Defective Cell Research Articles

Photon emission microscope analysis on surface defects of GaAs thin-film solar cells grown by molecular beam epitaxy

Surface defects seriously affect the electronic properties of the optoelectronic devices. In this paper, the surface defect analysis of GaAs thin-film solar cells grown by molecular beam epitaxy is carried out by a photon emission microscope. Two types of oval defects at the locations of the luminous spots are observed. The morphology and chemical composition analysis indicates that GaAs dust contamination on the wafer surface and excessive As clusters are the origins of oval defects. The electrical property analysis shows that oval defects in the epitaxial layer should be one of the important reasons for the nonideal leakage current of the GaAs thin-film solar cell.

Anode defects’ propagation in polymer electrolyte membrane fuel cells stack

This paper investigates how cell manufacturing defects can propagate within healthy areas of the same cell or to adjacent cells within a stack. To do so, a defective stack is assembled on the basis of 30 cells without defect and 5 defective cells with controlled lack of anode catalyst layer. The analysis of the degradation rate showed that the adjacent cells to the defective cells are the ones whose performance degraded the fastest, which implies that the presence of defects within the stack induces a propagation of the performance decrease. Post-mortem analyses are performed in the vicinity of the anode defect in the adjacent cell and highlight a significant degradation of perfluorosulfonic acid (PFSA) inducing hydrogen leakages through the membrane. The propagation of the degradation of the membrane in the surroundings of the anode defect to the adjacent cell can be discussed based on the stack design and operating conditions.

The dynamics and longevity of circulating CD4+ memory T cells depend on cell age and not the chronological age of the host.

Quantifying the kinetics with which memory T cell populations are generated and maintained is essential for identifying the determinants of the duration of immunity. The quality and persistence of circulating CD4 effector memory (TEM) and central memory (TCM) T cells in mice appear to shift with age, but it is unclear whether these changes are driven by the aging host environment, by cell age effects, or both. Here, we address these issues by combining DNA labelling methods, established fate-mapping systems, a novel reporter mouse strain, and mathematical models. Together, these allow us to quantify the dynamics of both young and established circulating memory CD4 T cell subsets, within both young and old mice. We show that that these cells and their descendents become more persistent the longer they reside within the TCM and TEM pools. This behaviour may limit memory CD4 T cell diversity by skewing TCR repertoires towards clones generated early in life, but may also compensate for functional defects in new memory cells generated in old age.

Performance analysis of perovskite solar cell in presence and absence of defects

Studies of the effect of defects in any solar cell are important in achieving a satisfactory level of its performance. A comparative study with a defect-free against the defect-induced cell carries instant and ready information on laboratory/industry-based fabricated cell performance, which is prone to unavoidably induced defects. In spite of good deal of works on defects of cells such a study in an organized and comparative way remains absent to the knowledge of the authors. Ready and classified presentation of such a study, therefore, is considered to be significant. Present work is a result of motivation to fulfil this gap. This article presents a study of the effects of bulk and interface defects in perovskite solar cells. On examining the effects of deep and shallow defect levels on key performance metrics such as open-circuit voltage, short-circuit current density, and fill factor, the resulting study discusses an analysis of the impact of the defects on cell efficiency. A defect-free cell with optimal perovskite, hole-transport layer (HTL), and electron-transport layer (ETL) dimensions are analysed simultaneously to assess the level at which the defects can degrade the performance of a defect-free cell. It is observed that the defects, particularly in the deep levels, significantly impair the performance of a cell, including the open circuit voltage, short circuit current density, fill factor, and efficiency, compared to those in shallow levels.

Overexpression of miR-20a-5p in mesenchymal stem cell derived-exosomes from systemic lupus erythematosus patients restored therapeutic effect and Treg immune regulation

We and other groups have documented that bone marrow-mesenchymal stem cells (BM-MSCs) from Systemic lupus erythematosus (SLE) patients demonstrated signs of senescence, including reduced ability of regulating Treg. Treg cell defects or Treg cell deficiency are regarded as significant factors in the progression of SLE. Exosomes, nanoscale vesicles, abound in molecular and genetic contents, play a critical role in intercellular communications. The purpose of this research is to investigate the mechanism of MSCs-exosomes regulating Tregs cells in SLE, further elucidate the mechanism of immune dysregulation of aging BM-MSCs, and provide theoretical basis and data support for new targets of SLE treatment. In the study, BM-MSCs and exosomes were isolated successfully. Exosomes could be up-taken by naïve CD4+T cells. MSCs-exosomes attenuated SLE clinical manifestation in vivo, but MSCs-exosomes from SLE patients were ineffective. MSCs-exosomes from SLE patients dysregulated Treg cells differentiation in vivo and in vitro. Exosomal miR-20a-5p contributed to the effect of MSCs-exosomes regulating Treg cells. Up-regulating the expression of miR-20a-5p in SLE MSCs-exosomes can restore their ability to promote Treg differentiation and treatment effect. This study further elucidated the role of in the immunomodulatory mechanism of BM-MSCs-exosomes and provided new ideas for the non-cellular autologous transplantation therapy of SLE.

A novel Se-diffused selenization strategy to suppress bulk and interfacial defects in Sb2Se3 thin film solar cell

In recent years, vacuum-based deposition of antimony selenide (Sb2Se3) thin films has garnered significant attention owing to its easy and impurity-free fabrication, along with exceptional power conversion efficiency (PCE). However, the necessary post-selenization process comes with a shortcoming of instigating buried Sb2Se3/molybdenum (Mo) back-contact interface defects. This study introduces a novel Se-diffusion post-selenization technique to precisely regulate the selenium reaction atmosphere, preventing void formation on the Sb2Se3 thin film surface and maintaining film quality for enhanced device efficiency. An optimized selenization condition with a precise Se precursor film thickness led to obtaining highly crystalline, preferentially (hk1) oriented, and large-grained Sb2Se3 films. Furthermore, a meticulous Se diffusion in Sb2Se3 film reduced the inevitable MoSe2 layer thickness at the Mo surface, thereby enhancing the quality of the back contact interface. The Sb2Se3 solar cell that was selenized to optimal level showed significant enhancements, raising the fill factor from 40.06 % to 45.12 % and improving the device efficiency from 2.89 % to 3.57 %. Our newly developed selenization strategy establishes a successful approach to regulate the Sb2Se3 film quality by addressing a crucial challenge in improving the efficiency of antimony chalcogenide solar cells.

MAZ-mediated up-regulation of BCKDK reprograms glucose metabolism and promotes growth by regulating glucose-6-phosphate dehydrogenase stability in triple-negative breast cancer

Tumour metabolic reprogramming is pivotal for tumour survival and proliferation. Investigating potential molecular mechanisms within the heterogeneous and clinically aggressive triple-negative breast cancer (TNBC) subtype is essential to identifying novel therapeutic targets. Accordingly, we investigated the role of branched-chain α-keto acid dehydrogenase kinase (BCKDK) in promoting tumorigenesis in TNBC. We analysed The Cancer Genome Atlas dataset and immunohistochemically stained surgical specimens to investigate BCKDK expression and its prognostic implications in TNBC. The effects of BCKDK on tumorigenesis were assessed using cell viability, colony formation, apoptosis, and cell cycle assays, and subsequently validated in vivo. Metabolomic screening was performed via isotope tracer studies. The downstream target was confirmed using mass spectrometry and a co-immunoprecipitation experiment coupled with immunofluorescence analysis. Upstream transcription factors were also examined using chromatin immunoprecipitation and luciferase assays. BCKDK was upregulated in TNBC tumour tissues and associated with poor prognosis. BCKDK depletion led to reduced cell proliferation both in vitro and vivo. MYC-associated zinc finger protein (MAZ) was confirmed as the major transcription factor directly regulating BCKDK expression in TNBC. Mechanistically, BCKDK interacted with glucose-6-phosphate dehydrogenase (G6PD), leading to increased flux in the pentose phosphate pathway for macromolecule synthesis and detoxification of reactive oxygen species. Forced expression of G6PD rescued the growth defect in BCKDK-deficient cells. Notably, the small-molecule inhibitor of BCKDK, 3,6-dichlorobenzo(b)thiophene-2-carboxylic acid, exhibited anti-tumour effects in a patient-derived tumour xenograft model. Our findings hold significant promise for developing targeted therapies aimed at disrupting the MAZ/BCKDK/G6PD signalling pathway, offering potential advancements in treating TNBC through metabolic reprogramming.

PD-DETR: towards efficient parallel hybrid matching with transformer for photovoltaic cell defects detection

Defect detection for photovoltaic (PV) cell images is a challenging task due to the small size of the defect features and the complexity of the background characteristics. Modern detectors rely mostly on proxy learning objectives for prediction and on manual post-processing components. One-to-one set matching is a critical design for DEtection TRansformer (DETR) in order to provide end-to-end capability, so that does not need a hand-crafted Efficient Non-Maximum Suppression NMS. In order to detect PV cell defects faster and better, a technology called the PV cell Defects DEtection Transformer (PD-DETR) is proposed. To address the issue of slow convergence caused by DETR’s direct translation of image feature mapping into target detection results, we created a hybrid feature module. To achieve a balance between performance and computation, the image features are passed through a scoring network and dilated convolution, respectively, to obtain the foreground fine feature and contour high-frequency feature. The two features are then adaptively intercepted and fused. The capacity of the model to detect small-scale defects under complex background conditions is improved by the addition of high-frequency information. Furthermore, too few positive queries will be assigned to the defect target via one-to-one set matching, which will result in sparse supervision of the encoder and impair the decoder’s ability of attention learning. Consequently, we enhanced the detection effect by combining the original DETR with the one-to-many matching branch. Specifically, two Faster RCNN detection heads were added during training. To maintain the end-to-end benefits of DETR, inference is still performed using the original one-to-one set matching. Our model implements 64.7% AP on the PVEL-AD dataset.

Prevalence of Zygomatic Air Cell defects in a sample of 6-18-year-old patients in Saudi Arabia and Yemen: a retrospective study

ObjectivesThis study aimed to comprehensively analyze the prevalence and influencing factors of Zygomatic Air Cell Defects (ZACD) among pediatric and adolescent populations in Saudi Arabia and Yemen.Materials and methodsA cross-sectional retrospective study was conducted, utilizing digital panoramic radiographs of dental outpatients aged 6 to 18 years. The data were collected from registered digital databases of dental clinics in Al-Qassim, Saudi Arabia, and an oral and maxillofacial radiology center in Sana’a, Yemen, covering the period from July 2018 to September 2022. The radiographs were evaluated based on inclusion and exclusion criteria, and ZACD was assessed using standardized descriptions. Statistical analysis, including logistic regression, was employed to examine the impact of the associated factors.ResultsThe study encompassed a total of 3,169 participants, revealing an overall ZACD prevalence of 28.5%. Age emerged as a significant predictor (p ≤ 0.0001), with the likelihood of ZACD increasing as the age of the individual advances. Gender and geographic region did not exhibit statistically significant differences in ZACD prevalence.ConclusionThis study provides crucial insights into the prevalence of Zygomatic Air Cell Defects among pediatric and adolescent populations in Saudi Arabia and Yemen. It underscores the prevalence of ZACD and the notable influence of age on its occurrence. Additionally, the research challenges prior notions of gender and regional variations in ZACD prevalence, emphasizing the complexity of the factors involved. Early detection is essential to avoid unwanted complications during any surgical intervention in this area.

Lipopolysaccharide-responsive beige-like anchor is involved in regulating NF-κB activation in B cells.

Lipopolysaccharide-responsive and beige-like anchor (LRBA) is a scaffolding protein that interacts with proteins such as CTLA-4 and PKA, the importance of which has been determined in various cell types, including T regulatory cells, B cells, and renal cells. LRBA deficiency is associated with an inborn error in immunity characterized by immunodeficiency and autoimmunity. In addition to defects in T regulatory cells, patients with LRBA deficiency also exhibit B cell defects, such as reduced cell number, low memory B cells, hypogammaglobulinemia, impaired B cell proliferation, and increased autophagy. Although Lrba-/- mice do not exhibit the immunodeficiency observed in humans, responses to B cell receptors (BCR) in B cells have not been explored. Therefore, a murine model is for elucidating the mechanism of Lrba mechanism in B cells. To compare and evaluate spleen-derived B cell responses to BCR crosslinking in C57BL6 Lrba-/- and Lrba+/+ mice. Spleen-derived B cells were obtained from 8 to 12-week-old mice. Subpopulations were determined by immunostaining and flow cytometry. BCR crosslinking was assessed by the F(ab')2 anti-μ chain. Activation, proliferation and viability assays were performed using flow cytometry and protein phosphorylation was evaluated by immunoblotting. The nuclear localization of p65 was determined using confocal microscopy. Nur77 expression was evaluated by Western blot. Lrba-/- B cells showed an activated phenotype and a decreased proportion of transitional 1 B cells, and both proliferation and survival were affected after BCR crosslinking in the Lrba-/- mice. The NF-κB pathway exhibited a basal activation status of several components, resulting in increased activation of p50, p65, and IκBα, basal p50 activation was reduced by the Plcγ2 inhibitor U73122. BCR crosslinking in Lrba-/ - B cells resulted in poor p50 phosphorylation and p65 nuclear localization. Increased levels of Nur77 were detected. These results indicate the importance of Lrba in controlling NF-κB activation driven by BCR. Basal activation of NF-κB could impact cellular processes, such as, activation, differentiation, proliferation, and maintenance of B cells after antigen encounter.

Fission yeast Pib2 localizes to vacuolar membranes and regulates TOR complex 1 through evolutionarily conserved domains.

TOR complex 1 (TORC1) is a multi-protein kinase complex that coordinates cellular growth with environmental cues. Recent studies have identified Pib2 as a critical activator of TORC1 in budding yeast. Here, we show that loss of Pib2 causes severe growth defects in fission yeast cells, particularly when basal TORC1 activity is diminished by hypomorphic mutations in tor2, the gene encoding the catalytic subunit of TORC1. Consistently, TORC1 activity is significantly compromised in the tor2 hypomorphic mutants lacking Pib2. Moreover, as in budding yeast, fission yeast Pib2 localizes to vacuolar membranes via its FYVE domain, with its tail motif indispensable for TORC1 activation. These results strongly suggest that Pib2-mediated positive regulation of TORC1 is evolutionarily conserved between the two yeast species.

Zebrafish myo7aa affects congenital hearing by regulating Rho-GTPase signaling.

myo7aa, the homolog of the human Usher 1B syndrome pathogenic gene, myo7A, plays an important role in stereociliary development and maintenance, therefore, is critical for hearing and balance. However, the molecular mechanisms that myo7aa regulate hearing and balance still need to be studied. In this study, we generated two independent zebrafish myo7aa knockout lines using CRISPR/Cas9 technology. To investigate the effects of myo7aa on hearing, YO-PRO-1 staining and startle response assay were used. To gain insight into the specific molecular mechanisms by which myo7aa affects hearing, transcriptome sequencing and bioinformatics analysis were employed. Our study showed that hair cells of myo7aa-/- zebrafish can not take up YO-PRO-1 fluorescent dye and are insensitive to acoustic stimulation in myo7aa-/- zebrafish compared to wild type. Genes related to the Rho GTPase signaling pathway, such as arhgap33, dab2ip, and arghef40, are significantly down-regulated in myo7aa-/- zebrafish embryos at 3 dpf. GTP and ATP compensation can partially rescue the hair cell defects in myo7aa knockout zebrafish. Our findings suggest that zebrafish myo7aa affects congenital hearing by regulating Rho GTPase signaling, and loss of myo7aa leads to abnormal Rho GTPase signaling and impairs hair cell function. myo7aa, myo7A, arhgap33, dab2ip, arghef40 and myo7aa-/- fonts in the abstract are italicized. -/- is a superscript format.

SMCHD1 activates the expression of genes required for the expansion of human myoblasts.

SMCHD1 is an epigenetic regulatory protein known to modulate the targeted repression of large chromatin domains. Diminished SMCHD1 function in muscle fibers causes Facioscapulohumeral Muscular Dystrophy (FSHD2) through derepression of the D4Z4 chromatin domain, an event which permits the aberrant expression of the disease-causing gene DUX4. Given that SMCHD1 plays a broader role in establishing the cellular epigenome, we examined whether loss of SMCHD1 function might affect muscle homeostasis through additional mechanisms. Here we show that acute depletion of SMCHD1 results in a DUX4-independent defect in myoblast proliferation. Genomic and transcriptomic experiments determined that SMCHD1 associates with enhancers of genes controlling cell cycle to activate their expression. Amongst these cell cycle regulatory genes, we identified LAP2 as a key target of SMCHD1 required for the expansion of myoblasts, where the ectopic expression of LAP2 rescues the proliferation defect of SMCHD1-depleted cells. Thus, the epigenetic regulator SMCHD1 can play the role of a transcriptional co-activator for maintaining the expression of genes required for muscle progenitor expansion. This DUX4-independent role for SMCHD1 in myoblasts suggests that the pathology of FSHD2 may be a consequence of defective muscle regeneration in addition to the muscle wasting caused by spurious DUX4 expression.

UPF1 plays critical roles in early B cell development

The ATP-dependent RNA helicase UPF1 plays a crucial role in various mRNA degradation pathways, most importantly in nonsense-mediated mRNA decay (NMD). Here, we show that UPF1 is upregulated during the early stages of B cell development and is important for early B cell development in the bone marrow. B-cell-specific Upf1 deletion in mice severely impedes the early to late LPre-B cell transition, in which VH-DHJH recombination occurs at the Igh gene. Furthermore, UPF1 is indispensable for VH-DHJH recombination, without affecting DH-JH recombination. Intriguingly, the genetic pre-arrangement of the Igh gene rescues the differentiation defect in early LPre-B cells under Upf1 deficient conditions. However, differentiation is blocked again following Ig light chain recombination, leading to a failure in development into immature B cells. Notably, UPF1 interacts with and regulates the expression of genes involved in immune responses, cell cycle control, NMD, and the unfolded protein response in B cells. Collectively, our findings underscore the critical roles of UPF1 during the early LPre-B cell stage and beyond, thus orchestrating B cell development.

Hypertrophic Cardiomyopathy Risk Factors in Infants of diabetic mothers

Abstract Background Diabetes mellitus (DM) is a systemic chronic metabolic disorder characterized by increased insulin resistance and/or β- cell defects. Maternal DM significantly affects the fetal heart and fetal–placental circulation in both structure and function. Cardiac defects, myocardial hypertrophy are three times more prevalent in infants of diabetic mothers (IDMs). Objective Assess the frequency of hypertrophic cardiomyopathy (HCM) among infants of diabetic mothers and its relationship to the maternal glycemic control and the birth weight for the gestational age. Patients and Methods This was a cross-sectional study conducted on (50) neonates with gestational age ≥ 35 weeks born to diabetic mothers recruited from the delivery room and Neonatal Observation Unit, Obstetrics and Gynecology Hospital, Ain shams university. Detailed history was taken for the duration of maternal diabetes, glycemic control and any associated complications and the level of hemoglobin A1C (HbA1C) was assessed for all the enrolled mothers. Neonates were subjected to full clinical examination and echocardiographic evaluation in the first week of life. Results Forty % of mothers had gestational diabetes mellitus (GDM), (20%) were pre-gestational diabetes type 1 and 40% were pre-GDM type 2. There were 18 infants (36%) had HCM. HCM was highly statistically significant (p-value < 0.001) more in cases with high maternal HbA1C (8.3 ± 0.9). The frequency of HCM among infants of pre-GDM mothers (15 patients, 50%) was significantly higher (p-value = 0.012) when compared to infants of GDM mothers (3 patients, 15%). But the frequency of HCM was equal in infants of pre-GDM type I mothers and those of pre-GDM type 2 mothers. HCM was more common with large for gestational age (LGA) infants (10 cases 55.6% of infants with HCM were LGA). Conclusion HCM is more frequent among infants of mothers with pre-GDM type 1 than infants of GDM. Poor maternal glycemic control and large for gestational age are associated with higher frequency of HCM among those infants.

Insights into mechanism of UV-induced degradation in silicon heterojunction solar cells

The ultraviolet-induced degradation (UVID), with losses of up to 11 % after 2000 h-exposure (Sinha et al., 2023) [1], impairs long-term stability of silicon heterojunction (SHJ) solar cells at present. However, the mechanism of UVID has remained only roughly understood till now. Herein, we shed light on the electrical properties of defects in SHJ solar cells to elucidate the underlying mechanism. Defect generation in SHJ solar cells after ultraviolet (UV) irradiation can be observed from photoluminescence (PL) images. Furthermore, we extract the density of states near Fermi level in hydrogenated amorphous silicon (a-Si:H) through analyzing carrier transport mechanism, and find the increment of state density induced by the UV irradiation. In conjunction with Fourier-transform infrared (FTIR) spectra, we ascribe the UV-induced defects to the rupture of Si–H and Si–H2 bonds. Besides, the intersection point between Fermi levels of the c-Si and a-Si:H/c-Si interface can be found shift toward valence band from admittance spectrum analysis, which is the cause of the higher interface state density based on the theory of Fermi energy dependent hydrogen diffusion energy. As a result, a potential mechanism of generation of recombination centers responsible for UVID in SHJ solar cells is proposed, which could provide insights into the possible solutions for UVID and enhance the long-term stability of SHJ solar cells.

Detection of Microcracks in Cz‐Si Wafer Manufacturing by Photoluminescence Imaging

Photoluminescence imaging (PLI) is a widely accepted, fast, and contactless method for detecting crystal defects in crystalline silicon solar cells and solar‐grade silicon wafers. However, it is less known by semiconductor wafer manufacturers despite the similarities between photovoltaic (PV) and semiconductor wafers. This study focuses on the detection of microcracks by PLI during high‐quality Czochralski silicon (Cz‐Si) wafer manufacturing. The results show that in case of low resistivity (<25 mΩ cm) wafers, microcracks can be detected at any stage of the processing—even after diamond‐wire slicing. When resistivity increases, visibility of microcracks reduces in process steps that produce uneven surfaces. Nevertheless, they can still be detected after slurry‐wire slicing, lapping, alkaline etching, and polishing. According to the results, unlike resistivity, other material parameters such as dopant species, crystal orientation, and wafer thickness have no similar impact on visibility of microcracks in PLI. Furthermore, all wafers produce a decent photoluminescence (PL) signal without a need for separate sample preparation. Based on these results, general recommendations for the in‐line detection of microcracks for Cz‐Si wafer manufactures are provided. While this study focuses on microcracks, the results and discussion include broader perspectives on the defect characterization in Cz‐Si wafer manufacturing via PLI.

Enhanced radiation sensitivity, decreased DNA damage repair, and differentiation defects in airway stem cells derived from patients with chronic obstructive pulmonary disease.

Radiation therapy (RT) is a common treatment for lung cancer. Still, it can lead to irreversible loss of pulmonary function and a significant reduction in quality of life for one-third of patients. Preexisting comorbidities, such as chronic obstructive pulmonary disease (COPD), are frequent in patients with lung cancer and further increase the risk of complications. Because lung stem cells are crucial for the regeneration of lung tissue following injury, we hypothesized that airway stem cells from patients with COPD with lung cancer might contribute to increased radiation sensitivity. We used the air-liquid interface model, a three-dimensional (3D) culture system, to compare the radiation response of primary human airway stem cells from healthy and patients with COPD. We found that COPD-derived airway stem cells, compared to healthy airway stem cell cultures, exhibited disproportionate pathological mucociliary differentiation, aberrant cell cycle checkpoints, residual DNA damage, reduced survival of stem cells and self-renewal, and terminally differentiated cells post-irradiation, which could be reversed by blocking the Notch pathway using small-molecule γ-secretase inhibitors. Our findings shed light on the mechanisms underlying the increased radiation sensitivity of COPD and suggest that airway stem cells reflect part of the pathological remodeling seen in lung tissue from patients with lung cancer receiving thoracic RT.

DDX41 haploinsufficiency causes inefficient hematopoiesis under stress and cooperates with p53 mutations to cause hematologic malignancy

Germline heterozygous mutations in DDX41 predispose individuals to hematologic malignancies in adulthood. Most of these DDX41 mutations result in a truncated protein, leading to loss of protein function. To investigate the impact of these mutations on hematopoiesis, we generated mice with hematopoietic-specific knockout of one Ddx41 allele. Under normal steady-state conditions, there was minimal effect on lifelong hematopoiesis, resulting in a mild yet persistent reduction in red blood cell counts. However, stress induced by transplantation of the Ddx41+/− BM resulted in hematopoietic stem/progenitor cell (HSPC) defects and onset of hematopoietic failure upon aging. Transcriptomic analysis of HSPC subsets from the transplanted BM revealed activation of cellular stress responses, including upregulation of p53 target genes in erythroid progenitors. To understand how the loss of p53 affects the phenotype of Ddx41+/− HSPCs, we generated mice with combined Ddx41 and Trp53 heterozygous deletions. The reduction in p53 expression rescued the fitness defects in HSPC caused by Ddx41 heterozygosity. However, the combined Ddx41 and Trp53 mutant mice were prone to developing hematologic malignancies that resemble human myelodysplastic syndrome and acute myeloid leukemia. In conclusion, DDX41 heterozygosity causes dysregulation of the response to hematopoietic stress, which increases the risk of transformation with a p53 mutation.

The dynamics and longevity of circulating CD4+ memory T cells depend on cell age and not the chronological age of the host.

Quantifying the kinetics with which memory T cell populations are generated and maintained is essential for identifying the determinants of the duration of immunity. The quality and persistence of circulating CD4+ effector memory (TEM) and central memory (TCM) T cells in mice appear to shift with age, but it is unclear whether these changes are driven by the aging host environment, by cell age effects, or both. Here we address these issues by combining DNA labelling methods, established fate-mapping systems, a novel reporter mouse strain, and mathematical models. Together, these allow us to quantify the dynamics of both young and established circulating memory CD4+ T cell subsets, within both young and old mice. We show that that these cells and their descendents become more persistent the longer they reside within the TCM and TEM pools. This behaviour may limit memory CD4 T cell diversity by skewing TCR repertoires towards clones generated early in life, but may also compensate for functional defects in new memory cells generated in old age.