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While young muscle faithfully regenerates damaged myofibers, aged muscle is impaired. Here the authors show the “anti-aging” protein α-Klotho is upregulated in young muscle after damage via promoter demethylation and this regulation is lost in aging, resulting in mitochondrial damage and an impaired healing response.

Through a collaborative effort across six Sub-Saharan African countries, using recognized international assessment techniques, 23 stocks of three tick species (Rhipicephalus microplus, Rhipicephalus appendiculatus and Amblyomma variegatum) of economic importance for rural small holder farming communities from East and West Africa were collected from cattle, and evaluated in in vitro larval packet tests (LPT). The results demonstrated medium to high resistance to chlorfenvinphos and amitraz across species. Rhipicephalus microplus demonstrated high level alpha-cypermethrin and cypermethrin resistance. Stocks of A. variegatum (West Africa) and R. appendiculatus (Uganda) demonstrated medium level ivermectin resistance.The four least susceptible stocks (East and West African R. microplus, A. variegatum and R. appendiculatus) were taken into in vivo controlled cattle studies where fipronil was found effective against West and East African R. microplus isolates although persistent efficacy failed to reach 90%. Cymiazole and cypermethrin, and ivermectin based acaricides were partially effective against R. microplus without persistent efficacy. Flumethrin spray-on killed A. variegatum within 72 h for up to 10 days posttreatment, however product application was directly to tick attachment sites, which may be impractical under field conditions. A flumethrin pour-on formulation on goats provided persistent efficacy against A. variegatum for up to one-month. Therapeutic control was achieved against R. appendiculatus through weekly spraying cattle with flumethrin, amitraz or combined cymiazole and cypermethrin. A fipronil pour-on product offered four-week residual control against R. appendiculatus (with slow onset of action).Few studies have assessed and directly compared acaricidal activity in vitro and in vivo. There was some discordance between efficacy indicated by LPT and in vivo results. This observation calls for more research into accurate and affordable assessment methods for acaricide resistance.No single active or product was effective against all three tick species, emphasising the need for the development of alternative integrated tick management solutions.

Software maintenance is a challenging and laborious software management activity, especially for open‐source software. The bugs reports of such software allow tracking maintenance activities and were used in several empirical studies to better predict the bug resolution effort. These reports are known for their large size and contain nonrelevant instances that need to be preprocessed to be suitable for use. To this end, instance selection (IS) has been proposed in the literature as a way to reduce the size of the datasets, while keeping the relevant instances. The objective of this study is to perform an empirical study that investigates the impact of data preprocessing through IS on the performance of bug resolution prediction classifiers. To deal with this, four IS algorithms, namely, edited nearest neighbor (ENN), repeated ENN, all‐k nearest neighbors, and model class selection, are applied on five large datasets, together with five machine learning techniques. Overall, 125 experiments were performed and compared. The findings of this study highlight the positive impact of IS in providing better estimates for bug resolution prediction classifiers, in particular using repeated ENN and ENN algorithms. [ABSTRACT FROM AUTHOR]

In canine leishmaniosis endemic areas, Leishmania infantum may occur in sympatry with the non-pathogenic Leishmania tarentolae, which is associated to reptiles. The potential infectivity of L. tarentolae for mammals raises questions about the interactions between the two Leishmania species, and the potential cross-immune protection in dogs. This study aimed to assess the outcome of experimental L. tarentolae infection in dogs, determining: i) the anti-L. tarentolae antibody production, ii) the duration of the immunity and cytokine expression, and iii) the possible pathogenic effect in the canine host. Twelve purpose-bred beagle dogs were randomly allocated to three groups (intravenous inoculation, G1; intradermal inoculation, G2; negative control, G3). G1 and G2 dogs were inoculated twice (day 0, day 28) with 108 promastigotes of L. tarentolae strain (RTAR/IT/21/RI-325) isolated from a Tarentola mauritanica gecko. The animals were followed until day 206. Blood, serum, conjunctival swabs and lymph node aspirate samples were collected monthly and bone marrow, liver and spleen biopsies on day 91. Hematological and biochemical parameters were assessed monthly, as well as serology (IFAT and ELISA) and molecular identification of L. tarentolae. Mononuclear cells (PBMC) were obtained to assess the cytokine expression through in vitro stimulation or (re-) infection. Data from this study demonstrated that DNA from L. tarentolae is detectable up to 3 months post-infection, with seroconversion after day 28. Moreover, the non-pathogenic nature of L. tarentolae was confirmed, with a neutral Th1/Th2 polarization, and a possible shift to Th1 phenotype after derived macrophages (re-) infection, as demonstrated by the expression of IFN-gamma. Therefore, L. tarentolae demonstrated a great potential as a surrogate pathogen and/or immune-prophylaxis/immune-therapy against Leishmania infections in dogs and humans. Author summary: The reptilian-associated Leishmania tarentolae may be infective for mammals, which raises questions about a potential cross-immune protection towards Leishmania infantum in dogs. This study aimed to assess the outcome of experimental L. tarentolae infection in the canine host. Twelve purpose-bred beagle dogs were allocated into three groups (intravenous inoculation, G1; intradermal inoculation, G2; negative control, G3). The first two groups were inoculated twice (day 0, day 28) with 108 promastigotes of L. tarentolae, and were followed until day 206. Hematological and biochemical parameters were assessed, as well as serology (IFAT and ELISA), molecular identification and cytokine expression. Results demonstrated that DNA from L. tarentolae is detectable up to 3 months post-infection, with seroconversion after day 28. Moreover, the non-pathogenic nature of L. tarentolae was confirmed, with a neutral Th1/Th2 polarization, and a possible shift to Th1 phenotype (i.e., expression of IFN-gamma). These results suggest that L. tarentolae could be a potential candidate for developing immune strategies, opening new avenues for the prevention of the canine leishmaniasis. [ABSTRACT FROM AUTHOR]

For centuries, the Saharan oasis agro-systems of Adrar region have fed many generations, based on an original organization, based on the efficiency of drainage water on the diversification of crop systems in association with small livestock farming. The aim of the work is to describe the systemic typology of oasis livestock farming in the Adrar region (southwest Algeria). In order to assess the livestock typology, a series of surveys were conducted on 164 farms in the oases of the study region. The analysis reveals that the production system, traditionally aimed at subsistence agriculture. The dominant production system is an intensive system, characterized by intensive mixed food crops (Phoenicuculture, arboriculture, herbaceous crops: cereals, fodder, market gardening, industrial and condiment crops), in association with livestock farming mainly of small ruminants (goats and sheep). The livestock system is characterized by a family type, small in size in traditional management. It is generally managed in stalls and its feed comes mainly from fodder crops, domestic waste and by-products of palm groves. Family livestock farming can be an important source to ensure a certain production of animal origin (milk and meat) for family self-consumption. As a result, it can contribute to ensuring food security, family financial security and improving soil fertility in oasis farm plots. [ABSTRACT FROM AUTHOR]

Fibrosis is a chronic disease with heterogeneous clinical presentation, rate of progression, and occurrence of comorbidities. Systemic sclerosis (scleroderma, SSc) is a rare rheumatic autoimmune disease that encompasses several aspects of fibrosis, including highly variable fibrotic manifestation and rate of progression. The development of effective treatments is limited by these variabilities. The fibrotic response is characterized by both chronic inflammation and extracellular remodeling. Therefore, there is a need for improved understanding of which inflammation-related genes contribute to the ongoing turnover of extracellular matrix that accompanies disease. We have developed a multi-tiered method using Naïve Bayes modeling that is capable of predicting level of disease and clinical assessment of patients based on expression of a curated 60-gene panel that profiles inflammation and extracellular matrix production in the fibrotic disease state. Our novel modeling design, incorporating global and parametric-based methods, was highly accurate in distinguishing between severity groups, highlighting the importance of these genes in disease. We refined this gene set to a 12-gene index that can accurately identify SSc patient disease state subsets and informs knowledge of the central regulatory pathways in disease progression.

In this work, we study boundary layer flows for thermo-dependent Newtonian fluids. We first show that the governing equations admit a self-similar solution. Furthermore, an asymptotic model is used to obtain correlations on heat transfer and the skin-friction coefficient. In addition, the numerical study of the complete problem enables us to specify the domain of validity of these correlations. Finally, the obtained numerical results are used to analyze the influence of the Prandtl number on the profiles of the stream function and the temperature field, and also on parameters such as the local Nusselt number and the thickness of the boundary layer. [ABSTRACT FROM AUTHOR]

In a world context focused on energy efficiency and sustainable construction, returning to the use of raw earth in construction constitutes a good alternative to concrete construction, a system more energy consuming and yet more used nowadays. This return is justified by the excellent energy performance and the high level of thermal comfort provided by earth constructions in different climates. In cold climates, adding an insulation on earth walls has proven to be effective in improving their thermal performances. However, the influence of adding an insulation on the energy performance of rammed earth buildings in hot and arid climates remains to this day little explored. The present work comes in this order of ideas; it is based on a comparative study of the energetic performances of a mud building before and after the addition of the insulation. In order to compare between their performances, we have performed a simulation of the thermal behaviour of each by the dynamic thermal simulation software Design Builder.

In this work, we perform preliminary group classification of boundary layer equations of a thermodependent fluid around any profile. These equations involve three parameters: the shear stress, the thermal conductivity, and the pressure gradient. Using optimal system of subalgebras method, we establish the existence of constitutive laws that give rise to self‐similar solutions compatible with the boundary conditions. [ABSTRACT FROM AUTHOR]

This study aims to characterize oasis livestock systems, through a typological analysis of their structure, management and zootechnical performances in the Saharan region of Beni Abbès (southwestern Algeria). The methodology adopted is based on field observations and a series of surveys with 55 oasis farmers in the three selected oases (Beni Abbès, Oued Khoudir, Tabelbala) in the wilaya of Beni Abbès. The results reveal the intensification of crops in association with livestock practices in oasis agrosystems. The production systems are characterized by intensive crop systems (three-stage: Phoeniciculture, Arboriculture and herbaceous crops) associated with livestock farming mainly consisting of small rustic ruminants with a good ability to adapt to desert conditions. The main types of livestock farming practiced in the oases are sheep, goat and poultry farming. These animals are well adapted to eco-oasis conditions, characterized by a continental desert climate. The main activity of the farmers 86% of the farms surveyed is mixed (crop-livestock) and 14% are of the crop-only type. It should be noted that livestock farming in oasis systems is based on family farming based on isolation, where sheep are separated for fattening, while goats and ewes are tangled for giving birth and milking, and chickens are raised for laying. Oasis livestock farming occupies a prominent place on the socio-economic level for local populations in order to satisfy the family's needs for milk, meat and eggs; and to provide manure for maintaining the fertility of the farms' soil. [ABSTRACT FROM AUTHOR]

Through a collaborative effort across six Sub-Saharan African countries, using recognized international assessment techniques, 23 stocks of three tick species (Rhipicephalus microplus, Rhipicephalus appendiculatus and Amblyomma variegatum) of economic importance for rural small holder farming communities from East and West Africa were collected from cattle , and evaluated in in vitro larval packet tests (LPT). The results demonstrated medium to high resistance to chlorfenvinphos and amitraz across species. Rhipicephalus microplus demonstrated high level alpha-cypermethrin and cypermethrin resistance. Stocks of A. variegatum (West Africa) and R. appendiculatus (Uganda) demonstrated medium level ivermectin resistance. The four least susceptible stocks (East and West African R. microplus, A. variegatum and R. appendiculatus) were taken into in vivo controlled cattle studies where fipronil was found effective against West and East African R. microplus isolates although persistent efficacy failed to reach 90%. Cymiazole and cypermethrin, and ivermectin based acaricides were partially effective against R. microplus without persistent efficacy. Flumethrin spray-on killed A. variegatum within 72 h for up to 10 days posttreatment, however product application was directly to tick attachment sites, which may be impractical under field conditions. A flumethrin pour-on formulation on goats provided persistent efficacy against A. variegatum for up to one-month. Therapeutic control was achieved against R. appendiculatus through weekly spraying cattle with flumethrin, amitraz or combined cymiazole and cypermethrin. A fipronil pour-on product offered four-week residual control against R. appendiculatus (with slow onset of action). Few studies have assessed and directly compared acaricidal activity in vitro and in vivo. There was some discordance between efficacy indicated by LPT and in vivo results. This observation calls for more research into accurate and affordable assessment methods for acaricide resistance. No single active or product was effective against all three tick species, emphasising the need for the development of alternative integrated tick management solutions. [Display omitted] • 23 tick stocks originating from six Sub-Saharan countries were challenged with acaricides representing all currently available classes in Larval Packet Tests. • Mono- and combination commercial acaricide formulations were evaluated against the most resistant tick stocks in vivo. • Fipronil controlled West/East African R. microplus and R. appendiculatus isolates. • Amidine and synthetic pyrethroid sprays provided therapeutic efficacy for A. variegatum. • No single acaricide demonstrated acceptable efficacy against targeted tick species. [ABSTRACT FROM AUTHOR]

Fibrosis is a chronic disease with heterogeneous clinical presentation, rate of progression, and occurrence of comorbidities. Systemic sclerosis (scleroderma, SSc) is a rare rheumatic autoimmune disease that encompasses several aspects of fibrosis, including highly variable fibrotic manifestation and rate of progression. The development of effective treatments is limited by these variabilities. The fibrotic response is characterized by both chronic inflammation and extracellular remodeling. Therefore, there is a need for improved understanding of which inflammation-related genes contribute to the ongoing turnover of extracellular matrix that accompanies disease. We have developed a multi-tiered method using Naïve Bayes modeling that is capable of predicting level of disease and clinical assessment of patients based on expression of a curated 60-gene panel that profiles inflammation and extracellular matrix production in the fibrotic disease state. Our novel modeling design, incorporating global and parametric-based methods, was highly accurate in distinguishing between severity groups, highlighting the importance of these genes in disease. We refined this gene set to a 12-gene index that can accurately identify SSc patient disease state subsets and informs knowledge of the central regulatory pathways in disease progression. [ABSTRACT FROM AUTHOR]

Arsenic exposure impairs muscle metabolism, maintenance, progenitor cell differentiation, and regeneration following acute injury. Low to moderate arsenic exposures target muscle fiber and progenitor cell mitochondria to epigenetically decrease muscle quality and regeneration. However, the mechanisms for how low levels of arsenic signal for prolonged mitochondrial dysfunction are not known. In this study, arsenic attenuated murine C2C12 myoblasts differentiation and resulted in abnormal undifferentiated myoblast proliferation. Arsenic prolonged ligand-independent phosphorylation of mitochondrially localized epidermal growth factor receptor (EGFR), a major driver of proliferation. Treating cells with a selective EGFR kinase inhibitor, AG-1478, prevented arsenic inhibition of myoblast differentiation. AG-1478 decreased arsenic-induced colocalization of pY845EGFR with mitochondrial cytochrome C oxidase subunit II, as well as arsenic-enhanced mitochondrial membrane potential, reactive oxygen species generation, and cell cycling. All of the arsenic effects on mitochondrial signaling and cell fate were mitigated or reversed by addition of mitochondrially targeted agents that restored mitochondrial integrity and function. Thus, arsenic-driven pathogenesis in skeletal muscle requires sustained mitochondrial EGFR activation that promotes progenitor cell cycling and proliferation at the detriment of proper differentiation. Collectively, these findings suggest that the arsenic-activated mitochondrial EGFR pathway drives pathogenic signaling for impaired myoblast metabolism and function. [ABSTRACT FROM AUTHOR]

The year 2017 marked the 20th anniversary of the first publication describing Klotho. This single protein was and is remarkable in that its absence in mice conferred an accelerated aging, or progeroid, phenotype with a dramatically shortened life span. On the other hand, genetic overexpression extended both health span and life span by an impressive 30%. Not only has Klotho deficiency been linked to a number of debilitating age-related illnesses but many subsequent reports have lent credence to the idea that Klotho can compress the period of morbidity and extend the life span of both model organisms and humans. This suggests that Klotho functions as an integrator of organ systems, making it both a promising tool for advancing our understanding of the biology of aging and an intriguing target for interventional studies. In this review, we highlight advances in our understanding of Klotho as well as key challenges that have somewhat limited our view, and thus translational potential, of this potent protein. [ABSTRACT FROM AUTHOR]

Background: Software product maintainability prediction (SPMP) is an important task to control software maintenance activity, and many SPMP techniques for improving software maintainability have been proposed. In this study, we performed a systematic mapping and review on SPMP studies to analyze and summarize the empirical evidence on the prediction accuracy of SPMP techniques in current research. Objective: The objective of this study is twofold: (1) to classify SPMP studies reported in the literature using the following criteria: publication year, publication source, research type, empirical approach, software application type, datasets, independent variables used as predictors, dependent variables (e.g. how maintainability is expressed in terms of the variable to be predicted), tools used to gather the predictors, the successful predictors and SPMP techniques, (2) to analyze these studies from three perspectives: prediction accuracy, techniques reported to be superior in comparative studies and accuracy comparison of these techniques. Methodology: We performed a systematic mapping and review of the SPMP empirical studies published from 2000 up to 2018 based on an automated search of nine electronic databases. Results: We identified 82 primary studies and classified them according to the above criteria. The mapping study revealed that most studies were solution proposals using a history-based empirical evaluation approach, the datasets most used were historical using object-oriented software applications, maintainability in terms of the independent variable to be predicted was most frequently expressed in terms of the number of changes made to the source code, maintainability predictors most used were those provided by Chidamber and Kemerer (C&K), Li and Henry (L&H) and source code size measures, while the most used techniques were ML techniques, in particular artificial neural networks. Detailed analysis revealed that fuzzy & neuro fuzzy (FNF), artificial neural network (ANN) showed good prediction for the change topic, while multilayer perceptron (MLP), support vector machine (SVM), and group method of data handling (GMDH) techniques presented greater accuracy prediction in comparative studies. Based on our findings SPMP is still limited. Developing more accurate techniques may facilitate their use in industry and well-formed, generalizable results be obtained. We also provide guidelines for improving the maintainability of software. [ABSTRACT FROM AUTHOR]

The interventricular septal dissection is an uncommon, and is occasionally associated with sinus of Valsalva aneurysm. A spontaneous dissection with a normal sinus of Valsalva is extremely rare and is mostly a result of a congenital defect. We report the case of a 23‐year‐old male admitted for complete heart block and presenting as an incidental finding during the TTE multiple and huge cystic‐like mass in the interventricular septum (IVS) which is the TTE characteristic of IVS dissection. Most patients remain asymptomatic until the anatomical and hemodynamic changes lead to complications like: severe aortic regurgitation with heart failure and conduction abnormalities. Although transthoracic echocardiogram (TTE) has been the first‐line imaging modality for such findings, cardiac computed tomography (CT) and magnetic resonance imaging have been increasingly used as supplemental or confirmatory tests. The imaging modalities showed a perforation of right sinus of Valsalva causing the expansion of the dissection to the apex. The patient underwent surgical repair with satisfying results. In conclusion, we report an extremely rare clinical case of spontaneous dissection of the interventricular septum using multiple imaging techniques and with a successful surgery. [ABSTRACT FROM AUTHOR]

As the complexity of software increases, the choice of the appropriate software architecture becomes a critical task. This paper provides a guideline for selecting the appropriate software architecture based on pertinent ISO 25010 quality characteristics. The guideline was established through an analytical survey of 113 papers published from 2010 to 2014. Through this survey, we first identified a set of commonly used software architectures in the software engineering literature. Secondly, we applied the Formal Concept Analysis technique to classify each one of these architectures according to ISO 25010 quality characteristics. Finally, we identified the relationships among ISO 25010 quality characteristics, which in turn helped us to develop a guideline on how to select the appropriate software architecture with respect to ISO 25010 quality characteristics. In order to make sure about the validation of the proposed guideline, a survey with industrial experts is in progress. Data were collected from two companies working in the software development field (ST2i and Telnet). [ABSTRACT FROM AUTHOR]

An e-government portal is a website that is offering various useful electronic services to the citizens. With the traditional government portals (offices), the services provided to the citizens need a lot of paperwork and many officers are required to conduct such services, and also the citizens need to be present personally, which means they have to leave their jobs for many hours. Thus, making these services as electronic ones through the web will result in great savings for governmental entities and citizens. This paper exploring the e-government portal's best practices collected from research and industry. Although these best practices exist in the literature, they are not classified or grouped in a logical way. In addition, this paper aims to provide a structured overview of these best practices according to three categories of best practices (i.e., back-end, front-end, and external). [ABSTRACT FROM AUTHOR]

Recognition of injured mitochondria for degradation by macroautophagy is essential for cellular health, but the mechanisms remain poorly understood. Cardiolipin is an inner mitochondrial membrane phospholipid. We found that rotenone, staurosporine, 6-hydroxydopamine and other pro-mitophagy stimuli caused externalization of cardiolipin to the mitochondrial surface in primary cortical neurons and SH-SY5Y cells. RNAi knockdown of cardiolipin synthase or of phospholipid scramblase-3, which transports cardiolipin to the outer mitochondrial membrane, decreased the delivery of mitochondria to autophagosomes. Furthermore, we found that the autophagy protein microtubule-associated-protein-1 light chain 3 (LC3), which mediates both autophagosome formation and cargo recognition, contains cardiolipin-binding sites important for the engulfment of mitochondria by the autophagic system. Mutation of LC3 residues predicted as cardiolipin-interaction sites by computational modelling inhibited its participation in mitophagy. These data indicate that redistribution of cardiolipin serves as an 'eat-me' signal for the elimination of damaged mitochondria from neuronal cells. [ABSTRACT FROM AUTHOR]

The article presents a reprint of the article "Investigation of the Links between External and In-Use Quality" by Laila Cheikhi and Alain Abran, which appeared in the previous issue of the periodical "Software Quality Professional." It discusses the external quality and in-use quality of software products and its relationships with respect to the study of impact of the external quality factors, with the application of Taguchi's parameter design.

It is important to ensure the quality of software in the early phases of the software life cycle so it will perform optimally once delivered to the customer. This article presents an empirical study investigating the relevance of the assumptions about the links between the internal, external, and in-use software quality models of the ISO 9126 standard. The strategy in this work is to conduct empirical studies using the Taguchi method, particularly the parameter design approach and Taguchi's orthogonal arrays, to plan the studies. The empirical studies the authors report here are based on the industrial data provided by the International Software Benchmarking Standards Group (ISBSG). Each case study explores the impact of a set of candidate factors on the quality characteristic observed in the output. The empirical data were analyzed using Taguchi's signal-to-noise ratio. Analysis of the results confirms some of the assumptions about the relationships among the three types of quality of the ISO 9126 standard, as follows: Internal quality has an impact on external quality, which in turn has an impact on the quality in use of the software product. The article highlights the advantages of the applicability of the Taguchi method, originally designed for industrial products, to software products. It also highlights the usefulness of this method, which is generally used to plan and conduct experiments, for analyzing existing software engineering datasets. [ABSTRACT FROM AUTHOR]

While young muscle is capable of restoring the original architecture of damaged myofibers, aged muscle displays a markedly reduced regeneration. We show that expression of the “anti-aging” protein, α-Klotho, is up-regulated within young injured muscle as a result of transient Klotho promoter demethylation. However, epigenetic control of the Klotho promoter is lost with aging. Genetic inhibition of α-Klotho in vivo disrupted muscle progenitor cell (MPC) lineage progression and impaired myofiber regeneration, revealing a critical role for α-Klotho in the regenerative cascade. Genetic silencing of Klotho in young MPCs drove mitochondrial DNA (mtDNA) damage and decreased cellular bioenergetics. Conversely, supplementation with α-Klotho restored mtDNA integrity and bioenergetics of aged MPCs to youthful levels in vitro and enhanced functional regeneration of aged muscle in vivo in a temporally-dependent manner. These studies identify a role for α-Klotho in the regulation of MPC mitochondrial function and implicate α-Klotho declines as a driver of impaired muscle regeneration with age. [ABSTRACT FROM AUTHOR]

AG490 is a member of tyrphostine family which blocks JAK2/3 phosphorylation and subsequently activation of Stat3 and Stats via the JAK-STAT pathway. AG490 has been broadly used to prevent rejection of allograft transplant and to prevent autoimmune diseases such as EAE with a mechanism yet to be determined. In this study we report AG490 treatment reprograms CD4[sup +]CD25[sup -] Fox3[sup -] T-cells into Foxp3 expressing T-cells which possess regulatory function both in-vitro and in-vivo. CD4[sup +]CD25[sup -] Fox3[sup -] T-cells from transgenic BALB/c DO11.10 mice became Foxp3[sup +] when treated in-vitro with AG490. These T-cells possessed regulatory function as they suppressed proliferation of syngenic responding population (CD4[sup +]CD25[sup -] T-cells) in response to OVA[sub 323-329] peptide in-vitro. Purified CD4 T-cells from BALB/c mice treated with AG490 failed to suppress proliferation of transgenic CD4[sup +]CD25[sup -] T-cells of BALB/c DO11.10 suggesting antigen-specific function of converted population. Our preliminary in-vivo studies regarding adoptive co-transfer of bulk CD4[sup +]CD25[sup -] Foxp3 T-cells treated with AG490 and diabetic splenocytes delayed onset of diabetes in 20% of treated mice for 9-weeks. Furthermore we show treatment of diabetic NOD.scid mice (recipient of diabetic splenocytes and CD4[sup +]CD25[sup -] T-cells) with AG490 increased numbers of CD4[sup +]CD25[sup +]Foxp3[sup +] T-cells when compared with the same population in B6 and NOD mice and posses regulatory function in-vitro. Splenocytes of treated mice were anergic to anti-CD3 and CD28 stimulation and purified CD4[sup +]CD25[sup +] T-cells suppressed proliferation of responding population in-vitro. In this report, we for the first time uncovered new properties of AG490 in the immune system by demonstrating upregulation of Foxp3 in CD4[sup +]CD25[sup -]T-cells and propose that this kinase inhibitor might be used to halt type 1 diabetes in NOD mice and in humans. The same mechanism described above may be responsible for AG490 to prevent rejection of allograft transplant and/or to prevent onset of EAE in mice. [ABSTRACT FROM AUTHOR]