Miracle-dz/UniFAR-FTUs huggingface dataset:
Cellular Therapies in Chronic Granulomatous Disease

Allogeneic hematopoietic stem cell transplantation (HSCT) has become the main curative treatment in patients with chronic granulomatous disease (CGD). CGD is caused by inherited defects of the phagolysomal NADPH-oxidase, leading to a lifelong propensity for invasive infections and granulomatous inflammation. After successful allogeneic HSCT, chronic infections and inflammation resolve and quality-of-life improves. Favorable long-term outcome after HSCT is dependent on the prevention of primary and secondary graft failure (GF), including falling myeloid donor chimerism (DC) below 10 %, and chronic graft-vs.-host-disease (cGVHD). The risk of GF and GvHD increases with the use of HLA-incompatible donors and this may outweigh the benefits of HSCT, mainly in patients with severe co-morbidities and in asymptomatic patients with residual NADPH-oxidase function. Seventeen scientific papers have reported on a total of 386 CGD-patients treated by HSCT with HLA-matched family/sibling (MFD/MSD), 9/10-/10/10-matched-unrelated volunteer (MUD) and cord blood donors. The median OS/EFS-rate of these 17 studies was 91 and 82%, respectively. The median rates of GF, cGVHD and de-novo autoimmune diseases were 14, 10, and 12%, respectively. Results after MFD/MSD and 10/10-MUD-transplants were rather similar, but outcome in adults with significant co-morbidities and after transplants with 9/10 HLA-MUD were less successful, mainly due to increased GF and chronic GVHD. Transplantation protocols using T-cell depleted haploidentical donors with post-transplant cyclophosphamide or TCR-alpha/beta depletion have recently reported promising results. Autologous gene-therapy after lentiviral transduction of HSC achieved OS/EFS-rates of 78/67%, respectively. Careful retrospective and prospective studies are mandatory to ascertain the most effective cellular therapies in patients with CGD.
The Use of Single Cell Mass Cytometry to Define the Molecular Mechanisms of Varicella-Zoster Virus Lymphotropism

Unraveling the heterogeneity in biological systems provides the key to understanding of the fundamental dynamics that regulate host pathogen relationships at the single cell level. While most studies have determined virus-host cell interactions using cultured cells in bulk, recent advances in deep protein profiling from single cells enable the understanding of the dynamic response equilibrium of single cells even within the same cell types. Mass cytometry allows the simultaneous detection of multiple proteins in single cells, which helps to evaluate alterations in multiple signaling networks that work in tandem in deciding the response of a cell to the presence of a pathogen or other stimulus. In applying this technique to studying varicella zoster virus (VZV), it was possible to better understand the molecular basis for lymphotropism of the virus and how virus-induced effects on T cells promoted skin tropism. While the ability of VZV to manifest itself in the skin is well established, how the virus is transported to the skin and causes the characteristic VZV skin lesions was not well elucidated. Through mass cytometry analysis of VZV-infected tonsil T cells, we were able to observe that VZV unleashes a “remodeling” program in the infected T cells that not only makes these T cells more skin tropic but also at the same time induces changes that make these T cells unlikely to respond to immune stimulation during the journey to the skin.
Porf-2 Inhibits Tumor Cell Migration Through the MMP-2/9 Signaling Pathway in Neuroblastoma and Glioma

Tumor migration and invasion are key pathological processes that contribute to cell metastasis as well as treatment failure in patients with malignant tumors. However, the mechanisms governing tumor cell migration remain poorly understood. By analyzing the tumor-related database and tumor cell lines, we found that preoptic regulatory factor-2 (Porf-2) is downexpressed in both neuroblastoma and glioma. Using in vitro assays, our data demonstrated that the expression of Porf-2 inhibits tumor cell migration both in neuroblastoma and glioma cell lines. Domain-mutated Porf-2 plasmids were then constructed, and it was found that the GAP domain, which plays a role in the inactivation of Rac1, is the functional domain for inhibiting tumor cell migration. Furthermore, by screening potential downstream effectors, we found that Porf-2 can reduce MMP-2 and MMP-9 expression. Overexpression of MMP-2 blocked the inhibitory effect of Porf-2 in tumor cell migration both in vitro and in vivo. Taken together, we show for the first time that Porf-2 is capable of suppressing tumor cell migration via its GAP domain and the downregulation of MMP-2/9, suggesting that targeting Porf-2 could be a promising therapeutic strategy for nervous system tumors.
Soil Fungal Community Characteristics and Mycelial Production Across a Disturbance Gradient in Lowland Dipterocarp Rainforest in Borneo

The rainforests of Southeast Asia are a global biodiversity hotspot under increasing pressure from human activity. Selective logging and forest conversion to oil palm plantation has major implications for biogeochemical cycling and carbon storage that are underpinned by plant-soil interactions. Soil fungi are key regulators of carbon and mineral nutrient flows between above- and below-ground organisms, yet understanding of fungal community-productivity relationships in hyper-diverse tropical forests is lacking. Recent studies suggest sensitivity of soil fungal communities to land-use change, although impacts on fungal productivity remain largely unresolved. To address this gap, we installed hyphal in-growth bags for 6 months in old-growth (OG) and selectively logged (SL) forest and oil palm plantation (OP) in Bornean lowland rainforest. Mycelial (actively foraging) fungal communities were characterized by ITS amplicon sequencing, and mycelial production estimated by measurement of fungal hyphae. Mycelial fungal community compositions were similar in OG and SL forest, whereas OP had significantly different communities of saprotrophic, mycorrhizal, and pathogenic fungi. In particular, total mycorrhizal and ectomycorrhizal fungal relative abundances, total mycorrhizal richness and mycelial production was reduced. However, due to restricted sampling replication in OP, effects associated with site could not be excluded. In forest plots (OG & SL), we further explored the broader drivers of mycelial fungal communities using tree community, structure and productivity data, and soil and environmental properties. Forest mycelial community dissimilarities were related to soil and vegetation characteristics, while mycelial production was broadly independent of these as well as fungal community attributes. An increase in arbuscular mycorrhizal relative abundance was also found with selective logging, which may have implications for carbon storage capacity in these forests, while an apparent retention of mycorrhizal mycelium in SL forest may act as a reservoir of inoculum that could aid forest restoration. Our results show that conversion of rainforest to oil palm plantation has significant consequences for fungal diversity-productivity relationships with implications for nutrient and carbon dynamics and restoration over large spatial scales.
Meridional flow in the Sun’s convection zone is a single cell in each hemisphere

The flow of plasma inside the Sun The activity of the Sun, including the occurrence of sunspots, is driven by magnetic fields that originate from the motion of charged plasma beneath the surface. Helioseismology uses acoustic oscillations to probe the Sun's interior, analogous to seismology's use of earthquakes to investigate Earth's interior. Gizon et al. analyzed helioseismology data from 1996 to 2019, covering two 11-year solar cycles. They measured the latitudinal and radial flow of plasma as a function of depth within the Sun and how it varies with time. The results support magnetic flux-transport dynamo models, which can explain the distribution of sunspots over each solar cycle. Science, this issue p. 1469 Helioseismology is used to measure the bulk flow of plasma within the Sun and how it varies with depth. The Sun’s magnetic field is generated by subsurface motions of the convecting plasma. The latitude at which the magnetic field emerges through the solar surface (as sunspots) drifts toward the equator over the course of the 11-year solar cycle. We use helioseismology to infer the meridional flow (in the latitudinal and radial directions) over two solar cycles covering 1996–2019. Two data sources are used, which agree during their overlap period of 2001–2011. The time-averaged meridional flow is shown to be a single cell in each hemisphere, carrying plasma toward the equator at the base of the convection zone with a speed of ~4 meters per second at 45° latitude. Our results support the flux-transport dynamo model, which explains the drift of sunspot-emergence latitudes through the meridional flow.
Age-Friendly Environments in ASEAN Plus Three: Case Studies from Japan, Malaysia, Myanmar, Vietnam, and Thailand

Promoting age-friendly environment is one of the appropriate approaches to support quality of life toward ageing populations. However, the information regarding age-friendly environments in the Association of Southeast Asian Nations (ASEAN) Plus Three countries is still limited. This study aimed to survey the perceived age-friendly environments among ASEAN Plus Three older populations. The study employed cross-sectional quantitative research using multistage cluster sampling to select a sample of older adults in the capital cities of Japan, Malaysia, Myanmar, Vietnam and Thailand. The final sample was composed of 2171 older adults aged 55 years and over, including 140 Japanese, 510 Thai, 537 Malaysian, 487 Myanmarese, and 497 Vietnamese older adults. Data collection was conducted using a quantitative questionnaire with 20 items of perceived age-friendly environments with the rating scale based on the World Health Organization (WHO) standard. The score from the 20 items were analyzed and examined high-risk groups of “bad perception level” age-friendly environments using ordinal logistic regression. The research indicated the five highest inadequacies of age-friendly environments including: (1) participating in an emergency-response training session or drill which addressed the needs of older residents; (2) enrolling in any form of education or training, either formal or non-formal in any subject; (3) having opportunities for paid employment; (4) involvement in decision making about important political, economic and social issues in the community; and (5) having personal care or assistance needs met in the older adult’s home setting by government/private care services. Information regarding the inadequacy of age-friendliness by region was evidenced to guide policy makers in providing the right interventions towards older adults’ needs.
Histological Study of Expression of Seedlessness in Citrus kinokuni ‘Mukaku Kishu’ and Its Progenies

The factors of seedless expression in Citrus kinokuni hort. ex Tanaka 'Mukaku Kishu', 'Southern Yellow' {'Tanikawa Buntan' pummelo (an uncertain hybrid with C. maxima (Burm.) Merr. ) · 'Mukaku Kishu'}, and the hybrid seedling BSY lines of 'Southern Yellow' · Bu1-7 pummelo (chance seedling of 'Suisho Buntan' pummelo (C. maxima)) were investigated histologically. 'Mukaku Kishu', 'Southern Yellow', BSY18, and BSY21 are completely seedless, whereas others are seedy. The percentage of abnormal embryo sacs and fertilization in seedless cultivars and lines showed no differences from seedy ones, indicating that the seedlessness of 'Mukaku Kishu' and its progenies was not involved in abnormal embryo sacs and unfertilized ovules. In seedy cultivars and lines, embryos developed to the cotyledon stage by 14 weeks after pollination. In the seedless cultivars and lines, however, embryos only developed to the early stages of zygote or embryo development. These results indicate that the seedless expression of the seedless progenies of 'Mukaku Kishu' coincides with 'Mukaku Kishu' and is caused by an arrested seed development at the early stage.
Homeostasis and Defense at the Surface of the Eye. The Conjunctival Microbiota

ABSTRACT The literature on ocular microbiome has grown tremendously over the past decade, and our knowledge of the different aspects and roles in homeostasis and protection is continuously growing. The development of 16 S rRNA sequencing has allowed the field to characterize communities of bacteria in health and ocular disease. Efforts should continue to further elucidate the interplay between microbiome and key players, such as age, comorbidities, and contact lens usage in order to have better control of the sight-threatening complications.
Discovery of Novel Recurrent Mutations and Clinically Meaningful Subgroups in Nodal Marginal Zone Lymphoma

Nodal marginal zone lymphoma (NMZL) is a rare B-cell neoplasm, the genetic and transcriptomic landscape of which are unclear. Using high-throughput sequencing for whole-exome and transcriptome, we investigated the genetic characteristics of NMZL in a discovery cohort (n = 8) and validated their features in an extended cohort (n = 30). Novel mutations in NFKBIE and ITPR2 were found in 7.9% (3/38) and 13.9% (5/36), respectively, suggesting roles for the NF-κB pathway and B-cell-receptor-mediated calcium signaling pathway in the pathogenesis of NMZL. RNA-seq showed that NMZLs were characterized by an aberrant marginal zone differentiation, associated with an altered IRF4-NOTCH2 axis and the enrichment of various oncogenic pathways. Based on gene expression profile, two subgroups were identified. Compared with subgroup 1, subgroup 2 showed the following: the significant enrichment of cell cycle-associated and MYC-signaling pathways, a more diverse repertoire of upstream regulators, and higher Ki-67 proliferation indices. We designated two subgroups according to Ki-67 labeling, and subgroup 2 was significantly associated with a shorter progression-free survival (p = 0.014), a greater proportion of large cells (p = 0.009), and higher MYC expression (p = 0.026). We suggest that NMZL has unique features and, in this study, we provide information as to the heterogeneity of this enigmatic entity.
Antibacterial activity of the ethanol extracts of Hibiscus rosa-sinensis leaves and flowers against clinical isolates of bacteria

Crude preparations of the different parts of Hibiscus rosa-sinensis have been traditionally used in folk medicine for various purposes. In the present study, we have evaluated the antibacterial activity of the extracts of H. rosa-sinensis leaves and flowers against some clinical isolates of bacteria by simple agar-well diffusion and bacteriological enumeration method. In the preliminary screening experiment, all of the bacterial isolates showed varying degrees of sensitivity to the flower extracts excluding Klebsiella pneumoniae. We found Staphylococcus aureus, a Gram-positive bacterium as the most sensitive to the extracts of flowers at the applied doses of 50 and 100 mg/well. On the other hand, most of the tested bacterial isolates were resistant to the extracts of leaves excluding S. aureus and Salmonella typhimurium. In bacteriological enumeration study, all of the bacterial isolates showed substantial extent of sensitivity to the different extracts used. Our findings clearly demonstrate that the flower extracts of H. rosa-sinensis had stronger antibacterial effects than that of leaves and raises the possibility of using the extracts as antibacterial agents in treating pathological conditions caused by S. aureus and S. typhimurium infection. Although the effect of the H. rosa-sinensis flowers and leaves against some pathogenic bacteria in vitro is promising, further microbiological and pharmacological studies will be required before starting clinical trials.
Modulation of Calcium signalling by F-actin during maturation and fertilization of starfish oocytes

The Calcium ion (Ca2+) is a universal intracellular messenger that is implicated in the regulation of a great variety of intracellular processes. Among them, there is the meiotic maturation of oocytes from several species and their fertilization. The cell model system chosen for the work of this thesis has been the starfish oocytes. They constitute an exceptional model to study the properties of the dynamic release of Ca2+. First, the cells are large and nearly transparent, making them suitable for imaging experiments after microinjection of fluorescent markers. Immature oocytes extracted from the gonad are arrested at the prophase stage of the first meiotic division. Overcoming the meiotic arrest (maturation), is induced by the application of the maturing hormone 1-Methyladenine (1-MA), whose action involves intracellular Ca2+ transients. During the maturation process, the oocytes develop their ability to be successfully activated by a fertilizing spermatozoon by liberating higher levels of calcium. 1-MA also induces dramatic actin cytoskeleton rearrangements. In the present work, the relevance of the actin cytoskeleton in the modulation of the Ca2+ signals generated by hormonal stimulation and by the sperm has been studied. For this purpose, actin-specific disrupting agents and a specific antibody targeting the actin binding protein depactin have been delivered into living cells by needle microinjection, to study their effects using confocal laser fluorescent microscopy. Thus, the Ca2+ increases induced either by 1-MA, by the fertilizing sperm or by the injection of exogenous InsP3. which is the canonical Ca2+ mobilizer second messenger, have been monitored with video fluorescent microscopy. The results described indicate that actin filaments play direct and indirect roles in modulating the intracellular Ca2+ mobilization induced by the maturation process triggered by 1-MA as well as in the Ca2+ responses induced by the sperm.
Environmental determinants of amphibian and reptile species richness in China

Understanding the factors that regulate geographical variation in species richness has been one of the fundamental questions in ecology for decades, but our knowledge of the cause of geographical variation in species richness remains poor. This is particularly true for herpetofaunas (including amphibians and reptiles). Here, using correlation and regression analyses, we examine the relationship of herpetofaunal species richness in 245 localities across China with 30 environmental factors, which include nearly all major environmental factors that are considered to explain broad-scale species richness gradients in such theories as ambient energy, water-energy dynamics, productivity, habitat heterogeneity, and climatic stability. We found that the species richness of amphibians and reptiles is moderately to strongly correlated with most of the environmental variables examined, and that the best fit models, which include explanatory variables of temperature, precipitation, net primary productivity, minimum elevation, and range in elevation, explain ca 70% the variance in species richness for both amphibians and reptiles after accounting for sample area. Although water and temperature are important explanatory variables to both amphibians and reptiles, water variables explain more variance in amphibian species richness than in reptile species richness whereas temperature variables explain more variance in reptile species richness than in amphibian species richness, which is consistent with different physiological requirements of the two groups of organisms.
Leiophron argentinensis Shaw (Hymenoptera: Braconidae): A New Species of Parasitoid from Argentina and Paraguay—Information on Life History and Potential for Controlling Lygus Bugs (Hemiptera: Miridae)

Abstract We discovered an undescribed species of Leiophron parasitizing mirid nymphs in Argentina and Paraguay; this euphorine braconid is described as Leiophron argentinensis Shaw n. sp. Wasps were reared from several mirid species collected on numerous host plants, but most parasitoids (>85%) were reared from Taylorilygus apicalis (Fieber), which was the most abundant mirid. Parasitism rates ranged from 0 to 37% and averaged ≈7% for the entire study. Excluding samples where parasitism was not observed, parasitism rates averaged ≈9%. Parasitism levels were highest in the summer. Host plant species significantly influenced parasitism levels of T. apicalis; nymphs on Conyza spp. suffered ≈16% parasitism, significantly more than nymphs on other host plants. L. argentinensis was collected throughout the study area (≈22–35° S), although the entire geographic range of this species is not yet known. We observed a transition from a male-biased sex ratio in the summer to a female-biased sex ratio in the fall. L. argentinensis has several generations per year and apparently produces some diapausing individuals in each generation. The incidence of diapause was lowest in the summer (≈40%). In laboratory trials, L. argentinensis readily parasitized Lygus lineolaris (Palisot de Beauvois) and Lygus hesperus Knight, suggesting that L. argentinensis has potential as a biological control agent for these pests in the United States.
Glycerol-preserved corneal tissue in emergency corneal transplantation: An alternative for fresh corneal tissue in COVID-19 crisis

Purpose: Due to the COVID-19 pandemic, most of the eye banks have limited/stopped corneal collection, as this is a highly contagious disease. This has led to shortage of donor corneas worldwide. Glycerol preservation of tissue remains a viable option in this scenario. The objective is to compare fresh corneal tissue (FCT) with glycerol-preserved cornea (GPC) in emergency corneal transplantation. Methods: This was a retrospective cohort study conducted in a tertiary care centre of Uttarakhand. Medical records of the patients who underwent therapeutic penetrating keratoplasty (TPK) were reviewed. FCT group included patients who underwent TPK with fresh corneal tissue and GPC group included patients who underwent TPK with glycerol preserved cornea. The indications and outcomes of TPK in the terms of therapeutic success were analysed and compared between both the groups. Results: A total of 94 eyes of 91 patients underwent TPK from October 2011 to August 2017. FCT group included 60 eyes of 57 patients and GPC group included 34 eyes of 34 patients. The primary indication of TPK was infectious keratitis in both the groups (FCT-81.6%; GPC - 91.2%) There was no significant difference in the therapeutic success in both the groups (P = 0.741, Odds ratio- 1.59 with 95% CI- 0.39-6.44). Complications included glaucoma (FCT-21.7%; GPC- 35.2%) graft infection (FCT- 18.33% GPC- 2.9%); graft rejection (FCT-11.66%, GPC- 0%); and graft failure (FCT-88.33%, GPC-100%). Conclusion: The GPC is comparable to FCTs in therapeutic transplant and can be a useful interim procedure in saving the eyes in cases of infective keratitis in the time of crisis.