The Wife of the Alcoholic; Sexist Stereotypes in the Alcoholism Literature

Current alcoholism literature, alcoholism education, and alcoholism treatment suggests that the wife of the alcoholic is every bit as sick (physically, mentally, and spiritually) as her practicing alcoholic husband. How did we come to this view of the wife of the alcoholic? This paper will review 1) how the wife of the alcoholic has been regarded over the years; 2) how these portraits of the wife of the alcoholic that appeared in the scholarly literature have influenced current thinking and treatment, and 3) how this body of literature and the popular concepts of the wife of the alcoholic that evolved from it, carry sexual biases and stereotyping that can potentially interfere with optimum treatment, full recovery, and effective marital and family functioning

Inferring Species Trees from Gene Trees in a Radiation of California Trapdoor Spiders (Araneae, Antrodiaetidae, Aliatypus)

The California Floristic Province is a biodiversity hotspot, reflecting a complex geologic history, strong selective gradients, and a heterogeneous landscape. These factors have led to high endemic diversity across many lifeforms within this region, including the richest diversity of mygalomorph spiders (tarantulas, trapdoor spiders, and kin) in North America. The trapdoor spider genus Aliatypus encompasses twelve described species, eleven of which are endemic to California. Several Aliatypus species show disjunct distributional patterns in California (some are found on both sides of the vast Central Valley), and the genus as a whole occupies an impressive variety of habitats.We collected specimens from 89 populations representing all described species. DNA sequence data were collected from seven gene regions, including two newly developed for spider systematics. Bayesian inference (in individual gene tree and species tree approaches) recovered a general "3 clade" structure for the genus (A. gulosus, californicus group, erebus group), with three other phylogenetically isolated species differing slightly in position across different phylogenetic analyses. Because of extremely high intraspecific divergences in mitochondrial COI sequences, the relatively slowly evolving 28S rRNA gene was found to be more useful than mitochondrial data for identification of morphologically indistinguishable immatures. For multiple species spanning the Central Valley, explicit hypothesis testing suggests a lack of monophyly for regional populations (e.g., western Coast Range populations). Phylogenetic evidence clearly shows that syntopy is restricted to distant phylogenetic relatives, consistent with ecological niche conservatism.This study provides fundamental insight into a radiation of trapdoor spiders found in the biodiversity hotspot of California. Species relationships are clarified and undescribed lineages are discovered, with more geographic sampling likely to lead to additional species diversity. These dispersal-limited taxa provide novel insight into the biogeography and Earth history processes of California

Inactivation of Cone-Specific Phototransduction Genes in Rod Monochromatic Cetaceans

Vertebrate vision is mediated by two types of photoreceptors, rod and cone cells. Rods are more sensitive than cones in dim light, but are incapable of color discrimination because they possess only one type of photosensitive opsin protein (rod opsin = RH1). By contrast, cones are more important for vision in bright light. Cones also facilitate dichromatic color vision in most mammals because there are two cone pigment genes (SWS1, LWS) that facilitate color discrimination. Cone monochromacy occurs when one of the cone opsins (usually SWS1) is inactivated and is present in assorted subterranean, nocturnal, and aquatic mammals. Rod monochromacy occurs when both cone photoreceptors are inactivated, resulting in a pure rod retina. The latter condition is extremely rare in mammals and has only been confirmed with genetic evidence in five cetacean lineages, golden moles, armadillos, and sloths. The first genetic evidence for rod monochromacy in these taxa consisted of inactivated copies of both of their cone pigment genes (SWS1, LWS). However, other components of the cone phototransduction cascade are also predicted to accumulate inactivating mutations in rod monochromats. Here, we employ genome sequences and exon capture data from four baleen whales (bowhead, two minke whales, fin whale) and five toothed whales (sperm whale, Yangtze River dolphin, beluga, killer whale, bottlenose dolphin) to test the hypothesis that rod monochromacy is associated with the inactivation of seven genes (GNAT2, GNB3, GNGT2, PDE6C, PDE6H, CNGA3, CNGB3) in the cone phototransduction cascade. Cone-monochromatic toothed whales that retain a functional copy of LWS (beluga whale, Yangtze River dolphin, killer whale, bottlenose dolphin) also retain intact copies of other cone-specific phototransduction genes, whereas rod monochromats (Antarctic minke whale, common minke whale, fin whale, bowhead whale, sperm whale) have inactivating mutations in five or more genes in the cone phototransduction cascade. The only shared inactivating mutations that were discovered occur in the three Balaenoptera species (two minke whales, fin whale), further suggesting that rod monochromacy evolved independently in two clades of baleen whales, Balaenopteroidea and Balaenidae. We estimate that rod monochromacy evolved first in Balaenopteroidea (∼28.8 Ma) followed by P. macrocephalus (∼19.5 Ma) and Balaenidae (∼13.0 Ma)

POTs: Protective Optimization Technologies

Algorithmic fairness aims to address the economic, moral, social, and political impact that digital systems have on populations through solutions that can be applied by service providers. Fairness frameworks do so, in part, by mapping these problems to a narrow definition and assuming the service providers can be trusted to deploy countermeasures. Not surprisingly, these decisions limit fairness frameworks' ability to capture a variety of harms caused by systems. We characterize fairness limitations using concepts from requirements engineering and from social sciences. We show that the focus on algorithms' inputs and outputs misses harms that arise from systems interacting with the world; that the focus on bias and discrimination omits broader harms on populations and their environments; and that relying on service providers excludes scenarios where they are not cooperative or intentionally adversarial. We propose Protective Optimization Technologies (POTs). POTs provide means for affected parties to address the negative impacts of systems in the environment, expanding avenues for political contestation. POTs intervene from outside the system, do not require service providers to cooperate, and can serve to correct, shift, or expose harms that systems impose on populations and their environments. We illustrate the potential and limitations of POTs in two case studies: countering road congestion caused by traffic-beating applications, and recalibrating credit scoring for loan applicants.Comment: Appears in Conference on Fairness, Accountability, and Transparency (FAT* 2020). Bogdan Kulynych and Rebekah Overdorf contributed equally to this work. Version v1/v2 by Seda G\"urses, Rebekah Overdorf, and Ero Balsa was presented at HotPETS 2018 and at PiMLAI 201

The cellular chloride channels CLIC1 and CLIC4 contribute to virus-mediated cell motility

Ion channels regulate many aspects of cell physiology, including cell proliferation, motility, and migration, and aberrant expression and activity of ion channels is associated with various stages of tumor development, with K⁺ and Cl⁻ channels now being considered the most active during tumorigenesis. Accordingly, emerging in vitro and preclinical studies have revealed that pharmacological manipulation of ion channel activity offers protection against several cancers. Merkel cell polyomavirus (MCPyV) is a major cause of Merkel cell carcinoma (MCC), primarily because of the expression of two early regulatory proteins termed small and large tumor antigens (ST and LT, respectively). Several molecular mechanisms have been attributed to MCPyV-mediated cancer formation but, thus far, no studies have investigated any potential link to cellular ion channels. Here we demonstrate that Cl⁻ channel modulation can reduce MCPyV ST-induced cell motility and invasiveness. Proteomic analysis revealed that MCPyV ST up-regulates two Cl⁻ channels, CLIC1 and CLIC4, which when silenced, inhibit MCPyV ST-induced motility and invasiveness, implicating their function as critical to MCPyV-induced metastatic processes. Consistent with these data, we confirmed that CLIC1 and CLIC4 are up-regulated in primary MCPyV-positive MCC patient samples. We therefore, for the first time, implicate cellular ion channels as a key host cell factor contributing to virus-mediated cellular transformation. Given the intense interest in ion channel modulating drugs for human disease. This highlights CLIC1 and CLIC4 activity as potential targets for MCPyV-induced MCC

Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro

The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2 . - by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients' neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2 . - production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis. © 2013 Dias et al

Studying Human Spatial Cognition in Large-Scale, Virtual Environments: Learning, Memory, and Representational Flexibility

The representation of space in humans is influenced by a variety of factors during learning including the size, geometry, and complexity of the environment as well as how we interact with it. While the networks that underlie human spatial cognition are believed to be similar or homologous to other mammalian species, we may be the only species that uses figural representations of space (i.e., maps) to improve navigational efficacy for prospective goals. Behavioral and neurophysiological evidence have suggested a framework whereby self-referenced egocentric representations and world-referenced allocentric representations develop independently but interact and influence one another such that information from one of these reference frames can be translated into the other and vice versa. This framework provides the cognitive flexibility required for navigating large, complex spaces such as cities. The study of these large-scale environments has benefitted greatly from recent advances in video game technology, including immersive virtual reality (VR), but the time and effort to integrate these tools can be detrimental to the empirical process. In this dissertation, I provide a brief overview of the theories, methods, and results that motivated this work (Chapter 1), introduce tools I have developed to aid researchers in designing and implementing VR experiments (Chapter 2), and report research findings in support of a view that egocentric and allocentric affordances during learning and demands at retrieval result in dynamic and flexible spatial representations (Chapters 3 & 4). Chapter 5 summarizes the theoretical linkage of my doctoral portfolio and provides avenues for future study

Molecular Evolution of Silk Genes in Mesothele and Mygalomorph Spiders, With Implications for the Early Evolution and Functional Divergence of Silk

The evolution of adaptively significant gene families is an important subject in the field of evolutionary genetics. For spiders, the gene families encoding silk proteins have received considerable attention due to the high performance capabilities of the fibers they produce. However, silk gene research has largely focused on spiders of the infraorder Araneomorphae, leaving much of the phylogenetic diversity of spiders unsampled for their silk genes. Here, I sample silk genes from spiders of the suborder Mesothelae and infraorder Mygalomorphae, which are distantly related to araneomorph spiders. Phylogenetic analyses of the spidroin genes indicate that numerous duplications occurred in the spidroin gene family after opisthotheles (mygalomorphs plus araneomorphs) split from mesotheles. However, while mesotheles appear to possess a single spidroin gene, they possess numerous copies of genes homologous to Egg Case Proteins, which are currently only known from one araneomorph species. Together these results indicate that the common ancestor of extant spiders possessed a diversity of silk genes. In addition to higher level species sampling of silk genes, I sequence repetitive and carboxy terminal regions of spidroins from all species of the trapdoor spider genus, Aliatypus. Gene tree analyses and tests of selection suggest that contrasting evolutionary forces influenced the different regions of the spidroin gene. I also investigate the expression of silk transcripts from the tarsi and silk glands of tarantulas. Tarantulas exude silk-like secretions from their tarsi, which is hypothesized to increase surface adhesion. I discovered that while known spidroin silk genes are not expressed in the tarsi, novel silk-like genes are expressed in tarantula silk glands and tarsi. Gene families of adaptive significance may also show phylogenetic signal. Here, I sample hemocyanin gene family sequences from a phylogenetically diverse sample of spider species and infer gene trees and species trees. Phylogenetic analyses reveal that despite instances of lineage specific duplication and loss of hemocyanin paralogs, hemocyanins have phylogenetic utility for most spider groups. This dissertation shows the importance of research on gene family evolution, the roles of gene families in adaptation, and the utility of gene families in phylogenetics