IU Indianapolis ScholarWorks :: Browsing by Subject "Evolution"

Browsing by Subject "Evolution"

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A pilot randomized controlled trial comparing a novel compassion and metacognition approach for schizotypal personality disorder with a combination of cognitive therapy and psychopharmacological treatment
(BMC, 2023-02-20) Cheli, Simone; Cavalletti, Veronica; Lysaker, Paul H.; Dimaggio, Giancarlo; Petrocchi, Nicola; Chiarello, Francesca; Enzo, Consuelo; Velicogna, Francesco; Mancini, Francesco; Goldzweig, Gil; Psychiatry, School of Medicine
Background: Schizotypal personality disorder is characterized by a pervasive pattern of maladaptive behavior that has been associated with the liability for schizophrenia. Little is known about effective psychosocial interventions. This pilot non-inferiority randomized controlled trial aimed to compare a novel form of psychotherapy tailored for this disorder and a combination of cognitive therapy and psychopharmacological treatment. The former treatment - namely, Evolutionary Systems Therapy for Schizotypy-integrated evolutionary, metacognitively oriented, and compassion focused approaches. Methods: Thirty-three participants were assessed for eligibility, twenty-four randomized on a 1:1 ratio, nineteen included in the final analysis. The treatments lasted 6 months (24 sessions). The primary outcome was change across nine measurements in personality pathology, the secondary outcomes were remission from diagnosis and pre-post changes in general symptomatology and metacognition. Results: Primary outcome suggested a non-inferiority of the experimental treatment in respect to control condition. Secondary outcomes reported mixed results. There was no significant difference in terms of remission, but experimental treatment showed a larger reduction of general symptomatology (η2 = 0.558) and a larger increase in metacognition (η2 = 0.734). Conclusions: This pilot study reported promising results about the effectiveness of the proposed novel approach. A confirmatory trial on large sample size is needed to provide evidence about relative effectiveness of the two treatment conditions.
Alzheimer's Disease Narratives and the Myth of Human Being
(2012-12-11) Rieske, Tegan Echo; Schultz, Jane E.; Johnson, Karen Ramsay; Tilley, John J.
The ‘loss of self’ trope is a pervasive shorthand for the prototypical process of Alzheimer's disease (AD) in the popular imagination. Turned into an effect of disease, the disappearance of the self accommodates a biomedical story of progressive deterioration and the further medicalization of AD, a process which has been storied as an organic pathology affecting the brain or, more recently, a matter of genetic calamity. This biomedical discourse of AD provides a generic framework for the disease and is reproduced in its illness narratives. The disappearance of self is a mythic element in AD narratives; it necessarily assumes the existence of a singular and coherent entity which, from the outside, can be counted as both belonging to and representing an individual person. The loss of self, as the rhetorical locus of AD narrative, limits the privatization of the experience and reinscribes cultural storylines---storylines about what it means to be a human person. The loss of self as it occurs in AD narratives functions most effectively in reasserting the presence of the human self, in contrast to an anonymous, inhuman nonself; as AD discourse details a loss of self, it necessarily follows that the thing which is lost (the self) always already existed. The private, narrative self of individual experience thus functions as proxy to a collective human identity predicated upon exceptionalism: an escape from nature and the conditions of the corporeal environment.
A Case for Hydrogen Sulfide Metabolism as an Oxygen Sensing Mechanism
(MDPI, 2021-10-21) Olson, Kenneth R.; Anatomy, Cell Biology and Physiology, School of Medicine
The ability to detect oxygen availability is a ubiquitous attribute of aerobic organisms. However, the mechanism(s) that transduce oxygen concentration or availability into appropriate physiological responses is less clear and often controversial. This review will make the case for oxygen-dependent metabolism of hydrogen sulfide (H2S) and polysulfides, collectively referred to as reactive sulfur species (RSS) as a physiologically relevant O2 sensing mechanism. This hypothesis is based on observations that H2S and RSS metabolism is inversely correlated with O2 tension, exogenous H2S elicits physiological responses identical to those produced by hypoxia, factors that affect H2S production or catabolism also affect tissue responses to hypoxia, and that RSS efficiently regulate downstream effectors of the hypoxic response in a manner consistent with a decrease in O2. H2S-mediated O2 sensing is then compared to the more generally accepted reactive oxygen species (ROS) mediated O2 sensing mechanism and a number of reasons are offered to resolve some of the confusion between the two.
Catalase as a sulfide-sulfur oxido-reductase: An ancient (and modern?) regulator of reactive sulfur species (RSS)
(Elsevier, 2017-08) Olson, Kenneth R.; Gao, Yan; DeLeon, Eric R.; Arif, Maaz; Arif, Faihaan; Arora, Nitin; Straub, Karl D.; Department of Medicine, IU School of Medicine
Catalase is well-known as an antioxidant dismutating H2O2 to O2 and H2O. However, catalases evolved when metabolism was largely sulfur-based, long before O2 and reactive oxygen species (ROS) became abundant, suggesting catalase metabolizes reactive sulfide species (RSS). Here we examine catalase metabolism of H2Sn, the sulfur analog of H2O2, hydrogen sulfide (H2S) and other sulfur-bearing molecules using H2S-specific amperometric electrodes and fluorophores to measure polysulfides (H2Sn; SSP4) and ROS (dichlorofluorescein, DCF). Catalase eliminated H2Sn, but did not anaerobically generate H2S, the expected product of dismutation. Instead, catalase concentration- and oxygen-dependently metabolized H2S and in so doing acted as a sulfide oxidase with a P50 of 20 mmHg. H2O2 had little effect on catalase-mediated H2S metabolism but in the presence of the catalase inhibitor, sodium azide (Az), H2O2 rapidly and efficiently expedited H2S metabolism in both normoxia and hypoxia suggesting H2O2 is an effective electron acceptor in this reaction. Unexpectedly, catalase concentration-dependently generated H2S from dithiothreitol (DTT) in both normoxia and hypoxia, concomitantly oxidizing H2S in the presence of O2. H2S production from DTT was inhibited by carbon monoxide and augmented by NADPH suggesting that catalase heme-iron is the catalytic site and that NADPH provides reducing equivalents. Catalase also generated H2S from garlic oil, diallyltrisulfide, thioredoxin and sulfur dioxide, but not from sulfite, metabisulfite, carbonyl sulfide, cysteine, cystine, glutathione or oxidized glutathione. Oxidase activity was also present in catalase from Aspergillus niger. These results show that catalase can act as either a sulfide oxidase or sulfur reductase and they suggest that these activities likely played a prominent role in sulfur metabolism during evolution and may continue do so in modern cells as well. This also appears to be the first observation of catalase reductase activity independent of peroxide dismutation.
Characterization of lunar crust with moon mineralogy mapper data
(2015-06-09) Sun, Ying; Lin, Li; Bird, Broxton; Johnson, Daniel; Licht, Kathy; Gilhooly, William P.
This dissertation has three main focuses: (1) identify the distribution of a new rock type (Mg-spinel lithology) on the Moon and explore the likely petrogenesis of Mg-spinel; (2) investigate the presence of olivine in the crater central peaks and analyze the sources of olivine; (3) determine the compositional variations of lunar crust with depth, and establish a new model to describe the structure of the lunar crust.
Evidence for a Strong Correlation Between Transcription Factor Protein Disorder and Organismic Complexity
(Oxford University Press, 2017-05-01) Yruela, Inmaculada; Oldfield, Christopher J.; Niklas, Karl J.; Dunker, A. Keith; Department of Biochemistry and Molecular Biology, School of Medicine
Studies of diverse phylogenetic lineages reveal that protein disorder increases in concert with organismic complexity but that differences nevertheless exist among lineages. To gain insight into this phenomenology, we analyzed all of the transcription factor (TF) families for which sequences are known for 17 species spanning bacteria, yeast, algae, land plants, and animals and for which the number of different cell types has been reported in the primary literature. Although the fraction of disordered residues in TF sequences is often moderately or poorly correlated with organismic complexity as gauged by cell-type number (r2 < 0.5), an unbiased and phylogenetically broad analysis shows that organismic complexity is positively and strongly correlated with the total number of TFs, the number of their spliced variants and their total disordered residues content (r2 > 0.8). Furthermore, the correlation between the fraction of disordered residues and cell-type number becomes stronger when confined to the TF families participating in cell cycle, cell size, cell division, cell differentiation, or cell proliferation, and other important developmental processes. The data also indicate that evolutionarily simpler organisms allow for the detection of subtle differences in the conserved IDRs of TFs as well as changes in variable IDRs, which can influence the DNA recognition and multifunctionality of TFs through direct or indirect mechanisms. Although strong correlations cannot be taken as evidence for cause-and-effect relationships, we interpret our data to indicate that increasing TF disorder likely was an important factor contributing to the evolution of organismic complexity and not merely a concurrent unrelated effect of increasing organismic complexity.
Hominids adapted to metabolize ethanol long before human-directed fermentation
(PNAS, 2015-01-13) Carrigan, Matthew A.; Uryasev, Oleg; Frye, Carole B.; Eckman, Blair L.; Myers, Candace R.; Hurley, Thomas D.; Benner, Steven A.; Department of Biochemistry & Molecular Biology, IU School of Medicine
Paleogenetics is an emerging field that resurrects ancestral proteins from now-extinct organisms to test, in the laboratory, models of protein function based on natural history and Darwinian evolution. Here, we resurrect digestive alcohol dehydrogenases (ADH4) from our primate ancestors to explore the history of primate-ethanol interactions. The evolving catalytic properties of these resurrected enzymes show that our ape ancestors gained a digestive dehydrogenase enzyme capable of metabolizing ethanol near the time that they began using the forest floor, about 10 million y ago. The ADH4 enzyme in our more ancient and arboreal ancestors did not efficiently oxidize ethanol. This change suggests that exposure to dietary sources of ethanol increased in hominids during the early stages of our adaptation to a terrestrial lifestyle. Because fruit collected from the forest floor is expected to contain higher concentrations of fermenting yeast and ethanol than similar fruits hanging on trees, this transition may also be the first time our ancestors were exposed to (and adapted to) substantial amounts of dietary ethanol.
Investigation of the Evolutionary Aspects of Thiamin Diphosphate-Dependent Decarboxylases
(2015) Rogers, Megan P.; McLeish, Michael J.
Thiamin diphosphate (ThDP)-dependent enzymes catalyze a wide range of reactions including the oxidative and nonoxidative decarboxylation of 2-keto acids, carboligation reactions, the cleavage of C-C bonds, and the formation of C-S, C-N, and C-O bonds. Surprisingly, given this diversity, all ThDP-dependent enzyme catalyzed reactions proceed through essentially the same intermediate. This suggests that these enzymes share a common ancestry and have evolved to become the diverse group of enzymes seen today. Sequence alignments have revealed that all ThDP-dependent enzymes share two common ThDP binding domains, the PYR domain and the PP domain. In addition to these conserved domains, over time, other domains have been added creating further diversity in this superfamily. For instance, the TH3 domain, found in many ThDP-dependent enzymes, serves the function of binding additional cofactors such as FAD in enzymes like acetohydroxyacid synthase (AHAS) but in others, like pyruvate decarboxylase (PDC), it has lost this function completely. The work presented here focuses on ThDP-dependent decarboxylases. In this thesis, several evolutionary aspects of this group of enzymes will be examined including (i) the characterization of an evolutionary forerunner in the presence of a mechanism-based inhibitor, (ii) the characterization of the minor isozymes of pyruvate decarboxylase from Saccharomyces cerevisiae, and (iii) the development of a selection method to increase the efficiency of the site-saturation mutagenesis used to study ThDP-dependent enzyme evolution.
Methane, arsenic, selenium and the origins of the DMSO reductase family
(Nature Publishing group, 2020-07-02) Wells, Michael; Kanmanii, Narthana Jeganathar; Al Zadjali, Al Muatasim; Janecka, Jan E.; Basu, Partha; Oremland, Ronald S.; Stolz, John F.; Chemistry and Chemical Biology, School of Science
Mononuclear molybdoenzymes of the dimethyl sulfoxide reductase (DMSOR) family catalyze a number of reactions essential to the carbon, nitrogen, sulfur, arsenic, and selenium biogeochemical cycles. These enzymes are also ancient, with many lineages likely predating the divergence of the last universal common ancestor into the Bacteria and Archaea domains. We have constructed rooted phylogenies for over 1,550 representatives of the DMSOR family using maximum likelihood methods to investigate the evolution of the arsenic biogeochemical cycle. The phylogenetic analysis provides compelling evidence that formylmethanofuran dehydrogenase B subunits, which catalyze the reduction of CO2 to formate during hydrogenotrophic methanogenesis, constitutes the most ancient lineage. Our analysis also provides robust support for selenocysteine as the ancestral ligand for the Mo/W atom. Finally, we demonstrate that anaerobic arsenite oxidase and respiratory arsenate reductase catalytic subunits represent a more ancient lineage of DMSORs compared to aerobic arsenite oxidase catalytic subunits, which evolved from the assimilatory nitrate reductase lineage. This provides substantial support for an active arsenic biogeochemical cycle on the anoxic Archean Earth. Our work emphasizes that the use of chalcophilic elements as substrates as well as the Mo/W ligand in DMSORs has indelibly shaped the diversification of these enzymes through deep time.
Molecular aspects of MERS-CoV
(Springer Nature, 2017) Rabaan, Ali A.; Bazzi, Ali M.; Al-Ahmed, Shamsah H.; Al-Tawfiq, Jaffar A.; Medicine, School of Medicine
Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus which can cause acute respiratory distress in humans and is associated with a relatively high mortality rate. Since it was first identified in a patient who died in a Jeddah hospital in 2012, the World Health Organization has been notified of 1735 laboratory-confirmed cases from 27 countries, including 628 deaths. Most cases have occurred in Saudi Arabia. MERS-CoVancestors may be found in OldWorld bats of the Vespertilionidae family. After a proposed bat to camel switching event, transmission of MERS-CoV to humans is likely to have been the result of multiple zoonotic transfers from dromedary camels. Human-to-human transmission appears to require close contact with infected persons, with outbreaks mainly occurring in hospital environments. Outbreaks have been associated with inadequate infection prevention and control implementation, resulting in recommendations on basic and more advanced infection prevention and control measures by the World Health Organization, and issuing of government guidelines based on these recommendations in affected countries including Saudi Arabia. Evolutionary changes in the virus, particularly in the viral spike protein which mediates virus-host cell contact may potentially increase transmission of this virus. Efforts are on-going to identify specific evidence-based therapies or vaccines. The broad-spectrum antiviral nitazoxanide has been shown to have in vitro activity against MERS-CoV. Synthetic peptides and candidate vaccines based on regions of the spike protein have shown promise in rodent and non-human primate models. GLS-5300, a prophylactic DNA-plasmid vaccine encoding S protein, is the first MERS-CoV vaccine to be tested in humans, while monoclonal antibody, m336 has given promising results in animal models and has potential for use in outbreak situations.

Browsing by Subject "Evolution"

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