Ecoepidemiology of Trypanosoma cruzi in Texas

This dissertation focused on elucidating factors affecting Trypanosoma cruzi transmission in the southern US, using triatomine, canine, and wildlife samples. Collection of triatomine vectors from 2012-2015 included standard entomological sampling, as well as submissions through a citizen science program. The insects were identified to species, dissected, and tested for T. cruzi infection. T. gerstaeckeri and T. sanguisuga were the most abundant species in the collection. Kissing bugs were captured primarily April-October, and peak activity varied by species. A T. cruzi infection prevalence of 58.9% was found in 1,226 triatomines of 6 species, and infection prevalence varied by species. Amplification and sequencing of the TcSC5D gene revealed Triatoma gerstaeckeri was approximately equally infected with TcI and TcIV, and 10 individuals showed mixed TcI/TcIV infections. In contrast, Triatoma sanguisuga was more frequently found infected with TcIV than TcI. Relative abundance of parasite DTUs varied spatially, with both TcI and TcIV co-circulating nearly equally in vectors in central Texas, while TcIV predominated in northern Texas. A study of T. cruzi infection in dogs in south central Texas using paired IFA and Chagas Stat-Pak serological testing showed a seroprevalence of 57.6%. The odds of being seropositive were greater for dogs older than 6 years of age than dogs less than 2 years of age. PCR analyses of blood revealed 26.7% of dogs, including both seronegative and seropositive dogs, harbored parasite DNA in their blood. Sequencing of the TcSC5D gene from blood and tissue samples showed TcI and TcIV were present, including a co-occurrence of both DTUs in an individual dog. Cardiac tissue and blood were collected from wildlife—including raccoons (Procyon lotor), coyotes (Canis latrans), gray foxes (Urocyon cinereoargenteus), and bobcats (Lynx rufus)—from central Texas. PCR analyses found 2 bobcats (14.3%), 12 coyotes (14.3%), 8 foxes (13.8%), and 49 raccoons (70.0%) were positive for T. cruzi in at least one sample (right ventricle, apex, and/or blood clot). Strain typing revealed raccoons infected with DTU TcIV, and a single raccoon with TcI/TcI

In My Head and Not Yours: Next-In- Line Effect for Therapists

When therapists are thinking about what interventions they want to implement, searching for the perfect question, or just wanting to say what they have in mind, then they are subject to missing what the client is saying. The next-in- line effect (Brenner, 1973; Bond, 1985) has shown that when people are next in line they may miss cues or fail to encode. Using the next in line effect as a teaching demonstration to reveal the effects of the phenomenon have been implemented (Desforges, 2007). The purpose of the current teaching demonstration is to highlight the application of the effect for student therapists

Others' Deception Attitude Measure: Investigating its Psychometric Properties

Many people hold negative attitudes toward others who lie (Curtis, 2013; Curtis, 2015; Curtis & Hart, 2015; Curtis, Huang, & Nicks, 2015). Recently, a scale has been developed to measure attitudes toward others who employ deception, referred to as the Others' Deception Attitude Measure (ODAM; Curtis & Dickens, 2016). The ODAM is an adaptation of the Therapists' Attitudes Towards Deception Scale (TATDS) and Attitudes Toward Patient Deception Scale (ATPDS) and has been used in research investigating therapists attitudes toward client deception and nursing students' attitudes toward patient deception (Curtis, 2015; Curtis & Hart, 2015). The TATDS and ATPDS consisted of 44 items which assessed attitudes towards patients/clients who lie. The TATDS had high internal consistency reliability (alpha = .83) as well as the ATPDS (alpha = .88). The ODAM consist of two subscales (specific and global attitudes) containing 23 of the 24 items from the TATDS and ATPDS that assesses attitudes toward deception. The ODAM changes the wording of patient or therapist to person. The purpose of the current study is to exam the psychometric properties of the ODAM. The inter item reliability and test-retest reliability of the ODAM will be explored. The ODAM will also be compared to other measures to explore its convergent validity and compared to a theoretically unrelated measure to explore its discriminate validity

Epidemiology and molecular typing of Trypanosoma cruzi in naturally-infected hound dogs and associated triatomine vectors in Texas, USA

Dataset associated with publicatio

Others' Deception Attitude Measure: Investigating its Psychometric Properties

Many people hold negative attitudes toward others who lie (Curtis, 2013; Curtis, 2015; Curtis & Hart, 2015; Curtis, Huang, & Nicks, 2015). Recently, a scale has been developed to measure attitudes toward others who employ deception, referred to as the Others' Deception Attitude Measure (ODAM; Curtis & Dickens, 2016). The ODAM is an adaptation of the Therapists' Attitudes Towards Deception Scale (TATDS) and Attitudes Toward Patient Deception Scale (ATPDS) and has been used in research investigating therapists attitudes toward client deception and nursing students' attitudes toward patient deception (Curtis, 2015; Curtis & Hart, 2015). The TATDS and ATPDS consisted of 44 items which assessed attitudes towards patients/clients who lie. The TATDS had high internal consistency reliability (alpha = .83) as well as the ATPDS (alpha = .88). The ODAM consist of two subscales (specific and global attitudes) containing 23 of the 24 items from the TATDS and ATPDS that assesses attitudes toward deception. The ODAM changes the wording of patient or therapist to person. The purpose of the current study is to exam the psychometric properties of the ODAM. The inter item reliability and test-retest reliability of the ODAM will be explored. The ODAM will also be compared to other measures to explore its convergent validity and compared to a theoretically unrelated measure to explore its discriminate validity

Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest

Bloom's syndrome is a rare autosomal recessive genetic disorder characterized by chromosomal aberrations, genetic instability, and cancer predisposition, all of which may be the result of abnormal signal transduction during DNA damage recognition. Here, we show that BLM is an intermediate responder to stalled DNA replication forks. BLM colocalized and physically interacted with the DNA damage response proteins 53BP1 and H2AX. Although BLM facilitated physical interaction between p53 and 53BP1, 53BP1 was required for efficient accumulation of both BLM and p53 at the sites of stalled replication. The accumulation of BLM/53BP1 foci and the physical interaction between them was independent of γ-H2AX. The active Chk1 kinase was essential for both the accurate focal colocalization of 53BP1 with BLM and the consequent stabilization of BLM. Once the ATR/Chk1- and 53BP1-mediated signal from replicational stress is received, BLM functions in multiple downstream repair processes, thereby fulfilling its role as a caretaker tumor suppressor

Macrophages, Nitric Oxide and microRNAs Are Associated with DNA Damage Response Pathway and Senescence in Inflammatory Bowel Disease

Background: Cellular senescence can be a functional barrier to carcinogenesis. We hypothesized that inflammation modulates carcinogenesis through senescence and DNA damage response (DDR). We examined the association between senescence and DDR with macrophage levels in inflammatory bowel disease (IBD). In vitro experiments tested the ability of macrophages to induce senescence in primary cells. Inflammation modulating microRNAs were identified in senescence colon tissue for further investigation. Methodology/Principal Findings: Quantitative immunohistochemistry identified protein expression by colon cell type. Increased cellular senescence (HP1γ; P = 0.01) or DDR (γH2A.X; P = 0.031, phospho-Chk2, P = 0.014) was associated with high macrophage infiltration in UC. Co-culture with macrophages (ANA-1) induced senescence in >80% of primary cells (fibroblasts MRC5, WI38), illustrating that macrophages induce senescence. Interestingly, macrophage-induced senescence was partly dependent on nitric oxide synthase, and clinically relevant NO• levels alone induced senescence. NO• induced DDR in vitro, as detected by immunofluorescence. In contrast to UC, we noted in Crohn’s disease (CD) that senescence (HP1γ; P<0.001) and DDR (γH2A.X; P<0.05, phospho-Chk2; P<0.001) were higher, and macrophages were not associated with senescence. We hypothesize that nitric oxide may modulate senescence in CD; epithelial cells of CD had higher levels of NOS2 expression than in UC (P = 0.001). Microarrays and quantitative-PCR identified miR-21 expression associated with macrophage infiltration and NOS2 expression. Conclusions: Senescence was observed in IBD with senescence-associated β-galactosidase and HP1γ. Macrophages were associated with senescence and DDR in UC, and in vitro experiments with primary human cells showed that macrophages induce senescence, partly through NO•, and that NO• can induce DDR associated with senescence. Future experiments will investigate the role of NO• and miR-21 in senescence. This is the first study to implicate macrophages and nitrosative stress in a direct effect on senescence and DDR, which is relevant to many diseases of inflammation, cancer, and aging.Cancer Research Institute (New York, N.Y.) (Intramural Research Program)National Cancer Institute (U.S.) (Cancer Research Training Award Fellowship)Danish Cancer SocietyDanish National Research FoundationEuropean Commission (projects: Infla-Care, Biomedreg and DDResponse

American triatomine species occurrences: updates and novelties in the DataTri database

The causative agent of Chagas disease (Trypanosoma cruzi) is transmitted to mammals, including humans, mainly by insect vectors of the subfamily Triatominae (Hemiptera: Reduviidae). Also known as “kissing bugs”, the subfamily currently includes 157 validated species (154 extant and three extinct), in 18 genera and five tribes. Here, we present a subdataset (7852 records) of American triatomine occurrences; an update to the most complete and integrated database available to date at a continental scale. New georeferenced records were obtained from a systematic review of published literature and colleague-provided data. New data correspond to 101 species and 14 genera from 22 American countries between 1935 and 2022. The most important novelties refer to (i) the inclusion of new species, (ii) synonymies and formal transferals of species, and (iii) temporal and geographical species records updates. These data will be a useful contribution to entomological surveillance implicated in Chagas disease.Centro de Estudios Parasitológicos y de Vectore

EML4-ALK induces cellular senescence in mortal normal human cells and promotes anchorage-independent growth in hTERT-transduced normal human cells

Background: Chromosomal inversions involving anaplastic lymphoma kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4) generate a fusion protein EML4-ALK in non-small cell lung cancer (NSCLC). The understanding of EML4-ALK function can be improved by a functional study using normal human cells. Methods: Here we for the first time conduct such study to examine the effects of EML4-ALK on cell proliferation, cellular senescence, DNA damage, gene expression profiles and transformed phenotypes. Results: The lentiviral expression of EML4-ALK in mortal, normal human fibroblasts caused, through its constitutive ALK kinase activity, an early induction of cellular senescence with accumulated DNA damage, upregulation of p16INK4A and p21WAF1, and senescence-associated β-galactosidase (SA-β-gal) activity. In contrast, when EML4-ALK was expressed in normal human fibroblasts transduced with telomerase reverse transcriptase (hTERT), which is activated in the vast majority of NSCLC, the cells showed accelerated proliferation and acquired anchorage-independent growth ability in soft-agar medium, without accumulated DNA damage, chromosome aberration, nor p53 mutation. EML4-ALK induced the phosphorylation of STAT3 in both mortal and hTERT-transduced cells, but RNA sequencing analysis suggested that the different signaling pathways contributed to the different phenotypic outcomes in these cells. While EML4-ALK also induced anchorage-independent growth in hTERT-immortalized human bronchial epithelial cells in vitro, the expression of EML4-ALK alone did not cause detectable in vivo tumorigenicity in immunodeficient mice. Conclusions: Our data indicate that the expression of hTERT is critical for EML4-ALK to manifest its in vitro transforming activity in human cells. This study provides the isogenic pairs of human cells with and without EML4-ALK expression

Active Spatial Perception in the Vibrissa Scanning Sensorimotor System

Haptic perception is an active process that provides an awareness of objects that are encountered as an organism scans its environment. In contrast to the sensation of touch produced by contact with an object, the perception of object location arises from the interpretation of tactile signals in the context of the changing configuration of the body. A discrete sensory representation and a low number of degrees of freedom in the motor plant make the ethologically prominent rat vibrissa system an ideal model for the study of the neuronal computations that underlie this perception. We found that rats with only a single vibrissa can combine touch and movement to distinguish the location of objects that vary in angle along the sweep of vibrissa motion. The patterns of this motion and of the corresponding behavioral responses show that rats can scan potential locations and decide which location contains a stimulus within 150 ms. This interval is consistent with just one to two whisk cycles and provides constraints on the underlying perceptual computation. Our data argue against strategies that do not require the integration of sensory and motor modalities. The ability to judge angular position with a single vibrissa thus connects previously described, motion-sensitive neurophysiological signals to perception in the behaving animal