Distinct Lines Of Evidence Research Articles

On a skeletally immature individual of Unaysaurus tolentinoi (Dinosauria: Sauropodomorpha) from the upper Triassic of southern Brazil.

The lineage of sauropodomorph dinosaurs raised some of the most impressive animals that ever walked on Earth. However, the massive titans of the Mesozoic Era originated from far smaller dinosaurs. The Triassic beds from Brazil yielded the earliest part of this evolutionary history. Despite the diverse fossil record of early sauropodomorphs, juvenile specimens, as well as certain species are poorly sampled. This is the case for Unaysaurus tolentinoi, an unaysaurid sauropodomorph from Caturrita Formation (ca. 225 Ma; early Norian, Late Triassic). The holotype and only specimen of U. tolentinoi was excavated from the Água Negra Locality (São Martinho da Serra, Rio Grande do Sul, Brazil) in 1998. More than two decades later, no other fossil vertebrates have been reported from the same fossiliferous site. Here we describe a skeletally immature specimen which was found in association with the holotype of U. tolentinoi. The specimen was discovered after a first-hand examination of the holotype and comprises some isolated vertebrae and elements from the posterior autopodium. According to linear regressions, its metatarsal I is approximately 41.7 mm in length, compared to approximately 75.9 mm in the holotype. The repeated elements and reduced size indicates that it does not belong to the elements originally used to erect U. tolentinoi. Rather, the specimen is assigned to U. tolentinoi by topotypy and shared morphology. In addition to the reduced size, distinct lines of evidence (e.g., neurocentral sutures; bone texture) support its assignment to a skeletally immature individual. In sum, the new material expands the record of U. tolentinoi, and represents an additional juvenile dinosaur from the Caturrita Formation.

Whether implicit attitudes exist is one question, and whether we can measure individual differences effectively is another.

Questions about measurement of individual differences in implicit attitudes, which have been the focus so far in this exchange, should be distinguished from more general questions about whether implicit attitudes exist and operate in our minds. Theorists frequently move too quickly from pessimistic results regarding the first set of questions to pessimistic conclusions about the second. That is, they take evidence that indirect measures such as the implicit association test (IAT) disappoint as individual difference measures and use it to (mistakenly) suggest that people do not in fact have implicit attitudes directed at stigmatized groups. In this commentary, I dissect this mistake in detail, drawing key lessons from a parallel debate that has unfolded in cognitive science about “conflict tasks” such as the Stroop task. I argue that the evidence overall supports a nuanced conclusion: Indirect measures such as the IAT measure individual differences in implicit attitudes poorly, but they—via distinct lines of evidence—still support the view that implicit attitudes exist.This article is categorized under:Psychology > Theory and Methods

Why Science and Faith Belong Together: Stories of Mutual Enrichment

Why Science and Faith Belong Together: Stories of Mutual Enrichment

Ecology and diagnosis of Enallodiplosis discordis (Diptera:Cecidomyiidae)

The coastal desert of Peru and Chile is home to Prosopis (Leguminosae: Mimosoideae) tree species that are exceptionally well-adapted to the hyperarid conditions and keystone in dry-forest ecosystems. From 2001 to 2018, Prosopis in Peru have suffered widespread defoliation and die-back, with consequent deforestation and collapse in pod production. This paper reports a new insect plague species of Prosopis forest in Peru: Enallodiplosis discordis Gagné 1994 (Diptera: Cecidomyiidae) as a fiercely defoliating agent contributing to widespread Prosopis mortality. An analysis of E. discordis larval taxonomy, life cycle and plague infestation, following El Niño Southern Oscillation (ENSO) 1998/99 is provided. Using distinct lines of evidence, its spread, distribution, and ecology are examined. Over two decades of fieldwork, Prosopis forest die-back and loss was observed devastating rural livelihoods and ecosystem services across lowland regions of southern (Ica), central and northern coastal Peru (Lambayeque, La Libertad, Piura). The collapse in production of Prosopis pods (algarroba, huaranga) and honey was recorded. Supplementary notes provide observations of: (i) plague development, changing land-use and climate, (ii) biological and physical control of E. discordis, (iii) the moth Melipotis aff. indomita (Lepidoptera: Noctuidae) as a concurrent defoliator of Prosopis.

Genetic and morphological variation of Oxymycterus (Rodentia: Sigmodontinae) in the Brazilian Atlantic Forest

Abstract We present a new assessment of the genetic and morphological variation within Oxymycterus quaestor Thomas, 1903, which currently includes the junior synonyms O. judex Thomas, 1909 and O. misionalis Sanborn, 1931. We integrate distinct lines of evidence, including variation of mitochondrial (Cytochrome b [Cytb]) and nuclear (intron 7 of beta fibrinogen gene [Fgb]) sequences, and the assessment of skull quantitative traits based on geometric morphometrics, throughout the Atlantic Forest of Southeastern-Southern Brazil, Argentina, and Paraguay. Phylogenetic relationships based on Cytb indicate that O. quaestor is structured in four well-supported clades (lineages A–D), one of them (lineage C) including topotypes of a previously associated nominal form (O. judex). However, these Cytb lineages exhibit lower levels of differentiation based on the Fgb locus, and are not recovered in the genealogies of this nuclear marker, representing a case of mitonuclear discordance. The Cytb lineages also broadly overlapped in the morphospace both in skull shape and size, which sustain the current wider concept of O. quaestor as one single young species (0.947 Myr) that is recently expanding, and ultimately branching out, in the Atlantic Forest.

SINGULARISM about Episodic Memory

In the philosophy of memory, singularism is the view that episodic memories are singular mental states about unique personally experienced past events. In this paper, I present an empirical challenge to singularism. I examine three distinct lines of evidence from the psychology of memory, concerning general event memories, the transformation of memory traces and the minimized role temporal information plays in major psychological theories of episodic memory. I argue that singularist views will have a hard time accommodating this evidence, facing a problem of transitional gradation. I then look at some potential consequences for the larger debate, highlighting the way in which singularism has featured in three important recent arguments in the philosophy of memory.

Clustered Mutations at the Murine and Human IgH Locus Exhibit Significant Linkage Consistent with Templated Mutagenesis.

Somatic hypermutation generates a myriad of Ab mutants in Ag-specific B cells, from which high-affinity mutants are selected. Chickens, sheep, and rabbits use nontemplated point mutations and templated mutations via gene conversion to diversify their expressed Ig loci, whereas mice and humans rely solely on untemplated somatic point mutations. In this study, we demonstrate that, in addition to untemplated point mutations, templated mutagenesis readily occurs at the murine and human Ig loci. We provide two distinct lines of evidence that are not explained by the Neuberger model of somatic hypermutation: 1) across multiple data sets there is significant linkage disequilibrium between individual mutations, especially among close mutations, and 2) among those mutations, those <8 bp apart are significantly more likely to match microhomologous regions in the IgHV repertoire than predicted by the mutation profiles of somatic hypermutation. Together, this supports the role of templated mutagenesis during somatic diversification of Ag-activated B cells.

Croton aemulus and C. graomogolensis (Euphorbiaceae): Two new species from Minas Gerais, Brazil, based on distinct lines of evidence and their relation to C. muscicapa and C. longibracteatus

Croton (Euphorbiaceae) includes more than 1,300 accepted species and new species of the genus are continuously being described, which are mainly from Brazil. Two new species, Croton aemulus and C. graomogolensis, are herein described, placed in C. sect. Barhamia subsect. Barhamia, and compared to C. muscicapa and C. longibracteatus. The new species are supported by their geographic distributions, ecology, and anatomical and morphological features. Both species are only known from the state of Minas Gerais, Brazil. Croton aemulus occurs in cerrado de altitude (mountain savannah) and C. graomogolensis occurs in campo rupestre (rupestrian grasslands) vegetation.

Identification of compound heterozygous variants in the noncoding RNU4ATAC gene in a Chinese family with two successive foetuses with severe microcephaly

BackgroundWhole-exome sequencing (WES) over the last few years has been increasingly employed for clinical diagnosis. However, one caveat with its use is that it inevitably fails to detect disease-causative variants that occur within noncoding RNA genes. Our experience in identifying pathogenic variants in the noncoding RNU4ATAC gene, in a Chinese family where two successive foetuses had been affected by severe microcephaly, is a case in point. These foetuses exhibited remarkably similar phenotypes in terms of their microcephaly and brain abnormalities; however, the paucity of other characteristic phenotypic features had made a precise diagnosis impossible. Given that no external causative factors had been reported/identified during the pregnancies, we sought a genetic cause for the phenotype in the proband, the second affected foetus.ResultsA search for chromosomal abnormalities and pathogenic copy number variants proved negative. WES was also negative. These initial failures prompted us to consider the potential role of RNU4ATAC, a noncoding gene implicated in microcephalic osteodysplastic primordial dwarfism type-1 (MOPD1), a severe autosomal recessive disease characterised by dwarfism, severe microcephaly and neurological abnormalities. Subsequent targeted sequencing of RNU4ATAC resulted in the identification of compound heterozygous variants, one being the most frequently reported MOPD1-causative mutation (51G>A), whereas the other was a novel 29T>A variant. Four distinct lines of evidence (allele frequency in normal populations, evolutionary conservation of the affected nucleotide, occurrence within a known mutational hotspot for MOPD1-causative variants and predicted effect on RNA secondary structure) allowed us to conclude that 29T>A is a new causative variant for MOPD1.ConclusionsOur findings highlight the limitations of WES in failing to detect variants within noncoding RNA genes and provide support for a role for whole-genome sequencing as a first-tier genetic test in paediatric medicine. Additionally, the identification of a novel RNU4ATAC variant within the mutational hotspot for MOPD1-causative variants further strengthens the critical role of the 5′ stem-loop structure of U4atac in health and disease. Finally, this analysis enabled us to provide prenatal diagnosis and genetic counselling for the mother’s third pregnancy, the first report of its kind in the context of inherited RNU4ATAC variants.

ANGPTL3 Deficiency and Protection Against Coronary Artery Disease

BackgroundFamilial combined hypolipidemia, a Mendelian condition characterized by substantial reductions in all 3 major lipid fractions, is caused by mutations that inactivate the gene angiopoietin-like 3 (ANGPTL3). Whether ANGPTL3 deficiency reduces risk of coronary artery disease (CAD) is unknown. ObjectivesThe study goal was to leverage 3 distinct lines of evidence—a family that included individuals with complete (compound heterozygote) ANGPTL3 deficiency, a population based-study of humans with partial (heterozygote) ANGPTL3 deficiency, and biomarker levels in patients with myocardial infarction (MI)—to test whether ANGPTL3 deficiency is associated with lower risk for CAD. MethodsWe assessed coronary atherosclerotic burden in 3 individuals with complete ANGPTL3 deficiency and 3 wild-type first-degree relatives using computed tomography angiography. In the population, ANGPTL3 loss-of-function (LOF) mutations were ascertained in up to 21,980 people with CAD and 158,200 control subjects. LOF mutations were defined as nonsense, frameshift, and splice-site variants, along with missense variants resulting in <25% of wild-type ANGPTL3 activity in a mouse model. In a biomarker study, circulating ANGPTL3 concentration was measured in 1,493 people who presented with MI and 3,232 control subjects. ResultsThe 3 individuals with complete ANGPTL3 deficiency showed no evidence of coronary atherosclerotic plaque. ANGPTL3 gene sequencing demonstrated that approximately 1 in 309 people was a heterozygous carrier for an LOF mutation. Compared with those without mutation, heterozygous carriers of ANGPTL3 LOF mutations demonstrated a 17% reduction in circulating triglycerides and a 12% reduction in low-density lipoprotein cholesterol. Carrier status was associated with a 34% reduction in odds of CAD (odds ratio: 0.66; 95% confidence interval: 0.44 to 0.98; p = 0.04). Individuals in the lowest tertile of circulating ANGPTL3 concentrations, compared with the highest, had reduced odds of MI (adjusted odds ratio: 0.65; 95% confidence interval: 0.55 to 0.77; p < 0.001). ConclusionsANGPTL3 deficiency is associated with protection from CAD.

PAK-dependent STAT5 serine phosphorylation is required for BCR-ABL-induced leukemogenesis

The transcription factor STAT5 (signal transducer and activator of transcription 5) is frequently activated in hematological malignancies and represents an essential signaling node downstream of the BCR-ABL oncogene. STAT5 can be phosphorylated at three positions, on a tyrosine and on the two serines S725 and S779. We have investigated the importance of STAT5 serine phosphorylation for BCR-ABL-induced leukemogenesis. In cultured bone marrow cells, expression of a STAT5 mutant lacking the S725 and S779 phosphorylation sites (STAT5SASA) prohibits transformation and induces apoptosis. Accordingly, STAT5SASA BCR-ABL+ cells display a strongly reduced leukemic potential in vivo, predominantly caused by loss of S779 phosphorylation that prevents the nuclear translocation of STAT5. Three distinct lines of evidence indicate that S779 is phosphorylated by group I p21-activated kinase (PAK). We show further that PAK-dependent serine phosphorylation of STAT5 is unaffected by BCR-ABL tyrosine kinase inhibitor treatment. Interfering with STAT5 phosphorylation could thus be a novel therapeutic approach to target BCR-ABL-induced malignancies.

Different effects of ionotropic and metabotropic glutamate receptor antagonists on attention and the attentional properties of nicotine

Distinct lines of evidence indicate that glutamate plays a primary role in modulating cognitive functions. Notably, competitive glutamate receptor antagonists acting at ionotropic N-methyl- d-aspartate (NMDA) or metabotropic glutamate 5 (mGlu5) receptors impair cognitive performance. Conversely, nicotine and other psychostimulants stimulate glutamatergic mechanisms and can act as cognitive enhancers. Hence we analysed the role of glutamate in performance of an attentional task and in nicotine-induced enhancement of attention by using the rodent five-choice serial reaction time task (5-CSRTT). Rats were trained to criterion performance and were then pre-dosed with either vehicle, the NMDA receptor antagonist (+)3-(2-carboxypiperazin-4-propyl)-1-propenyl-1-phosphonic acid (CPP, 0.3–2.0 mg/kg) or the mGlu5 antagonist 2-methyl-6-phenylethynyl-pyridine (MPEP, 1.0–9.0 mg/kg) and challenged with nicotine (0.2 mg/kg). Nicotine improved attentional performance, an effect that was weakened by doses of CPP that themselves had little impact on performance; importantly, CPP dose-dependently blunted the ability of nicotine to improve response accuracy, the major measure of signal detection in the paradigm. MPEP dose-dependently impaired signal detection under conditions with a high attentional load, an effect that was reversed by nicotine; thus, MPEP did not block nicotine-induced attentional enhancement. Co-administration of either CPP or MPEP with nicotine also produced a general slowing of performance characterised by increases in omission errors and response latencies and reduced anticipatory responding. It is concluded that activation of NMDA receptors may be an important determinant of the effects of nicotine in the 5-CSRTT. Stimulation of nicotinic receptors may also reverse attentional deficits associated with the impaired function of the glutamate network.

Environmental Tobacco Smoke: The Colic Connection

The ancient Greeks were the first to describe infant colic, a condition of inconsolable crying that may afflict as many as 28% of U.S. infants, yet the root causes of this malady remain a mystery. Among the theoretical risks are milk and soy allergies, infant temperament, and problems with the infant–caregiv-er interaction. Researchers now speculate that maternal smoking during or after pregnancy may result in gastrointestinal (GI) dysregula-tion and thus increase the risk of infant colic. This hypothesis, proposed by Brown University epidemiologist Edmond Shenassa and Mary Jean Brown, an adjunct assistant professor of society, human development, and health at Harvard, is based on a review of more than 80 papers in different fields. As reported in the October 2004 issue of Pediatrics, the focus of the researchers’ attention was the gut protein motilin. Infants with colic have higher motilin levels independent of how they are fed, suggesting this protein may play an important physiologic role in colic and other GI-related disorders among babies. Three distinct lines of evidence were used to construct the hypothesis. First, mothers who smoke are twice as likely to have infants with colic. Second, exposure to nicotine and other tobacco smoke metabolites causes higher-than-average blood motilin concentrations. Finally, pediatric studies suggest that high motilin levels may predispose infants to colic. Each year, more than 500,000 U.S. infants are born having already been exposed to secondhand smoke metabolites in utero. Many more are exposed in the first few years after birth. Exposure through breast milk may be just as serious as exposure in utero, because nicotine concentrations in breast milk may be up to three times higher than maternal blood levels. Further, says Brown, “Even if mothers don’t smoke, the impact of [their own exposure to] secondhand smoke may be substantial.” However, she says, there are no studies in which maternal exposure to environmental tobacco smoke has been directly quantified and linked to risk for colic. It also remains to be seen whether smoking interacts with other GI reactivity factors, such as milk allergy. “Given the available data, we can’t really speculate about possible interactions,” says Brown, “nor do we know what underlying mechanisms might cause interactions between risk factors.” Shenassa is presently conducting a prospective population-based study, recruiting pregnant mothers and following them for about eight weeks after birth. This will be the first study to carefully consider the effects of both smoking and motilin on infant colic. “It is significant that colic might have an environmental basis,” says S. Katharine Hammond, a professor of environmental health sciences at the University of California, Berkeley. “Unlike the costs of controlling many environmental hazards, in utero exposures to environmental tobacco smoke can be minimized with little cost through education and restricting smoking in workplaces and public places.”

An assessment of injury to sediments and sediment-dwelling organisms in the Grand Calumet River and Indiana Harbor Area of Concern, USA.

This article is the first in a series of three that describe the results of a Natural Resource Damage Assessment (NRDA) conducted in the Grand Calumet River and Indiana Harbor Area of Concern (IHAOC). The assessment area is located in northwest Indiana and was divided into nine reaches to facilitate the assessment. This component of the NRDA was undertaken to determine if sediments and sediment-dwelling organisms have been injured due to exposure to contaminants that have accumulated in sediments as a result of discharges of oil or releases of other hazardous substances from industrial, municipal, and nonpoint sources. To support this assessment, information was compiled on the chemical composition of sediment and pore water; on the toxicity of whole sediments, pore water, and elutriates; and on the status of benthic invertebrate communities. The data on each of these indicators were compared to regionally relevant benchmarks to assess the presence and extent of injury to surface water resources ( i.e., sediments) or biological resources ( i.e., sediment-dwelling organisms). The results of this assessment indicate that sediment injury has occurred throughout the assessment area, with up to four distinct lines of evidence demonstrating injury within the various reaches. The primary contaminants of concern ( i.e., those substances that are present at concentrations that are sufficient to cause or substantially contribute to sediment injury) include metals, polycyclic aromatic hydrocarbons, and total polychlorinated biphenyls.

Ecological risk assessment in a large river-reservoir: 2. Fish community

This paper summarizes the assessment of risks to fishes in the Clinch River Operable Unit due to contaminants released by the U.S. Department of Energy's activities on its Oak Ridge Reservation in Tennessee. This paper focuses on the most contaminated area, the Poplar Creek (PC) embayment. The assessment is of interest because of its use of five distinct lines of evidence: fish community surveys, fish body burdens, toxicity tests of ambient waters, suborganismal bioindicators, and single chemical toxicity tests. None of these lines of evidence provided unambiguous evidence of a significant risk, but the surveys indicated that the fish community in PC was depauperate, polychlorinated biphenyl body burdens may have been at toxic levels in catfish, one of the three tests of ambient water showed clear toxicity, some of the indicators were indicative of toxic effects, and concentrations that have been toxic in the laboratory were detected periodically. Interpretation was further complicated by upstream contamination of both the Clinch River and PC. The risk characterization was performed by evaluating each line of evidence separately and then weighing the evidence using an ecoepidemiological approach.

Methotrexate and sulfasalazine promote adenosine release by a mechanism that requires ecto-5'-nucleotidase-mediated conversion of adenine nucleotides.

We and others have shown that an increased extracellular concentration of adenosine mediates the antiinflammatory effects of methotrexate and sulfasalazine both in vitro and in vivo, but the mechanism by which these drugs increase extracellular adenosine remains unclear. The results of the experiments reported here provide three distinct lines of evidence that adenosine results from the ecto-5'-nucleotidase- mediated conversion of adenine nucleotides to adenosine. First, pretreatment of a human microvascular endothelial cell line (HMEC-1) with methotrexate increases extracellular adenosine after exposure of the pretreated cells to activated neutrophils; the ecto-5'-nucleotidase inhibitor alpha, beta-methylene adenosine-5'-diphosphate (APCP) abrogates completely the increase in extracellular adenosine. Second, there is no methotrexate-mediated increase in extracellular adenosine concentration in the supernate of cells deficient in ecto-5'-nucleotidase, but there is a marked increase in extracellular adenosine concentration in the supernates of these cells after transfection and surface expression of the enzyme. Finally, as we have shown previously, adenosine mediates the antiinflammatory effects of methotrexate and sulfasalazine in the murine air pouch model of inflammation, and injection of APCP, the ecto-5'-nucleotidase inhibitor, abrogates completely the increase in adenosine and the decrement in inflammation in this in vivo model. These results not only show that ecto-5'-nucleotidase activity is a critical mediator of methotrexate- and sulfasalazine-induced antiinflammatory activity in vitro and in vivo but also indicate that adenine nucleotides, released from cells, are the source of extracellular adenosine.

Proteinases and proteinase inhibitors as modulators of animal cell growth.

1. Three distinct lines of evidence indicate that proteinases are involved in the growth of cultured animal cells. 2. Endogenous growth-related proteinases have been identified, and exogenous proteinases can also stimulate cell proliferation, probably by different mechanisms. In some cases, higher concentrations of proteinases are cytotoxic. 3. Proteinase inhibitors, not surprisingly, inhibit cell growth, but can also be mitogenic at sub-inhibitory concentrations. 4. There must, therefore, be at least three major cellular processes in which proteinases or proteinase inhibitors can operate to exert a direct effect on cell proliferation. 5. Details of one action of an exogenous proteinase, typified by thrombin and the thrombin receptor, are becoming clear at the molecular level, but thrombin probably activates at least two intracellular signalling systems, as well as acting as a growth inhibitor in some situations. 6. Much remains to be investigated in other examples.

Isoquinolines, beta-carbolines and alcohol drinking: involvement of opioid and dopaminergic mechanisms.

Two classes of amine-aldehyde adducts, the tetrahydroisoquinoline (TIQ) and beta-carboline (THBC) compounds, have been implicated in the mechanism in the brain underlying the addictive drinking of alcohol. One part of this review focuses on the large amount of evidence unequivocally demonstrating not only the corporeal synthesis of the TIQs and THBCs but their sequestration in brain tissue as well. Experimental studies published recently have revealed that exposure to alcohol enhances markedly the endogenous formation of condensation products. Apart from their multiple neuropharmacological actions, certain adducts when delivered directly into the brain of either the rat or monkey, to circumvent the brain's blood-barrier system, can evoke an intense and dose-dependent increase in the voluntary drinking of solutions of alcohol even in noxious concentrations. That the abnormal intake of alcohol is related functionally to opioid receptors in the brain is likely on the basis of several distinct lines of evidence which include: the attenuation of alcohol drinking by opioid receptor antagonists; binding of a TIQ to opiate receptors in the brain; and marked differences in enkephalin values in animals genetically predisposed to the ingestion of alcohol. Finally, it is proposed that the dopaminergic reward pathways which traverse the meso-limbic-forebrain systems of the brain more than likely constitute an integrative anatomical substrate for the adduct-opioid cascade of neuronal events which promote and sustain the aberrant drinking of alcohol.

Structure and function in circadian timing systems: Evidence for multiple coupled circadian oscillators

Considerable progress has been made in elucidating the mechanisms underlying the generation of circadian rhythmicity. This review describes several distinct lines of evidence which converge on the general hypothesis that circadian timing systems consist of multiple circadian oscillators, coordinated by both hierarchical and non-hierarchical coupling relationships. Such a view is supported by the complex phenomenology of circadian systems, as well as by physiological considerations. We have attempted wherever possible to integrate these two sources of evidence, in order to define the current “state of the art” in bridging the gap between structure and function in the analysis of circadian timing systems. While we concentrate mainly on the mammalian, and particularly the rodent, circadian system, we also incorporate comparative evidence obtained from a variety of vertebrate and invertebrate species.