Cells Type Research Articles

Costello syndrome model mice with a Hras G12S mutation are susceptible to develop house dust mite-induced atopic dermatitis

Costello syndrome is an autosomal dominant disorder that is caused by germline HRAS mutations. Patients with Costello syndrome present craniofacial abnormalities, cardiac defects, and cancer predisposition, as well as skin abnormalities, including papillomas, keratosis pilaris, and eczematous dermatitis. However, the mechanisms underlying the dermatological abnormalities remain unclear. Here, we demonstrated that knock-in mice expressing an Hras G12S mutation (HrasG12S/+ mice) are susceptible to develop atopic dermatitis (AD)-like skin lesions, including eczema, pruritus, elevated serum IgE levels, acanthosis, and the infiltration of mast cells, basophils, and type-2 innate lymphoid cells in the dermis, after stimulation with house dust mite allergens (Dermatophagoides farinae, Dfb). Reduced skin barrier function, increased proliferation of phosphorylated ERK (p-ERK)-positive epidermal cells, and increased Th2-type cytokines as well as epithelial cell-derived cytokines, including IL-33, were observed in the skin tissue of HrasG12S/+ mice compared with Hras+/+ mice. Cultured HrasG12S/+ keratinocytes exhibited increased IL-33 expression after Dfb stimulation. PD0325901, an MEK inhibitor, ameliorated AD-like symptoms in HrasG12S/+ mice, showing decreased proliferation of p-ERK-positive epidermal cells and decreased expression of IL-33. Our findings indicate that the epidermis of HrasG12S/+ mice stimulated by Dfb strongly induced IL-33 expression and type-2 innate lymphoid cells, resulting in AD-like skin lesions. These results suggest that the epidermis of HrasG12S/+ mice are prone to development of eczematous dermatitis stimulated with house dust mite allergens.

Radiotherapy Cooperates with IL15 to Induce Antitumor Immune Responses.

Focal radiotherapy can promote cross-presentation of tumor antigens to T cells, but by itself, it is insufficient to induce therapeutically effective T-cell responses. The common gamma-chain cytokine IL15 promotes and sustains the proliferation and effector function of CD8+ T cells but has limited activity against poorly immunogenic tumors that do not elicit significant spontaneous T-cell responses. Here, we show that radiotherapy and subcutaneous IL15 had complementary effects and induced CD8+ T-cell-mediated tumor regression and long-term protective memory responses in two mouse carcinoma models unresponsive to IL15 alone. Mechanistically, radiotherapy-induced IFN type I production and Batf3-dependent conventional dendritic cells type 1 (cDC1) were required for priming of tumor-specific CD8+ T cells and for the therapeutic effect of the combination. IL15 cooperated with radiotherapy to activate and recruit cDC1s to the tumor. IL15 alone and in complex with a hybrid molecule containing the IL15α receptor have been tested in early-phase clinical trials in patients with cancer and demonstrated good tolerability, especially when given subcutaneously. Expansion of natural killer (NK) cells and CD8+ T cells was noted, without clear clinical activity, suggesting further testing of IL15 as a component of a combinatorial treatment with other agents. Our results provide the rationale for testing combinations of IL15 with radiotherapy in the clinic.

Recent advances in mechanisms of food allergy and anaphylaxis.

Food allergens are innocuous proteins that promote tolerogenic adaptive immune responses in healthy individuals yet in other individuals induce an allergic adaptive immune response characterized by the presence of antigen-specific immunoglobulin E and type-2 immune cells. The cellular and molecular processes that determine a tolerogenic versus non-tolerogenic immune response to dietary antigens are not fully elucidated. Recently, there have been advances in the identification of roles for microbial communities and anatomical sites of dietary antigen exposure and presentation that have provided new insights into the key regulatory steps in the tolerogenic versus non-tolerogenic decision-making processes. Herein, we will review and discuss recent findings in cellular and molecular processes underlying food sensitization and tolerance, immunological processes underlying severity of food-induced anaphylaxis, and insights obtained from immunotherapy trials.

Age-Dependent Progression of SARS-CoV-2 Infection in Syrian Hamsters.

In late 2019, an outbreak of a severe respiratory disease caused by an emerging coronavirus, SARS-CoV-2, resulted in high morbidity and mortality in infected humans. Complete understanding of COVID-19, the multi-faceted disease caused by SARS-CoV-2, requires suitable small animal models, as does the development and evaluation of vaccines and antivirals. Since age-dependent differences of COVID-19 were identified in humans, we compared the course of SARS-CoV-2 infection in young and aged Syrian hamsters. We show that virus replication in the upper and lower respiratory tract was independent of the age of the animals. However, older hamsters exhibited more pronounced and consistent weight loss. In situ hybridization in the lungs identified viral RNA in bronchial epithelium, alveolar epithelial cells type I and II, and macrophages. Histopathology revealed clear age-dependent differences, with young hamsters launching earlier and stronger immune cell influx than aged hamsters. The latter developed conspicuous alveolar and perivascular edema, indicating vascular leakage. In contrast, we observed rapid lung recovery at day 14 after infection only in young hamsters. We propose that comparative assessment in young versus aged hamsters of SARS-CoV-2 vaccines and treatments may yield valuable information, as this small-animal model appears to mirror age-dependent differences in human patients.

Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis

The cell type specific sequences of transcriptional programs during lung regeneration have remained elusive. Using time-series single cell RNA-seq of the bleomycin lung injury model, we resolved transcriptional dynamics for 28 cell types. Trajectory modeling together with lineage tracing revealed that airway and alveolar stem cells converge on a unique Krt8 + transitional stem cell state during alveolar regeneration. These cells have squamous morphology, feature p53 and NFkB activation and display transcriptional features of cellular senescence. The Krt8+ state appears in several independent models of lung injury and persists in human lung fibrosis, creating a distinct cell–cell communication network with mesenchyme and macrophages during repair. We generated a model of gene regulatory programs leading to Krt8+ transitional cells and their terminal differentiation to alveolar type-1 cells. We propose that in lung fibrosis, perturbed molecular checkpoints on the way to terminal differentiation can cause aberrant persistence of regenerative intermediate stem cell states.

Persistence of a regeneration-associated, transitional alveolar epithelial cell state in pulmonary fibrosis.

Stem cells undergo dynamic changes in response to injury to regenerate lost cells. However, the identity of transitional states and the mechanisms that drive their trajectories remain understudied. Using lung organoids, multiple in vivo repair models, single-cell transcriptomics and lineage tracing, we find that alveolar type-2 epithelial cells undergoing differentiation into type-1 cells acquire pre-alveolar type-1 transitional cell state (PATS) en route to terminal maturation. Transitional cells undergo extensive stretching during differentiation, making them vulnerable to DNA damage. Cells in the PATS show an enrichment of TP53, TGFβ, DNA-damage-response signalling and cellular senescence. Gain and loss of function as well as genomic binding assays revealed a direct transcriptional control of PATS by TP53 signalling. Notably, accumulation of PATS-like cells in human fibrotic lungs was observed, suggesting persistence of the transitional state in fibrosis. Our study thus implicates a transient state associated with senescence in normal epithelial tissue repair and its abnormal persistence in disease conditions.

COVID-19 y su asociación con los inhibidores de la enzima convertidora de angiotensina y los antagonistas de los receptores para angiotensina II

Worldwide, over 7 million people have been infected due to the pandemic of COVID-19. The comorbidities associated to this disease are: hypertension, diabetes mellitus, obesity, obstructive pulmonary disease (COPD), cardiovascular disease, chronic renal failure, smoking, immunosuppression, and hypertension. Angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2. This virus has an S protein that recognizes ACE2 as its receptor to enter the cell. ACE2 is a plasmatic protein expressed in alveolar cells type I, II, fibroblasts, endothelial cells and macrophages. Treatment with inhibitors of the angiotensin-converting enzyme (ACEi) or the receptor antagonist for angiotensin II (ARBs) notably increase the expression of ACE2. Therefore, in patients with these pathologies and treated with these medicines, the risk of developing the COVID-19 in a severe and fatal way could be increased. In Mexico, the major mortality due to COVID-19 is related to hypertension, diabetes mellitus, obesity and being over 65 years of age. Therefore, we suggest that during the SARS-CoV-2 pandemic, patients with hypertension treated with ACEi or ARBs, should receive alternative treatments such as L-type Ca2+ channel blockers (amlodipine) that have not been associated with ACE2 until now. Key words: COVID-19; SARS-CoV-2; captopril; losartan hypertension."

Features of cytokine signaling forming T-helper immune response in COPD of varying severity

Introduction — Currently, chronic obstructive pulmonary disease (COPD) is a global public health problem. However, molecular mechanisms of the development of this pathology are still poorly understood. The aim is to establish mechanisms of cytokine regulation of T-helper (Th) immune pathway in patients with COPD of varying severity. Material and Methods — The study included 112 patients with stable COPD (mild, moderate and severe grade) and 32 healthy volunteers (control group). We investigated serum cytokine levels (tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin 4 (IL-4), IL-6, IL-10, IL-17A) and the percentage of circulating Th cells (CD4+) expressing membrane receptor to IL-6 (IL-6R or CD126+), using flow cytometry. The levels of transforming growth factor-β1 (TGF-β1) and IL-21 were detected by ELISA. The direction of immune response in COPD patients was determined depending on the prevalence of cytokines playing a crucial role in the formation of certain Th cells type (Th1, Th17). Results — Th1-associated cytokine profile was expressed at the initial stage of COPD; the Th17-associated cytokine profile begins to prevail at severe COPD. Among COPD patients with Th1-associated cytokine profile, a statistically significant increase in the number of CD4+CD126+ cells in comparison with the control group was identified only in severe COPD. In the group of COPD patients with Th17-associated cytokine profile, an increase in the number of CD4+CD126+ cells were observed at all severity stages of the pathology. Conclusion — Moderate and severe COPD are characterized by the predominance of Th17-associated cytokine profile leading to chronic inflammation. The increase in IL-6R expression levels in circulating CD4+ cells serves as the mechanism for enhancing Th17-associated response in COPD.

Effective Prediction of Diabetes Mellitus using Nine different Machine Learning Techniques and their Performances

Diabetes is a disease where the predominant finding is high blood sugar. The high blood sugar may either be because of deficient insulin production (Type 1) or insulin resistance in peripheral tissue cells (Type 2). Many problems occur if diabetes remains untreated and unidentified. It is additional inventor of various varieties of disorders for example: coronary failure, blindness, urinary organ diseases etc. Nine different machine learning techniques are used in this research work for prediction of diabetes. A dataset of diabetic patient’s is taken and nine different machine learning techniques are applied on the dataset. Positive likelihood ratio, Negative likelihood ratio, Positive predictive value, Negative predictive value, Disease prevalence, Specificity, Precision, Recall, F1-Score ,True positive rate, False positive rate of the applied algorithms is discussed and compared. Diabetes is growing at an increasing in the world and it requires continuous monitoring. To check this we use Logical regression, Random forest, Logical regression CV, Support Vector Machine, Artificial Neural Network (ANN), Decision Tree, k-nearest neighbors (KNN), XGB classifier

Antiviral immune mechanism of Toll-like receptor 4-mediated human alveolar epithelial cells type Ⅱ.

Expression of Toll-like receptor (TLR)4 and its downstream substances, myeloid differentiation factor 88 (MyD88), NF-κB p65, tumor necrosis factor-α (TNF-α) and GR in human alveolar epithelial cells type Ⅱ (AEC Ⅱ) infected with respiratory syncytial virus (RSV) were investigated, and the antiviral immune mechanism mediated by TLR4 was explored. Human AEC Ⅱ were divided into TLR4-/- group, normal group and TLR4+ group, and also into control group, RSV group and RSV+MP (methylprednisolone) group. MTT assay was used to measure the survival of cells after TLR4 knockout and overexpression, and the survival of normal cells after treatment with MP. The concentration of TLR4, MyD88, NF-κB p65, TNF-α, and GR was measured by ELISA after TLR4 knockout and overexpression. Reverse transcription-quantitative PCR (RT-qPCR) was used to measure the mRNA expression of the gene knockout and overexpression groups. RT-qPCR and western blot analysis were used to determine the expression of TLR4, MyD88, NF-κB p65 and GR in RSV and RSV+MP groups. The concentration of the detected substances in the TLR4-/- group was significantly lower than that in the normal group (P<0.01 and <0.001), and in the TLR4+ group was significantly higher than that in the normal group (P<0.05, <0.01 and <0.001); the expression of RSV in the TLR4-/- group was significantly higher than that in the normal group (P<0.001), and in the TLR4+ group was significantly lower than that in the normal group (P<0.05). The expression levels of TLR4, MyD88 and NF-κB p65 in the RSV and RSV+MP groups were significantly higher than those in the control group (P<0.05, <0.01 and <0.001), and the increase presented in the RSV+MP group was significantly lower than that in the RSV group (P<0.05 and <0.01). TLR4-mediated antiviral immunity of human AEC Ⅱ can reduce the levels of TLR4, MyD88, NF-κB p65 and TNF-α and increase the level of GR, participating in the immune defense and reducing the damage of the viral epithelial cells of human type Ⅱ alveoli, thus improving human immunity.

Immunoglobulin gene rearrangement and BAFF responsive maturation defines a novel B cell population undergoing extra-BM development

Abstract Transitional type-1 (T1) cells are peripheral immature B cells known to populate the spleen (spl) after completing their BCR assembly in the bone marrow (BM). To advance the understanding of splenic T1 (CD19posCD24hiCD21neg) B cells, we addressed the heterogeneity and biology of these cells using flow cytometry combined with genetically modified mice. Most recent emigrant T1 cells were selected by excluding CD23pos and including CD93high (AA4.1) B cells termed T12123DN. Transcriptomic analysis identified RAG1 and 2 as signature genes for this B cell population. Further separation of T12123DN cells based on surface IgM expression revealed a previously undescribed cell subset with undetectable cell surface IgM (-IgMneg). The spl-IgMneg subsets expresses RAG1/2 and actively undergoes Igk gene rearrangement at levels comparable to BM pre-B cells. Upon in vitro exposure to BAFF or transplantation into immunodeficient hosts, spl-IgMneg cells can give rise to fully mature IgMposIgDpos B cells. Furthermore, BAFF-R and NF-kB pathways are required for their efficient maturation. Our findings suggest that the spl-T1 population encompasses a subset of B cells that resemble but are distinct from the developing B cells in the BM. These spl-IgMneg B cells may represent receptor editing B cells, and/or precursor B cells undergoing BCR assembly and selection in the periphery, possibly providing an opportunity for tolerance induction to tissue restricted self-antigens and microbiota-derived antigens.

A critical period of innate-immune development: Fetal origins of allergic asthma susceptibility

Abstract Our lab previously identified a developmentally-restricted hematopoietic stem cell (drHSC) that only exists during fetal development and specifically gives rise to innate-like lymphocytes that persist across the lifespan. The identification of a developmentally-limited cell of origin for innate-like immune cells defines a “critical window” for immune development, in which the phenotype of the developing immune system can be shaped via extrinsic inputs. To test how perturbation during this critical window drives immune dysfunction, we examined underlying changes to innate lymphoid cells (ILCs) in the lung. ILCs are a recently identified family of fetal-derived innate-like lymphocytes that mimic the adaptive T-helper arm of our immune system. In the lung, type-2 innate lymphoid cells (ILC2s) produce IL5 and IL13, cytokines important for eosinophil recruitment, activation and goblet cell hyperplasia during allergic airway inflammation. Surprisingly, a single low-dose injection of poly (i:c) at mid-gestation robustly increased proliferative capacity and cellularity of lung ILC2s in offspring at postnatal day (P)9 and P14, respectively, concomitant with drHSC and common-helper innate lymphoid progenitor (ChILP) cell expansion during fetal development. Additionally, in poly (i:c) perturbed offspring, lung ILC2s exhibited heightened IL5 and IL13 production upon in-vitro stimulation with PMA and ionomycin. Ongoing experiments will examine how perturbation of transient progenitors during fetal development may impact the ChILP cell immune trajectory, altering the establishment and function of neonatal lung ILC2s, and ultimately contributing to allergic asthma susceptibility into adulthood.

Lung ILC2 responses to Alternaria alternata fungal allergen are blunted in “dirty” mice with physiologically transmitted murine microbes

Abstract The objective of this study was to test the hypothesis that the increasing global incidence of allergy and atopy are due in part to improved hygiene and decreased microbial exposure. We have adopted a novel mouse model of normalized microbial exposure to test the impact of immune experience on subsequent responses to airway allergens. In this model, specific pathogen free (SPF) B6 mice are cohoused with mice from pet stores and become “dirty” – many commensals and pathogens are transmitted through cohousing and influence the immune cell populations systemically and in the lungs. We treated mice intranasally with a single dose of A. alternata fungal extract (Alt) and assessed production of type 2 cytokines. IL5 and IL13 levels in the lungs and bronchoalveolar lavage fluid were dramatically elevated by Alt in SPF mice but were not significantly increased by Alt in dirty mice. Type 2 innate lymphoid cells (ILC2) are the cells responsible for IL5 and IL13 after acute Alt treatment, and interestingly the number of lung ILC2 was unaltered by cohousing and their activation status appeared similar in both housing conditions. We treated mice with recombinant IL33, the alarmin released by lung epithelial cells in response to allergens, and the results suggest an impaired response to IL33 by dirty lung ILC2. In a repeated Alt exposure model, ILC2 cells expanded in SPF lungs and recruited eosinophils, neutrophils, and T cells. Most dirty mouse lungs contained these cell populations at steady state but were only modestly recruited with repeated Alt exposure. Lung function experiments are in progress. This study suggests that increased microbial exposure leads to more type-2 associated immune cells in the lungs, however responses to airway allergens are dampened.

GPER1 Signaling Initiates Migration of Female V-SVZ-Derived Cells.

SummaryIn the rodent ventricular-subventricular zone (V-SVZ) neurons are generated throughout life. They migrate along the rostral migratory stream (RMS) into the olfactory bulb before their final differentiation into interneurons and integration into local circuits. Estrogen receptors (ERs) are steroid hormone receptors with important functions in neurogenesis and synaptic plasticity. In this study, we show that the ER GPER1 is expressed in subsets of cells within the V-SVZ of female animals and provide evidence for a potential local estrogen source from aromatase-positive astrocytes surrounding the RMS. Blocking of GPER1 in Matrigel cultures of female animals significantly impairs migration of V-SVZ-derived cells. This outgrowth is accompanied by regulation of phosphorylation of the actin-binding protein cofilin by GPER1 signaling including an involvement of the p21-Ras pathway. Our results point to a prominent role of GPER1 in the initiation of neuronal migration from the V-SVZ to the olfactory bulb.

The Heat Shock Protein HSP70 Promotes Th17 Genes’ Expression via Specific Regulation of microRNA

T helper cells type 17 (Th17) are orchestrators of autoimmune conditions, including multiple sclerosis (MS), but mechanisms of Th17 pathogenicity remain unknown. MicroRNAs (miRNA) are known to control T cells. To understand the function of miRNA in Th17, we have established a T cell line, EL4-TCR+, that resembles the expression pattern of the Th17 cells. Subsequently, we have evaluated the crosstalk between miRNA and Th17 genes’ expression using a combination of gene expression profiling, gene expression manipulation, RNA and protein immunoprecipitation, as well as confocal microscopy. We have found that Th17-related miRNA were strongly expressed in EL4-TCR+ cells following the binding of the cluster of differentiation 3 (CD3) component of the T cell receptor (TCR). Furthermore, a specific inhibition of these miRNA resulted in downregulation of the critical Th17 genes’ expression. Surprisingly, this mechanism relied on the function of the stress signal regulator heat shock protein 70 (HSP70). Upon activation, HSP70 co-localized intracellularly with miRNA processing proteins. Precipitation of HSP70 resulted in enrichment of the Th17-associated miRNA. Finally, HSP70 inhibition led to downregulation of the Th17 genes’ expression and ameliorated development of autoimmune demyelination. Our study demonstrated that HSP70 facilitates specific miRNA function leading to Th17 genes’ expression, a mechanism linking stress and autoimmunity.

Aspirin-exacerbated respiratory disease

Aspirin-exacerbated respiratory disease (AERD) classically presents with severe asthma, nasal polyposis, and respiratory exacerbations in response to cyclooxygenase (COX)-1 inhibition. Recent advances in our understanding of AERD have revealed multiple facets of immune dysregulation, including diminished prostaglandin E2 (PGE2) function and elevated levels of both cysteinyl leukotrienes (CysLTs) and innate cytokines such as interleukin 33 (IL-33). Inflammatory mediators in AERD heighten the recruitment and activation of innate lymphoid cells type 2 (ILC2), mast cells, eosinophils, and platelet-adherent leukocytes. This contributes to a cyclical pattern of type 2 inflammation. Here, we highlight current understanding of the immunopathogenesis of AERD.

Nasal Epithelial Cells Activated with Alternaria and House Dust Mite Induce Not Only Th2 but Also Th1 Immune Responses.

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation. Airborne allergens are associated with upper and lower airway inflammatory disease. We investigated the effects of airborne allergen stimulation in the nasal epithelial cells and their effect on the peripheral blood mononuclear cells’ (PBMCs) Th immune polarization. Interleukin (IL)-10, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels were determined using the enzyme-linked immunosorbent assay (ELISA) in nasal polyp tissues. Cultured primary nasal epithelial cells were stimulated with Alternaria alternata, Aspergillus fumigatus, Dermatophagoides pteronyssinus (DP), and Dermatophagoides farina (DF) for 48 hours. IL-6, IL-25, IL-33, and TSLP production were measured by ELISA, and the nuclear factor-κB (NF-κB), activator protein 1 (AP-1), and mitogen-activated protein kinase (MAPK) expression were determined by western blot analyses. PBMCs were cultured with nasal epithelial cell-conditioned media (NECM), and IL-5, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were measured. Innate lymphoid type2 cells (ILC2) were analyzed with flowcytometry. IL-25, IL-33, and TSLP levels were significantly higher in eosinophilic nasal polyps. Alternaria, DP, and DF enhanced IL-33 and TSLP production from the nasal epithelial cells through the NF-κB, AP-1, and MAPK pathway. NECM induced IL-5, IFN-γ, and TNF-α production from PBMCs, without increasing ILC2 expression. Alternaria and house dust mites enhanced the chemical mediator production from nasal epithelial cells and these allergens may induce not only Th2 inflammatory responses but also Th1 inflammatory responses in the nasal mucosa.

Hepatic Tumour Cell Reduction with Quanta Energy – a Technological Exploration and Expanded Mathematical Model.

Manley (2014) developed several mathematical models based on the CSC concept that not only explain the growth of a tumour, but also its demise based on the applied radiation energy. If a population A of CSCs divide asymmetrically, they will yield one daughter cell of type A and one cancer cell of type B. The speed with which new type B cells emerge depends on the number of A cells – if there are 100 A cells, 100 B cells will emerge in a given unit of time; if the number of A cells is 200, 200 B cells will emerge in the same time window, twice as many as before. Therefore, one can model the growth or increase in numbers of B cells. which allows us to model the growth of B as differential equation. The basic form of this model has the number of CSCs (type A) constant, while the increase in differentiated tumor cells (type B) grows.In other words, the population of cancer cells grows linearly. One can introduce further parameters into this simple equation and distinguish between cancer stem cells A, differentiated tumour cells B and healthy cells H.If we further irradiate cells with energy from X‐rays, proton beams, or light of visible spectrum, photodynamic therapy (PDT) or invisible UV; there will have likely different effects on each cell type A, B and H. Manley (2014) established the following formulas with r1, r2 and r3 as specific effects of radiation or PDT on each of the cell types, the equation in diagram 1 is established.Where S is the desired number of stem cells, and M1 and M2 are the carrying capacity of B and H cells, respectively (Manley, 2014).If we use different assumptions for the parameters in these equations, we can come up with different long term behaviors of the cell lines. The most desirable situation is one in which the number of healthy cells remains constant, while the CSCs and tumor cells are reaching a number near zero. This would mean shrinkage of the tumor without affecting healthy tissue.The different ri values are effects the radiation energy will have on each cell type; one should be able to derive the effect from the wavelength or frequency of the used radiation, but the relationship is not entirely clear. The energy of one quantum of energy can be described using the classic equation of light and quanta.with c as the speed of light (c = 2.998 × 108 m/s) and h as Planck constant (h = 6.626 × 10−34 m2 kg/s. Since the above equations for dA/dt, dB/dt and dH/dt are all describing the total change in cell numbers as influenced or determined by time, r1, r2 and r3 must represent the number of cells that die off by application of energy with radiation of a certain frequency or wavelength in the visible or invisible spectrum of light. Importantly, cells may not be damaged if the radiation that we use to illuminate them with has a frequency that is too low.Simple model of linear tumour growthFigure 1GP Einstein Sigma Quanta tumor growth and development modelFigure 2

Tummy Time for ILC2

Little is known about host-microbiota interactions regulating anti-microbial immunity in the stomach. In this issue, Satoh-Takayama etal. describe an additional immune mechanism involving innate lymphoid cells type 2 (ILC2), which controls infection with Helicobacter pylori, a bacterium associated with inflammation and cancer.

영농형 태양광 발전 시스템 구성에 따른 하부 농지 일사량의 전산모사 연구

The share of agrophotovoltaics in the “renewable energy 3020”, which is the Korean government policy for revitalizing new and renewable energy, is increasing gradually. In this study, the distribution of solar radiation received by crops growing on virtual farmland under a range of conditions, such as module height, module angle, shading ratio, and module type, was quantified and analyzed using an Ecotect program, which allows insolation analysis during the period from spring to fall. As the module angle increases, transmissive modules increase the amount of solar radiation delivered to the lower farmland. In addition, the difference between 3x12 Cell Type and 4x9 Cells Type, which are types of photovoltaic modules used in practice, was found to be small. The analysis results can be used as a design standard for the future establishment of agrophotovoltaic systems.