Divergent Microbial Profiles in Tumor and Adjacent Normal Tissue across Cancer Types

Ph.D.Ph.D. Thesis. University of Hawaiʻi at Mānoa 201

Urinary Carnosinase-1 Excretion is Associated with Urinary Carnosine Depletion and Risk of Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Cohort Study

Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4–33.3] µmol/24 h versus 34.8 [IQR 25.6–46.8] µmol/24 h; p < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06–1.45]; p = 0.007). During median follow-up for 5.3 [4.5–6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44–2.08]; p < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted

Variations of biochemical and hematic parameters following Taoist qigong practice

Qigong is an ancient Chinese psychosomatic discipline which employs specially designed body movements to achieve mind-body integration, preserve health, and pursue longevity. The Taoist school of qigong, one of the main traditions within this Chinese discipline, has a particular approach that emphasizes naturalness for the achievement of those goals. Albeit diverse methods of qigong have already been shown to display significant psychobiological effects, Taoist qigong has been scarcely investigated to date. Thus, this research was carried out with the aim of shedding light on the effects of Taoist qigong on biochemical and hematic parameters measured shortly after practice. Forty five naive subjects participated in the study, twenty-eight in the experimental group and the rest in the control group. Experimental subjects underwent a qigong training program consisting of three half-hour guided sessions per week, for the period of one month. Blood samples for the quantification of biochemical and hematic parameters were drawn from all subjects the day before the experiment commenced and one hour after the last session of practice concluded. Analysis of covariance (ANCOVA) was performed as statistical analyses. Our results showed that after completing the qigong program, experimental subjects displayed lower levels of serum albumin, as well as lower values of Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC), when compared to control. These findings, therefore, reveal that the practice of Taoist qigong for a short period of one month exerted a peculiar biochemical and hematimetric influence, which suggests interesting psychobiological and clinical implications.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Towards teacher-led design inquiry of learning

This paper proposes “teacher-led design inquiry of learning” as a new model of educational practice and professional development. This model combines four existing models. It integrates teacher inquiry into student learning, learning design, and learning analytics, and aims to capture the essence of the synergy of these three fields. Furthermore, we identify how learning analytics and the integrated model inform each other and could help integrating learning analytics into teachers’ practice. The last claim is demonstrated through an illustrative scenario. We envision that the integration of the four models could help teachers align both the improvement of their practices and the orchestration of their classrooms. Future empirical investigation is envisaged using a design based research framework and participatory design approach to engage teachers with the integrated model in a professional development process. We envisage that the integrated model will promote quality enhancement in education at a personal and collective level, and will be used to design better learning analytics, learning design and learning enactment tools. The main limitation of the integrated model is that it requires organizational changes, and allocation of resources, in order to allow it to significantly impact practice

Stony Coral Tissue Loss Disease and Other Diseases Affect Adults and Recruits of Major Reef Builders at Different Spatial Scales in the Dominican Republic

Monitoring programs can help understand coral disease dynamics. Here, we present results from a national program in the Dominican Republic (DR) aimed at evaluating coral diseases 3 times a year following a nested spatial design. Prevalence of coral diseases in DR varied from sites to regions, suggesting that disease dynamics can be driven by local processes and/or across larger spatial scales. Three diseases were common: Dark Spot (DSD), Yellow Band (YBD) and Stony Coral Tissue Loss Disease (SCTLD). DSD and YBD were more prevalent across the western coast (north and south), whereas SCTLD was restricted for the study period to the northern coast. SCTLD has become endemic in the northwestern coast, epizootic in the northeastern, and absent in other sites across DR. SCTLD prevalence in the northwest was below 10% across sites, whereas in the northeast it varied from 2.13±3.69% (mean± sd) to 38.7±13.55% in Galeras and from 1.9±0.99% to 38.5±19.8% in Samaná. Over 10 coral species were affected by SCTLD in DR, with Pseudodiploria spp, Dendrogyra cylindrus, Eusmilia fastigiata, Siderastrea siderea, Montastraea cavernosa and Meandrina spp, being the most susceptible. We observed SCTLD affecting recruits and juvenile corals with 5% prevalence on average. Furthermore, we observed Oreaster reticulatus climbing on 1% healthy and 27% SCTLD P. strigosa colonies in Samaná. We conclude that SCTLD is a serious problem in DR, producing rapid loss of coral cover of major reef builders that are locally used for propagation efforts. This monitoring plan will provide future insights to design more effective disease responses

Multicentre study on the reproducibility of MALDI-TOF MS for nontuberculous mycobacteria identification

The ability of MALDI-TOF for the identification of nontuberculous mycobacteria (NTM) has improved recently thanks to updated databases and optimized protein extraction procedures. Few multicentre studies on the reproducibility of MALDI-TOF have been performed so far, none on mycobacteria. The aim of this study was to evaluate the reproducibility of MALDI-TOF for the identification of NTM in 15 laboratories in 9 European countries. A total of 98 NTM clinical isolates were grown on Lowenstein-Jensen. Biomass was collected in tubes with water and ethanol, anonymized and sent out to the 15 participating laboratories. Isolates were identified using MALDI Biotyper (Bruker Daltonics). Up to 1330 MALDI-TOF identifications were collected in the study. A score >= 1.6 was obtained for 100% of isolates in 5 laboratories (68.2-98.6% in the other). Species-level identification provided by MALDI-TOF was 100% correct in 8 centres and 100% correct to complex-level in 12 laboratories. In most cases, the misidentifications obtained were associated with closely related species. The variability observed for a few isolates could be due to variations in the protein extraction procedure or to MALDI-TOF system status in each centre. In conclusion, MALDI-TOF showed to be a highly reproducible method and suitable for its implementation for NTM identification

KAP1 regulates endogenous retroviruses in adult human cells and contributes to innate immune control

Endogenous retroviruses (ERVs) have accumulated in vertebrate genomes and contribute to the complexity of gene regulation. KAP1 represses ERVs during development by its recruitment to their repetitive sequences through KRAB zinc-finger proteins (KZNFs), but little is known about the regulation of ERVs in adult tissues. We observed that KAP1 repression of HERVK14C was conserved in differentiated human cells and performed KAP1 knockout to obtain an overview of KAP1 function. Our results show that KAP1 represses ERVs (including HERV-T and HERV-S) and ZNF genes, both of which overlap with KAP1 binding sites and H3K9me3 in multiple cell types. Furthermore, this pathway is functionally conserved in adult human peripheral blood mononuclear cells. Cytosine methylation that acts on KAP1 regulated loci is necessary to prevent an interferon response, and KAP1-depletion leads to activation of some interferon-stimulated genes. Finally, loss of KAP1 leads to a decrease in H3K9me3 enrichment at ERVs and ZNF genes and an RNA-sensing response mediated through MAVS signaling. These data indicate that the KAP1-KZNF pathway contributes to genome stability and innate immune control in adult human cells

HIV-1 Vpr antagonizes innate immune activation by targeting karyopherin-mediated NF-κB/IRF3 nuclear transport.

HIV-1 must replicate in cells that are equipped to defend themselves from infection through intracellular innate immune systems. HIV-1 evades innate immune sensing through encapsidated DNA synthesis and encodes accessory genes that antagonize specific antiviral effectors. Here, we show that both particle associated, and expressed HIV-1 Vpr, antagonize the stimulatory effect of a variety of pathogen associated molecular patterns by inhibiting IRF3 and NF-κB nuclear transport. Phosphorylation of IRF3 at S396, but not S386, was also inhibited. We propose that, rather than promoting HIV-1 nuclear import, Vpr interacts with karyopherins to disturb their import of IRF3 and NF-κB to promote replication in macrophages. Concordantly, we demonstrate Vpr-dependent rescue of HIV-1 replication in human macrophages from inhibition by cGAMP, the product of activated cGAS. We propose a model that unifies Vpr manipulation of nuclear import and inhibition of innate immune activation to promote HIV-1 replication and transmission