The Maturation of Agile Software Development Principles and Practice: Observations on Successive Industrial Studies in 2010 and 2012

The agile model of software development has been mainstream for several years, and is now in a phase where its principles and practices are maturing. The purpose of this paper is to describe the results of an industry survey aimed at understanding how maturation is progressing. The survey was taken across 40 software development companies in Northern Ireland at the beginning of 2012. The paper describes the design of the survey and examines maturity by comparing the results obtained in 2012 with those from a study of agile adoption in the same region in 2010. Both surveys aimed to achieve comprehensive coverage of a single area rather than rely on a voluntary sample. The main outcome from the work is a collection of ‘insights’ into the nature and practice of agile development, the main two of which are reported in this paper.

A Burkholderia cenocepacia gene encoding a non-functional tyrosine phosphatase is required for the delayed maturation of the bacteria-containing vacuoles in macrophages

Burkholderia cenocepacia infects patients with cystic fibrosis. We have previously shown that B. cenocepacia can survive in macrophages within membrane vacuoles (BcCVs) that preclude fusion with the lysosome. The bacterial factors involved in B. cenocepacia intracellular survival are not fully elucidated. We report here that deletion of BCAM0628, encoding a predicted low-molecular weight protein tyrosine phosphatase (LMW-PTP) that is restricted to B. cenocepacia strains of the transmissible ET-12 clone, accelerates the maturation of the BcCVs. Compared to parental strain and deletion mutants in other LMW-PTPs that are widely conserved in Burkholderia species, a greater proportion of BcCVs containing the BCAM0628 mutant were targeted to the lysosome. Accelerated BcCV maturation was not due to reduced intracellular viability since BCAM0628 survived and replicated in macrophages similarly to the parental strain. Therefore, BCAM0628 was referred to as dpm (delayed phagosome maturation). We provide evidence that the Dpm protein is secreted during growth in vitro and upon macrophage infection. Dpm secretion requires an N-terminal signal peptide. Heterologous expression of Dpm in B. multivorans confers to this bacterium a similar phagosomal maturation delay as found with B. cenocepacia. We demonstrate that Dpm is an inactive phosphatase, suggesting that its contribution to phagosomal maturation arrest must be unrelated to tyrosine phosphatase activity.

A decrease in bulk water and mannitol and accumulation of trehalose and trehalose-based oligosaccharides define a two-stage maturation process towards extreme stress resistance in ascospores of Neosartorya fischeri (Aspergillus fischeri)

Heme oxygenase-1 derived carbon monoxide permits maturation of myeloid cells

Critical functions of the immune system are maintained by the ability of myeloid progenitors to differentiate and mature into macrophages. We hypothesized that the cytoprotective gas molecule carbon monoxide (CO), generated endogenously by heme oxygenases (HO), promotes differentiation of progenitors into functional macrophages. Deletion of HO-1, specifically in the myeloid lineage (Lyz-Cre:Hmox1(flfl)), attenuated the ability of myeloid progenitors to differentiate toward macrophages and decreased the expression of macrophage markers, CD14 and macrophage colony-stimulating factor receptor (MCSFR). We showed that HO-1 and CO induced CD14 expression and efficiently increased expansion and differentiation of myeloid cells into macrophages. Further, CO sensitized myeloid cells to treatment with MCSF at low doses by increasing MCSFR expression, mediated partially through a PI3K-Akt-dependent mechanism. Exposure of mice to CO in a model of marginal bone marrow transplantation significantly improved donor myeloid cell engraftment efficiency, expansion and differentiation, which corresponded to increased serum levels of GM-CSF, IL-1α and MCP-1. Collectively, we conclude that HO-1 and CO in part are critical for myeloid cell differentiation. CO may prove to be a novel therapeutic agent to improve functional recovery of bone marrow cells in patients undergoing irradiation, chemotherapy and/or bone marrow transplantation.

For host factors weddings and a Koch’s bacillus funeral: actin, lipids, phagosome maturation and inflammasome activation

The chapter describes the 10 years research of Anes Laboratory on the interactions of M. tuberculosis with macrophages namely with the actin. modulation by lipids, phagosome maturation and inflammasome activation

Effect of sialic acid loss on dendritic cell maturation

Sialic acids are key structural determinants and contribute to the functionality of a number of immune cell receptors. Previously, we demonstrated that differentiation of human dendritic cells (DCs) is accompanied by an increased expression of sialylated cell surface structures, putatively through the activity of the ST3Gal.I and ST6Gal.I sialyltransferases. Furthermore, DC endocytosis was reduced upon removal of the cell surface sialic acid residues by neuraminidase. In the present work, we evaluate the contribution of the sialic acid modifications in DC maturation. We demonstrate that neuraminidase-treated human DCs have increased expression of major histocompatibility complex (MHC) and costimulatory molecules, increased gene expression of specific cytokines and induce a higher proliferative response of T lymphocytes. Together, the data suggest that clearance of cell surface sialic acids contributes to the development of a T helper type 1 proinflammatory response. This postulate is supported by mouse models, where elevated MHC class II and increased maturation of specific DC subsets were observed in DCs harvested from ST3Gal.I(-/-) and ST6Gal.I(-/-) mice. Moreover, important qualitative differences, particularly in the extent of reduced endocytosis and in the peripheral distribution of DC subsets, existed between the ST3Gal.I(-/-) and ST6Gal.I(-/-) strains. Together, the data strongly suggest not only a role of cell surface sialic acid modifications in maturation and functionality of DCs, but also that the sialic acid linkages created by different sialyltransferases are functionally distinct. Consequently, with particular relevance to DC-based therapies, cell surface sialylation, mediated by individual sialyltransferases, can influence the immunogenicity of DCs upon antigen loading.

T cell Maturation and Regulatory T Cell Differentiation:From the Thymus to the Periphery

Immunological tolerance, that is, the failure to mount an immune response to an otherwise immunogenic molecule, is one of the fundamental questions in immunology. The fact that lymphocytes express antigen receptors that are generated randomly and have the potential to recognize any conceivable antigen, adds another puzzle to the physiology of immunological tolerance. The other side of the coin, the general absence of immune responses to self antigens, is ensured by a tight regulation and several selection steps during T and B cell differentiation. One of these processes is the differentiation of regulatory T cells (Treg). While developing in the thymus, T cell clones bearing receptors with high affinity/avidity to antigens present at the time of differentiation may be eliminated by apoptosis or, alternatively, express Foxp3 and become Treg. Treg are key players in the regulation of immunological tolerance since humans and mice with complete loss of function variants of this gene develop fatal autoimmune conditions early in life.(...)

The neutrophil NLRC4 inflammasome selectively promotes IL-1β maturation without pyroptosis during acute Salmonella challenge.

The macrophage NLRC4 inflammasome drives potent innate immune responses against Salmonella by eliciting caspase-1-dependent proinflammatory cytokine production (e.g., interleukin-1β [IL-1β]) and pyroptotic cell death. However, the potential contribution of other cell types to inflammasome-mediated host defense against Salmonella was unclear. Here, we demonstrate that neutrophils, typically viewed as cellular targets of IL-1β, themselves activate the NLRC4 inflammasome during acute Salmonella infection and are a major cell compartment for IL-1β production during acute peritoneal challenge in vivo. Importantly, unlike macrophages, neutrophils do not undergo pyroptosis upon NLRC4 inflammasome activation. The resistance of neutrophils to pyroptotic death is unique among inflammasome-signaling cells so far described and allows neutrophils to sustain IL-1β production at a site of infection without compromising the crucial inflammasome-independent antimicrobial effector functions that would be lost if neutrophils rapidly lysed upon caspase-1 activation. Inflammasome pathway modification in neutrophils thus maximizes host proinflammatory and antimicrobial responses during pathogen challenge.

Propofol anesthesia impairs the maturation and survival of adult-born hippocampal neurons.

BACKGROUND: Adult neurogenesis occurs in the hippocampus of most mammals, including humans, and plays an important role in hippocampal-dependent learning. This process is highly regulated by neuronal activity and might therefore be vulnerable to anesthesia. In this article, the authors investigated this possibility by evaluating the impact of propofol anesthesia on mouse hippocampal neurons generated during adulthood, at two functionally distinct maturational stages of their development. METHODS: Adult-born hippocampal neurons were identified using the cell proliferation marker bromodeoxyuridine or a retroviral vector expressing the green fluorescent protein in dividing cells and their progenies. Eleven or 17 days after the labeling procedure, animals (n = 3-5 animals per group) underwent a 6-h-long propofol anesthesia. Twenty-one days after labeling, the authors analyzed the survival, differentiation, and morphologic maturation of adult-born neurons using confocal microscopy. RESULTS: Propofol impaired the survival and maturation of adult-born neurons in an age-dependent manner. Anesthesia induced a significant decrease in the survival of neurons that were 17 days old at the time of anesthesia, but not of neurons that were 11 days old. Similarly, propofol anesthesia significantly reduced the dendritic maturation of neurons generated 17 days before anesthesia, without interfering with the maturation of neurons generated 11 days before anesthesia. CONCLUSIONS: These results reveal that propofol impairs the survival and maturation of adult-born hippocampal neurons in a developmental stage-dependent manner in mice.

BAFF binds to the tumor necrosis factor receptor-like molecule B cell maturation antigen and is important for maintaining the peripheral B cell population.

The tumor necrosis factor (TNF) family member B cell activating factor (BAFF) binds B cells and enhances B cell receptor-triggered proliferation. We find that B cell maturation antigen (BCMA), a predicted member of the TNF receptor family expressed primarily in mature B cells, is a receptor for BAFF. Although BCMA was previously localized to the Golgi apparatus, BCMA was found to be expressed on the surface of transfected cells and tonsillar B cells. A soluble form of BCMA, which inhibited the binding of BAFF to a B cell line, induced a dramatic decrease in the number of peripheral B cells when administered in vivo. Moreover, culturing splenic cells in the presence of BAFF increased survival of a percentage of the B cells. These results are consistent with a role for BAFF in maintaining homeostasis of the B cell population.

Maturation and Functional Integration of New Granule Cells into the Adult Hippocampus.

The adult hippocampus generates functional dentate granule cells (GCs) that release glutamate onto target cells in the hilus and cornus ammonis (CA)3 region, and receive glutamatergic and γ-aminobutyric acid (GABA)ergic inputs that tightly control their spiking activity. The slow and sequential development of their excitatory and inhibitory inputs makes them particularly relevant for information processing. Although they are still immature, new neurons are recruited by afferent activity and display increased excitability, enhanced activity-dependent plasticity of their input and output connections, and a high rate of synaptogenesis. Once fully mature, new GCs show all the hallmarks of neurons generated during development. In this review, we focus on how developing neurons remodel the adult dentate gyrus and discuss key aspects that illustrate the potential of neurogenesis as a mechanism for circuit plasticity and function.

A comparison of cognitive processes and components of neurological maturation in 3-and-11 year-old children

The relationship between the child's cogni tive development and neurological maturation has been of theoretical interest for many year s. Due to diff iculties such as the lack of sophisticated techniques for measur ing neurolog ical changes and a paucity of normative data, few studies exist that have attempted to correlate the two factors. Recent theory on intellectual development has proposed that neurological maturation may be a factor in the increase of short-term memory storage space. Improved technology has allowed reliable recordings of neurolog ical maturation.. In an attempt to correlate cogni tive development and neurological maturation, this study tested 3-and II-year old children. Fine motor and gross motor short-term memory tests were used to index cogni tive development. Somatosensory evoked potentials elici ted by median nerve stimulation were used to measure the time required for the sensation to pass along the nerve to specific points on the somatosensory pathway. Times were recorded for N14, N20, and P22 interpeak latencies. Maturation of the central nervous system (brain and spinal cord) and the peripheral nervous system (outside the brain and spinal cord) was indi~ated by the recorded times. Signif icant developmental di fferences occurred between 3-and ll-year-olds in memory levels, per ipheral conduction velocity and central conduction times. Linear regression analyses showed that as age increased, memory levels increased and central conduction times decreased. Between the ll-year-old groups, there were no significant differences in central or peripheral nervous system maturation between subjects who achieved a 12 plus score on the digit span test of the WISC-R and those who scored 7 or lower on the same test. Levels achieved on the experimental gross and fine motor short-term memory tests differed significantly within the ll-year-old group.

Electrophysiology of Oculomotor Delayed Response Tasks: A Model for the Maturation of Visual-Spatial Working Memory Networks

In the literature, persistent neural activity over frontal and parietal areas during the delay period of oculomotor delayed response (ODR) tasks has been interpreted as an active representation of task relevant information and response preparation. Following a recent ERP study (Tekok-Kilic, Tays, & Tkach, 2011 ) that reported task related slow wave differences over frontal and parietal sites during the delay periods of three ODR tasks, the present investigation explored developmental differences in young adults and adolescents during the same ODR tasks using 128-channel dense electrode array methodology and source localization. This exploratory study showed that neural functioning underlying visual-spatial WM differed between age groups in the Match condition. More specifically, this difference is localized anteriorly during the late delay period. Given the protracted maturation of the frontal lobes, the observed variation at the frontal site may indicate that adolescents and young adults may recruit frontal-parietal resources differently.

Mécanismes moléculaires impliqués dans la régulation de l’acide polysialique (PSA) dans le néocortex visuel des souris durant la maturation des synapses GABAergiques

Le fonctionnement du cortex cérébral nécessite l’action coordonnée de deux des sous-types majeurs de neurones, soient les neurones à projections glutamatergiques et les interneurones GABAergiques. Les interneurones GABAergiques ne constituent que 20 à 30% des cellules corticales par rapport au grand nombre de neurones glutamatergiques. Leur rôle est toutefois prépondérant puisqu’ils modulent fortement la dynamique et la plasticité des réseaux néocorticaux. Il n’est donc pas surprenant que les altérations de développement des circuits GABAergiques soient associées à plusieurs maladies du cerveau, incluant l’épilepsie, le syndrome de Rett et la schizophrénie. La compréhension des mécanismes moléculaires régissant le développement des circuits GABAergiques est une étape essentielle menant vers une meilleure compréhension de la façon dont les anormalités se produisent. Conséquemment, nous nous intéressons au rôle de l’acide polysialique (PSA) dans le développement des synapses GABAergiques. PSA est un homopolymère de chaînons polysialylés en α-2,8, et est exclusivement lié à la molécule d’adhésion aux cellules neuronales (NCAM) dans les cerveaux de mammifères. PSA est impliqué dans plusieurs processus développementaux, y compris la formation et la plasticité des synapses glutamatergiques, mais son rôle dans les réseaux GABAergiques reste à préciser. Les données générées dans le laboratoire du Dr. Di Cristo démontrent que PSA est fortement exprimé post- natalement dans le néocortex des rongeurs, que son abondance diminue au cours du développement, et, faits importants, que son expression dépend de l’activité visuelle i et est inversement corrélée à la maturation des synapses GABAergiques. La présente propose de caractériser les mécanismes moléculaires régulant l’expression de PSA dans le néocortex visuel de la souris. Les enzymes polysialyltransférases ST8SiaII (STX) et ST8SiaIV (PST) sont responsables de la formation de la chaîne de PSA sur NCAM. En contrôlant ainsi la quantité de PSA sur NCAM, ils influenceraient le développement des synapses GABAergiques. Mon projet consiste à déterminer comment l’expression des polysialyltransférases est régulée dans le néocortex visuel des souris durant la période post-natale; ces données sont à la fois inconnues, et cruciales. Nous utilisons un système de cultures organotypiques dont la maturation des synapses GABAergiques est comparable au modèle in vivo. L’analyse de l’expression génique par qPCR a démontré que l’expression des polysialyltransférases diminue au cours du développement; une baisse majeure corrélant avec l’ouverture des yeux chez la souris. Nous avons de plus illustré pour la première fois que l’expression de STX, et non celle de PST, est activité-dépendante, et que ce processus requiert l’activation du récepteur NMDA, une augmentation du niveau de calcium intracellulaire et la protéine kinase C (PKC). Ces données démontrent que STX est l’enzyme régulant préférentiellement le niveau de PSA sur NCAM au cours de la période post-natale dans le cortex visuel des souris. Des données préliminaires d’un second volet de notre investigation suggèrent que l’acétylation des histones et la méthylation de l’ADN pourraient également contribuer à la régulation de la transcription de cette enzyme durant le développement. Plus d’investigations seront toutefois nécessaires afin de confirmer cette hypothèse. En somme, la connaissance des mécanismes par lesquels l’expression des ii polysialyltransférases est modulée est essentielle à la compréhension du processus de maturation des synapses GABAergiques. Ceci permettrait de moduler pharmacologiquement l’expression de ces enzymes; la sur-expression de STX et/ou PST pourrait produire une plus grande quantité de PSA, déstabiliser les synapses GABAergiques, et conséquemment, ré-induire la plasticité cérébrale.