Type I interferon-driven susceptibility to Mycobacterium tuberculosis is mediated by IL-1Ra.

The bacterium Mycobacterium tuberculosis (Mtb) causes tuberculosis and is responsible for more human mortality than any other single pathogen1. Progression to active disease occurs in only a fraction of infected individuals and is predicted by an elevated type I interferon (IFN) response2-7. Whether or how IFNs mediate susceptibility to Mtb has been difficult to study due to a lack of suitable mouse models6-11. Here, we examined B6.Sst1S congenic mice that carry the 'susceptible' allele of the Sst1 locus that results in exacerbated Mtb disease12-14. We found that enhanced production of type I IFNs was responsible for the susceptibility of B6.Sst1S mice to Mtb. Type I IFNs affect the expression of hundreds of genes, several of which have previously been implicated in susceptibility to bacterial infections6,7,15-18. Nevertheless, we found that heterozygous deficiency in just a single IFN target gene, Il1rn, which encodes interleukin-1 receptor antagonist (IL-1Ra), is sufficient to reverse IFN-driven susceptibility to Mtb in B6.Sst1S mice. In addition, antibody-mediated neutralization of IL-1Ra provided therapeutic benefit to Mtb-infected B6.Sst1S mice. Our results illustrate the value of the B6.Sst1S mouse to model IFN-driven susceptibility to Mtb, and demonstrate that IL-1Ra is an important mediator of type I IFN-driven susceptibility to Mtb infections in vivo

Information and Communication Technologies (ICT): Components, Dimensions, and its Correlates

Information and Communication Technologies (ICT) has been identified as one of the crucial factors that affect teaching effectiveness and student learning worldwide. UNESCO, many international organizations, and many governments emphasized the importance of ICT and try to incorporate ICT into education systems. This study examined self-assessed computer competency in thirteen ICT areas from two samples, e.g., the United States and Mexico. Reliability tests were conducted, and rank analysis was done among them. By using factor analysis, these thirteen areas were grouped into three categories: “basic ICT skills”; “advanced ICT skills;” and “multimedia skills and attitudes towards ICT”. Subjects showed the highest scores in basic ICT skills, which include knowledge of computer systems, use of the operating system, search internet and communication and networking. The multimedia skills and attitudes towards ICT demonstrated the second highest scores. Advanced ICT skills that include image processing, use of database, technological platforms, and web 2.0 tools was found to have the lowest competency scores among subjects. Multivariate analysis was also conducted and found that age and gender are two significant factors to predict ICT competency, and age was found to have a non-linear relationship on advanced ICT skills

Cloning and recombinant expression of two Arabidopsis 14-3-3 binding proteins expressed during seed development [abstract]

Abstract only availableAs a participant in cellular signaling, the 14-3-3 binding protein is essential to cellular function in both plants and animals. Two Arabidopsis thaliana 14-3-3 genes from phylogenetically different families were studied: the GF14-chi and GF14-231, 14-3-3 epsilon which were previously shown to be expressed in developing Arabidopsis seed. One of the principal functions of these proteins is to mediate signals by binding specific client proteins. One strategy to characterize these interacting client proteins is to use purified recombinant 14-3-3 proteins as bait in pull-down assays. The objective of this thesis was to create the expression constructs and purify the recombinant protein. To obtain a cloned gene, isolation of plasmid DNA was followed by PCR amplification. After a ligation reaction and transformation into E.coli Top 10, products were digested. The digested products were sent for sequencing. The GF14-231, 14-3-3 epsilon was successfully cloned. To express the 14-3-3 protein in E.coli, the construct was transformed in BL21 Star (DE3) One Shot cells. After transformation, IPTG was added to induce protein expression. Recombinant 14-3-3 protein was then purified by Ni-NTA column chromatography and analyzed by SDS-PAGE analysis. After obtaining purified protein an antibody will be developed. Future work will include a similar analysis of the GF14-chi.MU Monsanto Undergraduate Research Fellowshi

Identification of presumed pathogenic KRT3 and KRT12 gene mutations associated with Meesmann corneal dystrophy.

PurposeTo report potentially pathogenic mutations in the keratin 3 (KRT3) and keratin 12 (KRT12) genes in two individuals with clinically diagnosed Meesmann corneal dystrophy (MECD).MethodsSlit-lamp examination was performed on the probands and available family members to identify characteristic features of MECD. After informed consent was obtained, saliva samples were obtained as a source of genomic DNA, and screening of KRT3 and KRT12 was performed. Potentially pathogenic variants were screened for in 200 control chromosomes. PolyPhen-2, SIFT, and PANTHER were used to predict the functional impact of identified variants. Short tandem repeat genotyping was performed to confirm paternity.ResultsSlit-lamp examination of the first proband demonstrated bilateral, diffusely distributed, clear epithelial microcysts, consistent with MECD. Screening of KRT3 revealed a heterozygous missense variant in exon 1, c.250C>T (p.(Arg84Trp)), which has a minor allele frequency of 0.0076 and was not identified in 200 control chromosomes. In silico analysis with PolyPhen-2 and PANTHER predicted the variant to be damaging to protein function; however, SIFT analysis predicted tolerance of the variant. The second proband demonstrated bilateral, diffusely distributed epithelial opacities that appeared gray-white on direct illumination and translucent on retroillumination. Neither parent demonstrated corneal opacities. Screening of KRT12 revealed a novel heterozygous insertion/deletion variant in exon 6, c.1288_1293delinsAGCCCT (p.(Arg430_Arg431delinsSerPro)). This variant was not present in either of the proband's parents or in 200 control chromosomes and was predicted to be damaging by PolyPhen-2, PANTHER, and SIFT. Haplotype analysis confirmed paternity of the second proband, indicating that the variant arose de novo.ConclusionsWe present a novel KRT12 mutation, representing the first de novo mutation and the first indel in KRT12 associated with MECD. In addition, we report a variant of uncertain significance in KRT3 in an individual with MECD. Although the potential pathogenicity of this variant is unknown, it is the first variant affecting the head domain of K3 to be reported in an individual with MECD and suggests that disease-causing variants associated with MECD may not be restricted to primary sequence alterations of either the helix-initiation or helix-termination motifs of K3 and K12

A Previously Healthy Adolescent With Acute Psychosis and Severe Hyperhidrosis

A previously healthy 15-year-old boy presented with 3 months of progressive psychosis, insomnia, back and groin pain, and hyperhidrosis. On examination, the patient was disheveled, agitated, and soaked with sweat, with systolic blood pressure in the 160s and heart rate in the 130s. Aside from occasional auditory and visual hallucinations, his neurologic examination was normal. The patient was admitted for an extensive workup, including MRI of the brain and spine and lumbar puncture, which were normal. Through collaboration with various pediatric specialists, including psychiatry and neurology, a rare diagnosis was ultimately unveiled

Transit times and mean ages for nonautonomous and autonomous compartmental systems

We develop a theory for transit times and mean ages for nonautonomous compartmental systems. Using the McKendrick-von F\"orster equation, we show that the mean ages of mass in a compartmental system satisfy a linear nonautonomous ordinary differential equation that is exponentially stable. We then define a nonautonomous version of transit time as the mean age of mass leaving the compartmental system at a particular time and show that our nonautonomous theory generalises the autonomous case. We apply these results to study a nine-dimensional nonautonomous compartmental system modeling the terrestrial carbon cycle, which is a modification of the Carnegie-Ames-Stanford approach (CASA) model, and we demonstrate that the nonautonomous versions of transit time and mean age differ significantly from the autonomous quantities when calculated for that model

Detecting the redshifted 21cm forest during reionization

The 21cm forest -- HI absorption features in the spectra of high-redshift radio sources -- can potentially provide a unique probe of the largely neutral intergalactic medium (IGM) during the epoch of reionization. We present simulations of the 21cm forest due to the large scale structure of the reionization-era IGM, including a prescription for x-ray heating and the percolation of photoionization bubbles. We show that, if detected with future instruments such as the Square Kilometer Array (SKA), the 21cm forest can provide a significant constraint on the thermal history of the IGM. Detection will be aided by consideration of the sudden increase in signal variance at the onset of 21cm absorption. If radio foregrounds and the intrinsic source spectra are well understood, the flux decrement over wide bandwidths can also improve detection prospects. Our analysis accounts for the possibility of narrow absorption lines from intervening dense regions, but, unlike previous studies, our results do not depend on their properties. Assuming x-ray heating corresponding to a local stellar population, we estimate that a statistically significant detection of 21cm absorption could be made by SKA in less than a year of observing against a Cygnus A-type source at $z \sim 9$, as opposed to nearly a decade for a significant detection of the detailed forest features. We discuss observational challenges due to uncertainties regarding the abundance of background sources and the strength of the 21cm absorption signal.Comment: Submitted to MNRAS. Revised version includes updated and extended calculations, some corrections and added reference

Phase Changes in Ni-Ti Under Laser Shock Loading

Near-equiatomic Ni-Ti, known for its shape memory behavior, can decompose to martensitic phases and/or second phase compounds. This phase competition is investigated in NixTi100-x (494Ti3 but no martensite in the AQ state, consistent with resistivity and dilatometry results which showed no hysteresis indicative of first order phase changes over 1.9 K4Ti3 amounts (present in the AQ state) did change upon loading, indicating the importance of shock-induced heating. A thermodynamically complete equation of state (EOS) for NiTi in its B2 (CsCl) structure was generated by ab initio quantum mechanical calculations. This was tested by performing laser-launched flyer experiments, which showed consistency with the theoretical EOS, validating its use in the prediction of dynamic loading histories in the samples during direct drive loading

Deterministic Parallel Global Parameter Estimation for a Model of the Budding Yeast Cell Cycle

Two parallel deterministic direct search algorithms are used to find improved parameters for a system of differential equations designed to simulate the cell cycle of budding yeast. Comparing the model simulation results to experimental data is difficult because most of the experimental data is qualitative rather than quantitative. An algorithm to convert simulation results to mutant phenotypes is presented. Vectors of parameters defining the differential equation model are rated by a discontinuous objective function. Parallel results on a 2200 processor supercomputer are presented for a global optimization algorithm, DIRECT, a local optimization algorithm, MADS, and a hybrid of the two

Functional Profiling of Transcription Factor Genes in Neurospora crassa.

Regulation of gene expression by DNA-binding transcription factors is essential for proper control of growth and development in all organisms. In this study, we annotate and characterize growth and developmental phenotypes for transcription factor genes in the model filamentous fungus Neurospora crassa We identified 312 transcription factor genes, corresponding to 3.2% of the protein coding genes in the genome. The largest class was the fungal-specific Zn2Cys6 (C6) binuclear cluster, with 135 members, followed by the highly conserved C2H2 zinc finger group, with 61 genes. Viable knockout mutants were produced for 273 genes, and complete growth and developmental phenotypic data are available for 242 strains, with 64% possessing at least one defect. The most prominent defect observed was in growth of basal hyphae (43% of mutants analyzed), followed by asexual sporulation (38%), and the various stages of sexual development (19%). Two growth or developmental defects were observed for 21% of the mutants, while 8% were defective in all three major phenotypes tested. Analysis of available mRNA expression data for a time course of sexual development revealed mutants with sexual phenotypes that correlate with transcription factor transcript abundance in wild type. Inspection of this data also implicated cryptic roles in sexual development for several cotranscribed transcription factor genes that do not produce a phenotype when mutated