development and tissue homeostasis. With the completion of the cancer genome project, scientists were surprised to learn that huge numbers of mutated genes are annotated as cytoskeletal or associated proteins. Although most of these mutations are considered as passenger mutations during cancer development and evolution, some genes show high mutation rates that can even determine clinical outcomes. In addition, (phospho)proteomics study confirms that many cytoskeleton-associated proteins, e.g., β-catenin, PIK3CA, and MB21D2, are important signaling mediators, further suggesting their biofunctional roles in cancer development. With emerging evidence to indicate the involvement of mechanotransduction in stemness formation and cell differentiation, mutations in these key cytoskeleton components may change the physical/mechanical properties of the cells and determine the cell fate during cancer development. In particular, tumor microenvironment remodeling triggered by such alterations has been known to play important roles in autophagy, metabolism, cancer dormancy, and immune evasion. In this review paper, we will highlight the current understanding of how aberrant cytoskeleton networks affect cancer behaviors and cellular functions through mechanotransduction. [ABSTRACT FROM AUTHOR]

Cell type determination based on transcriptome profiles is a key application of single-cell RNA sequencing (scRNA-seq). It is usually achieved through unsupervised clustering. Good feature selection is capable of improving the clustering accuracy and is a crucial component of single-cell clustering pipelines. However, most current single-cell feature selection methods are univariable filter methods ignoring gene dependency. Even the multivariable filter methods developed in recent years only consider "one-to-many" relationship between genes. In this paper, a novel single-cell feature selection method based on convex analysis of mixtures (FSCAM) is proposed, which takes into account "many-to-many" relationship. Compared to the previous "one-to-many" methods, FSCAM selects genes with a combination of relevancy, redundancy and completeness. Pertinent benchmarking is conducted on the real datasets to validate the superiority of FSCAM. Through plugging into the framework of partition around medoids (PAM) clustering, a single-cell clustering algorithm based on FSCAM method (SCC_FSCAM) is further developed. Comparing SCC_FSCAM with existing advanced clustering algorithms, the results show that our algorithm has advantages in both internal criteria (clustering number) and external criteria (adjusted Rand index) and has a good stability. [ABSTRACT FROM AUTHOR]

It is known that blastoderm contains not only blastodermal cells (BCs) but also cellular "debris". These particles include yolk granules and lipid droplets. Some authors used AnnexinV (AnV) staining technique for determination of cell apoptosis. However, AnV is a protein with high affinity to lipids. So the aim of our study was to demonstrate the AnV binding in the blastoderm and yolk cell suspensions. Cell populations were obtained from fertilized chicken eggs. The blastoderms were isolated using filter paper ring method and mechanically fragmented. After that, samples were stained with AnV-FITC and analyzed by fluorescent microscopy (FM) and flow cytometry (FC). FM showed non-specific binding of AnV-FITC on the yolk and lipid particles. Therefore, the FC method using specific nuclear dye DRAQ5 was used to separate BCs from cellular debris. Only 1.82 ± 0.27 % cells were DRAQ5 positive. On the other hand, increase of total events (21 ± 3.30 %) of AnV positive cells without DRAQ5 dye was recorded. Moreover, the affinity of yolk to AnV by FC was also observed (10.45 ± 2.59 %). Significant differences among the groups (P < 0.001) were recorded. This trend was caused by non-specific binding of AnV to the lipid and yolk particles. So it is necessary to stain suspension with nuclear dye to separate BCs than co-stained with some marker of apoptosis. Based on the results we can summarized that AnV staining is inappropriate technique for apoptosis of BCs, however, using nuclear dye we can prevent of non-specific binding. [ABSTRACT FROM AUTHOR]

Screening and quantification of emerging contaminants in water is of enormous relevance due to its scarcity and harmful effects on aquatic life and human health. We present a simple and cost-effective electrochemical cell for determination of the antidepressant venlafaxine, an emerging contaminant included in the EU Watch list 2022. The cell consists of pencil leads used as electrodes and a microcentrifuge tube. Modification of the working electrode with carbon nanomaterials improved the signal. Cell-related (e.g., type of pencil leads or electroactive area) as well as experimental (e.g., pH, accumulation potential and time, and scan rate) parameters were thoroughly optimized. The adsorptive nature of venlafaxine process allowed the use of an adsorptive stripping square wave voltammetry methodology to increase the sensitivity. Under optimized variables, a linear range from 0.8 to 10 μmol L−1 with a correlation coefficient of 0.996, a sensitivity of 1.48 μmol L−1, a LOD of 0.4 μmol L−1 and a RSD of 2.4 % were achieved. Selectivity was also studied, especially with respect to the main metabolite, o -desmethylvenlafaxine. The methodology distinguishes its signal from that of the main compound, allowing its determination. A similar linear range was obtained for the metabolite, with a LOD of 0.6 μmol L−1. The platform developed was applied for venlafaxine quantification in spiked wastewaters from the Febros plant in Portugal, obtaining satisfactory recoveries. Furthermore, the versatility of pencil leads made it possible to combine them with modified paper for sampling and buffering in order to decentralize the determination, showing promising results. [Display omitted] [ABSTRACT FROM AUTHOR]

The concurrence of chronic obstructive pulmonary disease (COPD) and lung cancer has been widely reported and extensively addressed by pulmonologists and oncologists. However, most studies have focused on shared risk factors, DNA damage pathways, immune microenvironments, inflammation, and imbalanced proteases/antiproteases. In the present review, we explore the association between COPD and lung cancer in terms of airway pluripotent cell fate determination and discuss the various cell types and signaling pathways involved in the maintenance of lung epithelium homeostasis and their involvement in the pathogenesis of co-occurring COPD and lung cancer. [ABSTRACT FROM AUTHOR]

The initial fine-tuning processes are crucial for successful bone regeneration, as they guide skeletal stem cells through progenitor differentiation toward osteo- or chondrogenic fate. While fate determination processes are well-documented, the mechanisms preceding progenitor commitment remain poorly understood. Here, we identified a transcription factor, Zfp260, as pivotal for stem cell maturation into progenitors and directing osteogenic differentiation. Zfp260 is markedly up-regulated as cells transition from stem to progenitor stages; its dysfunction causes lineage arrest at the progenitor stage, impairing bone repair. Zfp260 is required for maintaining chromatin accessibility and regulates Runx2 expression by forming super-enhancer complexes. Furthermore, the PKCα kinase phosphorylates Zfp260 at residues Y173, S182, and S197, which are essential for its functional activity. Mutations at these residues significantly impair its functionality. These findings position Zfp260 as a vital factor bridging stem cell activation with progenitor cell fate determination, unveiling a element fundamental to successful bone regeneration. Yuteng, Wang and colleagues identify the transcription factor Zfp260, which promotes Runx2 expression and is required for differentiation of progenitors from skeletal stem cells and bone repair in mice. [ABSTRACT FROM AUTHOR]

The Human Cell Atlas (HCA) is a global partnership "to create comprehensive reference maps of all human cells—the fundamental units of life – as a basis for both understanding human health and diagnosing, monitoring, and treating disease." (https://www.humancellatlas.org/) The atlas shall characterize cells from diverse individuals across the globe to better understand human biology. HCA proactively considers the priorities of, and benefits accrued to, contributing communities. Here, we lay out principles and action items that have been adopted to affirm HCA's commitment to equity so that the atlas is beneficial to all of humanity. The Human Cell Atlas (HCA) aims to characterize cells from diverse individuals across the globe to better understand human biology. Here, the authors lay out principles and action items that have been adopted to affirm HCA's commitment to equity so that the atlas is beneficial to all of humanity. [ABSTRACT FROM AUTHOR]

Heterotopic ossification (HO), often arising in response to traumatic challenges, results from the aberrant osteochondral differentiation of mesenchymal stem cells (MSCs). Nevertheless, the impact of trauma‐induced inflammatory exposure on MSC fate determination remains ambiguous. In this study, the cellular diversity within inflammatory lesions is elucidated, comprising MSCs and several innate and adaptive immune cells. It is observed that quiescent MSCs transition into cycling MSCs, subsequently giving rise to chondrogenic (cMSC) and/or osteogenic (oMSC) lineages within the inflammatory microenvironment following muscle or tendon injuries, as revealed through single‐cell RNA sequencing (scRNA‐seq), spatial transcriptome and lineage tracing analysis. Moreover, these investigations demonstrate that neutrophils and natural killer (NK) cells enhance transition of quiescent MSCs into cycling MSCs, which is also controlled by M1 macrophages, a subpopulation of macrophages can also stimulate cMSC and oMSC production from cycling MSCs. Additionally, M2 macrophages, CD4+ and CD8+ T lymphocytes are found to promote chondrogenesis. Further analysis demonstrates that immune cells promotes the activation of signaling transducers and activators of transcription (STAT) pathway and phosphoinositide 3 (PI3K)/protein kinase B (AKT) pathway in MSC proliferation and osteochondral progenitors' production, respectively. These findings highlight the dynamics of MSC fate within the inflammatory lesion and unveil the molecular landscape of osteoimmunological interactions, which holds promise for advancing HO treatment. [ABSTRACT FROM AUTHOR]

TET-family members play a critical role in cell fate commitment. Indeed, TET3 is essential to postnatal development due to yet unknown reasons. To define TET3 function in cell differentiation, we have profiled the intestinal epithelium at single-cell level from wild-type and Tet3 knockout mice. We have found that Tet3 is mostly expressed in differentiated enterocytes. In the absence of TET3, enterocytes exhibit an aberrant differentiation trajectory and do not acquire a physiological cell identity due to an impairment in oxidative phosphorylation, specifically due to an ATP synthase assembly deficiency. Moreover, spatial metabolomics analysis has revealed that Tet3 knockout enterocytes exhibit an unphysiological metabolic profile when compared with their wild-type counterparts. In contrast, no metabolic differences have been observed between both genotypes in the stem cell compartment where Tet3 is mainly not expressed. Collectively, our findings suggest a mechanism by which TET3 regulates mitochondrial function and, thus, terminal cell differentiation at the metabolic level. TET3 is essential to postnatal development due to unknown reasons. Here Mulet et al. demonstrate that TET3 is required for ATP synthase assembly in differentiated cells and that its loss leads to an unphysiological metabolic profile. [ABSTRACT FROM AUTHOR]

Cyst nematodes use a stylet to secrete CLE-like peptide effector mimics into selected root cells of their host plants to hijack endogenous plant CLE signaling pathways for feeding site (syncytium) formation. Here, we identified ATHB8, encoding a HD-ZIP III family transcription factor, as a downstream component of the CLE signaling pathway in syncytium formation. ATHB8 is expressed in the early stages of syncytium initiation, and then transitions to neighboring cells of the syncytium as it expands; an expression pattern coincident with auxin response at the infection site. Conversely, MIR165a, which expresses in endodermal cells and moves into the vasculature to suppress HD-ZIP III TFs, is down-regulated near the infection site. Knocking down HD-ZIP III TFs by inducible over-expression of MIR165a in Arabidopsis dramatically reduced female development of the sugar beet cyst nematode (Heterodera schachtii). HD-ZIP III TFs are known to function downstream of auxin to promote cellular quiescence and define stem cell organizer cells in vascular patterning. Taken together, our results suggest that HD-ZIP III TFs function together with a CLE and auxin signaling network to promote syncytium formation, possibly by inducing root cells into a quiescent status and priming them for initial syncytial cell establishment and/or subsequent cellular incorporation. Author summary: Plant-parasitic cyst nematodes are one of the most damaging pathogens impacting crop production. These nematodes establish a permanent feeding site called a syncytium to withdraw nutrients from plant roots, causing plant malnutrition and reduced crop yield. The syncytium is induced by nematode stylet-secreted effectors, many of which hijack innate plant developmental programs to convert a normal plant cell to a syncytial cell. One such group of effectors functions by mimicking plant CLE peptide hormones, which are important in plant cell fate determination, and play a crucial role in syncytium formation. In this study, we show that nematode secreted CLE-like effectors induce the expression of the ATHB8 gene, a member of the Class III HD-ZIP transcription factor family, at early stages of syncytium formation. Reducing the level of HD-ZIP III family genes compromised the nematode's ability to feed on plants, indicating that HD-ZIP III transcription factors are important for cyst nematode parasitism. [ABSTRACT FROM AUTHOR]

Competitive athletes are often exposed to extreme physiological loading, resulting in over excessive mechanotransduction during their acute intensive training sessions and competitions. Individual differences in their genetics often affect how they cope with these challenges, as reflected in their high performances. Olympic Medalists are prohibited from providing atypical values in the Hematological Module of the Athlete Biological Passport. Since there was no aphysiological result and the Athlete maintained his innocence, a whole genome sequence analysis was carried out on him and his parents, with the primary focus on the PIEZO ion channels encoding gene. PIEZO1 is known to participate in homeostatic regulation even on a whole-body level, including the regulation of physical performance, circulatory longevity of red blood cells and cell fate determination of mesenchymal stem cells in relation to hydrostatic pressure. However, PIEZO2 was found to be the principal mechanosensory ion channel for proprioception. These regulatory mechanisms play a pivotal role in mechanotransduction and intensive exercise moments. Interestingly, two variances of uncertain significance of PIEZO1 were found that may explain the atypical values of the Athlete. Furthermore, two additional variances in SDC2, the syndcan-2 encoding gene, were identified in trans position that may influence the crosstalk between PIEZO2 and PIEZO1, with more likely relevance to the detected atypical values. After all, based on the found variances of PIEZO1 and syndecan-2, it cannot be ruled out that these VUS variants may have caused or impacted the exhibited outlier findings of the ABP Hematological Module of the Athlete. [ABSTRACT FROM AUTHOR]

Since cancer has emerged as one of the most serious threats to human health, the highly sensitive determination of cancer cells is of significant importance to improve the accuracy of early clinical diagnosis. In our investigation, a novel cascade Fermat spiral microfluidic mixer chip (CFSMMC) combined with fluorescence sensors as a point-of-care (POC) testing system is successfully fabricated to detect and differentiate cancer cells (MCF-7) from normal cells with excellent sensitivity and selectivity. Here, copper ions (Cu2+) with peroxidase properties can catalyze the oxidation of the non-fluorescent substrate Amplex Red (AR) to the highly fluorescent resorufin (ox-AR) in the presence of hydrogen peroxide (H2O2). Subsequently, thanks to the quenching response of AS1411-AuNPs to ox-AR in the microchannel and the binding of AS1411 to nucleolin on the surface of cancer cells, a CFSMMC-based POC system is established for the highly sensitive detection and identification of human breast cancer cells in a "turn on" manner. The change in fluorescence intensity is linearly related to the concentration of MCF-7, ranging from 102 to 107 cells per mL with a limit of detection (LOD) as low as 17 cells per mL. Interestingly, the cascaded AND logic gate is integrated with CFSMMC for the first time to distinguish cancer cells from normal cells under the control of logic functions, which exhibits great potential in the development of one-step rapid and intelligent detection and logic discrimination. [ABSTRACT FROM AUTHOR]

Seed dormancy ensures plant survival but many mechanisms remain unclear. A high-throughput RNA-seq analysis investigated the mechanisms involved in the establishment of dormancy in dimorphic seeds of Xanthium strumarium (L.) developing in one single burr. Results showed that DOG1, the main dormancy gene in Arabidopsis thaliana L., was over-represented in the dormant seed leading to the formation of two seeds with different cell wall properties. Less expression of DME/EMB1649, UBP26, EMF2, MOM, SNL2, and AGO4 in the non-dormant seed was observed, which function in the chromatin remodelling of dormancy-associated genes through DNA methylation. However, higher levels of ATXR7/SDG25, ELF6, and JMJ16/PKDM7D in the nondormant seed that act at the level of histone demethylation and activate germination were found. Dramatically lower expression in the splicing factors SUA, PWI, and FY in non-dormant seed may indicate that variation in RNA splicing for ABA sensitivity and transcriptional elongation control of DOG1 is of importance for inducing seed dormancy. Seed size and germination may be influenced by respiratory factors, and alterations in ABA content and auxin distribution and responses. TOR (a serine/threonine-protein kinase) is likely at the centre of a regulatory hub controlling seed metabolism, maturation, and germination. Over-representation of the respirationassociated genes (ACO3, PEPC3, and D2HGDH) was detected in non-dormant seed, suggesting differential energy supplies in the two seeds. Degradation of ABA biosynthesis and/or proper auxin signalling in the large seed may control germinability, and suppression of endoreduplication in the small seed may be a mechanism for cell differentiation and cell size determination. [ABSTRACT FROM AUTHOR]

Two new copper(II) complexes of sparfloxacin (sf), [Cu(Hsf)(HPB)(H2O)](ClO4)2 (1) and [Cu(Hsf)(PBT)(H2O)](ClO4)2 (2) (where HPB = 2-(2′-pyridyl)benzimidazole and PBT = 2-(4′-pyridyl) benzothiazole), have been synthesized and characterized by physicochemical and spectroscopic techniques. The oil–water partition coefficient (log P) values of complexes 1 and 2 were 1.47 and 1.71, respectively. By studying the interaction between the complexes and DNA, it was found that the complexes could bind to DNA through an intercalation mode. Moreover, both complexes were evaluated for antitumor activity, revealing that the complexes displayed good inhibitory activity toward the tested cancer cell lines (human lung carcinoma A549 cells, human hepatocellular carcinoma Bel-7402 cells and human esophageal carcinoma Eca-109 cells), but showed relatively low toxicity against normal human hepatic LO2 cells. In particular, the antitumor mechanism of the complexes on Eca-109 cells was investigated by morphological analysis, apoptosis analysis and determination of cell cycle arrest, mitochondrial membrane potential, reactive oxygen species (ROS) levels, and release of cytochrome c and Ca2+. The results demonstrated that the complexes could induce loss of intracellular mitochondrial functions and increase of ROS levels, which led to an increase of Ca2+ levels and the release of cytochrome c into the cytoplasm. In addition, the cell cycle was arrested in the G2/M phase, and western blot analysis showed that the caspase family was activated. These results fully proved that the complexes could induce apoptosis through DNA damage and loss of mitochondrial functions, accompanied by the regulation of endogenous proteins. [ABSTRACT FROM AUTHOR]

One of the most critical axes for cell fate determination is how cells respond to excessive reactive oxygen species (ROS)--oxidative stress. Extensive lipid peroxidation commits cells to death via a distinct cell death paradigm termed ferroptosis. However, the molecular mechanism regulating cellular fates to distinct ROS remains incompletely understood. Through siRNA against human receptor-interacting protein kinase (RIPK) family members, we found that RIPK4 is crucial for oxidative stress and ferroptotic death. Upon ROS induction, RIPK4 is rapidly activated, and the kinase activity of RIPK4 is indispensable to induce cell death. Specific ablation of RIPK4 in kidney proximal tubules protects mice from acute kidney injury induced by cisplatin and renal ischemia/reperfusion. RNA sequencing revealed the dramatically decreased expression of acyl-CoA synthetase medium-chain (ACSM) family members induced by cisplatin treatment which is compromised in RIPK4-deficient mice. Among these ACSM family members, suppression of ACSM1 strongly augments oxidative stress and ferroptotic cell death with induced expression of ACS long-chain family member 4, an important component for ferroptosis execution. Our lipidome analysis revealed that overexpression of ACSM1 leads to the accumulation of monounsaturated fatty acids, attenuation of polyunsaturated fatty acid (PUFAs) production, and thereby cellular resistance to ferroptosis. Hence, knockdown of ACSM1 resensitizes RIPK4 KO cells to oxidative stress and ferroptotic death. In conclusion, RIPK4 is a key player involved in oxidative stress and ferroptotic death, which is potentially important for a broad spectrum of human pathologies. The link between the RIPK4-ASCM1 axis to PUFAs and ferroptosis reveals a unique mechanism to oxidative stress-induced necrosis and ferroptosis. [ABSTRACT FROM AUTHOR]

Metabolism has been implicated in cell fate determination, particularly through epigenetic modifications. Similarly, lipid remodeling also plays a role in regulating cell fate. Here, we present comprehensive lipidomics analysis during BMP4-driven primed to naive pluripotency transition or BiPNT and demonstrate that lipid remodeling plays an essential role. We further identify Cpt1a as a rate-limiting factor in BiPNT, driving lipid remodeling and metabolic reprogramming while simultaneously increasing intracellular acetyl-CoA levels and enhancing H3K27ac at chromatin open sites. Perturbation of BiPNT by histone acetylation inhibitors suppresses lipid remodeling and pluripotency transition. Together, our study suggests that lipid remodeling promotes pluripotency transitions and further regulates cell fate decisions, implicating Cpt1a as a critical regulator between primed-naive cell fate control. The metabolomic landscape characterizing the PNT process elucidates the crucial role of CPT1A in driving lipid remodeling, thereby regulating the transition of cellular fate [ABSTRACT FROM AUTHOR]

Post-larval hematopoiesis in Drosophila largely depends upon the stockpile of progenitors present in the blood-forming organ/lymph gland of the larvae. During larval stages, the lymph gland progenitors gradually accumulate reactive oxygen species (ROS), which is essential to prime them for differentiation. Studies have shown that ROS triggers the activation of JNK (c-Jun Kinase), which upregulates fatty acid oxidation (FAO) to facilitate progenitor differentiation. Intriguingly, despite having ROS, the entire progenitor pool does not differentiate simultaneously in the late larval stages. Using expression analyses, genetic manipulation and pharmacological approaches, we found that the Drosophila NF-κB transcription factor Relish (Rel) shields the progenitor pool from the metabolic pathway that inducts them into the differentiation program by curtailing the activation of JNK. Although ROS serves as the metabolic signal for progenitor differentiation, the input from ROS is monitored by the developmental signal TAK1, which is regulated by Relish. This developmental circuit ensures that the stockpile of ROS-primed progenitors is not exhausted entirely. Our study sheds light on how, during development, integrating NF-κB-like factors with metabolic pathways seem crucial to regulating cell fate transition during development. Author summary: The determination of cell fate in stem/progenitor cells is crucial for normal development and various pathophysiological conditions. Our research focuses on the Drosophila larval blood-forming organ, the lymph gland, as a model to gain further insights into this intricate process. Interestingly, while the entire progenitor pool within this organ is enriched in Reactive Oxygen Species (ROS), which is a known trigger for differentiation, they do not differentiate entirely. We show that Relish, a component of the Immune Deficiency Pathway (IMD), plays a role in preventing premature differentiation of the progenitors. Relish hinders TAK1 (transforming growth factor-β-activated kinase 1), thereby reducing JNK activation downstream of ROS. This inhibition on JNK delays progenitor differentiation. Our study reveals an interplay between developmental signaling and metabolic factors that govern the fate specification and maintenance of blood progenitors. Given that the process of blood development in flies shares several similarities with mammalian hematopoiesis, including the presence of high ROS in the myeloid progenitors, it would be worth exploring whether similar interactions are at play in vertebrate hematopoiesis. In addition, it would be fascinating to investigate whether similar coordination between metabolic and developmental signals regulates the differentiation of stem/progenitor cells in other biological systems. [ABSTRACT FROM AUTHOR]

Circadian clocks are biochemical timers regulating many physiological and molecular processes according to the day/night cycles. The function of the oscillator relies on negative transcriptional/translational feedback loops operated by the so-called clock genes and the encoded clock proteins. Previously, we identified the small GTPase LIGHT INSENSITIVE PERIOD 1 (LIP1) as a circadian-clock-associated protein that regulates light input to the clock in the model plant Arabidopsis thaliana. We showed that LIP1 is also required for suppressing red and blue light-mediated photomorphogenesis, pavement cell shape determination and tolerance to salt stress. Here, we demonstrate that LIP1 is present in a complex of clock proteins GIGANTEA (GI), ZEITLUPE (ZTL) and TIMING OF CAB 1 (TOC1). LIP1 participates in this complex via GUANINE EX-CHANGE FACTOR 7. Analysis of genetic interactions proved that LIP1 affects the oscillator via modulating the function of GI. We show that LIP1 and GI independently and additively regulate photomorphogenesis and salt stress responses, whereas controlling cell shape and photoperiodic flowering are not shared functions of LIP1 and GI. Collectively, our results suggest that LIP1 affects a specific function of GI, possibly by altering binding of GI to downstream signalling components. [ABSTRACT FROM AUTHOR]

Avian Pasteurella multocida infection, can cause serious economic losses to the poultry industry every year. The inactivated vaccines of avian Pasteurella multocida are used to prevent infection. Increasing the cell density of avian Pasteurella multocida is the key to the application of these inactivated vaccines. This can be achieved by controlling the feeding strategy. This study aimed to achieve high-cell-density cultivation of avian Pasteurella multocida by applying an appropriate medium and a rational feeding strategy based on viable cell growth and dissolved oxygen level variation during a fermentation process. An optimized medium suited for the growth of avian P. multocida was used. Meanwhile, besides the online real-time determination of viable cell density, the concentration of glucose was maintained at 1.5 g/L using a glucose-stat feeding strategy after 2 h. The selected nutrient mixture, including yeast extract, tryptone, betaine, VB1, and VH, was fed using a dissolved oxygen feedback feeding strategy after 4 h. As a result, the viable cell density and cell count of avian P. multocida under optimized conditions were increased to OD600: 9.38 and 4.58×1010 CFU/mL, which were higher by 7.27 and 7.26 times than those under the original conditions, respectively. [ABSTRACT FROM AUTHOR]

In this study, biomass-derived carbon quantum dots (CQDs) were synthesized by an one-step hydrothermal method using folium cycas as a carbon source. By optimizing the reaction conditions, the fluorescence quantum yield of CQDs was obtained to be as high as 8.91%, and strong blue emission light was emitted. The characterization results showed that the CQDs were quasi-spherical with an average particle size of 2.69 ± 0.08 nm and contained a large number of hydrophilic functional groups with excellent water solubility and photostability. The CQDs showed high selectivity and sensitivity for the detection of Fe3+, with a low limit of detection of 0.72 μM and a wide linear range of 0–200 μM. The practical applicability of the CQDs was further established by carrying out Fe3+ detection in environmental sample analysis. Besides, CQDs have been successfully applied to in vitro cell imaging and bioimaging. The final by-product of the hydrothermal reaction, biochar, is used for dye adsorption. This work identifies the importance of using a relatively green process and an inexpensive biomass precursor to produce high-quality CQDs that hold a promising future for use in metal ion detection, bioimaging, and practical sensing applications. [ABSTRACT FROM AUTHOR]

Osteochondral lesions may be due to trauma or congenital conditions. In both cases, therapy is limited because of the difficulty of tissue repair. Tissue engineering is a promising approach that relies on designed scaffolds with variable mechanical attributes to favor cell attachment and differentiation. Human adipose-derived stem cells (hASCs) are a very promising cell source in regenerative medicine with osteochondrogenic potential. Based on the assumption that stiffness influences cell commitment, we investigated three different scaffolds: a semisynthetic animal-derived GelMA hydrogel, a combined scaffold made of rigid PEGDA coated with a thin GelMA layer and a decellularized plant-based scaffold. We investigated the role of different biomechanical stimulations in the scaffold-induced osteochondral differentiation of hASCs. We demonstrated that all scaffolds support cell viability and spontaneous osteochondral differentiation without any exogenous factors. In particular, we observed mainly osteogenic commitment in higher stiffness microenvironments, as in the plant-based one, whereas in a dense and softer matrix, such as in GelMA hydrogel or GelMA-coated-PEGDA scaffold, chondrogenesis prevailed. We can induce a specific cell commitment by combining hASCs and scaffolds with particular mechanical attributes. However, in vivo studies are needed to fully elucidate the regenerative process and to eventually suggest it as a potential approach for regenerative medicine. [ABSTRACT FROM AUTHOR]

The development of multicellular organisms requires coordinated changes in gene expression that are often mediated by the interaction between transcription factors (TFs) and their corresponding cis-regulatory elements (CREs). During development and differentiation, the accessibility of CREs is dynamically modulated by the epigenome. How the epigenome, CREs, and TFs together exert control over cell fate commitment remains to be fully understood. In the Arabidopsis leaf epidermis, meristemoids undergo a series of stereotyped cell divisions, then switch fate to commit to stomatal differentiation. Newly created or reanalyzed scRNA-seq and ChIP-seq data confirm that stomatal development involves distinctive phases of transcriptional regulation and that differentially regulated genes are bound by the stomatal basic helix–loop–helix (bHLH) TFs. Targets of the bHLHs often reside in repressive chromatin before activation. MNase-seq evidence further suggests that the repressive state can be overcome and remodeled upon activation by specific stomatal bHLHs. We propose that chromatin remodeling is mediated through the recruitment of a set of physical interactors that we identified through proximity labeling—the ATPase-dependent chromatin remodeling SWI/SNF complex and the histone acetyltransferase HAC1. The bHLHs and chromatin remodelers localize to overlapping genomic regions in a hierarchical order. Furthermore, plants with stage-specific knockdown of the SWI/SNF components or HAC1 fail to activate specific bHLH targets and display stomatal development defects. Together, these data converge on a model for how stomatal TFs and epigenetic machinery cooperatively regulate transcription and chromatin remodeling during progressive fate specification. The development of multicellular organisms requires coordinated changes in gene expression. Here, the authors analyze transcriptional regulation in Arabidopsis during stomata development, revealing that cell fate decisions depend on complex interactions between master bHLH transcription factors and the epigenetic machinery. [ABSTRACT FROM AUTHOR]

The search for new Natural Products is one of the oldest interests for research in chemistry. The history of this discipline is very prolific, from its initial uses as medicine to advanced omics strategies to understand the mechanics of biological controls in living cells. The discoveries of morphine, penicillin, taxol and many other natural products revolutionized human health. During the last 40 years, excellent reviews published by Dr. David Newman and Dr. Gordon Crag have revealed that the pharmaceutical industry's research into natural products has lost some of its steam. Nevertheless, new natural products for antimicrobials, antifungals, and anticancer drugs remained the main alternative. Furthermore, research institutes have seen great vigor, and several startup companies have emerged worldwide, seeking therapeutic alternatives based in natural products. Innovations on spectrometric hardware, allowing broader coverage of chemical classes and spatial mapping, and in software, enabling the interpretation of large volumes of data, afforded a renewed interest in natural products and are considered the most important enabling technology for the new companies. In this perspective article we give some historical context to exciting developments, on software and spatial resolution, that promise to pave the way for a bright future of Natural Products research. [ABSTRACT FROM AUTHOR]

Due to importance of cell voltage and caustic current efficiency (CCE) in chlor-alkali industry, the necessity of accurate approach for prediction these parameters has become evident. In the current work, an extreme learning machine (ELM) approach is used to this end. Determination of the statistical qualities including R2 and different types of error reveals the fact that ELM method is suitable tool for calculation of CCE and cell voltage. The determined R2 values for CCE and cell voltage are equal to 1. Furthermore, RMSE values are 0.00002 and 1.3 × 10−6 for cell voltage and CCE, respectively. On the other hand, different graphical methods confirmed this acclaim. Moreover a sensitivity analysis is used to show effect of brine concentration, current density, operating temperature, electrolyte velocity, run time and pH on cell voltage and CCE. This analysis concluded to the fact that brine concentration and current density have the most effects on CCE and Cell voltage, respectively. [ABSTRACT FROM AUTHOR]

White adipose tissue (WAT) makes up about 20–25% of total body mass in healthy individuals and is crucial for regulating various metabolic processes, including energy metabolism, endocrine function, immunity, and reproduction. In adipose tissue research, "adipogenesis" is commonly used to refer to the process of adipocyte formation, spanning from stem cell commitment to the development of mature, functional adipocytes. Although, this term should encompass a wide range of processes beyond commitment and differentiation, to also include other stages of adipose tissue development such as hypertrophy, hyperplasia, angiogenesis, macrophage infiltration, polarization, etc.... collectively, referred to herein as the adipogenic cycle. The term "differentiation", conversely, should only be used to refer to the process by which committed stem cells progress through distinct phases of subsequent differentiation. Recognizing this distinction is essential for accurately interpreting research findings on the mechanisms and stages of adipose tissue development and function. In this review, we focus on the molecular regulation of white adipose tissue development, from commitment to terminal differentiation, and examine key functional aspects of WAT that are crucial for normal physiology and systemic metabolic homeostasis. [ABSTRACT FROM AUTHOR]

Obesity, characterized by the accumulation of excess fat, is a complex condition resulting from the combination of genetic and epigenetic factors. Recent studies have found correspondence between DNA methylation and cell differentiation, suggesting a role of the former in cell fate determination. There is a lack of comprehensive understanding concerning the underpinnings of preadipocyte differentiation, specifically when cells are undergoing terminal differentiation (TD). To gain insight into dynamic genome-wide methylation, 3T3 L1 preadipocyte cells were differentiated by a hormone cocktail. The genomic DNA was isolated from undifferentiated cells and 4 hours, 2 days postdifferentiated cells, and 15 days TD cells. We employed whole-genome bisulfite sequencing (WGBS) to ascertain global genomic DNA methylation alterations at single base resolution as preadipocyte cells differentiate. The genome-wide distribution of DNA methylation showed similar overall patterns in pre-, post-, and terminally differentiated adipocytes, according to WGBS analysis. DNA methylation decreases at 4 hours after differentiation initiation, followed by methylation gain as cells approach TD. Studies revealed novel differentially methylated regions (DMRs) associated with adipogenesis. DMR analysis suggested that though DNA methylation is global, noticeable changes are observed at specific sites known as "hotspots." Hotspots are genomic regions rich in transcription factor (TF) binding sites and exhibit methylation-dependent TF binding. Subsequent analysis indicated hotspots as part of DMRs. The gene expression profile of key adipogenic genes in differentiating adipocytes is context-dependent, as we found a direct and inverse relationship between promoter DNA methylation and gene expression. [ABSTRACT FROM AUTHOR]

Summary: Inter‐subspecific indica–japonica hybrid rice (Oryza sativa) has the potential for increased yields over traditional indica intra‐subspecies hybrid rice, but limited yield of F1 hybrid seed production (FHSP) hinders the development of indica–japonica hybrid rice breeding. Diurnal flower‐opening time (DFOT) divergence between indica and japonica rice has been a major contributing factor to this issue, but few DFOT genes have been cloned. Here, we found that manipulating the expression of jasmonate (JA) pathway genes can effectively modulate DFOT to improve the yield of FHSP in rice. Treating japonica cultivar Zhonghua 11 (ZH11) with methyl jasmonate (MeJA) substantially advanced DFOT. Furthermore, overexpressing the JA biosynthesis gene OPDA REDUCTASE 7 (OsOPR7) and knocking out the JA inactivation gene CHILLING TOLERANCE 1 (OsHAN1) in ZH11 advanced DFOT by 1‐ and 2‐h respectively; and knockout of the JA signal suppressor genes JASMONATE ZIM‐DOMAIN PROTEIN 7 (OsJAZ7) and OsJAZ9 resulted in 50‐min and 1.5‐h earlier DFOT respectively. The yields of FHSP using japonica male‐sterile lines GAZS with manipulated JA pathway genes were significantly higher than that of GAZS wildtype. Transcriptome analysis, cytological observations, measurements of elastic modulus and determination of cell wall components indicated that the JA pathway could affect the loosening of the lodicule cell walls by regulating their composition through controlling sugar metabolism, which in turn influences DFOT. This research has vital implications for breeding japonica rice cultivars with early DFOT to facilitate indica–japonica hybrid rice breeding. [ABSTRACT FROM AUTHOR]

It is well established that microRNA-21 (miR-21) targets phosphatase and tensin homolog (PTEN), facilitating epithelial-to-mesenchymal transition (EMT) and drug resistance in cancer. Recent evidence indicates that PTEN activates its pseudogene-derived long non-coding RNA, PTENP1, which in turn inhibits miR-21. However, the dynamics of PTEN, miR-21, and PTENP1 in the DNA damage response (DDR) remain unclear. Thus, we propose a dynamic Boolean network model by integrating the published literature from various cancers. Our model shows good agreement with the experimental findings from breast cancer, hepatocellular carcinoma (HCC), and oral squamous cell carcinoma (OSCC), elucidating how DDR activation transitions from the intra-S phase to the G2 checkpoint, leading to a cascade of cellular responses such as cell cycle arrest, senescence, autophagy, apoptosis, drug resistance, and EMT. Model validation underscores the roles of PTENP1, miR-21, and PTEN in modulating EMT and drug resistance. Furthermore, our analysis reveals nine novel feedback loops, eight positive and one negative, mediated by PTEN and implicated in DDR cell fate determination, including pathways related to drug resistance and EMT. Our work presents a comprehensive framework for investigating cellular responses following DDR, underscoring the therapeutic potential of targeting PTEN, miR-21, and PTENP1 in cancer treatment. [ABSTRACT FROM AUTHOR]

Christine J. Watson is Professor of Cell and Cancer Biology at the University of Cambridge. Christine obtained her Bachelor's (honors) degree in Biochemistry at the University of Glasgow in 1975 and, after a soujourn in Glauco Tocchini‐Valentini's lab at the Institute of Cell Biology, Consiglio Nazionale delle Ricerche in Rome, she undertook a PhD in Molecular Genetics at Imperial College London. During her PhD, she looked at differences in gene expression between differentiated and undifferentiated embryonal carcinoma stem cells, inspiring an early interest in gene expression and cell fate determination. Between 1986 and 1992, Christine undertook three postdoctoral research positions that took her from London back to Scotland, where she was first introduced to mammary gland biology through her work with John Clark at the Roslin Institute in Edinburgh. During her time in the Clark lab, Christine identified a factor – later shown to be STAT5 – that binds to the promoter of the milk protein gene β‐lactoglobulin. This prompted further work identifying the key role played by the STAT family of transcription factors in mammary gland development. Shortly afterwards, Christine became a group leader at the Roslin Institute and later relocated to the University of Edinburgh to collaborate with Andrew Wyllie. This led to her recruitment to the University of Cambridge in 1998, where she has remained to date. Over the last two decades, the Watson lab has focused on elucidating the mechanisms underlying lineage commitment of mammary stem and progenitor cells and the regulation of cell death in involuting mammary gland. In this interview, Christine discusses her research highlights and provides a glimpse into her personal interests, as she moves towards retirement. [ABSTRACT FROM AUTHOR]

Adult neural stem cells (NSCs) reside in the dentate gyrus of the hippocampus, and their capacity to generate neurons and glia plays a role in learning and memory. In addition, neurodegenerative diseases are known to be caused by a loss of neurons and glial cells, resulting in a need to better understand stem cell fate commitment processes. We previously showed that NSC fate commitment toward a neuronal or glial lineage is strongly influenced by extracellular matrix stiffness, a property of elastic materials. However, tissues in vivo are not purely elastic and have varying degrees of viscous character. Relatively little is known about how the viscoelastic properties of the substrate impact NSC fate commitment. Here, we introduce a polyacrylamide-based cell culture platform that incorporates mismatched DNA oligonucleotide-based cross-links as well as covalent cross-links. This platform allows for tunable viscous stress relaxation properties via variation in the number of mismatched base pairs. We find that NSCs exhibit increased astrocytic differentiation as the degree of stress relaxation is increased. Furthermore, culturing NSCs on increasingly stress-relaxing substrates impacts cytoskeletal dynamics by decreasing intracellular actin flow rates and stimulating cyclic activation of the mechanosensitive protein RhoA. Additionally, inhibition of motor-clutch model components such as myosin II and focal adhesion kinase partially or completely reverts cells to lineage distributions observed on elastic substrates. Collectively, our results introduce a unique system for controlling matrix stress relaxation properties and offer insight into how NSCs integrate viscoelastic cues to direct fate commitment. [ABSTRACT FROM AUTHOR]

Environmental and physiological situations can challenge the balance between protein synthesis and folding capacity of the endoplasmic reticulum (ER) and cause ER stress, a potentially lethal condition. The unfolded protein response (UPR) restores ER homeostasis or actuates programmed cell death (PCD) when ER stress is unresolved. The cell fate determination mechanisms of the UPR are not well understood, especially in plants. Here, we integrate genetics and ER stress profiling with natural variation and quantitative trait locus analysis of 350 natural accessions of the model species Arabidopsis thaliana. Our analyses implicate a single nucleotide polymorphism to the loss of function of the general PCD regulator BON-ASSOCIATED PROTEIN2 (BAP2) in UPR outcomes. We establish that ER stress-induced BAP2 expression is antagonistically regulated by the UPR master regulator, inositol-requiring enzyme 1 (IRE1), and that BAP2 controls adaptive UPR amplitude in ER stress and ignites pro-death mechanisms in conditions of UPR insufficiency. The unfolded protein response (UPR) is a cellular stress response related to endoplasmic reticulum stress, which is activated upon stress challenging. Here, the authors report that the programmed cell death regulator BAP2 is a plant UPR modulator upstream of the essential UPR master regulator IRE1. [ABSTRACT FROM AUTHOR]

Cell hashing, a nucleotide barcode-based method that allows users to pool multiple samples and demultiplex in downstream analysis, has gained widespread popularity in single-cell sequencing due to its compatibility, simplicity, and cost-effectiveness. Despite these advantages, the performance of this method remains unsatisfactory under certain circumstances, especially in experiments that have imbalanced sample sizes or use many hashtag antibodies. Here, we introduce a hybrid demultiplexing strategy that increases accuracy and cell recovery in multi-sample single-cell experiments. This approach correlates the results of cell hashing and genetic variant clustering, enabling precise and efficient cell identity determination without additional experimental costs or efforts. In addition, we developed HTOreader, a demultiplexing tool for cell hashing that improves the accuracy of cut-off calling by avoiding the dominance of negative signals in experiments with many hashtags or imbalanced sample sizes. When compared to existing methods using real-world datasets, this hybrid approach and HTOreader consistently generate reliable results with increased accuracy and cell recovery. [ABSTRACT FROM AUTHOR]

Yes-associated protein (YAP) and a transcriptional co-activator with PDZ-binding motif (TAZ) genes are crucial for regulating the size of mammalian tissues and organs as well as for many biological processes such as bone formation, cell lineage determination, tissue regeneration, and cell proliferation. The purpose of this study was to characterize the YAP and TAZ gene polymorphisms in 266 Guanzhong Dairy Goats and 299 Shanbei White Cashmere Goats and to explore their potential relationship with growth characteristics such as body weight and body length. After genotyping and using PCR amplification and Sanger sequencing to find polymorphisms in the YAP and TAZ genes, five InDels loci were found in the goat YAP gene and three InDels loci in the TAZ gene. The findings of the association analysis demonstrated that the goats' body weight, height, cannon circumference, chest depth, chest breadth, and chest circumference were all substantially influenced by five InDels loci in the YAP gene (p<0.05). Goat body height, trunk breadth, trunk length, body length, and body weight were all substantially impacted by three InDels loci in the TAZ gene (p<0.05). In conclusion, eight InDels loci of goat YAP and TAZ were found in this study, and their impacts on goat phenotype were disclosed. These results might offer fresh avenues for boosting goat molecular breeding. [ABSTRACT FROM AUTHOR]

Interactions between osteolineage cells and myeloid cells play important roles in maintaining skeletal homeostasis. Herein, we find that osteolineage cells transfer mitochondria to myeloid cells. Impairment of the transfer of mitochondria by deleting MIRO1 in osteolineage cells leads to increased myeloid cell commitment toward osteoclastic lineage cells and promotes bone resorption. In detail, impaired mitochondrial transfer from osteolineage cells alters glutathione metabolism and protects osteoclastic lineage cells from ferroptosis, thus promoting osteoclast activities. Furthermore, mitochondrial transfer from osteolineage cells to myeloid cells is involved in the regulation of glucocorticoid-induced osteoporosis, and glutathione depletion alleviates the progression of glucocorticoid-induced osteoporosis. These findings reveal an unappreciated mechanism underlying the interaction between osteolineage cells and myeloid cells to regulate skeletal metabolic homeostasis and provide insights into glucocorticoid-induced osteoporosis progression. Bone and blood lineage cells communicate with each other to maintain skeletal homeostasis. Here, the authors show that MIRO1-mediated mitochondrial transfer from osteolineage to myeloid lineage cells regulates bone resorption by altering glutathione metabolism. [ABSTRACT FROM AUTHOR]

Excessive bone marrow adipocytes (BMAds) accumulation often occurs under diverse pathophysiological conditions associated with bone deterioration. Estrogen-related receptor α (ESRRA) is a key regulator responding to metabolic stress. Here, we show that adipocyte-specific ESRRA deficiency preserves osteogenesis and vascular formation in adipocyte-rich bone marrow upon estrogen deficiency or obesity. Mechanistically, adipocyte ESRRA interferes with E2/ESR1 signaling resulting in transcriptional repression of secreted phosphoprotein 1 (Spp1); yet positively modulates leptin expression by binding to its promoter. ESRRA abrogation results in enhanced SPP1 and decreased leptin secretion from both visceral adipocytes and BMAds, concertedly dictating bone marrow stromal stem cell fate commitment and restoring type H vessel formation, constituting a feed-forward loop for bone formation. Pharmacological inhibition of ESRRA protects obese mice against bone loss and high marrow adiposity. Thus, our findings highlight a therapeutic approach via targeting adipocyte ESRRA to preserve bone formation especially in detrimental adipocyte-rich bone milieu. Excessive bone marrow adipocytes accumulation is involved in bone deterioration. Here, the authors show that adipocyte ESRRA abrogation promotes osteogenesis and vascular formation in adipocyte-rich bone marrow via oppositely regulating the expression and secretion of leptin and SPP1. [ABSTRACT FROM AUTHOR]

There is always a concern about the quality of cell-based products in terms of the contamination of the cells and their lack of efficiency. Therefore, it is of prime importance to ensure these cells' identity, purity, efficacy, and suitability for the production of biological products and diagnostic uses. Hence, cells must be identified, evaluated, documented, and stored to be used consistently and efficiently. With these conditions, vaccine manufacturers have a suitable reserve of efficient and valuable cells for the production and quality control of biological products. In this review article, a strategic plan was drawn for cell-substrate well-characterization and identification according to scientific principles, the author's work experience, and regulatory guidance for the optimal use of that cell in research and diagnostic studies especially for the biological product production process. For this purpose, all aspects of cell identification, cell evaluation, and cell characterization are discussed. Because of the importance of cell identity in the competence of a cell substrate, in the cell identification section, all aspects of cell identification, including general cell information and specific cell characteristics, especially in terms of cell passage history, cell storage conditions, and cell coding and labeling, were studied. In the part of cell evaluation and determination of cell characteristics, all required tests to determine cell characteristics from various aspects, including determination of cell identity, cell growth conditions, cell quality, efficiency, and the possibility of cell contamination with adventitious agents, including cellular, viral, bacterial, mycoplasma, and mycobacterial agents were introduced. Due to the importance of endogenous virus contamination, this topic is specially discussed. In addition, the stability of the cell both from the aspect of genetic stability and from the aspect of stability of cell efficiency, were discussed. In the end, while reviewing the necessary documents to be under the control of the cell for use in the laboratory, based on the studies conducted, the certificate of the cell has been compiled. Therefore, on this basis, the studied cell can be used for research and diagnostic studies of virology, especially for the production and quality control of biological products. [ABSTRACT FROM AUTHOR]

Asymmetric cell division is a fundamental process conserved throughout evolution, employed by both prokaryotic and eukaryotic organisms. Its significance lies in its ability to govern cell fate and facilitate the generation of diverse cell types. Therefore, attaining a detailed mechanistic understanding of asymmetric cell division becomes essential for unraveling the complexities of cell fate determination in both healthy and pathological conditions. However, the role of asymmetric division in T-cell biology has only recently been unveiled. Here, we provide an overview of the T-cell asymmetric division field with the particular emphasis on experimental methods and models with the aim to guide the researchers in the selection of appropriate in vitro/in vivo models to study asymmetric division in T cells. We present a comprehensive investigation into the mechanisms governing the asymmetric division in various T-cell subsets underscoring the importance of the asymmetry in fate-determining factor segregation and transcriptional and epigenetic regulation. Furthermore, the intricate interplay of T-cell receptor signaling and the asymmetric division geometry are explored, shedding light on the spatial organization and the impact on cellular fate. [ABSTRACT FROM AUTHOR]

The formation of hematopoietic cells relies on the chromatin remodeling activities of ISWI ATPase SMARCA5 (SNF2H) and its complexes. The Smarca5 null and conditional alleles have been used to study its functions in embryonic and organ development in mice. These mouse model phenotypes vary from embryonic lethality of constitutive knockout to less severe phenotypes observed in tissue-specific Smarca5 deletions, e.g., in the hematopoietic system. Here we show that, in a gene dosage-dependent manner, the hypomorphic allele of SMARCA5 (S5tg) can rescue not only the developmental arrest in hematopoiesis in the hCD2iCre model but also the lethal phenotypes associated with constitutive Smarca5 deletion or Vav1iCre-driven conditional knockout in hematopoietic progenitor cells. Interestingly, the latter model also provided evidence for the role of SMARCA5 expression level in hematopoietic stem cells, as the Vav1iCre S5tg animals accumulate stem and progenitor cells. Furthermore, their hematopoietic stem cells exhibited impaired lymphoid lineage entry and differentiation. This observation contrasts with the myeloid lineage which is developing without significant disturbances. Our findings indicate that animals with low expression of SMARCA5 exhibit normal embryonic development with altered lymphoid entry within the hematopoietic stem cell compartment. This transgenic mouse study based on different protein levels of the ISWI ATPase SMARCA5 shows accumulation of multipotent hematopoietic progenitors with block of B and T lymphopoiesis and, to a lesser extent, erythropoiesis at low SMARCA5 levels. [ABSTRACT FROM AUTHOR]