Deciphering the regulatory network of microRNAs in tuberculosis infected macrophages : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Genetics at Massey University, Albany, New Zealand

Tuberculosis is an infectious disease that is caused by Mycobacterium tuberculosis (Mtb), an intracellular pathogen that uses macrophages as a host for replication. The outcome of the disease depends highly on Mtb’s strategies to circumvent the immune responses of macrophages. MicroRNAs (miRNAs) are small regulatory RNAs that influence gene functions post-transcriptionally. Recent studies indicate that miRNAs have prominent roles in cellular host-pathogen interactions. The aim of this study is to advance our understanding of the regulatory mechanisms that control key miRNAs in mouse M1 macrophages during Mtb infection using network analysis. The study began with a construction of a mouse miRNA-centric regulatory network model by combining a network of miRNA-controlling transcription factors (TFs) with a miRNA target network. The final network places miRNAs at the center of a comprehensive regulatory network of TFs, miRNAs and their targets. This network represents a useful resource for investigating miRNA functions and their control. Subsequently, we populated the network with CAGE-derived expression data for either Mtb-infected mouse M1 macrophages or non-infected controls. We used network analysis to determine key regulatory elements during the infection process. As a result, we identified a core set of TFs and miRNAs, which are likely critical regulatory elements during M1 macrophage host and Mtb interactions. Our results also demonstrate that among the core set of regulatory elements three highly activated miRNAs, mmu-mir-149, mmu-mir-449a, and mmu-mir-449b, work in unison with mmu-mir-155, the top-ranked miRNA. They co-regulate a set of downstream tuberculosis immune response related genes. Four top-ranked TFs, Fosl1, Bhlhe40, Egr1, and Egr2, were identified that they transcriptionally control this group of miRNAs. The TFs and miRNAs, together with their targets constitute a mmu-mir-155 regulatory sub-network. Our results also imply that Bhlhe40 is likely an important TF that modulates the activities of the mmu-mir-155 regulatory sub-network. Bhlhe40 and the mmu-mir-155 regulatory sub-network may be exploited by Mtb to manipulate the host immune defense for advancing survival interests. The findings of this study provide new insights into the host immune regulatory mechanisms of activated macrophages that are essential to control tuberculosis

C=N-containing azaarenes as activating groups in enantioselective catalysis

Nitrogen-containing aromatic heterocycles (azaarenes) are of widespread chemical significance, and chi-ral compounds containing azaarenes feature prominently in pharmaceuticals, agrochemicals, and natural products. This Perspective highlights the use of a relatively underdeveloped strategy to prepare chiral azaarene-containing compounds: exploitation of the C=N bond embedded within certain azaarenes to activate adjacent functionality in catalytic asym-metric reactions. Work in this area has resulted in the development of several different types of catalytic enantioselec-tive processes, including reductions, nucleophilic additions, and reductive couplings. It is hoped that this Perspective will encourage more researchers to work in this promising area

Optimal feeding and swimming gaits of biflagellated organisms

Locomotion is widely observed in life at micrometric scales and is exhibited by many eukaryotic unicellular organisms. Motility of such organisms can be achieved through periodic deformations of a tail-like projection called the eukaryotic flagellum. Although the mechanism allowing the flagellum to deform is largely understood, questions related to the functional significance of the observed beating patterns remain unresolved. Here, we focus our attention on the stroke patterns of biflagellated phytoplanktons resembling the green alga Chlamydomonas. Such organisms have been widely observed to beat their flagella in two different ways - a breast-stroke and an undulatory stroke-both of which are prototypical of general beating patterns observed in eukaryotes. We develop a general optimization procedure to determine the existence of optimal swimming gaits and investigate their functional significance with respect to locomotion and nutrient uptake. Both the undulatory and the breaststroke represent local optima for efficient swimming. With respect to the generation of feeding currents, we found the breaststroke to be optimal and to enhance nutrient uptake significantly, particularly when the organism is immersed in a gradient of nutrients. Keywords: optimization; stroke kinematics; low Reynolds number; efficiencyNational Science Foundation (U.S.) (Grant CCF-0323672)National Science Foundation (U.S.) (Grant CTS-0624830

Synthetic boundary conditions for image deblurring

AbstractIn this paper we introduce a new boundary condition that can be used when reconstructing an image from observed blurred and noisy data. Our approach uses information from the observed image to enforce boundary conditions that continue image features such as edges and texture across the boundary. Because of its similarity to methods used in texture synthesis, we call our approach synthetic boundary conditions. We provide an efficient algorithm for implementing the new boundary condition, and provide a linear algebraic framework for the approach that puts it in the context of more classical and well known image boundary conditions, including zero, periodic, reflective, and anti-reflective. Extensive numerical experiments show that our new synthetic boundary conditions provide a more accurate approximation of the true image scene outside the image boundary, and thus allow for better reconstructions of the unknown, true image scene

Conectividade social e satisfação no trabalho em teletrabalhadores mexicanos durante a pandemia: o papel mediador do bem-estar afetivo

The purpose of this study was to examine the relationship between social connectedness outside of work and job satisfaction in Mexican teleworkers during the COVID-19 pandemic. The research method was correlational, non-experimental, and cross-sectional. Employing an online, self-administered survey, the data were collected in a non-probabilistic sample of 214 individuals. The results suggest that the relationship between social connectedness outside of work and job satisfaction is positive and mediated by positive affective well-being. The mediating effect of positive affective well-being is not moderated by optimistic attributional style. Social connectedness outside of work is important to keep job satisfaction high. Therefore, organizations should facilitate a frequent interaction of their teleworkers with others outside the work domain.El propósito de este estudio fue examinar la relación entre la conectividad social fuera del trabajo y la satisfacción laboral en teletrabajadores mexicanos durante la pandemia por COVID-19. El método de investigación fue correlacional, no experimental y transversal. Los datos se recolectaron en una muestra no probabilística de 214 individuos mediante una encuesta autoadministrada en línea. Los resultados sugieren que la relación entre la conectividad social fuera del trabajo y la satisfacción laboral es positiva y está mediada por el bienestar afectivo positivo. El efecto mediator del bienestar afectivo positivo no está moderado por el estilo atribucional optimista. Dada la importancia de la satisfacción laboral, las organizaciones deberían facilitar la interacción frecuente de sus empleados con personas fuera del trabajo.O objetivo deste estudo foi examinar a relação entre conectividade social fora do trabalho e a satisfação no trabalho em teletrabalhadores mexicanos durante a pandemia COVID-19. O método de pesquisa foi correlacional, não experimental e transversal. Os dados foram coletados em uma amostra não probabilística de 214 indivíduos por meio de um questionário online autoaplicável. Os resultados sugerem que a relação entre conectividade social fora do trabalho e satisfação no trabalho é positiva e mediada por bem-estar afetivo positivo. O efeito mediador do bem-estar afetivo positivo não é moderado pelo estilo de atribuição otimista. Dada a importância da satisfação no trabalho, as organizações devem facilitar a interação frequente de seus funcionários com pessoas fora do trabalho

KINEMATICS ANALYSIS OF AN ANKLE INVERSION LIGAMENTOUS SPRAIN INJURY CASE IN BASKETBALL

Ankle inversion ligamentous sprain is one of the most common sports injuries. Model-Based Image Matching (MBIM) motion analysis technique allows us to understand the injury mechanism quantitatively by analyzing the three-dimensional human motion. In this study, the basketball player had performed an unwanted excessive ankle inversion by landing on the foot of the opponent. The ankle joint kinematics was presented within 0.1 second after footstrike. Result had further conformed that plantarflexion is not necessarily a criterion to sprain an ankle. Internal rotation associated with a sudden inversion would be the main phenomenon. An acceleration of inversion velocity is being suggested to be another important phenomenon of ankle inversion sprain injury. The quantified data in this study can serve as a base of development to investigate ankle joint motion

Copper-catalyzed borylative coupling of vinylazaarenes and N-Boc imines

Cu-catalyzed three-component couplings of vinylazaarenes, B2(pin)2, and N-Boc imines are described. Oxidation of the initially formed boronate gives azaarene-containing, Boc-protected amino alcohols with reasonable to good diastereoselectivities

Direct Synthesis of 5-Aryl Barbituric Acids by Rhodium(II)-Catalyzed Reactions of Arenes with Diazo Compounds

A commercially available rhodium(II) complex catalyzes the direct arylation of 5‐diazobarbituric acids with arenes, allowing straightforward access to 5‐aryl barbituric acids. Free N--H groups are tolerated on the barbituric acid, with no complications arising from N--H insertion processes. This method was applied to the concise synthesis of a potent matrix metalloproteinase (MMP) inhibitor